Applied Evidence

CASE Alice D is 20 years old and has type 1 diabetes, as well as retinopathy, hypertension, bipolar I disorder, and hyperlipidemia. She is a new patient at your clinic and reports that she is ­“occasionally homeless” and has difficulty affording food.

You renew Ms. D’s prescriptions during the visit, discuss nutrition with her, and order lab testing, including a test of hemoglobin A1C, a lipid panel, and a basic metabolic panel. You ask her to follow up in 1 week to discuss the test results and next steps in her care.

© Masterfile

According to a 2016 report from the US Department of Agriculture (USDA) Economic Research Service, an estimated 12.3% of households in the United States are “food insecure.”¹ To ascertain what food security and insecurity are, the USDA measured numerous variables, including household structure, race and ethnicity, geography, and income. The report of the Economic Research Service stands as one of the largest domestic sources of information about food insecurity.

Food insecurity is defined as “food intake of household members [that is] reduced and normal eating patterns that are disrupted.”¹ It is often measured “per household,” but those data must be interpreted carefully because food insecurity affects household members differently. Some members, such as children, might be affected only mildly; adults, on the other hand, might be more severely affected. (Adults may, for instance, disrupt or skip their meals to maintain normal diets and meal patterns for their children.) In some households, food insecurity affects only a single member—such as an older adult—because of conditions unique to the people living in the home.

Adults may disrupt or skip their meals to maintain normal diets and meal patterns for their children.

In this article, we review variables that can give rise to food insecurity in children, adults, and the elderly, and offer ­strategies to the family physician for identifying and alleviating the burden of food insecurity in these populations.

Food insecurity threatens children’s health, development

In 2016, households with children faced a higher level of food insecurity (16.5%) than the national average (12.3%).¹ In a study of more than 280,000 households, food ­insecurity was sometimes so severe that children skipped meals or did not eat for the whole day.¹ Although income strongly correlates with food insecurity, evidence shows that families above and below the poverty line suffer from food insecurity.^2,3

According to the USDA, the rate of food insecurity is higher than the national average of 12.3% in several subgroups of ­children¹:

• households with children < 6 years of age (16.6%)
• households with children headed by a single woman (31.6%) or single man (21.7%)
• households headed by a black non-Hispanic (22.5%) or Hispanic (18.5%) person
• low-income households in which the annual income is < 185% of the poverty threshold (31.6%).

Continue to: Evidence suggests that...

Evidence suggests that children in food-insecure homes experience poor diet, impaired cognitive development, an increased risk of chronic illness in adulthood, and emotional and behavioral problems.^4-7 For caregivers in food-insecure homes, purchase price is the most influential factor when making food purchasing decisions. Thus, caregivers often purchase cheaper, more calorie-dense foods, rather than more expensive, nutrient-rich foods—leading to childhood obesity.⁸

Food insecurity affects 12% of households in the United States.

Relief eludes many. Federal programs, such as the National School Lunch Program, School Breakfast Program, the Summer Food Service Program, and the Child and Adult Care Food Program, provide free or reduced-price meals for school-age children. Although these programs reduce food insecurity in households that participate, program policy has established that participation is based on household income.⁹ This is problematic: According to the literature,² the income of 50% of households that are food-insecure is above the federal poverty level.

It would be more effective to have these programs target families based on geography, not income, because programs would then benefit those who are food-insecure but who live above the poverty line. Location is a significant factor in identifying food-insecure populations: Households outside metropolitan areas are disproportionately affected.¹ If these programs were to privilege geography over income, they would include (for example): families in school districts with a low number of grocery stores; families with poor access to public transportation; and families that live in a “food desert”—ie, where fresh, low-cost food options are overshadowed by fast food.

One such program closely applied the model of privilege based on geography: In 2010, the Healthy, Hunger-Free Kids Act was passed, with a Community Eligibility Provision (CEP) that funded school districts in which ≥ 40% of students lived below the poverty line, so that students in those districts received a free school lunch.¹⁰ Although eligibility for CEP is still based on income, benefits go to all students who live in the district, including food-insecure students who live in a household above the poverty line. If eligibility criteria were expanded with CEP so that more school districts could participate, it might solve many obstacles faced by other existing programs.

Programs that provide nutrition for households with an infant or young child—eg, the Women, Infants and Children Special Supplemental Nutrition Program (WIC) and the Supplemental Nutrition Assistance Program (SNAP)—reduce food insecurity in households by 20%. However, several unstudied factors can affect food insecurity in families beyond these programs¹¹; some assumptions about food insecurity, for example, strongly point to the influence of maternal mental health.¹²

Continue to: Data from the...

Data from the Early Childhood Longitudinal Study, Birth Cohort showed that mothers (with an infant) who were suffering from depression had a significantly increased risk of food insecurity.¹³ To better identify infants at risk of food insecurity, it would be beneficial to identify women suffering from depression during pregnancy or postpartum.¹³ These patients could then be referred to WIC and for SNAP benefits.

What you can do. The American Academy of Pediatrics recommends that physicians identify families that are food-insecure by conducting a validated¹⁴ 2-question survey about food insecurity at every health-­maintenance visit, as long as the child is a patient in the practice (TABLE 1).¹⁵ Physicians can then refer families that screen positively to local WIC and SNAP centers.

Ideally, physicians should be prepared to facilitate more active engagement by providing patients with the contact information of staff members working in such local programs. Staffing the practice with a patient-care manager can be an efficient way to navigate this process.

CASE Over the 6 weeks following Ms. D’s visit with you, she is admitted 5 times to the hospital in diabetic ketoacidosis, always with a significantly elevated blood glucose level. At each admission, she admits to “sometimes forgetting” to take insulin. Hospital staff members do not ask about her food intake. During each hospitalization, Ms. D is treated with insulin and intravenous fluids and discharged to home on her prior insulin regimen.

During a follow-up appointment with you and the clinic’s nurse–care manager, she talks about missing doses of insulin. She tells you that she has been getting food from the local food pantry, where available stocks are typically carbohydrate-based, including bread, rice, and cereal. She admits that she cannot afford other kinds of food—specifically, those that contain protein and monosaturated and polyunsaturated fats.

Continue to: Adults...

The correlation between food insecurity and income is strong—evidenced by the spike in the number of adults who reported food insecurity during the 2008-2011 recession in the United States, to a high of 14.9%.¹ As noted, households with children are more likely to report food insecurity. In addition, studies show that limited resources, race and ethnicity, underemployment or unemployment, and high housing costs are also strongly associated with food insecurity.¹⁶ Even subtle economic fluctuations—for example, an increase in the price of gasoline, natural gas, or electricity—contribute to food insecurity.¹⁷ Debt and coping mechanisms influence whether a household living below the poverty line is food-secure or food-insecure. Additional factors contributing to food insecurity include participation in SNAP, education, and severe depression.

To identify families that are food-insecure, conduct the 2-question AAP survey on food insecurity at every healthmaintenance visit.

Food insecurity in adults reduces the quality of food and nutritional intake, and is associated with chronic morbidity, such as type 2 diabetes, hypertension, and obesity.^5-7 Adults in food-insecure homes are more likely to purchase cheap, calorie-dense, nutritionally poor foods (or refrain from purchasing food altogether, to pay other debts).^17,18 The literature further suggests that food insecurity is associated with diseases that limit function and lead to disability, such as arthritis, stroke, and coronary artery disease, in adults and older adults (> 65 years of age; see the next section).^5,6,19 These studies are weak, however, in their ability to show directionality: Does food insecurity cause disability or does disability cause food insecurity?

Patchwork of programs. Programs such as WIC are available for women who are pregnant or have children < 5 years of age. Federal programs for adults who do not have children are scarce, however, and the burden of food insecurity for this population is typically addressed by local programs, such as food banks and food kitchens. Evidence shows that (1) combining the efforts of federal and local food programs is the most effective method of stymieing food insecurity in adults and (2) it would benefit food-insecure adults to have access to such programs. Regrettably, many food programs are underutilized because of barriers that include poor outreach, ineffectual application, and ineligibility.

What you can do. Although it might not be an official, professional society guideline to include questions about food security in a patient wellness survey, physicians should consider creating one for their practice that they (or the office staff) can administer. Furthermore, physicians (or, again, the office staff) should familiarize themselves with programs in the community, such as SNAP or a food bank, to which they can refer patients, as needed.

CASE You ask the nurse–care manager to consult with staff of the food bank and request that, based on your evaluation and recommendation, Ms. D be given more protein-based foods, including peanut butter and beans, when she visits the food bank. The nurse–care manager also makes arrangements to procure an insulin pump for Ms. D.

Continue to: In a short time...

In a short time, Ms. D’s blood glucose level normalizes. She has no further admissions for diabetic ketoacidosis.

Older adults: Interplay of risk factors takes a toll

The USDA Economic Research Report on food insecurity¹ states that older adults (≥ 65 years of age) report a lower rate of food insecurity—ie, 7.8% of households with an older adult and 8.9% of households in which the older adult lives alone—compared with the national average.¹ The report is limited, however, in its ability to extrapolate data from older adults on food insecurity because its focus is on factors specific to adults and children.

Factors that contribute to food insecurity in the elderly include race and ethnicity, education, income, being a SNAP recipient, and severe depression.^1,2,17,20,21 Older adult subgroups more likely to be food-insecure are Hispanic and black non-Hispanic—both significantly associated with being food-­insecure, with Hispanic populations reporting the highest rates of food insecurity.^20,21 This is a particularly interesting observation: Many traditional Hispanic homes are multigenerational and maintain a culture in which older adults are cared for by their children; that value system might be an indication of why many Hispanic households are disproportionately affected by food insecurity.

Adults in food-insecure homes are more likely to purchase cheap, calorie-dense food that lacks nutrition.

Other problems directly caused or exacerbated by food insecurity in the older population include a higher risk of malnutrition from periodontal disease, more frequent hospital admissions with longer length of stay, and an increased rate of falls and fractures. Polypharmacy, which can cause food–drug interactions that inhibit uptake of vitamins or create a higher demand for certain vitamins, is a noteworthy problem associated with food insecurity.

Problems with functionality might prevent older adults from performing physical tasks, such as shopping and preparing foods.^21,22 Older adults who reported functional impairment in performing activities of daily living are more likely to report food insecurity.^21,22 Last,older adults who live alone are more likely to have diminished nutritional intake than those who live with a spouse or partner.^2,22,23

Continue to: Legislation enacted in 2010...

Legislation enacted in 2010 under the existing Older Americans Act provided home-delivered meals, nutritional screening, and education counseling to Americans > 60 years of age. That provision was not based on an income test, however, and served only 18% of the older population.²³ (Other programs, such as SNAP, are utilized to a greater degree: 30% of eligible older adults participate, 75% of whom live alone.²³) Possible reasons for underutilization include restricted funding, lower education level, lack of outreach, a confusing application process, and the impression that the process is intrusive.^24-26

What you can do. To improve the nutritional intake of older adults, reconcile the patient’s medications at each visit to ensure that polypharmacy does not play a role in causing or exacerbating underlying conditions that can lead to poor nutritional intake. AARP (formerly the American Association of Retired Persons) recommends devising and conducting a survey of food insecurity with older adults that includes the 2-question American Academy of Pediatrics survey described earlier²⁷ (TABLE 2^15,27).Such a survey, which can be administered by office staff, should also include a screen for depression, financial stability, ability to perform activities of daily living (eg, shopping and driving), and changes in diet that are a result of periodontal disease. The survey should also inquire about the effects of current or chronic disability on day-to-day life.

For all patients: Refer to community resources

The problems of food insecurity presented here only broadly address what each of these 3 groups face. Although the overall trend in food insecurity has been downward since 2011, deeper issues of food insecurity need to be studied more within each population. This is particularly true among the geriatric population, whose numbers are increasing, and among ethnic minorities, including black non-Hispanics, and Hispanics, who face additional daily stressors because of implicit biases in society.

Ask older adults about any decline in performing activities of daily living, which can lead to food insecurity and poor nutritional intake.

More study is needed to decrease the rate of food insecurity across all populations in the United States. In the interim, family physicians should take advantage of their role in the care of families, children, and older people to address the problem of food insecurity in their patient population by applying the interventions we’ve outlined, with an emphasis on referral to resources in the community.

CORRESPONDENCE
Lillian Amèzquita, BS, The Warren Alpert Medical School, Brown University, Box G-9999, 222 Richmond Street, Providence, RI; [email protected].

CASE Alice D is 20 years old and has type 1 diabetes, as well as retinopathy, hypertension, bipolar I disorder, and hyperlipidemia. She is a new patient at your clinic and reports that she is ­“occasionally homeless” and has difficulty affording food.

You renew Ms. D’s prescriptions during the visit, discuss nutrition with her, and order lab testing, including a test of hemoglobin A1C, a lipid panel, and a basic metabolic panel. You ask her to follow up in 1 week to discuss the test results and next steps in her care.

© Masterfile

According to a 2016 report from the US Department of Agriculture (USDA) Economic Research Service, an estimated 12.3% of households in the United States are “food insecure.”¹ To ascertain what food security and insecurity are, the USDA measured numerous variables, including household structure, race and ethnicity, geography, and income. The report of the Economic Research Service stands as one of the largest domestic sources of information about food insecurity.

Food insecurity is defined as “food intake of household members [that is] reduced and normal eating patterns that are disrupted.”¹ It is often measured “per household,” but those data must be interpreted carefully because food insecurity affects household members differently. Some members, such as children, might be affected only mildly; adults, on the other hand, might be more severely affected. (Adults may, for instance, disrupt or skip their meals to maintain normal diets and meal patterns for their children.) In some households, food insecurity affects only a single member—such as an older adult—because of conditions unique to the people living in the home.

Adults may disrupt or skip their meals to maintain normal diets and meal patterns for their children.

In this article, we review variables that can give rise to food insecurity in children, adults, and the elderly, and offer ­strategies to the family physician for identifying and alleviating the burden of food insecurity in these populations.

Food insecurity threatens children’s health, development

In 2016, households with children faced a higher level of food insecurity (16.5%) than the national average (12.3%).¹ In a study of more than 280,000 households, food ­insecurity was sometimes so severe that children skipped meals or did not eat for the whole day.¹ Although income strongly correlates with food insecurity, evidence shows that families above and below the poverty line suffer from food insecurity.^2,3

According to the USDA, the rate of food insecurity is higher than the national average of 12.3% in several subgroups of ­children¹:

• households with children < 6 years of age (16.6%)
• households with children headed by a single woman (31.6%) or single man (21.7%)
• households headed by a black non-Hispanic (22.5%) or Hispanic (18.5%) person
• low-income households in which the annual income is < 185% of the poverty threshold (31.6%).

Continue to: Evidence suggests that...

Evidence suggests that children in food-insecure homes experience poor diet, impaired cognitive development, an increased risk of chronic illness in adulthood, and emotional and behavioral problems.^4-7 For caregivers in food-insecure homes, purchase price is the most influential factor when making food purchasing decisions. Thus, caregivers often purchase cheaper, more calorie-dense foods, rather than more expensive, nutrient-rich foods—leading to childhood obesity.⁸

Food insecurity affects 12% of households in the United States.

Relief eludes many. Federal programs, such as the National School Lunch Program, School Breakfast Program, the Summer Food Service Program, and the Child and Adult Care Food Program, provide free or reduced-price meals for school-age children. Although these programs reduce food insecurity in households that participate, program policy has established that participation is based on household income.⁹ This is problematic: According to the literature,² the income of 50% of households that are food-insecure is above the federal poverty level.

It would be more effective to have these programs target families based on geography, not income, because programs would then benefit those who are food-insecure but who live above the poverty line. Location is a significant factor in identifying food-insecure populations: Households outside metropolitan areas are disproportionately affected.¹ If these programs were to privilege geography over income, they would include (for example): families in school districts with a low number of grocery stores; families with poor access to public transportation; and families that live in a “food desert”—ie, where fresh, low-cost food options are overshadowed by fast food.

One such program closely applied the model of privilege based on geography: In 2010, the Healthy, Hunger-Free Kids Act was passed, with a Community Eligibility Provision (CEP) that funded school districts in which ≥ 40% of students lived below the poverty line, so that students in those districts received a free school lunch.¹⁰ Although eligibility for CEP is still based on income, benefits go to all students who live in the district, including food-insecure students who live in a household above the poverty line. If eligibility criteria were expanded with CEP so that more school districts could participate, it might solve many obstacles faced by other existing programs.

Programs that provide nutrition for households with an infant or young child—eg, the Women, Infants and Children Special Supplemental Nutrition Program (WIC) and the Supplemental Nutrition Assistance Program (SNAP)—reduce food insecurity in households by 20%. However, several unstudied factors can affect food insecurity in families beyond these programs¹¹; some assumptions about food insecurity, for example, strongly point to the influence of maternal mental health.¹²

Continue to: Data from the...

Data from the Early Childhood Longitudinal Study, Birth Cohort showed that mothers (with an infant) who were suffering from depression had a significantly increased risk of food insecurity.¹³ To better identify infants at risk of food insecurity, it would be beneficial to identify women suffering from depression during pregnancy or postpartum.¹³ These patients could then be referred to WIC and for SNAP benefits.

What you can do. The American Academy of Pediatrics recommends that physicians identify families that are food-insecure by conducting a validated¹⁴ 2-question survey about food insecurity at every health-­maintenance visit, as long as the child is a patient in the practice (TABLE 1).¹⁵ Physicians can then refer families that screen positively to local WIC and SNAP centers.

Ideally, physicians should be prepared to facilitate more active engagement by providing patients with the contact information of staff members working in such local programs. Staffing the practice with a patient-care manager can be an efficient way to navigate this process.

CASE Over the 6 weeks following Ms. D’s visit with you, she is admitted 5 times to the hospital in diabetic ketoacidosis, always with a significantly elevated blood glucose level. At each admission, she admits to “sometimes forgetting” to take insulin. Hospital staff members do not ask about her food intake. During each hospitalization, Ms. D is treated with insulin and intravenous fluids and discharged to home on her prior insulin regimen.

During a follow-up appointment with you and the clinic’s nurse–care manager, she talks about missing doses of insulin. She tells you that she has been getting food from the local food pantry, where available stocks are typically carbohydrate-based, including bread, rice, and cereal. She admits that she cannot afford other kinds of food—specifically, those that contain protein and monosaturated and polyunsaturated fats.

Continue to: Adults...

The correlation between food insecurity and income is strong—evidenced by the spike in the number of adults who reported food insecurity during the 2008-2011 recession in the United States, to a high of 14.9%.¹ As noted, households with children are more likely to report food insecurity. In addition, studies show that limited resources, race and ethnicity, underemployment or unemployment, and high housing costs are also strongly associated with food insecurity.¹⁶ Even subtle economic fluctuations—for example, an increase in the price of gasoline, natural gas, or electricity—contribute to food insecurity.¹⁷ Debt and coping mechanisms influence whether a household living below the poverty line is food-secure or food-insecure. Additional factors contributing to food insecurity include participation in SNAP, education, and severe depression.

To identify families that are food-insecure, conduct the 2-question AAP survey on food insecurity at every healthmaintenance visit.

Food insecurity in adults reduces the quality of food and nutritional intake, and is associated with chronic morbidity, such as type 2 diabetes, hypertension, and obesity.^5-7 Adults in food-insecure homes are more likely to purchase cheap, calorie-dense, nutritionally poor foods (or refrain from purchasing food altogether, to pay other debts).^17,18 The literature further suggests that food insecurity is associated with diseases that limit function and lead to disability, such as arthritis, stroke, and coronary artery disease, in adults and older adults (> 65 years of age; see the next section).^5,6,19 These studies are weak, however, in their ability to show directionality: Does food insecurity cause disability or does disability cause food insecurity?

Patchwork of programs. Programs such as WIC are available for women who are pregnant or have children < 5 years of age. Federal programs for adults who do not have children are scarce, however, and the burden of food insecurity for this population is typically addressed by local programs, such as food banks and food kitchens. Evidence shows that (1) combining the efforts of federal and local food programs is the most effective method of stymieing food insecurity in adults and (2) it would benefit food-insecure adults to have access to such programs. Regrettably, many food programs are underutilized because of barriers that include poor outreach, ineffectual application, and ineligibility.

What you can do. Although it might not be an official, professional society guideline to include questions about food security in a patient wellness survey, physicians should consider creating one for their practice that they (or the office staff) can administer. Furthermore, physicians (or, again, the office staff) should familiarize themselves with programs in the community, such as SNAP or a food bank, to which they can refer patients, as needed.

CASE You ask the nurse–care manager to consult with staff of the food bank and request that, based on your evaluation and recommendation, Ms. D be given more protein-based foods, including peanut butter and beans, when she visits the food bank. The nurse–care manager also makes arrangements to procure an insulin pump for Ms. D.

Continue to: In a short time...

In a short time, Ms. D’s blood glucose level normalizes. She has no further admissions for diabetic ketoacidosis.

Older adults: Interplay of risk factors takes a toll

The USDA Economic Research Report on food insecurity¹ states that older adults (≥ 65 years of age) report a lower rate of food insecurity—ie, 7.8% of households with an older adult and 8.9% of households in which the older adult lives alone—compared with the national average.¹ The report is limited, however, in its ability to extrapolate data from older adults on food insecurity because its focus is on factors specific to adults and children.

Factors that contribute to food insecurity in the elderly include race and ethnicity, education, income, being a SNAP recipient, and severe depression.^1,2,17,20,21 Older adult subgroups more likely to be food-insecure are Hispanic and black non-Hispanic—both significantly associated with being food-­insecure, with Hispanic populations reporting the highest rates of food insecurity.^20,21 This is a particularly interesting observation: Many traditional Hispanic homes are multigenerational and maintain a culture in which older adults are cared for by their children; that value system might be an indication of why many Hispanic households are disproportionately affected by food insecurity.

Adults in food-insecure homes are more likely to purchase cheap, calorie-dense food that lacks nutrition.

Other problems directly caused or exacerbated by food insecurity in the older population include a higher risk of malnutrition from periodontal disease, more frequent hospital admissions with longer length of stay, and an increased rate of falls and fractures. Polypharmacy, which can cause food–drug interactions that inhibit uptake of vitamins or create a higher demand for certain vitamins, is a noteworthy problem associated with food insecurity.

Problems with functionality might prevent older adults from performing physical tasks, such as shopping and preparing foods.^21,22 Older adults who reported functional impairment in performing activities of daily living are more likely to report food insecurity.^21,22 Last,older adults who live alone are more likely to have diminished nutritional intake than those who live with a spouse or partner.^2,22,23

Continue to: Legislation enacted in 2010...

Legislation enacted in 2010 under the existing Older Americans Act provided home-delivered meals, nutritional screening, and education counseling to Americans > 60 years of age. That provision was not based on an income test, however, and served only 18% of the older population.²³ (Other programs, such as SNAP, are utilized to a greater degree: 30% of eligible older adults participate, 75% of whom live alone.²³) Possible reasons for underutilization include restricted funding, lower education level, lack of outreach, a confusing application process, and the impression that the process is intrusive.^24-26

What you can do. To improve the nutritional intake of older adults, reconcile the patient’s medications at each visit to ensure that polypharmacy does not play a role in causing or exacerbating underlying conditions that can lead to poor nutritional intake. AARP (formerly the American Association of Retired Persons) recommends devising and conducting a survey of food insecurity with older adults that includes the 2-question American Academy of Pediatrics survey described earlier²⁷ (TABLE 2^15,27).Such a survey, which can be administered by office staff, should also include a screen for depression, financial stability, ability to perform activities of daily living (eg, shopping and driving), and changes in diet that are a result of periodontal disease. The survey should also inquire about the effects of current or chronic disability on day-to-day life.

For all patients: Refer to community resources

The problems of food insecurity presented here only broadly address what each of these 3 groups face. Although the overall trend in food insecurity has been downward since 2011, deeper issues of food insecurity need to be studied more within each population. This is particularly true among the geriatric population, whose numbers are increasing, and among ethnic minorities, including black non-Hispanics, and Hispanics, who face additional daily stressors because of implicit biases in society.

Ask older adults about any decline in performing activities of daily living, which can lead to food insecurity and poor nutritional intake.

More study is needed to decrease the rate of food insecurity across all populations in the United States. In the interim, family physicians should take advantage of their role in the care of families, children, and older people to address the problem of food insecurity in their patient population by applying the interventions we’ve outlined, with an emphasis on referral to resources in the community.

CORRESPONDENCE
Lillian Amèzquita, BS, The Warren Alpert Medical School, Brown University, Box G-9999, 222 Richmond Street, Providence, RI; [email protected].

CASE Alice D is 20 years old and has type 1 diabetes, as well as retinopathy, hypertension, bipolar I disorder, and hyperlipidemia. She is a new patient at your clinic and reports that she is ­“occasionally homeless” and has difficulty affording food.

You renew Ms. D’s prescriptions during the visit, discuss nutrition with her, and order lab testing, including a test of hemoglobin A1C, a lipid panel, and a basic metabolic panel. You ask her to follow up in 1 week to discuss the test results and next steps in her care.

© Masterfile

According to a 2016 report from the US Department of Agriculture (USDA) Economic Research Service, an estimated 12.3% of households in the United States are “food insecure.”¹ To ascertain what food security and insecurity are, the USDA measured numerous variables, including household structure, race and ethnicity, geography, and income. The report of the Economic Research Service stands as one of the largest domestic sources of information about food insecurity.

Food insecurity is defined as “food intake of household members [that is] reduced and normal eating patterns that are disrupted.”¹ It is often measured “per household,” but those data must be interpreted carefully because food insecurity affects household members differently. Some members, such as children, might be affected only mildly; adults, on the other hand, might be more severely affected. (Adults may, for instance, disrupt or skip their meals to maintain normal diets and meal patterns for their children.) In some households, food insecurity affects only a single member—such as an older adult—because of conditions unique to the people living in the home.

Adults may disrupt or skip their meals to maintain normal diets and meal patterns for their children.

In this article, we review variables that can give rise to food insecurity in children, adults, and the elderly, and offer ­strategies to the family physician for identifying and alleviating the burden of food insecurity in these populations.

Food insecurity threatens children’s health, development

In 2016, households with children faced a higher level of food insecurity (16.5%) than the national average (12.3%).¹ In a study of more than 280,000 households, food ­insecurity was sometimes so severe that children skipped meals or did not eat for the whole day.¹ Although income strongly correlates with food insecurity, evidence shows that families above and below the poverty line suffer from food insecurity.^2,3

According to the USDA, the rate of food insecurity is higher than the national average of 12.3% in several subgroups of ­children¹:

• households with children < 6 years of age (16.6%)
• households with children headed by a single woman (31.6%) or single man (21.7%)
• households headed by a black non-Hispanic (22.5%) or Hispanic (18.5%) person
• low-income households in which the annual income is < 185% of the poverty threshold (31.6%).

Continue to: Evidence suggests that...

Evidence suggests that children in food-insecure homes experience poor diet, impaired cognitive development, an increased risk of chronic illness in adulthood, and emotional and behavioral problems.^4-7 For caregivers in food-insecure homes, purchase price is the most influential factor when making food purchasing decisions. Thus, caregivers often purchase cheaper, more calorie-dense foods, rather than more expensive, nutrient-rich foods—leading to childhood obesity.⁸

Food insecurity affects 12% of households in the United States.

Relief eludes many. Federal programs, such as the National School Lunch Program, School Breakfast Program, the Summer Food Service Program, and the Child and Adult Care Food Program, provide free or reduced-price meals for school-age children. Although these programs reduce food insecurity in households that participate, program policy has established that participation is based on household income.⁹ This is problematic: According to the literature,² the income of 50% of households that are food-insecure is above the federal poverty level.

It would be more effective to have these programs target families based on geography, not income, because programs would then benefit those who are food-insecure but who live above the poverty line. Location is a significant factor in identifying food-insecure populations: Households outside metropolitan areas are disproportionately affected.¹ If these programs were to privilege geography over income, they would include (for example): families in school districts with a low number of grocery stores; families with poor access to public transportation; and families that live in a “food desert”—ie, where fresh, low-cost food options are overshadowed by fast food.

One such program closely applied the model of privilege based on geography: In 2010, the Healthy, Hunger-Free Kids Act was passed, with a Community Eligibility Provision (CEP) that funded school districts in which ≥ 40% of students lived below the poverty line, so that students in those districts received a free school lunch.¹⁰ Although eligibility for CEP is still based on income, benefits go to all students who live in the district, including food-insecure students who live in a household above the poverty line. If eligibility criteria were expanded with CEP so that more school districts could participate, it might solve many obstacles faced by other existing programs.

Programs that provide nutrition for households with an infant or young child—eg, the Women, Infants and Children Special Supplemental Nutrition Program (WIC) and the Supplemental Nutrition Assistance Program (SNAP)—reduce food insecurity in households by 20%. However, several unstudied factors can affect food insecurity in families beyond these programs¹¹; some assumptions about food insecurity, for example, strongly point to the influence of maternal mental health.¹²

Continue to: Data from the...

Data from the Early Childhood Longitudinal Study, Birth Cohort showed that mothers (with an infant) who were suffering from depression had a significantly increased risk of food insecurity.¹³ To better identify infants at risk of food insecurity, it would be beneficial to identify women suffering from depression during pregnancy or postpartum.¹³ These patients could then be referred to WIC and for SNAP benefits.

What you can do. The American Academy of Pediatrics recommends that physicians identify families that are food-insecure by conducting a validated¹⁴ 2-question survey about food insecurity at every health-­maintenance visit, as long as the child is a patient in the practice (TABLE 1).¹⁵ Physicians can then refer families that screen positively to local WIC and SNAP centers.

Ideally, physicians should be prepared to facilitate more active engagement by providing patients with the contact information of staff members working in such local programs. Staffing the practice with a patient-care manager can be an efficient way to navigate this process.

CASE Over the 6 weeks following Ms. D’s visit with you, she is admitted 5 times to the hospital in diabetic ketoacidosis, always with a significantly elevated blood glucose level. At each admission, she admits to “sometimes forgetting” to take insulin. Hospital staff members do not ask about her food intake. During each hospitalization, Ms. D is treated with insulin and intravenous fluids and discharged to home on her prior insulin regimen.

During a follow-up appointment with you and the clinic’s nurse–care manager, she talks about missing doses of insulin. She tells you that she has been getting food from the local food pantry, where available stocks are typically carbohydrate-based, including bread, rice, and cereal. She admits that she cannot afford other kinds of food—specifically, those that contain protein and monosaturated and polyunsaturated fats.

Continue to: Adults...

The correlation between food insecurity and income is strong—evidenced by the spike in the number of adults who reported food insecurity during the 2008-2011 recession in the United States, to a high of 14.9%.¹ As noted, households with children are more likely to report food insecurity. In addition, studies show that limited resources, race and ethnicity, underemployment or unemployment, and high housing costs are also strongly associated with food insecurity.¹⁶ Even subtle economic fluctuations—for example, an increase in the price of gasoline, natural gas, or electricity—contribute to food insecurity.¹⁷ Debt and coping mechanisms influence whether a household living below the poverty line is food-secure or food-insecure. Additional factors contributing to food insecurity include participation in SNAP, education, and severe depression.

To identify families that are food-insecure, conduct the 2-question AAP survey on food insecurity at every healthmaintenance visit.

Food insecurity in adults reduces the quality of food and nutritional intake, and is associated with chronic morbidity, such as type 2 diabetes, hypertension, and obesity.^5-7 Adults in food-insecure homes are more likely to purchase cheap, calorie-dense, nutritionally poor foods (or refrain from purchasing food altogether, to pay other debts).^17,18 The literature further suggests that food insecurity is associated with diseases that limit function and lead to disability, such as arthritis, stroke, and coronary artery disease, in adults and older adults (> 65 years of age; see the next section).^5,6,19 These studies are weak, however, in their ability to show directionality: Does food insecurity cause disability or does disability cause food insecurity?

Patchwork of programs. Programs such as WIC are available for women who are pregnant or have children < 5 years of age. Federal programs for adults who do not have children are scarce, however, and the burden of food insecurity for this population is typically addressed by local programs, such as food banks and food kitchens. Evidence shows that (1) combining the efforts of federal and local food programs is the most effective method of stymieing food insecurity in adults and (2) it would benefit food-insecure adults to have access to such programs. Regrettably, many food programs are underutilized because of barriers that include poor outreach, ineffectual application, and ineligibility.

What you can do. Although it might not be an official, professional society guideline to include questions about food security in a patient wellness survey, physicians should consider creating one for their practice that they (or the office staff) can administer. Furthermore, physicians (or, again, the office staff) should familiarize themselves with programs in the community, such as SNAP or a food bank, to which they can refer patients, as needed.

CASE You ask the nurse–care manager to consult with staff of the food bank and request that, based on your evaluation and recommendation, Ms. D be given more protein-based foods, including peanut butter and beans, when she visits the food bank. The nurse–care manager also makes arrangements to procure an insulin pump for Ms. D.

Continue to: In a short time...

In a short time, Ms. D’s blood glucose level normalizes. She has no further admissions for diabetic ketoacidosis.

Older adults: Interplay of risk factors takes a toll

The USDA Economic Research Report on food insecurity¹ states that older adults (≥ 65 years of age) report a lower rate of food insecurity—ie, 7.8% of households with an older adult and 8.9% of households in which the older adult lives alone—compared with the national average.¹ The report is limited, however, in its ability to extrapolate data from older adults on food insecurity because its focus is on factors specific to adults and children.

Factors that contribute to food insecurity in the elderly include race and ethnicity, education, income, being a SNAP recipient, and severe depression.^1,2,17,20,21 Older adult subgroups more likely to be food-insecure are Hispanic and black non-Hispanic—both significantly associated with being food-­insecure, with Hispanic populations reporting the highest rates of food insecurity.^20,21 This is a particularly interesting observation: Many traditional Hispanic homes are multigenerational and maintain a culture in which older adults are cared for by their children; that value system might be an indication of why many Hispanic households are disproportionately affected by food insecurity.

Adults in food-insecure homes are more likely to purchase cheap, calorie-dense food that lacks nutrition.

Other problems directly caused or exacerbated by food insecurity in the older population include a higher risk of malnutrition from periodontal disease, more frequent hospital admissions with longer length of stay, and an increased rate of falls and fractures. Polypharmacy, which can cause food–drug interactions that inhibit uptake of vitamins or create a higher demand for certain vitamins, is a noteworthy problem associated with food insecurity.

Problems with functionality might prevent older adults from performing physical tasks, such as shopping and preparing foods.^21,22 Older adults who reported functional impairment in performing activities of daily living are more likely to report food insecurity.^21,22 Last,older adults who live alone are more likely to have diminished nutritional intake than those who live with a spouse or partner.^2,22,23

Continue to: Legislation enacted in 2010...

Legislation enacted in 2010 under the existing Older Americans Act provided home-delivered meals, nutritional screening, and education counseling to Americans > 60 years of age. That provision was not based on an income test, however, and served only 18% of the older population.²³ (Other programs, such as SNAP, are utilized to a greater degree: 30% of eligible older adults participate, 75% of whom live alone.²³) Possible reasons for underutilization include restricted funding, lower education level, lack of outreach, a confusing application process, and the impression that the process is intrusive.^24-26

What you can do. To improve the nutritional intake of older adults, reconcile the patient’s medications at each visit to ensure that polypharmacy does not play a role in causing or exacerbating underlying conditions that can lead to poor nutritional intake. AARP (formerly the American Association of Retired Persons) recommends devising and conducting a survey of food insecurity with older adults that includes the 2-question American Academy of Pediatrics survey described earlier²⁷ (TABLE 2^15,27).Such a survey, which can be administered by office staff, should also include a screen for depression, financial stability, ability to perform activities of daily living (eg, shopping and driving), and changes in diet that are a result of periodontal disease. The survey should also inquire about the effects of current or chronic disability on day-to-day life.

For all patients: Refer to community resources

The problems of food insecurity presented here only broadly address what each of these 3 groups face. Although the overall trend in food insecurity has been downward since 2011, deeper issues of food insecurity need to be studied more within each population. This is particularly true among the geriatric population, whose numbers are increasing, and among ethnic minorities, including black non-Hispanics, and Hispanics, who face additional daily stressors because of implicit biases in society.

Ask older adults about any decline in performing activities of daily living, which can lead to food insecurity and poor nutritional intake.

More study is needed to decrease the rate of food insecurity across all populations in the United States. In the interim, family physicians should take advantage of their role in the care of families, children, and older people to address the problem of food insecurity in their patient population by applying the interventions we’ve outlined, with an emphasis on referral to resources in the community.

CORRESPONDENCE
Lillian Amèzquita, BS, The Warren Alpert Medical School, Brown University, Box G-9999, 222 Richmond Street, Providence, RI; [email protected].

CASE

A 30-year-old G2P2 woman presents for a well-woman visit and reports 6 months of premenstrual symptoms including irritability, depression, breast pain, and headaches. She is not taking any medications or hormonal contraceptives. She is sexually active and currently not interested in becoming pregnant. She asks what you can do for her symptoms, as they are affecting her life at home and at work.

Symptoms and definitions vary

Although more than 150 premenstrual symptoms have been reported, the most common psychological and behavioral ones are mood swings, depression, anxiety, irritability, crying, social withdrawal, forgetfulness, and problems concentrating.^1-3 The most common physical symptoms are fatigue, abdominal bloating, weight gain, breast tenderness, acne, change in appetite or food cravings, edema, headache, and gastrointestinal upset. The etiology of these symptoms is usually multifactorial, with some combination of hormonal, neurotransmitter, lifestyle, environmental, and psychosocial factors playing a role.

Premenstrual disorder. In reviewing diagnostic criteria for the various premenstrual syndromes and disorders from different organizations (eg, the International Society for Premenstrual Disorders; the American College of Obstetricians and Gynecologists; the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), there is agreement on the following criteria for premenstrual syndrome (PMS)^4-6:

• The woman must be ovulating. (Women who no longer menstruate [eg, because of hysterectomy or endometrial ablation] can have premenstrual disorders as long as ovarian function remains intact.)
• The woman experiences a constellation of disabling physical and/or psychological symptoms that appears in the luteal phase of her menstrual cycle.
• The symptoms improve soon after the onset of menses.
• There is a symptom-free interval before ovulation.
• There is prospective documentation of symptoms for at least 2 consecutive cycles.
• The symptoms are sufficient in severity to affect activities of daily living and/or important relationships.

Premenstrual dysphoric disorder. PMDD is another common premenstrual disorder. It is distinguished by significant premenstrual psychological symptoms and requires the presence of marked affective lability, marked irritability or anger, markedly depressed mood, and/or marked anxiety (TABLE 1).⁷

Exacerbation of other ailments. Another premenstrual disorder is the premenstrual exacerbation of underlying chronic medical or psychological problems such as migraines, seizures, asthma, diabetes, irritable bowel syndrome, fibromyalgia, anxiety, or depression.

Differences in interpretation lead to variations in prevalence

Differences in the interpretation of significant premenstrual symptoms have led to variations in estimated prevalence. For example, 80% to 95% of women report premenstrual symptoms, but only 30% to 40% meet criteria for PMS and only 3% to 8% meet criteria for PMDD.⁸ Many women who report premenstrual symptoms in a retrospective questionnaire do not meet criteria for PMS or PMDD based on prospective symptom charting. The Daily Record of Severity of Problems (DRSP), a prospective tracking tool for premenstrual symptoms, is sensitive and specific for diagnosing PMS and PMDD if administered on the first day of menstruation.⁹

Ask about symptoms and use a tracking tool

When you see a woman for a well-woman visit or a gynecologic problem, inquire about physical/emotional symptoms and their severity during the week that precedes menstruation. If a patient reports few symptoms of a mild nature, then no further work-up is needed.

Continue to: If patients report significant...

Women who no longer menstruate can have premenstrual disorders as long as ovarian function remains intact.

If patients report significant premenstrual symptoms, recommend the use of a tool to track the symptoms. Older tools such as the DRSP and the Premenstrual Symptoms Screening Tool (PSST), newer symptom diaries that can be used for both PMS and PMDD,and questionnaires that have been used in research situations can be time consuming and difficult for patients to complete.^10-12 Instead, physicians can easily construct their own charting tool, as we did for patients to use when tracking their most bothersome symptoms (FIGURE 1). Tracking helps to confirm the diagnosis and helps you and the patient focus on treatment goals.

Keep in mind other diagnoses (eg, anemia, thyroid disorders, perimenopause, anxiety, depression, eating disorders, substance abuse) that can cause or exacerbate the psychological/physical symptoms the patient is reporting. If you suspect any of these other diagnoses, laboratory evaluation (eg, complete blood count, thyroid-stimulating hormone level or other hormonal testing, urine drug screen, etc) may be warranted to rule out other etiologies for the reported symptoms.

Develop a Tx plan that ­considers symptoms, family-planning needs

Focus treatment on the patient’s predominant symptoms whether they are physical, psychological, or mixed (FIGURE 2). The patient’s preferences regarding family planning are another important consideration. Women who are using a fertility awareness–based method of family planning may not desire a contraceptive hormonal treatment for their premenstrual disorder. Also, patients may have cultural and/or religious beliefs that need to be respected.

Although the definitions for PMS and PMDD require at least 2 cycles of prospective documentation of symptoms, dietary and lifestyle changes can begin immediately. Regular follow-up to document improvement of symptoms is important; using the patient’s symptoms charting tool can help with this.

Focus on diet and lifestyle right away

Experts in the field of PMS/PMDD suggest that simple dietary changes may be a reasonable first step to help improve symptoms. Researchers have found that diets high in fiber, vegetables, and whole grains are inversely related to PMS.¹³ Older studies have suggested an increased prevalence and severity of PMS with increased caffeine intake; however, a newer study found no such association.¹⁴

Continue to: A case-control study nested...

Focus treatment on the patient’s predominant symptoms, whether they are physical, psychological, or mixed.

A case-control study nested within the Nurses’ Health Study II cohort showed that a high intake of both dietary calcium and vitamin D prevented the development of PMS in women ages 27 to 44.¹⁵ B vitamins, such as thiamine and riboflavin, from food sources have been associated with a lower risk of PMS.¹⁶ A variety of older clinical studies showed benefit from aerobic exercise on PMS symptoms,^17-19 but a newer cross-sectional study of young adult women found no association between physical activity and the prevalence of PMS.²⁰ Acupuncture has demonstrated efficacy for the treatment of the physical symptoms of PMS and PMDD, but more rigorous studies are needed.^21,22 Cognitive behavioral therapy has been studied as a treatment, but data to support this approach are limited so it cannot be recommended at this time.²³

Make the most of supplements—especially calcium

Calcium is the nutritional supplement with the most evidence to support its use to relieve symptoms of PMS and PMDD (TABLE 2^21,22,24-45). Research indicates that disturbances in calcium regulation and calcium deficiency may be responsible for various premenstrual symptoms. One study showed that, compared with placebo, women who took 1200 mg/d calcium carbonate for 3 menstrual cycles had a 48% decrease in both somatic and affective symptoms.²⁴ Another trial demonstrated improvement in PMS symptoms of early tiredness, appetite changes, and depression with calcium therapy.²⁵

Pyridoxine (vitamin B6) has potential benefit in treating PMS due to its ability to increase levels of serotonin, norepinephrine, histamine, dopamine, and taurine.²⁶ An older systematic review showed benefit for symptoms associated with PMS, but the authors concluded that larger randomized controlled trials (RCTs) were needed before definitive recommendations could be made.²⁷

Chasteberry. A number of studies have evaluated the effect of vitex agnus castus (VAC), commonly referred to as chasteberry, on PMS and PMDD symptoms. The exact mechanism of VAC is unknown, but in vitro studies show binding of VAC extracts to dopamine-2 receptors and opioid receptors, and an affinity for estrogen receptors.²⁸

A recent meta-analysis concluded that VAC extracts are not superior to selective serotonin reuptake inhibitors (SSRIs) or oral contraceptives (OCs) for PMS/PMDD.²⁸ The authors suggested a possible benefit of VAC compared with placebo or other nutritional supplements; however, the studies supporting its use are limited by small sample size and potential bias.

Continue to: Magnesium

Magnesium. Many small studies have evaluated the role of other herbal and nutritional supplements for the treatment of PMS/PMDD. A systematic review of studies on the effect of magnesium supplementation on anxiety and stress showed that magnesium may have a potential role in the treatment of the premenstrual symptom of anxiety.²⁹ Other studies have demonstrated a potential role in the treatment of premenstrual migraine.^30,31

Vitamin E has demonstrated benefit in the treatment of cyclic mastalgia; however, evidence for using vitamin E for mood and depressive symptoms associated with PMS and PMDD is inconsistent.^32-34 Other studies involving vitamin D, St. John’s wort, black cohosh, evening primrose oil, saffron, and ginkgo biloba either showed these agents to be nonefficacious in relieving PMS/PMDD symptoms or to require more data before they can be recommended for use.^34,46

Patient doesn’t respond? Start an SSRI

Pharmacotherapy with antidepressants is typically reserved for those who do not respond to nonpharmacologic therapies and are experiencing more moderate to severe symptoms of PMS or PMDD. Reduced levels of serotonin and serotonergic activity in the brain may be linked to symptoms of PMS and PMDD.⁴⁷ Studies have shown SSRIs to be effective in reducing many psychological symptoms (eg, depression, anxiety, lethargy, irritability) and some physical symptoms (eg, headache, breast tenderness, muscle or joint pain) associated with PMS and PMDD.

A Cochrane review of 31 RCTs compared various SSRIs to placebo. When taken either continuously or intermittently (administration during luteal phase), SSRIs were similarly effective in relieving symptoms when compared with placebo.³⁵ Psychological symptoms are more likely to improve with both low and moderate doses of SSRIs, while physical symptoms may only improve with moderate or higher doses. A direct comparison of the various SSRIs for the treatment of PMS or PMDD is lacking; therefore, the selection of SSRI may be based on patient characteristics and preference.

The benefits of SSRIs are noted much earlier in the treatment of PMS/PMDD than they are observed in their use for depression or anxiety.³⁶ This suggests that the mechanism by which SSRIs relieve PMS/PMDD symptoms is different than that for depression or anxiety. Intermittent dosing capitalizes upon the rapid effect seen with these medications and the cyclical nature of these disorders. In most studies, the benefit of intermittent dosing is similar to continuous dosing; however, one meta-analysis did note that continuous dosing had a larger effect.³⁷

Continue to: The doses of SSRIs...

Although the definitions for PMS and PMDD require at least 2 cycles of prospective documentation of symptoms, diet and lifestyle changes can begin immediately.

The doses of SSRIs used in most PMS/PMDD trials were lower than those typically used for the treatment of depression and anxiety. The withdrawal effect that can be seen with abrupt cessation of SSRIs has not been reported in the intermittent-dosing studies for PMS/PMDD.³⁸ While this might imply a more tolerable safety profile, the most common adverse effects reported in trials were still as expected: sleep disturbances, headache, nausea, and sexual dysfunction. It is important to note that SSRIs should be used with caution during pregnancy, and paroxetine should be avoided in women considering pregnancy in the near future.

Other antidepressant classes have been studied to a lesser extent than SSRIs. Continuously dosed venlafaxine, a serotonin and norepinephrine reuptake inhibitor, demonstrated efficacy in PMS/PMDD treatment when compared with placebo within the first cycle of therapy.³⁹ The response seen was comparable to that associated with SSRI treatments in other trials.

Buspirone, an anxiolytic with serotonin receptor activity that is different from that of the SSRIs, demonstrated efficacy in reducing the symptom of irritability.⁴⁸ Buspirone may have a role to play in those presenting with irritability as a primary symptom or in those who are unable to tolerate the adverse effects of SSRIs. Tricyclic antidepressants, bupropion, and alprazolam have either limited data regarding efficacy or are associated with adverse effects that limit their use.³⁸

Hormonal treatments may be worth considering

One commonly prescribed hormonal therapy for PMS and PMDD is continuous OCs. A 2012 Cochrane review of OCs containing drospirenone evaluated 5 trials and a total of 1920 women.⁴⁰ Two placebo-controlled trials of women with severe premenstrual symptoms (PMDD) showed improvement after 3 months of taking daily drospirenone 3 mg with ethinyl estradiol 20 mcg, compared with placebo.

While experiencing greater benefit, these groups also experienced significantly more adverse effects including nausea, intermenstrual bleeding, and breast pain. The respective odds ratios for the 3 adverse effects were 3.15 (95% confidence interval [CI], 1.90-5.22), 4.92 (95% CI, 3.03-7.96), and 2.67 (95% CI, 1.50-4.78). The review concluded that drospirenone 3 mg with ethinyl estradiol 20 mcg may help in the treatment of severe premenstrual symptoms (PMDD) but that it is unknown whether this treatment is appropriate for patients with less severe premenstrual symptoms.

Continue to: Another multicenter RCT

Another multicenter RCT evaluated women with PMDD who received levonorgestrel 90 mcg with ethinyl estradiol 20 mcg or placebo daily for 112 days.⁴¹ Symptoms were recorded utilizing the DRSP. Significantly more women taking the daily combination hormone (52%) than placebo (40%) had a positive response (≥ 50% improvement in the DRSP 7-day late luteal phase score and Clinical Global Impression of Severity score of ≥ 1 improvement, evaluated at the last “on-therapy” cycle [P = .025]). Twenty-three of 186 patients in the treatment arm dropped out because of adverse effects.

Noncontraceptive estrogen-containing preparations. Hormone therapy preparations containing lower doses of estrogen than seen in OC preparations have also been studied for PMS management. A 2017 Cochrane review of noncontraceptive estrogen-containing preparations found very low-quality evidence to support the effectiveness of continuous estrogen (transdermal patches or subcutaneous implants) plus progestogen.⁴⁹

Progesterone. The cyclic use of progesterone in the luteal phase has been reviewed as a hormonal treatment for PMS. A 2012 Cochrane review of the efficacy of progesterone for PMS was inconclusive; however, route of administration, dose, and duration differed across studies.⁴²

Another systematic review of 10 trials involving 531 women concluded that progesterone was no better than placebo in the treatment of PMS.⁴³ However, it should be noted that each trial evaluated a different dose of progesterone, and all but 1 of the trials administered progesterone by using the calendar method to predict the beginning of the luteal phase. The only trial to use an objective confirmation of ovulation prior to beginning progesterone therapy did demonstrate significant improvement in premenstrual symptoms.

This 1985 study by Dennerstein et al⁴⁴ prescribed progesterone for 10 days of each menstrual cycle starting 3 days after ovulation. In each cycle, ovulation was confirmed by determinations of urinary 24-hour pregnanediol and total estrogen concentrations. Progesterone was then prescribed during the objectively identified luteal phase, resulting in significant improvement in symptoms.

Continue to: Another study evaluated...

The benefits of SSRIs are noted much earlier in the treatment of PMS/PMDD than they are observed in their use for depression or anxiety.

Another study evaluated the post-ovulatory progesterone profiles of 77 women with symptoms of PMS and found lower levels of progesterone and a sharper rate of decline in the women with PMS vs the control group.⁴⁵ Subsequent progesterone treatment during the objectively identified luteal phase significantly improved PMS symptoms. These studies would seem to suggest that progesterone replacement when administered during an objectively identified luteal phase may offer some benefit in the treatment of PMS, but larger RCTs are needed to confirm this.

CASE

You provide the patient with diet and lifestyle education as well as a recommendation for calcium supplementation. The patient agrees to prospectively chart her most significant premenstrual symptoms. You review additional treatment options including SSRI medications and hormonal approaches. She is using a fertility awareness–based method of family planning that allows her to confidently identify her luteal phase. She agrees to take sertraline 50 mg/d during the luteal phase of her cycle. At her follow-up office visit 3 months later, she reports improvement in her premenstrual symptoms. Her charting of symptoms confirms this.

CORRESPONDENCE
Peter Danis, MD, Mercy Family Medicine St. Louis, 12680 Olive Boulevard, St. Louis, MO 63141; [email protected].

CASE

A 30-year-old G2P2 woman presents for a well-woman visit and reports 6 months of premenstrual symptoms including irritability, depression, breast pain, and headaches. She is not taking any medications or hormonal contraceptives. She is sexually active and currently not interested in becoming pregnant. She asks what you can do for her symptoms, as they are affecting her life at home and at work.

Symptoms and definitions vary

Although more than 150 premenstrual symptoms have been reported, the most common psychological and behavioral ones are mood swings, depression, anxiety, irritability, crying, social withdrawal, forgetfulness, and problems concentrating.^1-3 The most common physical symptoms are fatigue, abdominal bloating, weight gain, breast tenderness, acne, change in appetite or food cravings, edema, headache, and gastrointestinal upset. The etiology of these symptoms is usually multifactorial, with some combination of hormonal, neurotransmitter, lifestyle, environmental, and psychosocial factors playing a role.

Premenstrual disorder. In reviewing diagnostic criteria for the various premenstrual syndromes and disorders from different organizations (eg, the International Society for Premenstrual Disorders; the American College of Obstetricians and Gynecologists; the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), there is agreement on the following criteria for premenstrual syndrome (PMS)^4-6:

• The woman must be ovulating. (Women who no longer menstruate [eg, because of hysterectomy or endometrial ablation] can have premenstrual disorders as long as ovarian function remains intact.)
• The woman experiences a constellation of disabling physical and/or psychological symptoms that appears in the luteal phase of her menstrual cycle.
• The symptoms improve soon after the onset of menses.
• There is a symptom-free interval before ovulation.
• There is prospective documentation of symptoms for at least 2 consecutive cycles.
• The symptoms are sufficient in severity to affect activities of daily living and/or important relationships.

Premenstrual dysphoric disorder. PMDD is another common premenstrual disorder. It is distinguished by significant premenstrual psychological symptoms and requires the presence of marked affective lability, marked irritability or anger, markedly depressed mood, and/or marked anxiety (TABLE 1).⁷

Exacerbation of other ailments. Another premenstrual disorder is the premenstrual exacerbation of underlying chronic medical or psychological problems such as migraines, seizures, asthma, diabetes, irritable bowel syndrome, fibromyalgia, anxiety, or depression.

Differences in interpretation lead to variations in prevalence

Differences in the interpretation of significant premenstrual symptoms have led to variations in estimated prevalence. For example, 80% to 95% of women report premenstrual symptoms, but only 30% to 40% meet criteria for PMS and only 3% to 8% meet criteria for PMDD.⁸ Many women who report premenstrual symptoms in a retrospective questionnaire do not meet criteria for PMS or PMDD based on prospective symptom charting. The Daily Record of Severity of Problems (DRSP), a prospective tracking tool for premenstrual symptoms, is sensitive and specific for diagnosing PMS and PMDD if administered on the first day of menstruation.⁹

Ask about symptoms and use a tracking tool

When you see a woman for a well-woman visit or a gynecologic problem, inquire about physical/emotional symptoms and their severity during the week that precedes menstruation. If a patient reports few symptoms of a mild nature, then no further work-up is needed.

Continue to: If patients report significant...

Women who no longer menstruate can have premenstrual disorders as long as ovarian function remains intact.

If patients report significant premenstrual symptoms, recommend the use of a tool to track the symptoms. Older tools such as the DRSP and the Premenstrual Symptoms Screening Tool (PSST), newer symptom diaries that can be used for both PMS and PMDD,and questionnaires that have been used in research situations can be time consuming and difficult for patients to complete.^10-12 Instead, physicians can easily construct their own charting tool, as we did for patients to use when tracking their most bothersome symptoms (FIGURE 1). Tracking helps to confirm the diagnosis and helps you and the patient focus on treatment goals.

Keep in mind other diagnoses (eg, anemia, thyroid disorders, perimenopause, anxiety, depression, eating disorders, substance abuse) that can cause or exacerbate the psychological/physical symptoms the patient is reporting. If you suspect any of these other diagnoses, laboratory evaluation (eg, complete blood count, thyroid-stimulating hormone level or other hormonal testing, urine drug screen, etc) may be warranted to rule out other etiologies for the reported symptoms.

Develop a Tx plan that ­considers symptoms, family-planning needs

Focus treatment on the patient’s predominant symptoms whether they are physical, psychological, or mixed (FIGURE 2). The patient’s preferences regarding family planning are another important consideration. Women who are using a fertility awareness–based method of family planning may not desire a contraceptive hormonal treatment for their premenstrual disorder. Also, patients may have cultural and/or religious beliefs that need to be respected.

Although the definitions for PMS and PMDD require at least 2 cycles of prospective documentation of symptoms, dietary and lifestyle changes can begin immediately. Regular follow-up to document improvement of symptoms is important; using the patient’s symptoms charting tool can help with this.

Focus on diet and lifestyle right away

Experts in the field of PMS/PMDD suggest that simple dietary changes may be a reasonable first step to help improve symptoms. Researchers have found that diets high in fiber, vegetables, and whole grains are inversely related to PMS.¹³ Older studies have suggested an increased prevalence and severity of PMS with increased caffeine intake; however, a newer study found no such association.¹⁴

Continue to: A case-control study nested...

Focus treatment on the patient’s predominant symptoms, whether they are physical, psychological, or mixed.

A case-control study nested within the Nurses’ Health Study II cohort showed that a high intake of both dietary calcium and vitamin D prevented the development of PMS in women ages 27 to 44.¹⁵ B vitamins, such as thiamine and riboflavin, from food sources have been associated with a lower risk of PMS.¹⁶ A variety of older clinical studies showed benefit from aerobic exercise on PMS symptoms,^17-19 but a newer cross-sectional study of young adult women found no association between physical activity and the prevalence of PMS.²⁰ Acupuncture has demonstrated efficacy for the treatment of the physical symptoms of PMS and PMDD, but more rigorous studies are needed.^21,22 Cognitive behavioral therapy has been studied as a treatment, but data to support this approach are limited so it cannot be recommended at this time.²³

Make the most of supplements—especially calcium

Calcium is the nutritional supplement with the most evidence to support its use to relieve symptoms of PMS and PMDD (TABLE 2^21,22,24-45). Research indicates that disturbances in calcium regulation and calcium deficiency may be responsible for various premenstrual symptoms. One study showed that, compared with placebo, women who took 1200 mg/d calcium carbonate for 3 menstrual cycles had a 48% decrease in both somatic and affective symptoms.²⁴ Another trial demonstrated improvement in PMS symptoms of early tiredness, appetite changes, and depression with calcium therapy.²⁵

Pyridoxine (vitamin B6) has potential benefit in treating PMS due to its ability to increase levels of serotonin, norepinephrine, histamine, dopamine, and taurine.²⁶ An older systematic review showed benefit for symptoms associated with PMS, but the authors concluded that larger randomized controlled trials (RCTs) were needed before definitive recommendations could be made.²⁷

Chasteberry. A number of studies have evaluated the effect of vitex agnus castus (VAC), commonly referred to as chasteberry, on PMS and PMDD symptoms. The exact mechanism of VAC is unknown, but in vitro studies show binding of VAC extracts to dopamine-2 receptors and opioid receptors, and an affinity for estrogen receptors.²⁸

A recent meta-analysis concluded that VAC extracts are not superior to selective serotonin reuptake inhibitors (SSRIs) or oral contraceptives (OCs) for PMS/PMDD.²⁸ The authors suggested a possible benefit of VAC compared with placebo or other nutritional supplements; however, the studies supporting its use are limited by small sample size and potential bias.

Continue to: Magnesium

Magnesium. Many small studies have evaluated the role of other herbal and nutritional supplements for the treatment of PMS/PMDD. A systematic review of studies on the effect of magnesium supplementation on anxiety and stress showed that magnesium may have a potential role in the treatment of the premenstrual symptom of anxiety.²⁹ Other studies have demonstrated a potential role in the treatment of premenstrual migraine.^30,31

Vitamin E has demonstrated benefit in the treatment of cyclic mastalgia; however, evidence for using vitamin E for mood and depressive symptoms associated with PMS and PMDD is inconsistent.^32-34 Other studies involving vitamin D, St. John’s wort, black cohosh, evening primrose oil, saffron, and ginkgo biloba either showed these agents to be nonefficacious in relieving PMS/PMDD symptoms or to require more data before they can be recommended for use.^34,46

Patient doesn’t respond? Start an SSRI

Pharmacotherapy with antidepressants is typically reserved for those who do not respond to nonpharmacologic therapies and are experiencing more moderate to severe symptoms of PMS or PMDD. Reduced levels of serotonin and serotonergic activity in the brain may be linked to symptoms of PMS and PMDD.⁴⁷ Studies have shown SSRIs to be effective in reducing many psychological symptoms (eg, depression, anxiety, lethargy, irritability) and some physical symptoms (eg, headache, breast tenderness, muscle or joint pain) associated with PMS and PMDD.

A Cochrane review of 31 RCTs compared various SSRIs to placebo. When taken either continuously or intermittently (administration during luteal phase), SSRIs were similarly effective in relieving symptoms when compared with placebo.³⁵ Psychological symptoms are more likely to improve with both low and moderate doses of SSRIs, while physical symptoms may only improve with moderate or higher doses. A direct comparison of the various SSRIs for the treatment of PMS or PMDD is lacking; therefore, the selection of SSRI may be based on patient characteristics and preference.

The benefits of SSRIs are noted much earlier in the treatment of PMS/PMDD than they are observed in their use for depression or anxiety.³⁶ This suggests that the mechanism by which SSRIs relieve PMS/PMDD symptoms is different than that for depression or anxiety. Intermittent dosing capitalizes upon the rapid effect seen with these medications and the cyclical nature of these disorders. In most studies, the benefit of intermittent dosing is similar to continuous dosing; however, one meta-analysis did note that continuous dosing had a larger effect.³⁷

Continue to: The doses of SSRIs...

Although the definitions for PMS and PMDD require at least 2 cycles of prospective documentation of symptoms, diet and lifestyle changes can begin immediately.

The doses of SSRIs used in most PMS/PMDD trials were lower than those typically used for the treatment of depression and anxiety. The withdrawal effect that can be seen with abrupt cessation of SSRIs has not been reported in the intermittent-dosing studies for PMS/PMDD.³⁸ While this might imply a more tolerable safety profile, the most common adverse effects reported in trials were still as expected: sleep disturbances, headache, nausea, and sexual dysfunction. It is important to note that SSRIs should be used with caution during pregnancy, and paroxetine should be avoided in women considering pregnancy in the near future.

Other antidepressant classes have been studied to a lesser extent than SSRIs. Continuously dosed venlafaxine, a serotonin and norepinephrine reuptake inhibitor, demonstrated efficacy in PMS/PMDD treatment when compared with placebo within the first cycle of therapy.³⁹ The response seen was comparable to that associated with SSRI treatments in other trials.

Buspirone, an anxiolytic with serotonin receptor activity that is different from that of the SSRIs, demonstrated efficacy in reducing the symptom of irritability.⁴⁸ Buspirone may have a role to play in those presenting with irritability as a primary symptom or in those who are unable to tolerate the adverse effects of SSRIs. Tricyclic antidepressants, bupropion, and alprazolam have either limited data regarding efficacy or are associated with adverse effects that limit their use.³⁸

Hormonal treatments may be worth considering

One commonly prescribed hormonal therapy for PMS and PMDD is continuous OCs. A 2012 Cochrane review of OCs containing drospirenone evaluated 5 trials and a total of 1920 women.⁴⁰ Two placebo-controlled trials of women with severe premenstrual symptoms (PMDD) showed improvement after 3 months of taking daily drospirenone 3 mg with ethinyl estradiol 20 mcg, compared with placebo.

While experiencing greater benefit, these groups also experienced significantly more adverse effects including nausea, intermenstrual bleeding, and breast pain. The respective odds ratios for the 3 adverse effects were 3.15 (95% confidence interval [CI], 1.90-5.22), 4.92 (95% CI, 3.03-7.96), and 2.67 (95% CI, 1.50-4.78). The review concluded that drospirenone 3 mg with ethinyl estradiol 20 mcg may help in the treatment of severe premenstrual symptoms (PMDD) but that it is unknown whether this treatment is appropriate for patients with less severe premenstrual symptoms.

Continue to: Another multicenter RCT

Another multicenter RCT evaluated women with PMDD who received levonorgestrel 90 mcg with ethinyl estradiol 20 mcg or placebo daily for 112 days.⁴¹ Symptoms were recorded utilizing the DRSP. Significantly more women taking the daily combination hormone (52%) than placebo (40%) had a positive response (≥ 50% improvement in the DRSP 7-day late luteal phase score and Clinical Global Impression of Severity score of ≥ 1 improvement, evaluated at the last “on-therapy” cycle [P = .025]). Twenty-three of 186 patients in the treatment arm dropped out because of adverse effects.

Noncontraceptive estrogen-containing preparations. Hormone therapy preparations containing lower doses of estrogen than seen in OC preparations have also been studied for PMS management. A 2017 Cochrane review of noncontraceptive estrogen-containing preparations found very low-quality evidence to support the effectiveness of continuous estrogen (transdermal patches or subcutaneous implants) plus progestogen.⁴⁹

Progesterone. The cyclic use of progesterone in the luteal phase has been reviewed as a hormonal treatment for PMS. A 2012 Cochrane review of the efficacy of progesterone for PMS was inconclusive; however, route of administration, dose, and duration differed across studies.⁴²

Another systematic review of 10 trials involving 531 women concluded that progesterone was no better than placebo in the treatment of PMS.⁴³ However, it should be noted that each trial evaluated a different dose of progesterone, and all but 1 of the trials administered progesterone by using the calendar method to predict the beginning of the luteal phase. The only trial to use an objective confirmation of ovulation prior to beginning progesterone therapy did demonstrate significant improvement in premenstrual symptoms.

This 1985 study by Dennerstein et al⁴⁴ prescribed progesterone for 10 days of each menstrual cycle starting 3 days after ovulation. In each cycle, ovulation was confirmed by determinations of urinary 24-hour pregnanediol and total estrogen concentrations. Progesterone was then prescribed during the objectively identified luteal phase, resulting in significant improvement in symptoms.

Continue to: Another study evaluated...

The benefits of SSRIs are noted much earlier in the treatment of PMS/PMDD than they are observed in their use for depression or anxiety.

Another study evaluated the post-ovulatory progesterone profiles of 77 women with symptoms of PMS and found lower levels of progesterone and a sharper rate of decline in the women with PMS vs the control group.⁴⁵ Subsequent progesterone treatment during the objectively identified luteal phase significantly improved PMS symptoms. These studies would seem to suggest that progesterone replacement when administered during an objectively identified luteal phase may offer some benefit in the treatment of PMS, but larger RCTs are needed to confirm this.

CASE

You provide the patient with diet and lifestyle education as well as a recommendation for calcium supplementation. The patient agrees to prospectively chart her most significant premenstrual symptoms. You review additional treatment options including SSRI medications and hormonal approaches. She is using a fertility awareness–based method of family planning that allows her to confidently identify her luteal phase. She agrees to take sertraline 50 mg/d during the luteal phase of her cycle. At her follow-up office visit 3 months later, she reports improvement in her premenstrual symptoms. Her charting of symptoms confirms this.

CORRESPONDENCE
Peter Danis, MD, Mercy Family Medicine St. Louis, 12680 Olive Boulevard, St. Louis, MO 63141; [email protected].

CASE

A 30-year-old G2P2 woman presents for a well-woman visit and reports 6 months of premenstrual symptoms including irritability, depression, breast pain, and headaches. She is not taking any medications or hormonal contraceptives. She is sexually active and currently not interested in becoming pregnant. She asks what you can do for her symptoms, as they are affecting her life at home and at work.

Symptoms and definitions vary

Although more than 150 premenstrual symptoms have been reported, the most common psychological and behavioral ones are mood swings, depression, anxiety, irritability, crying, social withdrawal, forgetfulness, and problems concentrating.^1-3 The most common physical symptoms are fatigue, abdominal bloating, weight gain, breast tenderness, acne, change in appetite or food cravings, edema, headache, and gastrointestinal upset. The etiology of these symptoms is usually multifactorial, with some combination of hormonal, neurotransmitter, lifestyle, environmental, and psychosocial factors playing a role.

Premenstrual disorder. In reviewing diagnostic criteria for the various premenstrual syndromes and disorders from different organizations (eg, the International Society for Premenstrual Disorders; the American College of Obstetricians and Gynecologists; the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), there is agreement on the following criteria for premenstrual syndrome (PMS)^4-6:

• The woman must be ovulating. (Women who no longer menstruate [eg, because of hysterectomy or endometrial ablation] can have premenstrual disorders as long as ovarian function remains intact.)
• The woman experiences a constellation of disabling physical and/or psychological symptoms that appears in the luteal phase of her menstrual cycle.
• The symptoms improve soon after the onset of menses.
• There is a symptom-free interval before ovulation.
• There is prospective documentation of symptoms for at least 2 consecutive cycles.
• The symptoms are sufficient in severity to affect activities of daily living and/or important relationships.

Premenstrual dysphoric disorder. PMDD is another common premenstrual disorder. It is distinguished by significant premenstrual psychological symptoms and requires the presence of marked affective lability, marked irritability or anger, markedly depressed mood, and/or marked anxiety (TABLE 1).⁷

Exacerbation of other ailments. Another premenstrual disorder is the premenstrual exacerbation of underlying chronic medical or psychological problems such as migraines, seizures, asthma, diabetes, irritable bowel syndrome, fibromyalgia, anxiety, or depression.

Differences in interpretation lead to variations in prevalence

Differences in the interpretation of significant premenstrual symptoms have led to variations in estimated prevalence. For example, 80% to 95% of women report premenstrual symptoms, but only 30% to 40% meet criteria for PMS and only 3% to 8% meet criteria for PMDD.⁸ Many women who report premenstrual symptoms in a retrospective questionnaire do not meet criteria for PMS or PMDD based on prospective symptom charting. The Daily Record of Severity of Problems (DRSP), a prospective tracking tool for premenstrual symptoms, is sensitive and specific for diagnosing PMS and PMDD if administered on the first day of menstruation.⁹

Ask about symptoms and use a tracking tool

When you see a woman for a well-woman visit or a gynecologic problem, inquire about physical/emotional symptoms and their severity during the week that precedes menstruation. If a patient reports few symptoms of a mild nature, then no further work-up is needed.

Continue to: If patients report significant...

Women who no longer menstruate can have premenstrual disorders as long as ovarian function remains intact.

If patients report significant premenstrual symptoms, recommend the use of a tool to track the symptoms. Older tools such as the DRSP and the Premenstrual Symptoms Screening Tool (PSST), newer symptom diaries that can be used for both PMS and PMDD,and questionnaires that have been used in research situations can be time consuming and difficult for patients to complete.^10-12 Instead, physicians can easily construct their own charting tool, as we did for patients to use when tracking their most bothersome symptoms (FIGURE 1). Tracking helps to confirm the diagnosis and helps you and the patient focus on treatment goals.

Keep in mind other diagnoses (eg, anemia, thyroid disorders, perimenopause, anxiety, depression, eating disorders, substance abuse) that can cause or exacerbate the psychological/physical symptoms the patient is reporting. If you suspect any of these other diagnoses, laboratory evaluation (eg, complete blood count, thyroid-stimulating hormone level or other hormonal testing, urine drug screen, etc) may be warranted to rule out other etiologies for the reported symptoms.

Develop a Tx plan that ­considers symptoms, family-planning needs

Focus treatment on the patient’s predominant symptoms whether they are physical, psychological, or mixed (FIGURE 2). The patient’s preferences regarding family planning are another important consideration. Women who are using a fertility awareness–based method of family planning may not desire a contraceptive hormonal treatment for their premenstrual disorder. Also, patients may have cultural and/or religious beliefs that need to be respected.

Although the definitions for PMS and PMDD require at least 2 cycles of prospective documentation of symptoms, dietary and lifestyle changes can begin immediately. Regular follow-up to document improvement of symptoms is important; using the patient’s symptoms charting tool can help with this.

Focus on diet and lifestyle right away

Experts in the field of PMS/PMDD suggest that simple dietary changes may be a reasonable first step to help improve symptoms. Researchers have found that diets high in fiber, vegetables, and whole grains are inversely related to PMS.¹³ Older studies have suggested an increased prevalence and severity of PMS with increased caffeine intake; however, a newer study found no such association.¹⁴

Continue to: A case-control study nested...

Focus treatment on the patient’s predominant symptoms, whether they are physical, psychological, or mixed.

A case-control study nested within the Nurses’ Health Study II cohort showed that a high intake of both dietary calcium and vitamin D prevented the development of PMS in women ages 27 to 44.¹⁵ B vitamins, such as thiamine and riboflavin, from food sources have been associated with a lower risk of PMS.¹⁶ A variety of older clinical studies showed benefit from aerobic exercise on PMS symptoms,^17-19 but a newer cross-sectional study of young adult women found no association between physical activity and the prevalence of PMS.²⁰ Acupuncture has demonstrated efficacy for the treatment of the physical symptoms of PMS and PMDD, but more rigorous studies are needed.^21,22 Cognitive behavioral therapy has been studied as a treatment, but data to support this approach are limited so it cannot be recommended at this time.²³

Make the most of supplements—especially calcium

Calcium is the nutritional supplement with the most evidence to support its use to relieve symptoms of PMS and PMDD (TABLE 2^21,22,24-45). Research indicates that disturbances in calcium regulation and calcium deficiency may be responsible for various premenstrual symptoms. One study showed that, compared with placebo, women who took 1200 mg/d calcium carbonate for 3 menstrual cycles had a 48% decrease in both somatic and affective symptoms.²⁴ Another trial demonstrated improvement in PMS symptoms of early tiredness, appetite changes, and depression with calcium therapy.²⁵

Pyridoxine (vitamin B6) has potential benefit in treating PMS due to its ability to increase levels of serotonin, norepinephrine, histamine, dopamine, and taurine.²⁶ An older systematic review showed benefit for symptoms associated with PMS, but the authors concluded that larger randomized controlled trials (RCTs) were needed before definitive recommendations could be made.²⁷

Chasteberry. A number of studies have evaluated the effect of vitex agnus castus (VAC), commonly referred to as chasteberry, on PMS and PMDD symptoms. The exact mechanism of VAC is unknown, but in vitro studies show binding of VAC extracts to dopamine-2 receptors and opioid receptors, and an affinity for estrogen receptors.²⁸

A recent meta-analysis concluded that VAC extracts are not superior to selective serotonin reuptake inhibitors (SSRIs) or oral contraceptives (OCs) for PMS/PMDD.²⁸ The authors suggested a possible benefit of VAC compared with placebo or other nutritional supplements; however, the studies supporting its use are limited by small sample size and potential bias.

Continue to: Magnesium

Magnesium. Many small studies have evaluated the role of other herbal and nutritional supplements for the treatment of PMS/PMDD. A systematic review of studies on the effect of magnesium supplementation on anxiety and stress showed that magnesium may have a potential role in the treatment of the premenstrual symptom of anxiety.²⁹ Other studies have demonstrated a potential role in the treatment of premenstrual migraine.^30,31

Vitamin E has demonstrated benefit in the treatment of cyclic mastalgia; however, evidence for using vitamin E for mood and depressive symptoms associated with PMS and PMDD is inconsistent.^32-34 Other studies involving vitamin D, St. John’s wort, black cohosh, evening primrose oil, saffron, and ginkgo biloba either showed these agents to be nonefficacious in relieving PMS/PMDD symptoms or to require more data before they can be recommended for use.^34,46

Patient doesn’t respond? Start an SSRI

Pharmacotherapy with antidepressants is typically reserved for those who do not respond to nonpharmacologic therapies and are experiencing more moderate to severe symptoms of PMS or PMDD. Reduced levels of serotonin and serotonergic activity in the brain may be linked to symptoms of PMS and PMDD.⁴⁷ Studies have shown SSRIs to be effective in reducing many psychological symptoms (eg, depression, anxiety, lethargy, irritability) and some physical symptoms (eg, headache, breast tenderness, muscle or joint pain) associated with PMS and PMDD.

A Cochrane review of 31 RCTs compared various SSRIs to placebo. When taken either continuously or intermittently (administration during luteal phase), SSRIs were similarly effective in relieving symptoms when compared with placebo.³⁵ Psychological symptoms are more likely to improve with both low and moderate doses of SSRIs, while physical symptoms may only improve with moderate or higher doses. A direct comparison of the various SSRIs for the treatment of PMS or PMDD is lacking; therefore, the selection of SSRI may be based on patient characteristics and preference.

The benefits of SSRIs are noted much earlier in the treatment of PMS/PMDD than they are observed in their use for depression or anxiety.³⁶ This suggests that the mechanism by which SSRIs relieve PMS/PMDD symptoms is different than that for depression or anxiety. Intermittent dosing capitalizes upon the rapid effect seen with these medications and the cyclical nature of these disorders. In most studies, the benefit of intermittent dosing is similar to continuous dosing; however, one meta-analysis did note that continuous dosing had a larger effect.³⁷

Continue to: The doses of SSRIs...

Although the definitions for PMS and PMDD require at least 2 cycles of prospective documentation of symptoms, diet and lifestyle changes can begin immediately.

The doses of SSRIs used in most PMS/PMDD trials were lower than those typically used for the treatment of depression and anxiety. The withdrawal effect that can be seen with abrupt cessation of SSRIs has not been reported in the intermittent-dosing studies for PMS/PMDD.³⁸ While this might imply a more tolerable safety profile, the most common adverse effects reported in trials were still as expected: sleep disturbances, headache, nausea, and sexual dysfunction. It is important to note that SSRIs should be used with caution during pregnancy, and paroxetine should be avoided in women considering pregnancy in the near future.

Other antidepressant classes have been studied to a lesser extent than SSRIs. Continuously dosed venlafaxine, a serotonin and norepinephrine reuptake inhibitor, demonstrated efficacy in PMS/PMDD treatment when compared with placebo within the first cycle of therapy.³⁹ The response seen was comparable to that associated with SSRI treatments in other trials.

Buspirone, an anxiolytic with serotonin receptor activity that is different from that of the SSRIs, demonstrated efficacy in reducing the symptom of irritability.⁴⁸ Buspirone may have a role to play in those presenting with irritability as a primary symptom or in those who are unable to tolerate the adverse effects of SSRIs. Tricyclic antidepressants, bupropion, and alprazolam have either limited data regarding efficacy or are associated with adverse effects that limit their use.³⁸

Hormonal treatments may be worth considering

One commonly prescribed hormonal therapy for PMS and PMDD is continuous OCs. A 2012 Cochrane review of OCs containing drospirenone evaluated 5 trials and a total of 1920 women.⁴⁰ Two placebo-controlled trials of women with severe premenstrual symptoms (PMDD) showed improvement after 3 months of taking daily drospirenone 3 mg with ethinyl estradiol 20 mcg, compared with placebo.

While experiencing greater benefit, these groups also experienced significantly more adverse effects including nausea, intermenstrual bleeding, and breast pain. The respective odds ratios for the 3 adverse effects were 3.15 (95% confidence interval [CI], 1.90-5.22), 4.92 (95% CI, 3.03-7.96), and 2.67 (95% CI, 1.50-4.78). The review concluded that drospirenone 3 mg with ethinyl estradiol 20 mcg may help in the treatment of severe premenstrual symptoms (PMDD) but that it is unknown whether this treatment is appropriate for patients with less severe premenstrual symptoms.

Continue to: Another multicenter RCT

Another multicenter RCT evaluated women with PMDD who received levonorgestrel 90 mcg with ethinyl estradiol 20 mcg or placebo daily for 112 days.⁴¹ Symptoms were recorded utilizing the DRSP. Significantly more women taking the daily combination hormone (52%) than placebo (40%) had a positive response (≥ 50% improvement in the DRSP 7-day late luteal phase score and Clinical Global Impression of Severity score of ≥ 1 improvement, evaluated at the last “on-therapy” cycle [P = .025]). Twenty-three of 186 patients in the treatment arm dropped out because of adverse effects.

Noncontraceptive estrogen-containing preparations. Hormone therapy preparations containing lower doses of estrogen than seen in OC preparations have also been studied for PMS management. A 2017 Cochrane review of noncontraceptive estrogen-containing preparations found very low-quality evidence to support the effectiveness of continuous estrogen (transdermal patches or subcutaneous implants) plus progestogen.⁴⁹

Progesterone. The cyclic use of progesterone in the luteal phase has been reviewed as a hormonal treatment for PMS. A 2012 Cochrane review of the efficacy of progesterone for PMS was inconclusive; however, route of administration, dose, and duration differed across studies.⁴²

Another systematic review of 10 trials involving 531 women concluded that progesterone was no better than placebo in the treatment of PMS.⁴³ However, it should be noted that each trial evaluated a different dose of progesterone, and all but 1 of the trials administered progesterone by using the calendar method to predict the beginning of the luteal phase. The only trial to use an objective confirmation of ovulation prior to beginning progesterone therapy did demonstrate significant improvement in premenstrual symptoms.

This 1985 study by Dennerstein et al⁴⁴ prescribed progesterone for 10 days of each menstrual cycle starting 3 days after ovulation. In each cycle, ovulation was confirmed by determinations of urinary 24-hour pregnanediol and total estrogen concentrations. Progesterone was then prescribed during the objectively identified luteal phase, resulting in significant improvement in symptoms.

Continue to: Another study evaluated...

The benefits of SSRIs are noted much earlier in the treatment of PMS/PMDD than they are observed in their use for depression or anxiety.

Another study evaluated the post-ovulatory progesterone profiles of 77 women with symptoms of PMS and found lower levels of progesterone and a sharper rate of decline in the women with PMS vs the control group.⁴⁵ Subsequent progesterone treatment during the objectively identified luteal phase significantly improved PMS symptoms. These studies would seem to suggest that progesterone replacement when administered during an objectively identified luteal phase may offer some benefit in the treatment of PMS, but larger RCTs are needed to confirm this.

CASE

You provide the patient with diet and lifestyle education as well as a recommendation for calcium supplementation. The patient agrees to prospectively chart her most significant premenstrual symptoms. You review additional treatment options including SSRI medications and hormonal approaches. She is using a fertility awareness–based method of family planning that allows her to confidently identify her luteal phase. She agrees to take sertraline 50 mg/d during the luteal phase of her cycle. At her follow-up office visit 3 months later, she reports improvement in her premenstrual symptoms. Her charting of symptoms confirms this.

CORRESPONDENCE
Peter Danis, MD, Mercy Family Medicine St. Louis, 12680 Olive Boulevard, St. Louis, MO 63141; [email protected].

Hand infections, if not treated properly, can cause severe chronic morbidity. The conditions I review here range from superficial to deep seated: herpetic whitlow located in the epidermis; felon in subcutaneous tissue; pyogenic flexor tenosynovitis (FTS) in the tendon sheath; and human bite infection at any level including possibly synovium and bone.

Superficial infections usually respond to nonsurgical management. However, antimicrobial therapy is not straightforward. There is no single regimen that covers all possible pathogens. Combination therapy must usually be started and then tailored once an organism and its susceptibility are known. Subcutaneous, tendon sheath, synovial, and bone infections frequently require surgical management.

Herpetic whitlow

Herpes simplex virus type 1 (HSV-1) is common, with as much as 90% of the population exposed by 60 years of age.¹ Initial infection usually occurs in the oropharynx and is known as a fever blister or cold sore. However, HSV-1 also can cause herpetic whitlow, a primary infection in the fingertip in which the virus penetrates the subcutaneous tissue, usually after a breakdown in the skin barrier either from infected saliva or the lips of an infected individual.¹

What you’ll see. The lesion is characterized by pain, swelling, erythema, and nonpurulent vesicle formation ­(FIGURE 1). The condition is usually self-limiting, with the inflammation resolving spontaneously, leaving normal healthy skin within 1 to 2 weeks. Herpetic whitlow is an occupational hazard for medical, nursing, paramedical, and dental personnel, and standard precautions should be used when handling secretions (Strength of Recommendation [SOR]: A).²

Herpetic whitlow is distinguished from a felon by its formation of vesicles, lack of a tense pulp space, and serous, not purulent, drainage.

Reactivation of HSV-1 (and HSV-2) is common, with a prodrome of a “tingling sensation” and subsequent blister formation in the same location as the previous infection. It can cause pain and discomfort and may render the individual unable to perform usual activities.^1,3 This lesion is often confused with bacterial (pyogenic) infections of the pulp of the finger or thumb (felon).¹ Herpetic whitlow can be distinguished from a felon by its formation of vesicles, lack of a tense pulp space, and serous, rather than purulent, drainage. Scarring is not associated with herpes infection because penetration is limited to the epidermal area. Superimposed bacterial infection can be mistaken for an abscess (felon) and lead to unnecessary incision and drainage, causing associated morbidity and potential scarring in the affected area.¹

How it’s treated. Treatment of herpetic whitlow is usually conservative, and topical application of acyclovir 5% appears to be beneficial (SOR: C).⁴ Two studies also suggest that oral acyclovir is beneficial for herpetic whitlow and may reduce the frequency of recurrence.^5,6 Controlled studies in the use of acyclovir for herpetic whitlow have not been conducted. Despite a lack of direct evidence, acyclovir, famciclovir, and valacyclovir are accepted therapies for herpetic whitlow (TABLE 1⁷) (SOR: B).^6,8

Felon

A felon is a closed-space infection affecting the pulp of the fingers or thumb. The anatomy of the finger is unique in that there are multiple septa attaching the periosteum to the skin, thereby creating several closed spaces prone to develop pockets of infection.

Continue to: What you'll see

What you’ll see. Clinical signs and symptoms include pain in the pulp of the finger with tenderness and swelling. Bacteria are usually introduced into fingertip space (fat pad) by a penetrating object. Some reported cases have involved individuals with diabetes who regularly check their blood sugar (FIGURE 2).⁹ A defining characteristic is that the infection usually does not extend past the interphalangeal joint. Radiologic evaluation may be necessary to detect the presence of foreign bodies or to assess bone involvement (osteomyelitis of the distal phalanx).¹⁰ The differential diagnosis includes paronychia, in which the infection starts in the nail area and pain is not as intense as in a felon infection.¹¹

How it’s treated. Surgical treatment of felon is controversial. There is no doubt that pus should be drained; how the incision is best performed, however, has been debated.¹² Before surgical debridement, obtain a sample of pus for Gram stain and for cultures of aerobic and anaerobic organisms, acid-fast bacilli (AFB), and fungi (SOR: A).^13,14 Several surgical techniques and their pitfalls are described in the literature.

Lateral and tip incisions may help avoid painful scars. However, multiple reports of this procedure describe injury to neurovascular bundles, leading to ischemia and anesthesia.¹² The “fish-mouth” incision and the “hockey stick” or “J” incision, as well as the transverse palmar incision, are no longer recommended due to painful sequelae, sensorial alterations, and risk of cutting the digital nerves.¹⁵ The preferred surgical procedure at this time is to make a very short incision over the area of maximum tenderness, then open and drain the abscess. Avoid placing ­packing in the affected area. Post-surgical management includes elevation, immobilization with an appropriate splint, and application of compresses until the wound has healed.^12,15,16

Since Staphylococcus aureus and Streptococcus sp are the most common bacteria causing felon, start empiric treatment with an antistaphylococcal penicillin, a first-generation cephalosporin, or clindamycin. Once a microbe has been isolated, treatment can be tailored as needed. Treatment may take up to 10 to 14 days and depends on the location and resolution of symptoms.¹³ Assess tetanus status and give prophylaxis as needed (SOR: A).¹⁷

Acute pyogenic flexor tenosynovitis

FTS is an aggressive closed-space bacterial infection that involves the flexor tendon synovial sheath. FTS accounts for up to 10% of acute hand infections and requires prompt medical attention with wound lavage, surgical management, and antimicrobial therapy to minimize serious consequences to the digit.¹⁸

Continue to: What you'll see

What you’ll see. FTS is diagnosed using clinical criteria^19,20: fusiform swelling of the finger; exquisite tenderness over the entire course of the flexor tendon sheath; pain on passive extension; and flexed posture of the digit (FIGURE 3). Patients usually recall some type of trauma or puncture wound to the affected area, but hematogenous spread of Neisseria gonorrhoeae also has been reported.²¹ The most common bacterial pathogens are Staphylococcus sp or Streptococcus sp. However, obtain a sample for Gram stain and culture for aerobic, anaerobic, AFB, and fungal agents before irrigating the wound with copious fluids and initiating empirical antibiotic therapy.¹⁴ Once a pathogen has been isolated, tailor antimicrobial therapy based on identified sensitivities and local ­antibiogram.¹³

How it’s treated. Early treatment of FTS is of utmost importance to avoid adverse outcomes. If FTS is diagnosed early, manage conservatively with elevation of the hand, splinting in a neutral position, and intravenous (IV) antibiotics. The use of adjunct antibiotics has improved range-of-motion outcomes compared with elevation and splinting alone (54% excellent vs 14% excellent) (SOR: A).²²In the most complex or fulminant cases, when conservative treatment has failed to show improvement (FIGURE 4), surgical management is indicated.²²

Surgical management of FTS has involved either an open or closed method. The open approach consists of open incision and drainage with exposure of the flexor tendon sheath, followed by large-volume sheath irrigation and closure of incision, in some cases over a drain. The closed approach with irrigation, rather than open washout, has been associated with improved outcomes (71% excellent vs 26% excellent).²² As a result, the procedure of choice is the closed approach, which uses closed catheter irrigation. An incision and placement of an angiocatheter allows for gentle irrigation of the wound until all purulent material has been evacuated (SOR: C).^22,23

Human bite injuries

A human bite injury occurs in 1 of 2 ways, and each has a distinct pattern.

What you’ll see

Closed-fist injury occurs when a clenched fist strikes the teeth of another person. The resulting lesion can easily fool a clinician by appearing to show very little damage. If not appropriately evaluated and treated, the lesion can cause considerable morbidity ­(FIGURE 5). Injury to the extensor mechanism and joint capsule can also damage the articular cartilage and bone, allowing bacteria to grow in a closed environment. This usually affects the metacarpophalangeal joint (MCP) due to its prominence when a hand is clenched. Initially the lesion seems to be minor, with a small laceration of 3 to 5 mm on the overlying skin, thus inoculating mouth flora deep in the hand tissue. Once the hand is relaxed, the broken skin retracts proximally, covering the wound and making it look innocuous.²⁴

Continue to: Occlusive bite injury...

Occlusive bite injury occurs when one individual forcibly bites another. Such wounds tend to be less penetrating than clenched-fist injuries. However, they can vary from superficial lacerations to wounds with tissue loss, including traumatic finger amputation.^24,25

One randomized prospective study compared mechanical wound care alone with combined mechanical wound care and oral or IV antibiotics and found that 47% of patients receiving wound care alone became infected vs no infection among those given oral or parenteral antibiotics (SOR: C).²⁶ Experts in the field advise examining the wound after administering a local anesthetic, thereby allowing better visualization of possible tendon damage, joint penetration, fracture, or deep-tissue infection. The procedure should be performed by a physician experienced in treating hand wounds, whether in the emergency department (ED) or in an operating suite.

How it’s treated. There is controversy regarding whether an affected patient can be adequately treated as an outpatient. Most traumatic bite lesions occur in men, and in those abusing drugs or alcohol.²⁵ In the latter case, individuals may be less likely to return for subsequent care or to finish the antibiotic course as prescribed. It is therefore strongly suggested that those individuals be admitted to receive IV antibiotics and physical therapy to expedite healing and avoid morbidity and sequelae of the lesions (SOR: C).^25,27

Obtain cultures from the wound after giving analgesia but before starting the procedure. The sample should be sent to the Microbiology Department or outpatient reference lab for aerobic, anaerobic, AFB, and fungal cultures. Recommend that the laboratory use 10% CO₂-enriched media for ­Eikenella ­corrodens isolation (SOR: A).^28,29

Among oral human flora are large concentrations of anaerobic bacteria such as Bacteroides sp (including B fragilis), ­Prevotella sp, Peptostreptococcus sp, Fusobacterium sp, Veillonella sp, Enterobateriaceae, and Clostridum. B fragilis accounts for up to 41% of isolates in some studies.³⁰ Most of them are beta-lactamase producers. The most common aerobic bacteria are alpha- and beta-hemolytic Streptococci, S aureus, Staphylococcus epidermis, Corynebacterium, and E corrodens. E corrodens accounts for up to 25% of bacteria isolated in clenched-fist injuries.^27,29

Continue to: HSV-1 and HSV-2...

HSV-1 and HSV-2, as well as hepatitis B and C and human immunodeficiency virus (HIV) can be isolated in saliva of infected individuals and can be transmitted when contaminated blood is exposed to an open wound. Still, the presence of HIV in saliva is unlikely to result in disease transmission, due to salivary inhibitors rendering the virus non-infective in most cases.²⁵ Obtain HIV and hepatitis B and C serology at baseline and at 3 and 6 months.²⁵ If HIV infection is known or suspected, or if there was exposure to blood in the wound, the Centers for Disease Control and Prevention recommends postexposure prophylaxis with a 28-day course of anti-­retroviral medication (SOR: A).^24,31

Hepatitis B virus has an infectivity ­100-fold greater than HIV.²⁷ If possible, the 2 people involved in the altercation should be tested for hepatitis B surface antigen. If the result is positive, the individual with the skin wound should receive hepatitis B immune globulin (0.06 mL/kg/dose),³² and the vaccination schedule started if not done previously (SOR: A).³³

Most experts recommend early antibiotic therapy given over 3 to 5 days for fresh, superficial wounds and specifically for wounds affecting hands, feet, joint, and genital area.¹¹ For treatment of cellulitis or abscess, 10 to 14 days is sufficient; tenosynovitis requires 2 to 3 weeks; osteomyelitis requires 4 to 6 weeks.²⁴ Wound care associated with daily dressing changes and antimicrobial therapy was superior to wound care alone (0% vs 47%).³⁰ Assess tetanus status in all cases (SOR: A).^17,33,34

Antimicrobial therapy for contamination with oral secretion is not straightforward. No one medication covers all possible pathogens. Use a combination therapy initially and then narrow coverage once the microorganism has been identified and susceptibilities are known. Empirical oral therapy with amoxicillin-clavulanate would be reasonable.

If IV therapy is needed, consider using ampicillin-sulbactam, cefazolin, or clindamycin. These antibiotics usually cover S aureus, Streptococcus sp, E corrodens and some anaerobes. Dicloxacillin will cover S aureus but provides poor coverage for E corrodens. First-generation cephalosporins cover S aureus, but E corrodens resistance is common. For penicillin-allergic individuals, use trimethoprim-sulfamethoxazole to cover E corrodens. Doxycycline can be used in children older than 8 years and in adults; avoid it in pregnant women.

Continue to: General principles guiding wound care, microbiology, and antibiotic management

General principles guiding wound care, microbiology, and antibiotic management

Elapsed time between injury and seeking medical attention is characterized as an early (24 hours), late (1-7 days), or delayed (> 7 days) presentation. The timing of an individual’s presentation and a determination of whether the wound is “clean” or “dirty” are both factors in the risk of infection and in ­associated morbidity and long-term ­sequelae.

General principles of surgery are important. The cornerstones of treatment are the use of topical anesthesia to provide pain control, which allows for better examination of the wound, debridement of devitalized tissue, collection of wound cultures, and irrigation of the wound with large volume of fluids to mechanically remove dirt, foreign bodies, and bacteria.

Surgical knowledge of hand anatomy increases the likelihood of favorable outcomes in morbidity and functionality. Depending on the circumstances and location, this procedure may be performed by an experienced hand surgeon or an ED physician. (Diversity in settings and available resources may explain why there is so much variability in the composition of patient populations and outcomes found in the medical literature.)

To maximize appropriate bacteriologic success, the Microbiology Department or lab needs to be informed of the type of samples that have been collected. Cultures should be sent for aerobic, anaerobic, AFB, and fungal cultures. Enrichment of aerobic culture with 10% CO₂ increases the likelihood of isolating E corrodens (fastidious bacterium), which has been identified in approximately 25% of clenched-fist wounds.

Populations at heightened risk for human bite injuries include alcohol and drug abusers and those of poor socioeconomic status who may not have the resources to visit a medical facility early enough to obtain appropriate medical care. These patients are at risk for being lost to follow-up as well as medication noncompliance, so inpatient admission may diminish the possibilities of incomplete medical treatment, complications, and adverse outcomes such as loss of functionality of the affected extremity.

Continue to: Antimicrobial therapy is not easy

Antimicrobial therapy is not easy. No single regimen covers all possibilities. Start antimicrobial treatment empirically with wide-spectrum coverage, and tailor the regimen, as needed, based on microbiology ­results.

In clean surgical procedures, S aureus is the most common pathogen. It is acceptable to start empirical treatment with an antistaphylococcal penicillin, first-generation cephalosporin, or clindamycin. In contaminated wounds, gram-negative bacteria, anaerobes, fungal organisms, and mixed infections are more commonly seen.^35-37

Felon has occurred in individuals with diabetes, who regularly check their blood-sugar level.

First-generation cephalosporin provides good coverage for gram-positive and gram-negative bacteria in clean wounds. However, in contaminated wounds with devitalized tissue, a more aggressive scheme is recommended: start with a penicillin and aminoglycoside.^35-37 In some cases, monotherapy with either ampicillin/sulbactam, imipenem, meropenem, piperacillin/tazobactam, or tigecylline may be sufficient until culture results are available; at that point, antibiotic coverage can be narrowed as indicated (TABLE 2⁷).^35,36

CORRESPONDENCE
Carlos A. Arango, MD, 8399 Bayberry Road, Jacksonville, FL 32256; [email protected].

Hand infections, if not treated properly, can cause severe chronic morbidity. The conditions I review here range from superficial to deep seated: herpetic whitlow located in the epidermis; felon in subcutaneous tissue; pyogenic flexor tenosynovitis (FTS) in the tendon sheath; and human bite infection at any level including possibly synovium and bone.

Superficial infections usually respond to nonsurgical management. However, antimicrobial therapy is not straightforward. There is no single regimen that covers all possible pathogens. Combination therapy must usually be started and then tailored once an organism and its susceptibility are known. Subcutaneous, tendon sheath, synovial, and bone infections frequently require surgical management.

Herpetic whitlow

Herpes simplex virus type 1 (HSV-1) is common, with as much as 90% of the population exposed by 60 years of age.¹ Initial infection usually occurs in the oropharynx and is known as a fever blister or cold sore. However, HSV-1 also can cause herpetic whitlow, a primary infection in the fingertip in which the virus penetrates the subcutaneous tissue, usually after a breakdown in the skin barrier either from infected saliva or the lips of an infected individual.¹

What you’ll see. The lesion is characterized by pain, swelling, erythema, and nonpurulent vesicle formation ­(FIGURE 1). The condition is usually self-limiting, with the inflammation resolving spontaneously, leaving normal healthy skin within 1 to 2 weeks. Herpetic whitlow is an occupational hazard for medical, nursing, paramedical, and dental personnel, and standard precautions should be used when handling secretions (Strength of Recommendation [SOR]: A).²

Herpetic whitlow is distinguished from a felon by its formation of vesicles, lack of a tense pulp space, and serous, not purulent, drainage.

Reactivation of HSV-1 (and HSV-2) is common, with a prodrome of a “tingling sensation” and subsequent blister formation in the same location as the previous infection. It can cause pain and discomfort and may render the individual unable to perform usual activities.^1,3 This lesion is often confused with bacterial (pyogenic) infections of the pulp of the finger or thumb (felon).¹ Herpetic whitlow can be distinguished from a felon by its formation of vesicles, lack of a tense pulp space, and serous, rather than purulent, drainage. Scarring is not associated with herpes infection because penetration is limited to the epidermal area. Superimposed bacterial infection can be mistaken for an abscess (felon) and lead to unnecessary incision and drainage, causing associated morbidity and potential scarring in the affected area.¹

How it’s treated. Treatment of herpetic whitlow is usually conservative, and topical application of acyclovir 5% appears to be beneficial (SOR: C).⁴ Two studies also suggest that oral acyclovir is beneficial for herpetic whitlow and may reduce the frequency of recurrence.^5,6 Controlled studies in the use of acyclovir for herpetic whitlow have not been conducted. Despite a lack of direct evidence, acyclovir, famciclovir, and valacyclovir are accepted therapies for herpetic whitlow (TABLE 1⁷) (SOR: B).^6,8

Felon

A felon is a closed-space infection affecting the pulp of the fingers or thumb. The anatomy of the finger is unique in that there are multiple septa attaching the periosteum to the skin, thereby creating several closed spaces prone to develop pockets of infection.

Continue to: What you'll see

What you’ll see. Clinical signs and symptoms include pain in the pulp of the finger with tenderness and swelling. Bacteria are usually introduced into fingertip space (fat pad) by a penetrating object. Some reported cases have involved individuals with diabetes who regularly check their blood sugar (FIGURE 2).⁹ A defining characteristic is that the infection usually does not extend past the interphalangeal joint. Radiologic evaluation may be necessary to detect the presence of foreign bodies or to assess bone involvement (osteomyelitis of the distal phalanx).¹⁰ The differential diagnosis includes paronychia, in which the infection starts in the nail area and pain is not as intense as in a felon infection.¹¹

How it’s treated. Surgical treatment of felon is controversial. There is no doubt that pus should be drained; how the incision is best performed, however, has been debated.¹² Before surgical debridement, obtain a sample of pus for Gram stain and for cultures of aerobic and anaerobic organisms, acid-fast bacilli (AFB), and fungi (SOR: A).^13,14 Several surgical techniques and their pitfalls are described in the literature.

Lateral and tip incisions may help avoid painful scars. However, multiple reports of this procedure describe injury to neurovascular bundles, leading to ischemia and anesthesia.¹² The “fish-mouth” incision and the “hockey stick” or “J” incision, as well as the transverse palmar incision, are no longer recommended due to painful sequelae, sensorial alterations, and risk of cutting the digital nerves.¹⁵ The preferred surgical procedure at this time is to make a very short incision over the area of maximum tenderness, then open and drain the abscess. Avoid placing ­packing in the affected area. Post-surgical management includes elevation, immobilization with an appropriate splint, and application of compresses until the wound has healed.^12,15,16

Since Staphylococcus aureus and Streptococcus sp are the most common bacteria causing felon, start empiric treatment with an antistaphylococcal penicillin, a first-generation cephalosporin, or clindamycin. Once a microbe has been isolated, treatment can be tailored as needed. Treatment may take up to 10 to 14 days and depends on the location and resolution of symptoms.¹³ Assess tetanus status and give prophylaxis as needed (SOR: A).¹⁷

Acute pyogenic flexor tenosynovitis

FTS is an aggressive closed-space bacterial infection that involves the flexor tendon synovial sheath. FTS accounts for up to 10% of acute hand infections and requires prompt medical attention with wound lavage, surgical management, and antimicrobial therapy to minimize serious consequences to the digit.¹⁸

Continue to: What you'll see

What you’ll see. FTS is diagnosed using clinical criteria^19,20: fusiform swelling of the finger; exquisite tenderness over the entire course of the flexor tendon sheath; pain on passive extension; and flexed posture of the digit (FIGURE 3). Patients usually recall some type of trauma or puncture wound to the affected area, but hematogenous spread of Neisseria gonorrhoeae also has been reported.²¹ The most common bacterial pathogens are Staphylococcus sp or Streptococcus sp. However, obtain a sample for Gram stain and culture for aerobic, anaerobic, AFB, and fungal agents before irrigating the wound with copious fluids and initiating empirical antibiotic therapy.¹⁴ Once a pathogen has been isolated, tailor antimicrobial therapy based on identified sensitivities and local ­antibiogram.¹³

How it’s treated. Early treatment of FTS is of utmost importance to avoid adverse outcomes. If FTS is diagnosed early, manage conservatively with elevation of the hand, splinting in a neutral position, and intravenous (IV) antibiotics. The use of adjunct antibiotics has improved range-of-motion outcomes compared with elevation and splinting alone (54% excellent vs 14% excellent) (SOR: A).²²In the most complex or fulminant cases, when conservative treatment has failed to show improvement (FIGURE 4), surgical management is indicated.²²

Surgical management of FTS has involved either an open or closed method. The open approach consists of open incision and drainage with exposure of the flexor tendon sheath, followed by large-volume sheath irrigation and closure of incision, in some cases over a drain. The closed approach with irrigation, rather than open washout, has been associated with improved outcomes (71% excellent vs 26% excellent).²² As a result, the procedure of choice is the closed approach, which uses closed catheter irrigation. An incision and placement of an angiocatheter allows for gentle irrigation of the wound until all purulent material has been evacuated (SOR: C).^22,23

Human bite injuries

A human bite injury occurs in 1 of 2 ways, and each has a distinct pattern.

What you’ll see

Closed-fist injury occurs when a clenched fist strikes the teeth of another person. The resulting lesion can easily fool a clinician by appearing to show very little damage. If not appropriately evaluated and treated, the lesion can cause considerable morbidity ­(FIGURE 5). Injury to the extensor mechanism and joint capsule can also damage the articular cartilage and bone, allowing bacteria to grow in a closed environment. This usually affects the metacarpophalangeal joint (MCP) due to its prominence when a hand is clenched. Initially the lesion seems to be minor, with a small laceration of 3 to 5 mm on the overlying skin, thus inoculating mouth flora deep in the hand tissue. Once the hand is relaxed, the broken skin retracts proximally, covering the wound and making it look innocuous.²⁴

Continue to: Occlusive bite injury...

Occlusive bite injury occurs when one individual forcibly bites another. Such wounds tend to be less penetrating than clenched-fist injuries. However, they can vary from superficial lacerations to wounds with tissue loss, including traumatic finger amputation.^24,25

One randomized prospective study compared mechanical wound care alone with combined mechanical wound care and oral or IV antibiotics and found that 47% of patients receiving wound care alone became infected vs no infection among those given oral or parenteral antibiotics (SOR: C).²⁶ Experts in the field advise examining the wound after administering a local anesthetic, thereby allowing better visualization of possible tendon damage, joint penetration, fracture, or deep-tissue infection. The procedure should be performed by a physician experienced in treating hand wounds, whether in the emergency department (ED) or in an operating suite.

How it’s treated. There is controversy regarding whether an affected patient can be adequately treated as an outpatient. Most traumatic bite lesions occur in men, and in those abusing drugs or alcohol.²⁵ In the latter case, individuals may be less likely to return for subsequent care or to finish the antibiotic course as prescribed. It is therefore strongly suggested that those individuals be admitted to receive IV antibiotics and physical therapy to expedite healing and avoid morbidity and sequelae of the lesions (SOR: C).^25,27

Obtain cultures from the wound after giving analgesia but before starting the procedure. The sample should be sent to the Microbiology Department or outpatient reference lab for aerobic, anaerobic, AFB, and fungal cultures. Recommend that the laboratory use 10% CO₂-enriched media for ­Eikenella ­corrodens isolation (SOR: A).^28,29

Among oral human flora are large concentrations of anaerobic bacteria such as Bacteroides sp (including B fragilis), ­Prevotella sp, Peptostreptococcus sp, Fusobacterium sp, Veillonella sp, Enterobateriaceae, and Clostridum. B fragilis accounts for up to 41% of isolates in some studies.³⁰ Most of them are beta-lactamase producers. The most common aerobic bacteria are alpha- and beta-hemolytic Streptococci, S aureus, Staphylococcus epidermis, Corynebacterium, and E corrodens. E corrodens accounts for up to 25% of bacteria isolated in clenched-fist injuries.^27,29

Continue to: HSV-1 and HSV-2...

HSV-1 and HSV-2, as well as hepatitis B and C and human immunodeficiency virus (HIV) can be isolated in saliva of infected individuals and can be transmitted when contaminated blood is exposed to an open wound. Still, the presence of HIV in saliva is unlikely to result in disease transmission, due to salivary inhibitors rendering the virus non-infective in most cases.²⁵ Obtain HIV and hepatitis B and C serology at baseline and at 3 and 6 months.²⁵ If HIV infection is known or suspected, or if there was exposure to blood in the wound, the Centers for Disease Control and Prevention recommends postexposure prophylaxis with a 28-day course of anti-­retroviral medication (SOR: A).^24,31

Hepatitis B virus has an infectivity ­100-fold greater than HIV.²⁷ If possible, the 2 people involved in the altercation should be tested for hepatitis B surface antigen. If the result is positive, the individual with the skin wound should receive hepatitis B immune globulin (0.06 mL/kg/dose),³² and the vaccination schedule started if not done previously (SOR: A).³³

Most experts recommend early antibiotic therapy given over 3 to 5 days for fresh, superficial wounds and specifically for wounds affecting hands, feet, joint, and genital area.¹¹ For treatment of cellulitis or abscess, 10 to 14 days is sufficient; tenosynovitis requires 2 to 3 weeks; osteomyelitis requires 4 to 6 weeks.²⁴ Wound care associated with daily dressing changes and antimicrobial therapy was superior to wound care alone (0% vs 47%).³⁰ Assess tetanus status in all cases (SOR: A).^17,33,34

Antimicrobial therapy for contamination with oral secretion is not straightforward. No one medication covers all possible pathogens. Use a combination therapy initially and then narrow coverage once the microorganism has been identified and susceptibilities are known. Empirical oral therapy with amoxicillin-clavulanate would be reasonable.

If IV therapy is needed, consider using ampicillin-sulbactam, cefazolin, or clindamycin. These antibiotics usually cover S aureus, Streptococcus sp, E corrodens and some anaerobes. Dicloxacillin will cover S aureus but provides poor coverage for E corrodens. First-generation cephalosporins cover S aureus, but E corrodens resistance is common. For penicillin-allergic individuals, use trimethoprim-sulfamethoxazole to cover E corrodens. Doxycycline can be used in children older than 8 years and in adults; avoid it in pregnant women.

Continue to: General principles guiding wound care, microbiology, and antibiotic management

General principles guiding wound care, microbiology, and antibiotic management

Elapsed time between injury and seeking medical attention is characterized as an early (24 hours), late (1-7 days), or delayed (> 7 days) presentation. The timing of an individual’s presentation and a determination of whether the wound is “clean” or “dirty” are both factors in the risk of infection and in ­associated morbidity and long-term ­sequelae.

General principles of surgery are important. The cornerstones of treatment are the use of topical anesthesia to provide pain control, which allows for better examination of the wound, debridement of devitalized tissue, collection of wound cultures, and irrigation of the wound with large volume of fluids to mechanically remove dirt, foreign bodies, and bacteria.

Surgical knowledge of hand anatomy increases the likelihood of favorable outcomes in morbidity and functionality. Depending on the circumstances and location, this procedure may be performed by an experienced hand surgeon or an ED physician. (Diversity in settings and available resources may explain why there is so much variability in the composition of patient populations and outcomes found in the medical literature.)

To maximize appropriate bacteriologic success, the Microbiology Department or lab needs to be informed of the type of samples that have been collected. Cultures should be sent for aerobic, anaerobic, AFB, and fungal cultures. Enrichment of aerobic culture with 10% CO₂ increases the likelihood of isolating E corrodens (fastidious bacterium), which has been identified in approximately 25% of clenched-fist wounds.

Populations at heightened risk for human bite injuries include alcohol and drug abusers and those of poor socioeconomic status who may not have the resources to visit a medical facility early enough to obtain appropriate medical care. These patients are at risk for being lost to follow-up as well as medication noncompliance, so inpatient admission may diminish the possibilities of incomplete medical treatment, complications, and adverse outcomes such as loss of functionality of the affected extremity.

Continue to: Antimicrobial therapy is not easy

Antimicrobial therapy is not easy. No single regimen covers all possibilities. Start antimicrobial treatment empirically with wide-spectrum coverage, and tailor the regimen, as needed, based on microbiology ­results.

In clean surgical procedures, S aureus is the most common pathogen. It is acceptable to start empirical treatment with an antistaphylococcal penicillin, first-generation cephalosporin, or clindamycin. In contaminated wounds, gram-negative bacteria, anaerobes, fungal organisms, and mixed infections are more commonly seen.^35-37

Felon has occurred in individuals with diabetes, who regularly check their blood-sugar level.

First-generation cephalosporin provides good coverage for gram-positive and gram-negative bacteria in clean wounds. However, in contaminated wounds with devitalized tissue, a more aggressive scheme is recommended: start with a penicillin and aminoglycoside.^35-37 In some cases, monotherapy with either ampicillin/sulbactam, imipenem, meropenem, piperacillin/tazobactam, or tigecylline may be sufficient until culture results are available; at that point, antibiotic coverage can be narrowed as indicated (TABLE 2⁷).^35,36

CORRESPONDENCE
Carlos A. Arango, MD, 8399 Bayberry Road, Jacksonville, FL 32256; [email protected].

Hand infections, if not treated properly, can cause severe chronic morbidity. The conditions I review here range from superficial to deep seated: herpetic whitlow located in the epidermis; felon in subcutaneous tissue; pyogenic flexor tenosynovitis (FTS) in the tendon sheath; and human bite infection at any level including possibly synovium and bone.

Superficial infections usually respond to nonsurgical management. However, antimicrobial therapy is not straightforward. There is no single regimen that covers all possible pathogens. Combination therapy must usually be started and then tailored once an organism and its susceptibility are known. Subcutaneous, tendon sheath, synovial, and bone infections frequently require surgical management.

Herpetic whitlow

Herpes simplex virus type 1 (HSV-1) is common, with as much as 90% of the population exposed by 60 years of age.¹ Initial infection usually occurs in the oropharynx and is known as a fever blister or cold sore. However, HSV-1 also can cause herpetic whitlow, a primary infection in the fingertip in which the virus penetrates the subcutaneous tissue, usually after a breakdown in the skin barrier either from infected saliva or the lips of an infected individual.¹

What you’ll see. The lesion is characterized by pain, swelling, erythema, and nonpurulent vesicle formation ­(FIGURE 1). The condition is usually self-limiting, with the inflammation resolving spontaneously, leaving normal healthy skin within 1 to 2 weeks. Herpetic whitlow is an occupational hazard for medical, nursing, paramedical, and dental personnel, and standard precautions should be used when handling secretions (Strength of Recommendation [SOR]: A).²

Herpetic whitlow is distinguished from a felon by its formation of vesicles, lack of a tense pulp space, and serous, not purulent, drainage.

Reactivation of HSV-1 (and HSV-2) is common, with a prodrome of a “tingling sensation” and subsequent blister formation in the same location as the previous infection. It can cause pain and discomfort and may render the individual unable to perform usual activities.^1,3 This lesion is often confused with bacterial (pyogenic) infections of the pulp of the finger or thumb (felon).¹ Herpetic whitlow can be distinguished from a felon by its formation of vesicles, lack of a tense pulp space, and serous, rather than purulent, drainage. Scarring is not associated with herpes infection because penetration is limited to the epidermal area. Superimposed bacterial infection can be mistaken for an abscess (felon) and lead to unnecessary incision and drainage, causing associated morbidity and potential scarring in the affected area.¹

How it’s treated. Treatment of herpetic whitlow is usually conservative, and topical application of acyclovir 5% appears to be beneficial (SOR: C).⁴ Two studies also suggest that oral acyclovir is beneficial for herpetic whitlow and may reduce the frequency of recurrence.^5,6 Controlled studies in the use of acyclovir for herpetic whitlow have not been conducted. Despite a lack of direct evidence, acyclovir, famciclovir, and valacyclovir are accepted therapies for herpetic whitlow (TABLE 1⁷) (SOR: B).^6,8

Felon

A felon is a closed-space infection affecting the pulp of the fingers or thumb. The anatomy of the finger is unique in that there are multiple septa attaching the periosteum to the skin, thereby creating several closed spaces prone to develop pockets of infection.

Continue to: What you'll see

What you’ll see. Clinical signs and symptoms include pain in the pulp of the finger with tenderness and swelling. Bacteria are usually introduced into fingertip space (fat pad) by a penetrating object. Some reported cases have involved individuals with diabetes who regularly check their blood sugar (FIGURE 2).⁹ A defining characteristic is that the infection usually does not extend past the interphalangeal joint. Radiologic evaluation may be necessary to detect the presence of foreign bodies or to assess bone involvement (osteomyelitis of the distal phalanx).¹⁰ The differential diagnosis includes paronychia, in which the infection starts in the nail area and pain is not as intense as in a felon infection.¹¹

How it’s treated. Surgical treatment of felon is controversial. There is no doubt that pus should be drained; how the incision is best performed, however, has been debated.¹² Before surgical debridement, obtain a sample of pus for Gram stain and for cultures of aerobic and anaerobic organisms, acid-fast bacilli (AFB), and fungi (SOR: A).^13,14 Several surgical techniques and their pitfalls are described in the literature.

Lateral and tip incisions may help avoid painful scars. However, multiple reports of this procedure describe injury to neurovascular bundles, leading to ischemia and anesthesia.¹² The “fish-mouth” incision and the “hockey stick” or “J” incision, as well as the transverse palmar incision, are no longer recommended due to painful sequelae, sensorial alterations, and risk of cutting the digital nerves.¹⁵ The preferred surgical procedure at this time is to make a very short incision over the area of maximum tenderness, then open and drain the abscess. Avoid placing ­packing in the affected area. Post-surgical management includes elevation, immobilization with an appropriate splint, and application of compresses until the wound has healed.^12,15,16

Since Staphylococcus aureus and Streptococcus sp are the most common bacteria causing felon, start empiric treatment with an antistaphylococcal penicillin, a first-generation cephalosporin, or clindamycin. Once a microbe has been isolated, treatment can be tailored as needed. Treatment may take up to 10 to 14 days and depends on the location and resolution of symptoms.¹³ Assess tetanus status and give prophylaxis as needed (SOR: A).¹⁷

Acute pyogenic flexor tenosynovitis

FTS is an aggressive closed-space bacterial infection that involves the flexor tendon synovial sheath. FTS accounts for up to 10% of acute hand infections and requires prompt medical attention with wound lavage, surgical management, and antimicrobial therapy to minimize serious consequences to the digit.¹⁸

Continue to: What you'll see

What you’ll see. FTS is diagnosed using clinical criteria^19,20: fusiform swelling of the finger; exquisite tenderness over the entire course of the flexor tendon sheath; pain on passive extension; and flexed posture of the digit (FIGURE 3). Patients usually recall some type of trauma or puncture wound to the affected area, but hematogenous spread of Neisseria gonorrhoeae also has been reported.²¹ The most common bacterial pathogens are Staphylococcus sp or Streptococcus sp. However, obtain a sample for Gram stain and culture for aerobic, anaerobic, AFB, and fungal agents before irrigating the wound with copious fluids and initiating empirical antibiotic therapy.¹⁴ Once a pathogen has been isolated, tailor antimicrobial therapy based on identified sensitivities and local ­antibiogram.¹³

How it’s treated. Early treatment of FTS is of utmost importance to avoid adverse outcomes. If FTS is diagnosed early, manage conservatively with elevation of the hand, splinting in a neutral position, and intravenous (IV) antibiotics. The use of adjunct antibiotics has improved range-of-motion outcomes compared with elevation and splinting alone (54% excellent vs 14% excellent) (SOR: A).²²In the most complex or fulminant cases, when conservative treatment has failed to show improvement (FIGURE 4), surgical management is indicated.²²

Surgical management of FTS has involved either an open or closed method. The open approach consists of open incision and drainage with exposure of the flexor tendon sheath, followed by large-volume sheath irrigation and closure of incision, in some cases over a drain. The closed approach with irrigation, rather than open washout, has been associated with improved outcomes (71% excellent vs 26% excellent).²² As a result, the procedure of choice is the closed approach, which uses closed catheter irrigation. An incision and placement of an angiocatheter allows for gentle irrigation of the wound until all purulent material has been evacuated (SOR: C).^22,23

Human bite injuries

A human bite injury occurs in 1 of 2 ways, and each has a distinct pattern.

What you’ll see

Closed-fist injury occurs when a clenched fist strikes the teeth of another person. The resulting lesion can easily fool a clinician by appearing to show very little damage. If not appropriately evaluated and treated, the lesion can cause considerable morbidity ­(FIGURE 5). Injury to the extensor mechanism and joint capsule can also damage the articular cartilage and bone, allowing bacteria to grow in a closed environment. This usually affects the metacarpophalangeal joint (MCP) due to its prominence when a hand is clenched. Initially the lesion seems to be minor, with a small laceration of 3 to 5 mm on the overlying skin, thus inoculating mouth flora deep in the hand tissue. Once the hand is relaxed, the broken skin retracts proximally, covering the wound and making it look innocuous.²⁴

Continue to: Occlusive bite injury...

Occlusive bite injury occurs when one individual forcibly bites another. Such wounds tend to be less penetrating than clenched-fist injuries. However, they can vary from superficial lacerations to wounds with tissue loss, including traumatic finger amputation.^24,25

One randomized prospective study compared mechanical wound care alone with combined mechanical wound care and oral or IV antibiotics and found that 47% of patients receiving wound care alone became infected vs no infection among those given oral or parenteral antibiotics (SOR: C).²⁶ Experts in the field advise examining the wound after administering a local anesthetic, thereby allowing better visualization of possible tendon damage, joint penetration, fracture, or deep-tissue infection. The procedure should be performed by a physician experienced in treating hand wounds, whether in the emergency department (ED) or in an operating suite.

How it’s treated. There is controversy regarding whether an affected patient can be adequately treated as an outpatient. Most traumatic bite lesions occur in men, and in those abusing drugs or alcohol.²⁵ In the latter case, individuals may be less likely to return for subsequent care or to finish the antibiotic course as prescribed. It is therefore strongly suggested that those individuals be admitted to receive IV antibiotics and physical therapy to expedite healing and avoid morbidity and sequelae of the lesions (SOR: C).^25,27

Obtain cultures from the wound after giving analgesia but before starting the procedure. The sample should be sent to the Microbiology Department or outpatient reference lab for aerobic, anaerobic, AFB, and fungal cultures. Recommend that the laboratory use 10% CO₂-enriched media for ­Eikenella ­corrodens isolation (SOR: A).^28,29

Among oral human flora are large concentrations of anaerobic bacteria such as Bacteroides sp (including B fragilis), ­Prevotella sp, Peptostreptococcus sp, Fusobacterium sp, Veillonella sp, Enterobateriaceae, and Clostridum. B fragilis accounts for up to 41% of isolates in some studies.³⁰ Most of them are beta-lactamase producers. The most common aerobic bacteria are alpha- and beta-hemolytic Streptococci, S aureus, Staphylococcus epidermis, Corynebacterium, and E corrodens. E corrodens accounts for up to 25% of bacteria isolated in clenched-fist injuries.^27,29

Continue to: HSV-1 and HSV-2...

HSV-1 and HSV-2, as well as hepatitis B and C and human immunodeficiency virus (HIV) can be isolated in saliva of infected individuals and can be transmitted when contaminated blood is exposed to an open wound. Still, the presence of HIV in saliva is unlikely to result in disease transmission, due to salivary inhibitors rendering the virus non-infective in most cases.²⁵ Obtain HIV and hepatitis B and C serology at baseline and at 3 and 6 months.²⁵ If HIV infection is known or suspected, or if there was exposure to blood in the wound, the Centers for Disease Control and Prevention recommends postexposure prophylaxis with a 28-day course of anti-­retroviral medication (SOR: A).^24,31

Hepatitis B virus has an infectivity ­100-fold greater than HIV.²⁷ If possible, the 2 people involved in the altercation should be tested for hepatitis B surface antigen. If the result is positive, the individual with the skin wound should receive hepatitis B immune globulin (0.06 mL/kg/dose),³² and the vaccination schedule started if not done previously (SOR: A).³³

Most experts recommend early antibiotic therapy given over 3 to 5 days for fresh, superficial wounds and specifically for wounds affecting hands, feet, joint, and genital area.¹¹ For treatment of cellulitis or abscess, 10 to 14 days is sufficient; tenosynovitis requires 2 to 3 weeks; osteomyelitis requires 4 to 6 weeks.²⁴ Wound care associated with daily dressing changes and antimicrobial therapy was superior to wound care alone (0% vs 47%).³⁰ Assess tetanus status in all cases (SOR: A).^17,33,34

Antimicrobial therapy for contamination with oral secretion is not straightforward. No one medication covers all possible pathogens. Use a combination therapy initially and then narrow coverage once the microorganism has been identified and susceptibilities are known. Empirical oral therapy with amoxicillin-clavulanate would be reasonable.

If IV therapy is needed, consider using ampicillin-sulbactam, cefazolin, or clindamycin. These antibiotics usually cover S aureus, Streptococcus sp, E corrodens and some anaerobes. Dicloxacillin will cover S aureus but provides poor coverage for E corrodens. First-generation cephalosporins cover S aureus, but E corrodens resistance is common. For penicillin-allergic individuals, use trimethoprim-sulfamethoxazole to cover E corrodens. Doxycycline can be used in children older than 8 years and in adults; avoid it in pregnant women.

Continue to: General principles guiding wound care, microbiology, and antibiotic management

General principles guiding wound care, microbiology, and antibiotic management

Elapsed time between injury and seeking medical attention is characterized as an early (24 hours), late (1-7 days), or delayed (> 7 days) presentation. The timing of an individual’s presentation and a determination of whether the wound is “clean” or “dirty” are both factors in the risk of infection and in ­associated morbidity and long-term ­sequelae.

General principles of surgery are important. The cornerstones of treatment are the use of topical anesthesia to provide pain control, which allows for better examination of the wound, debridement of devitalized tissue, collection of wound cultures, and irrigation of the wound with large volume of fluids to mechanically remove dirt, foreign bodies, and bacteria.

Surgical knowledge of hand anatomy increases the likelihood of favorable outcomes in morbidity and functionality. Depending on the circumstances and location, this procedure may be performed by an experienced hand surgeon or an ED physician. (Diversity in settings and available resources may explain why there is so much variability in the composition of patient populations and outcomes found in the medical literature.)

To maximize appropriate bacteriologic success, the Microbiology Department or lab needs to be informed of the type of samples that have been collected. Cultures should be sent for aerobic, anaerobic, AFB, and fungal cultures. Enrichment of aerobic culture with 10% CO₂ increases the likelihood of isolating E corrodens (fastidious bacterium), which has been identified in approximately 25% of clenched-fist wounds.

Populations at heightened risk for human bite injuries include alcohol and drug abusers and those of poor socioeconomic status who may not have the resources to visit a medical facility early enough to obtain appropriate medical care. These patients are at risk for being lost to follow-up as well as medication noncompliance, so inpatient admission may diminish the possibilities of incomplete medical treatment, complications, and adverse outcomes such as loss of functionality of the affected extremity.

Continue to: Antimicrobial therapy is not easy

Antimicrobial therapy is not easy. No single regimen covers all possibilities. Start antimicrobial treatment empirically with wide-spectrum coverage, and tailor the regimen, as needed, based on microbiology ­results.

In clean surgical procedures, S aureus is the most common pathogen. It is acceptable to start empirical treatment with an antistaphylococcal penicillin, first-generation cephalosporin, or clindamycin. In contaminated wounds, gram-negative bacteria, anaerobes, fungal organisms, and mixed infections are more commonly seen.^35-37

Felon has occurred in individuals with diabetes, who regularly check their blood-sugar level.

First-generation cephalosporin provides good coverage for gram-positive and gram-negative bacteria in clean wounds. However, in contaminated wounds with devitalized tissue, a more aggressive scheme is recommended: start with a penicillin and aminoglycoside.^35-37 In some cases, monotherapy with either ampicillin/sulbactam, imipenem, meropenem, piperacillin/tazobactam, or tigecylline may be sufficient until culture results are available; at that point, antibiotic coverage can be narrowed as indicated (TABLE 2⁷).^35,36

CORRESPONDENCE
Carlos A. Arango, MD, 8399 Bayberry Road, Jacksonville, FL 32256; [email protected].

Prostate cancer is the most frequently diagnosed cancer in men and the third leading cause of cancer death in men worldwide.¹ An estimated 174,650 new cases are diagnosed each year in the United States; 31,620 American men die annually from the disease.² Although prostate cancer can be a serious disease, many men do not die from it. In fact, 2.9 million men who were diagnosed with prostate cancer at some point are alive today.³

Risk factors. Prostate cancer develops mainly in men ages ≥ 65 years and rarely occurs before age 40. In addition to age, family history and African American ethnicity are the major nonmodifiable risk factors for prostate cancer.⁴ From the 1970s to the most recent statistical analysis of the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program, African American men have continued to have significantly higher incidence of, and mortality rates from, prostate cancer than their European American counterparts. African American men are also more likely than men of European ancestry to have aggressive prostate cancers.⁵ Other risk factors include geographic location (higher risk in Northern Europe, North America, and Australia; lower risk in Asia, Africa, and South and Central America), mutations in the BRCA2 gene, and hereditary non-polyposis colon cancer syndrome.⁴

Prostate-specific antigen (PSA) was first used as a screening tool for prostate cancer in 1991.⁶ Prostate cancer incidence, especially organ-confined disease, has dramatically increased since then.⁷ PSA testing has a low sensitivity and specificity for the detection of prostate cancer, and there is no clear threshold at which biopsy can or should be offered. The most commonly used cutoff value of 4 ng/mL has a false-positive rate of about 70%.⁸

Benign prostatic conditions such as hypertrophy and infection can elevate PSA levels. In addition, the PSA test does not distinguish between aggressive and slow-growing cancers, and about 15% of patients with prostate cancer have a normal PSA level.⁹

A word about the digital rectal exam. While PSA testing has been the mainstay of prostate cancer screening, a few studies have included digital rectal exam (DRE) in their protocols. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial showed that DRE captured an additional 2% of men with prostate cancer in the setting of a normal PSA test result.¹⁰ In the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, the overall detection rate for prostate cancer was found to be better when DRE was combined with PSA and prostate biopsy than when DRE was used alone (4.5% vs 2.5%).¹¹ Nevertheless, generally speaking, DRE can be omitted in the era of PSA screening.

Screening guidelines vary

Recommendations for prostate cancer screening vary by organization and are summarized in TABLE 1.^9,12-14 In 2012, the US Preventive Services Task Force (USPSTF) recommended against PSA-based screening for prostate cancer (Category D).¹⁵ In 2018, ­USPSTF provided an update with a new recommendation that clinicians inform men ages 55 to 69 years about the potential benefits and harms of PSA-based screening (Category C).¹⁴ The USPSTF continues to recommend against PSA-based screening for men ages ≥ 70 years (Category D).¹⁴

Does PSA-based screening improve patient-centered outcomes?

Several randomized controlled trials (RCTs) such as the Quebec Prospective Randomized Controlled Trial,¹⁶ the Norrköping Sweden Study,¹⁷ ERSPC,¹¹ and PLCO¹⁰ have been conducted to assess the benefits of PSA testing. PLCO and ERSPC have contributed significantly to our understanding of prostate cancer screening even though their 13-year follow-up results are conflicting (TABLE 2).^10,11,18

Continue to: In the ERSPC 13-year follow-up publication...

In the ERSPC 13-year follow-up publication, the authors concluded that a substantial reduction in prostate cancer mortality is attributable to testing with PSA.¹⁸ Despite limitations in the study design (eg, France entered after 2 years, screening intervals varied between 2 and 4 years, biopsy indications varied, and screening was discontinued at different times), PSA screening detected more prostate cancer than was detected in the control arm (10.2% vs 6.8%).

In the initial 11 years of follow-up, the study group experienced a 21% reduction in prostate cancer mortality, even though the absolute decrease ranged from only 0.6% (545 per 89,352) to 0.5% (355 per 72,891). The updated absolute risk reduction of death from prostate cancer at 13 years of follow-up showed a larger benefit: 0.11 per 1000 person-years or 1.28 per 1000 men randomized, which is equivalent to 1 prostate cancer death averted per 781 (95% confidence interval [CI], 490-1929) men invited for screening, or 1 per 27 (17-66) additional prostate cancers detected.

The PLCO trial did not show any significant difference in prostate cancer detection (11.1% screened vs 9.9% control), and there was no improvement in prostate cancer mortality (3.7 vs 3.4 death per 10,000 person-years).¹⁰ However, the PLCO trial suffered from issues of contamination, which may have influenced the overall results. About 52% of men in the control (usual care) group received a PSA test at some point during the study. And more than two-thirds of the men who had a prostate biopsy because of a positive PSA test did not have prostate cancer.

Community standards for the PSA threshold for biopsy were applied in various centers (> 4 ng/ml in general) in PLCO, whereas in ­ERSPC, a cut-off PSA value ≥ 3 ng/mL was used for biopsy. Because of the lower PSA threshold, ERSPC may have identified cancers that would have had good outcomes without any intervention.

The harms of PSA screening

While it is unclear whether PSA screening results in any improvement in patient-centered outcomes, it does lead to downstream intervention due to overdiagnosis, which precipitates unnecessary anxiety, biopsies, and overtreatment (eg, excess radiation, overuse of androgen deprivation therapy).¹⁹ Biopsies carry the risk of hematuria (22.6%), hematospermia (50.4%), and urinary tract infection.²⁰ Data from SEER-Medicare showed that prostate biopsy was associated with a 2.65-fold increased risk of hospitalization within 30 days of the procedure compared to a control population.²¹

Continue to: Overdiagnosis leads to overtreatment...

Overdiagnosis leads to overtreatment of low-risk prostate cancer. Both traditional treatment options for prostate cancer—radical prostatectomy and radiotherapy—are associated with urinary incontinence, erectile dysfunction, and issues with bowel function.^22,23

The Prostate Cancer Intervention vs Observation Trial (PIVOT),²⁴ the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4),²⁵ and the Prostate Testing for Cancer and Treatment (ProtecT) trial,^22,23 are the major RCTs that looked at the outcomes of treatment modalities for localized prostate cancer in the modern era of PSA testing.

PIVOT compared passive observation with radical prostatectomy.²⁴ After 20 years of follow-up on 731 patients, the researchers concluded that radical prostatectomy did not reduce all-cause or prostate cancer–related mortality (TABLE 3).²⁴

SPCG-4 showed survival benefits for men who underwent radical prostatectomy compared with men in a watchful waiting group, but only 5% of the study cohort had cancer detected by PSA screening (TABLE 4).²⁵ The rest had either palpable tumors or symptoms of a tumor.

ProtecT, which followed patients with localized prostate cancer for more than 10 years,compared the outcomes and adverse effects of active surveillance, radical prostatectomy, and radiotherapy.²³ Prostate cancer–specific mortality was low irrespective of the treatment,²³ and there was no significant difference in all-cause mortality or prostate cancer–specific mortality between the 3 treatment groups.²³ The active surveillance group had considerably fewer adverse events.^22,23 The incidence rates of erectile dysfunction and urinary incontinence at the 1- and 6-year follow-up marks are outlined in TABLE 5.²²

Continue to: The purpose of active monitoring...

The purpose of active monitoring is to minimize overtreatment by avoiding immediate radical intervention. Radical treatments with curative intent can be undertaken at any point while patients are being actively monitored. It is important to note that the active monitoring that took place in ProtecT²³ was very different from the passive surveillance of PIVOT²⁴ and SPCG-4.²⁵ In ProtecT, once an elevated serum PSA level was noted, PSA levels were monitored every 3 months in the first year and every 6 to 12 months thereafter.²³ Triggers to reassess patients and consider a change in clinical management were based largely on changes in PSA levels. Participants with an increase of at least 50% in PSA level during the previous 12 months were offered either continued monitoring or treatment after further testing.

Making individualized decisions about prostate cancer screening

Traditionally, the goal of cancer screening has been to maximize the number of people screened. Generally, the information provided to patients about cancer screening emphasizes the benefits and minimizes the harms. Recently, however, there has been a shift in communication about cancer screening with the emphasis now being placed on informed decision-making and encouraging patients to make individual decisions about screening participation.²⁶

Although current guidelines regarding PSA screening differ by organization, generally speaking, PSA screening should be offered only to men with a life expectancy > 10 years.

The treatment option of active surveillance, with its lower incidence of adverse outcomes, is an important reason for patients to make individualized decisions about prostate cancer screening.

Another reason relates to 5-alpha-­reductase inhibitors. Although their role in the management of prostate cancer is currently not well defined, a reduction of almost 25% in the risk of prostate cancer and improvement in the performance of PSA has been reported.²⁷

The PSA test has low sensitivity and specificity and lacks a clear cut-off value that warrants prostate biopsy.

And yet another reason is that there are alternate strategies to manage the majority of patients who have been diagnosed with low-risk disease through transrectal ultrasound biopsy. The ERSPC study mentions multiparametric magnetic resonance imaging combined with targeted biopsy to identify high-grade disease.^28,29 Genetic and epigenetic assays of the biopsied tissue can help grade disease based on aggressiveness.³⁰ Transperineal mapping biopsy using a mapping software program can identify specific disease sites within the prostate gland, so that patients can be offered the option of targeted therapy.³⁰

Continue to: Applying shared decision-making to prostate cancer screening

Balancing errors of omission with errors of commission is challenging. Shared decision-making (SDM) is an approach whereby clinicians and patients share the best available evidence when faced with the task of medical decision-making and in which patients are supported while they consider their options and achieve their preferences.³¹ SDM is well supported by evidence from a number of RCTs and results in increased knowledge, involvement, and confidence on the part of patients.³² An individualized approach using the schematic diagram (FIGURE 1^3,18) may be helpful.

Barriers to SDM success. Many factors can interfere with the success of SDM including limited or poor communication; lack of time during busy office visits; and patients’ cultural, informational, and/or emotional needs. To improve patient-centered communication, we can: (1) make information understandable and available to patients and families; (2) prioritize training in communication; (3) use decision aid tools to facilitate communication; and (4) work to improve the payment model to incentivize patient-centered communication. Tools that facilitate SDM include videotapes, patient group discussions, brief scripts read to patients, and informational pamphlets. One such tool is the American Society for Clinical Oncology’s decision aid tool for PSA testing.³³

Limited knowledge among patients. Decisions regarding treatment among men diagnosed with localized prostate cancer can be difficult because there are several treatment options with similar prognoses, but there are differences in adverse effects. One population-based cohort study of men with newly diagnosed localized prostate cancer found that most men had significant knowledge deficits regarding the survival benefits of the 2 major treatment options—surgery and radiation.³⁴ In a large population-based study, 38% of men with localized prostate cancer reported receiving help from their primary care providers in the decision-making process for treatment.³⁵

Learning to employ SDM. Elwyn et al proposed a 3-step model to incorporate SDM into clinical practice.³¹ They described key steps that include: choice talk (making sure patients are informed about the reasonable options), option talk (providing more detailed information about the options), and decision talk (supporting the work of patients considering their preferences and deciding what is best). Properly employing these methods requires training using simulations.³¹

The bottom line

Although current guidelines regarding PSA screening differ by organization, generally speaking PSA screening should be offered only to men with a life expectancy > 10 years. The PSA test has low sensitivity and specificity and lacks a clear cut-off value that warrants prostate biopsy. Men who choose to have PSA testing increase their chances of detecting prostate cancer, but most prostate cancers are slow growing and do not cause death. The decision to undergo PSA screening should be made by both the provider and the patient, after a discussion of the limited benefits and associated harms. The interval of follow-up screening may vary from 2 to 4 years depending on patient age, level of PSA, and whether a patient is taking medications such as 5-alpha-reductase inhibitors.

CORRESPONDENCE
Jaividhya Dasarathy, MD, FAAFP, 2500 Metro Health Medical Drive, Cleveland, Ohio 44109; [email protected].

Prostate cancer is the most frequently diagnosed cancer in men and the third leading cause of cancer death in men worldwide.¹ An estimated 174,650 new cases are diagnosed each year in the United States; 31,620 American men die annually from the disease.² Although prostate cancer can be a serious disease, many men do not die from it. In fact, 2.9 million men who were diagnosed with prostate cancer at some point are alive today.³

Risk factors. Prostate cancer develops mainly in men ages ≥ 65 years and rarely occurs before age 40. In addition to age, family history and African American ethnicity are the major nonmodifiable risk factors for prostate cancer.⁴ From the 1970s to the most recent statistical analysis of the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program, African American men have continued to have significantly higher incidence of, and mortality rates from, prostate cancer than their European American counterparts. African American men are also more likely than men of European ancestry to have aggressive prostate cancers.⁵ Other risk factors include geographic location (higher risk in Northern Europe, North America, and Australia; lower risk in Asia, Africa, and South and Central America), mutations in the BRCA2 gene, and hereditary non-polyposis colon cancer syndrome.⁴

Prostate-specific antigen (PSA) was first used as a screening tool for prostate cancer in 1991.⁶ Prostate cancer incidence, especially organ-confined disease, has dramatically increased since then.⁷ PSA testing has a low sensitivity and specificity for the detection of prostate cancer, and there is no clear threshold at which biopsy can or should be offered. The most commonly used cutoff value of 4 ng/mL has a false-positive rate of about 70%.⁸

Benign prostatic conditions such as hypertrophy and infection can elevate PSA levels. In addition, the PSA test does not distinguish between aggressive and slow-growing cancers, and about 15% of patients with prostate cancer have a normal PSA level.⁹

A word about the digital rectal exam. While PSA testing has been the mainstay of prostate cancer screening, a few studies have included digital rectal exam (DRE) in their protocols. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial showed that DRE captured an additional 2% of men with prostate cancer in the setting of a normal PSA test result.¹⁰ In the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, the overall detection rate for prostate cancer was found to be better when DRE was combined with PSA and prostate biopsy than when DRE was used alone (4.5% vs 2.5%).¹¹ Nevertheless, generally speaking, DRE can be omitted in the era of PSA screening.

Screening guidelines vary

Recommendations for prostate cancer screening vary by organization and are summarized in TABLE 1.^9,12-14 In 2012, the US Preventive Services Task Force (USPSTF) recommended against PSA-based screening for prostate cancer (Category D).¹⁵ In 2018, ­USPSTF provided an update with a new recommendation that clinicians inform men ages 55 to 69 years about the potential benefits and harms of PSA-based screening (Category C).¹⁴ The USPSTF continues to recommend against PSA-based screening for men ages ≥ 70 years (Category D).¹⁴

Does PSA-based screening improve patient-centered outcomes?

Several randomized controlled trials (RCTs) such as the Quebec Prospective Randomized Controlled Trial,¹⁶ the Norrköping Sweden Study,¹⁷ ERSPC,¹¹ and PLCO¹⁰ have been conducted to assess the benefits of PSA testing. PLCO and ERSPC have contributed significantly to our understanding of prostate cancer screening even though their 13-year follow-up results are conflicting (TABLE 2).^10,11,18

Continue to: In the ERSPC 13-year follow-up publication...

In the ERSPC 13-year follow-up publication, the authors concluded that a substantial reduction in prostate cancer mortality is attributable to testing with PSA.¹⁸ Despite limitations in the study design (eg, France entered after 2 years, screening intervals varied between 2 and 4 years, biopsy indications varied, and screening was discontinued at different times), PSA screening detected more prostate cancer than was detected in the control arm (10.2% vs 6.8%).

In the initial 11 years of follow-up, the study group experienced a 21% reduction in prostate cancer mortality, even though the absolute decrease ranged from only 0.6% (545 per 89,352) to 0.5% (355 per 72,891). The updated absolute risk reduction of death from prostate cancer at 13 years of follow-up showed a larger benefit: 0.11 per 1000 person-years or 1.28 per 1000 men randomized, which is equivalent to 1 prostate cancer death averted per 781 (95% confidence interval [CI], 490-1929) men invited for screening, or 1 per 27 (17-66) additional prostate cancers detected.

The PLCO trial did not show any significant difference in prostate cancer detection (11.1% screened vs 9.9% control), and there was no improvement in prostate cancer mortality (3.7 vs 3.4 death per 10,000 person-years).¹⁰ However, the PLCO trial suffered from issues of contamination, which may have influenced the overall results. About 52% of men in the control (usual care) group received a PSA test at some point during the study. And more than two-thirds of the men who had a prostate biopsy because of a positive PSA test did not have prostate cancer.

Community standards for the PSA threshold for biopsy were applied in various centers (> 4 ng/ml in general) in PLCO, whereas in ­ERSPC, a cut-off PSA value ≥ 3 ng/mL was used for biopsy. Because of the lower PSA threshold, ERSPC may have identified cancers that would have had good outcomes without any intervention.

The harms of PSA screening

While it is unclear whether PSA screening results in any improvement in patient-centered outcomes, it does lead to downstream intervention due to overdiagnosis, which precipitates unnecessary anxiety, biopsies, and overtreatment (eg, excess radiation, overuse of androgen deprivation therapy).¹⁹ Biopsies carry the risk of hematuria (22.6%), hematospermia (50.4%), and urinary tract infection.²⁰ Data from SEER-Medicare showed that prostate biopsy was associated with a 2.65-fold increased risk of hospitalization within 30 days of the procedure compared to a control population.²¹

Continue to: Overdiagnosis leads to overtreatment...

Overdiagnosis leads to overtreatment of low-risk prostate cancer. Both traditional treatment options for prostate cancer—radical prostatectomy and radiotherapy—are associated with urinary incontinence, erectile dysfunction, and issues with bowel function.^22,23

The Prostate Cancer Intervention vs Observation Trial (PIVOT),²⁴ the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4),²⁵ and the Prostate Testing for Cancer and Treatment (ProtecT) trial,^22,23 are the major RCTs that looked at the outcomes of treatment modalities for localized prostate cancer in the modern era of PSA testing.

PIVOT compared passive observation with radical prostatectomy.²⁴ After 20 years of follow-up on 731 patients, the researchers concluded that radical prostatectomy did not reduce all-cause or prostate cancer–related mortality (TABLE 3).²⁴

SPCG-4 showed survival benefits for men who underwent radical prostatectomy compared with men in a watchful waiting group, but only 5% of the study cohort had cancer detected by PSA screening (TABLE 4).²⁵ The rest had either palpable tumors or symptoms of a tumor.

ProtecT, which followed patients with localized prostate cancer for more than 10 years,compared the outcomes and adverse effects of active surveillance, radical prostatectomy, and radiotherapy.²³ Prostate cancer–specific mortality was low irrespective of the treatment,²³ and there was no significant difference in all-cause mortality or prostate cancer–specific mortality between the 3 treatment groups.²³ The active surveillance group had considerably fewer adverse events.^22,23 The incidence rates of erectile dysfunction and urinary incontinence at the 1- and 6-year follow-up marks are outlined in TABLE 5.²²

Continue to: The purpose of active monitoring...

The purpose of active monitoring is to minimize overtreatment by avoiding immediate radical intervention. Radical treatments with curative intent can be undertaken at any point while patients are being actively monitored. It is important to note that the active monitoring that took place in ProtecT²³ was very different from the passive surveillance of PIVOT²⁴ and SPCG-4.²⁵ In ProtecT, once an elevated serum PSA level was noted, PSA levels were monitored every 3 months in the first year and every 6 to 12 months thereafter.²³ Triggers to reassess patients and consider a change in clinical management were based largely on changes in PSA levels. Participants with an increase of at least 50% in PSA level during the previous 12 months were offered either continued monitoring or treatment after further testing.

Making individualized decisions about prostate cancer screening

Traditionally, the goal of cancer screening has been to maximize the number of people screened. Generally, the information provided to patients about cancer screening emphasizes the benefits and minimizes the harms. Recently, however, there has been a shift in communication about cancer screening with the emphasis now being placed on informed decision-making and encouraging patients to make individual decisions about screening participation.²⁶

Although current guidelines regarding PSA screening differ by organization, generally speaking, PSA screening should be offered only to men with a life expectancy > 10 years.

The treatment option of active surveillance, with its lower incidence of adverse outcomes, is an important reason for patients to make individualized decisions about prostate cancer screening.

Another reason relates to 5-alpha-­reductase inhibitors. Although their role in the management of prostate cancer is currently not well defined, a reduction of almost 25% in the risk of prostate cancer and improvement in the performance of PSA has been reported.²⁷

The PSA test has low sensitivity and specificity and lacks a clear cut-off value that warrants prostate biopsy.

And yet another reason is that there are alternate strategies to manage the majority of patients who have been diagnosed with low-risk disease through transrectal ultrasound biopsy. The ERSPC study mentions multiparametric magnetic resonance imaging combined with targeted biopsy to identify high-grade disease.^28,29 Genetic and epigenetic assays of the biopsied tissue can help grade disease based on aggressiveness.³⁰ Transperineal mapping biopsy using a mapping software program can identify specific disease sites within the prostate gland, so that patients can be offered the option of targeted therapy.³⁰

Continue to: Applying shared decision-making to prostate cancer screening

Balancing errors of omission with errors of commission is challenging. Shared decision-making (SDM) is an approach whereby clinicians and patients share the best available evidence when faced with the task of medical decision-making and in which patients are supported while they consider their options and achieve their preferences.³¹ SDM is well supported by evidence from a number of RCTs and results in increased knowledge, involvement, and confidence on the part of patients.³² An individualized approach using the schematic diagram (FIGURE 1^3,18) may be helpful.

Barriers to SDM success. Many factors can interfere with the success of SDM including limited or poor communication; lack of time during busy office visits; and patients’ cultural, informational, and/or emotional needs. To improve patient-centered communication, we can: (1) make information understandable and available to patients and families; (2) prioritize training in communication; (3) use decision aid tools to facilitate communication; and (4) work to improve the payment model to incentivize patient-centered communication. Tools that facilitate SDM include videotapes, patient group discussions, brief scripts read to patients, and informational pamphlets. One such tool is the American Society for Clinical Oncology’s decision aid tool for PSA testing.³³

Limited knowledge among patients. Decisions regarding treatment among men diagnosed with localized prostate cancer can be difficult because there are several treatment options with similar prognoses, but there are differences in adverse effects. One population-based cohort study of men with newly diagnosed localized prostate cancer found that most men had significant knowledge deficits regarding the survival benefits of the 2 major treatment options—surgery and radiation.³⁴ In a large population-based study, 38% of men with localized prostate cancer reported receiving help from their primary care providers in the decision-making process for treatment.³⁵

Learning to employ SDM. Elwyn et al proposed a 3-step model to incorporate SDM into clinical practice.³¹ They described key steps that include: choice talk (making sure patients are informed about the reasonable options), option talk (providing more detailed information about the options), and decision talk (supporting the work of patients considering their preferences and deciding what is best). Properly employing these methods requires training using simulations.³¹

The bottom line

Although current guidelines regarding PSA screening differ by organization, generally speaking PSA screening should be offered only to men with a life expectancy > 10 years. The PSA test has low sensitivity and specificity and lacks a clear cut-off value that warrants prostate biopsy. Men who choose to have PSA testing increase their chances of detecting prostate cancer, but most prostate cancers are slow growing and do not cause death. The decision to undergo PSA screening should be made by both the provider and the patient, after a discussion of the limited benefits and associated harms. The interval of follow-up screening may vary from 2 to 4 years depending on patient age, level of PSA, and whether a patient is taking medications such as 5-alpha-reductase inhibitors.

CORRESPONDENCE
Jaividhya Dasarathy, MD, FAAFP, 2500 Metro Health Medical Drive, Cleveland, Ohio 44109; [email protected].

Prostate cancer is the most frequently diagnosed cancer in men and the third leading cause of cancer death in men worldwide.¹ An estimated 174,650 new cases are diagnosed each year in the United States; 31,620 American men die annually from the disease.² Although prostate cancer can be a serious disease, many men do not die from it. In fact, 2.9 million men who were diagnosed with prostate cancer at some point are alive today.³

Risk factors. Prostate cancer develops mainly in men ages ≥ 65 years and rarely occurs before age 40. In addition to age, family history and African American ethnicity are the major nonmodifiable risk factors for prostate cancer.⁴ From the 1970s to the most recent statistical analysis of the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program, African American men have continued to have significantly higher incidence of, and mortality rates from, prostate cancer than their European American counterparts. African American men are also more likely than men of European ancestry to have aggressive prostate cancers.⁵ Other risk factors include geographic location (higher risk in Northern Europe, North America, and Australia; lower risk in Asia, Africa, and South and Central America), mutations in the BRCA2 gene, and hereditary non-polyposis colon cancer syndrome.⁴

Prostate-specific antigen (PSA) was first used as a screening tool for prostate cancer in 1991.⁶ Prostate cancer incidence, especially organ-confined disease, has dramatically increased since then.⁷ PSA testing has a low sensitivity and specificity for the detection of prostate cancer, and there is no clear threshold at which biopsy can or should be offered. The most commonly used cutoff value of 4 ng/mL has a false-positive rate of about 70%.⁸

Benign prostatic conditions such as hypertrophy and infection can elevate PSA levels. In addition, the PSA test does not distinguish between aggressive and slow-growing cancers, and about 15% of patients with prostate cancer have a normal PSA level.⁹

A word about the digital rectal exam. While PSA testing has been the mainstay of prostate cancer screening, a few studies have included digital rectal exam (DRE) in their protocols. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial showed that DRE captured an additional 2% of men with prostate cancer in the setting of a normal PSA test result.¹⁰ In the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, the overall detection rate for prostate cancer was found to be better when DRE was combined with PSA and prostate biopsy than when DRE was used alone (4.5% vs 2.5%).¹¹ Nevertheless, generally speaking, DRE can be omitted in the era of PSA screening.

Screening guidelines vary

Recommendations for prostate cancer screening vary by organization and are summarized in TABLE 1.^9,12-14 In 2012, the US Preventive Services Task Force (USPSTF) recommended against PSA-based screening for prostate cancer (Category D).¹⁵ In 2018, ­USPSTF provided an update with a new recommendation that clinicians inform men ages 55 to 69 years about the potential benefits and harms of PSA-based screening (Category C).¹⁴ The USPSTF continues to recommend against PSA-based screening for men ages ≥ 70 years (Category D).¹⁴

Does PSA-based screening improve patient-centered outcomes?

Several randomized controlled trials (RCTs) such as the Quebec Prospective Randomized Controlled Trial,¹⁶ the Norrköping Sweden Study,¹⁷ ERSPC,¹¹ and PLCO¹⁰ have been conducted to assess the benefits of PSA testing. PLCO and ERSPC have contributed significantly to our understanding of prostate cancer screening even though their 13-year follow-up results are conflicting (TABLE 2).^10,11,18

Continue to: In the ERSPC 13-year follow-up publication...

In the ERSPC 13-year follow-up publication, the authors concluded that a substantial reduction in prostate cancer mortality is attributable to testing with PSA.¹⁸ Despite limitations in the study design (eg, France entered after 2 years, screening intervals varied between 2 and 4 years, biopsy indications varied, and screening was discontinued at different times), PSA screening detected more prostate cancer than was detected in the control arm (10.2% vs 6.8%).

In the initial 11 years of follow-up, the study group experienced a 21% reduction in prostate cancer mortality, even though the absolute decrease ranged from only 0.6% (545 per 89,352) to 0.5% (355 per 72,891). The updated absolute risk reduction of death from prostate cancer at 13 years of follow-up showed a larger benefit: 0.11 per 1000 person-years or 1.28 per 1000 men randomized, which is equivalent to 1 prostate cancer death averted per 781 (95% confidence interval [CI], 490-1929) men invited for screening, or 1 per 27 (17-66) additional prostate cancers detected.

The PLCO trial did not show any significant difference in prostate cancer detection (11.1% screened vs 9.9% control), and there was no improvement in prostate cancer mortality (3.7 vs 3.4 death per 10,000 person-years).¹⁰ However, the PLCO trial suffered from issues of contamination, which may have influenced the overall results. About 52% of men in the control (usual care) group received a PSA test at some point during the study. And more than two-thirds of the men who had a prostate biopsy because of a positive PSA test did not have prostate cancer.

Community standards for the PSA threshold for biopsy were applied in various centers (> 4 ng/ml in general) in PLCO, whereas in ­ERSPC, a cut-off PSA value ≥ 3 ng/mL was used for biopsy. Because of the lower PSA threshold, ERSPC may have identified cancers that would have had good outcomes without any intervention.

The harms of PSA screening

While it is unclear whether PSA screening results in any improvement in patient-centered outcomes, it does lead to downstream intervention due to overdiagnosis, which precipitates unnecessary anxiety, biopsies, and overtreatment (eg, excess radiation, overuse of androgen deprivation therapy).¹⁹ Biopsies carry the risk of hematuria (22.6%), hematospermia (50.4%), and urinary tract infection.²⁰ Data from SEER-Medicare showed that prostate biopsy was associated with a 2.65-fold increased risk of hospitalization within 30 days of the procedure compared to a control population.²¹

Continue to: Overdiagnosis leads to overtreatment...

Overdiagnosis leads to overtreatment of low-risk prostate cancer. Both traditional treatment options for prostate cancer—radical prostatectomy and radiotherapy—are associated with urinary incontinence, erectile dysfunction, and issues with bowel function.^22,23

The Prostate Cancer Intervention vs Observation Trial (PIVOT),²⁴ the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4),²⁵ and the Prostate Testing for Cancer and Treatment (ProtecT) trial,^22,23 are the major RCTs that looked at the outcomes of treatment modalities for localized prostate cancer in the modern era of PSA testing.

PIVOT compared passive observation with radical prostatectomy.²⁴ After 20 years of follow-up on 731 patients, the researchers concluded that radical prostatectomy did not reduce all-cause or prostate cancer–related mortality (TABLE 3).²⁴

SPCG-4 showed survival benefits for men who underwent radical prostatectomy compared with men in a watchful waiting group, but only 5% of the study cohort had cancer detected by PSA screening (TABLE 4).²⁵ The rest had either palpable tumors or symptoms of a tumor.

ProtecT, which followed patients with localized prostate cancer for more than 10 years,compared the outcomes and adverse effects of active surveillance, radical prostatectomy, and radiotherapy.²³ Prostate cancer–specific mortality was low irrespective of the treatment,²³ and there was no significant difference in all-cause mortality or prostate cancer–specific mortality between the 3 treatment groups.²³ The active surveillance group had considerably fewer adverse events.^22,23 The incidence rates of erectile dysfunction and urinary incontinence at the 1- and 6-year follow-up marks are outlined in TABLE 5.²²

Continue to: The purpose of active monitoring...

The purpose of active monitoring is to minimize overtreatment by avoiding immediate radical intervention. Radical treatments with curative intent can be undertaken at any point while patients are being actively monitored. It is important to note that the active monitoring that took place in ProtecT²³ was very different from the passive surveillance of PIVOT²⁴ and SPCG-4.²⁵ In ProtecT, once an elevated serum PSA level was noted, PSA levels were monitored every 3 months in the first year and every 6 to 12 months thereafter.²³ Triggers to reassess patients and consider a change in clinical management were based largely on changes in PSA levels. Participants with an increase of at least 50% in PSA level during the previous 12 months were offered either continued monitoring or treatment after further testing.

Making individualized decisions about prostate cancer screening

Traditionally, the goal of cancer screening has been to maximize the number of people screened. Generally, the information provided to patients about cancer screening emphasizes the benefits and minimizes the harms. Recently, however, there has been a shift in communication about cancer screening with the emphasis now being placed on informed decision-making and encouraging patients to make individual decisions about screening participation.²⁶

Although current guidelines regarding PSA screening differ by organization, generally speaking, PSA screening should be offered only to men with a life expectancy > 10 years.

The treatment option of active surveillance, with its lower incidence of adverse outcomes, is an important reason for patients to make individualized decisions about prostate cancer screening.

Another reason relates to 5-alpha-­reductase inhibitors. Although their role in the management of prostate cancer is currently not well defined, a reduction of almost 25% in the risk of prostate cancer and improvement in the performance of PSA has been reported.²⁷

The PSA test has low sensitivity and specificity and lacks a clear cut-off value that warrants prostate biopsy.

And yet another reason is that there are alternate strategies to manage the majority of patients who have been diagnosed with low-risk disease through transrectal ultrasound biopsy. The ERSPC study mentions multiparametric magnetic resonance imaging combined with targeted biopsy to identify high-grade disease.^28,29 Genetic and epigenetic assays of the biopsied tissue can help grade disease based on aggressiveness.³⁰ Transperineal mapping biopsy using a mapping software program can identify specific disease sites within the prostate gland, so that patients can be offered the option of targeted therapy.³⁰

Continue to: Applying shared decision-making to prostate cancer screening

Balancing errors of omission with errors of commission is challenging. Shared decision-making (SDM) is an approach whereby clinicians and patients share the best available evidence when faced with the task of medical decision-making and in which patients are supported while they consider their options and achieve their preferences.³¹ SDM is well supported by evidence from a number of RCTs and results in increased knowledge, involvement, and confidence on the part of patients.³² An individualized approach using the schematic diagram (FIGURE 1^3,18) may be helpful.

Barriers to SDM success. Many factors can interfere with the success of SDM including limited or poor communication; lack of time during busy office visits; and patients’ cultural, informational, and/or emotional needs. To improve patient-centered communication, we can: (1) make information understandable and available to patients and families; (2) prioritize training in communication; (3) use decision aid tools to facilitate communication; and (4) work to improve the payment model to incentivize patient-centered communication. Tools that facilitate SDM include videotapes, patient group discussions, brief scripts read to patients, and informational pamphlets. One such tool is the American Society for Clinical Oncology’s decision aid tool for PSA testing.³³

Limited knowledge among patients. Decisions regarding treatment among men diagnosed with localized prostate cancer can be difficult because there are several treatment options with similar prognoses, but there are differences in adverse effects. One population-based cohort study of men with newly diagnosed localized prostate cancer found that most men had significant knowledge deficits regarding the survival benefits of the 2 major treatment options—surgery and radiation.³⁴ In a large population-based study, 38% of men with localized prostate cancer reported receiving help from their primary care providers in the decision-making process for treatment.³⁵

Learning to employ SDM. Elwyn et al proposed a 3-step model to incorporate SDM into clinical practice.³¹ They described key steps that include: choice talk (making sure patients are informed about the reasonable options), option talk (providing more detailed information about the options), and decision talk (supporting the work of patients considering their preferences and deciding what is best). Properly employing these methods requires training using simulations.³¹

The bottom line

Although current guidelines regarding PSA screening differ by organization, generally speaking PSA screening should be offered only to men with a life expectancy > 10 years. The PSA test has low sensitivity and specificity and lacks a clear cut-off value that warrants prostate biopsy. Men who choose to have PSA testing increase their chances of detecting prostate cancer, but most prostate cancers are slow growing and do not cause death. The decision to undergo PSA screening should be made by both the provider and the patient, after a discussion of the limited benefits and associated harms. The interval of follow-up screening may vary from 2 to 4 years depending on patient age, level of PSA, and whether a patient is taking medications such as 5-alpha-reductase inhibitors.

CORRESPONDENCE
Jaividhya Dasarathy, MD, FAAFP, 2500 Metro Health Medical Drive, Cleveland, Ohio 44109; [email protected].

It is estimated that up to 45% of cases of scabies are misdiagnosed as another condition.¹ This can occur when common clinical features are overlooked, a skin exam is rushed (and the rash is chalked up to dermatitis), or the wrong part of the pruritic lesion is scraped (the papule, rather than the burrow). There are also atypical presentations of scabies, which can confound even the most astute clinician.¹ Misdiagnosis can increase health care costs due to repeat office visits or multiple referrals. In this article, we review the typical and atypical presentations of scabies and provide recommendations to aid physicians in its early recognition and correct diagnosis.

The scope of scabies infection, and its clinical stages

The prevalence of scabies, a common skin infection caused by the mite Sarcoptes scabiei, is estimated at 300 million cases worldwide annually, with the greatest incidence occurring in children and adolescents.¹ In the developing world, its clinical burden is highest among the homeless, those of lower socioeconomic status, and those with poor hygiene. In the developed world, the clinical burden is highest among hospitalized patients and residents of long-term living facilities.

The S scabiei mite is an obligate parasite that elicits an adaptive immune response in susceptible hosts. The female mite lays 60 to 90 eggs that mature into adult mites after completing the mite life cycle in human hosts. In immunocompetent patients, roughly 10 to 15 surviving mites can be found at any given point in the disease process.² In crusted or disseminated scabies, which often occur in immunocompromised patients, thousands of mites may be found at any given point in the disease process. ²

Scabies infection has 2 stages: the latent primary infection and the symptomatic secondary infection.

The primary infection starts with the initial mite invasion, typically with the transfer of impregnated females during person-to-person contact. Females deposit eggs as they burrow into the epidermis at the level of the stratum corneum with the use of proteolytic enzymes (creating the mite burrow). Surviving eggs hatch into larvae that then mature into nymphs and adult mites. After these adult mites mate, the impregnated females create new burrows and lay additional eggs.³ Patients may be asymptomatic during this initial stage and the infection may be transmitted from person to person through direct skin contact.

In children with scabies, vesicles, pustules, and nodular pruritic lesions may coexist with eczema and impetigo.

The second stage of infection is when patients experience severe pruritus with inflammatory papules seen on exam. The pruritus associated with scabies results from a delayed type IV hypersensitivity reaction to mite infestation. This requires host sensitization to the scabies mite. Clinically, there is a delayed onset (weeks) of numerous erythematous papules and, later, excoriated papules.

Conditions that scabies can mimic

The differential of typical scabies includes diagnoses manifesting with moderate to severe pruritus. In the immunocompetent adult, conditions to consider are atopic dermatitis, tinea corporis, papular urticaria, seborrheic dermatitis, poison ivy and other causes of contact dermatitis, drug eruptions, and irritant dermatitis. In immunocompetent infants, think of seborrheic dermatitis, atopic dermatitis, acropustulosis, and viral exanthems.

Continue to: Nodular scabies variants...

Nodular scabies variants can masquerade as pseudolymphoma, lymphoma, or leukemia cutis. In immunocompromised and elderly individuals, crusted scabies is often mistaken for psoriasis, atopic dermatitis, keratoderma, and lichen planus.^2,4,5

Scabies’ classic presentation

Typically, scabies causes intensely pruritic erythematous papules. Areas commonly affected are the webs and sides of fingers ­(FIGURE 1A and 1B), proximal palm and wrist flexors, extensor aspects of the arms and legs, axillary folds, periumbilical areas, the peri-areolar region in women, buttocks and thigh creases, and, in males, the genitals. The head may also be affected in children (FIGURE 1C), but seldom in adults. Interestingly, the back is usually spared across all age groups, though not always (FIGURE 2).

IMAGE COURTESY OF VISUALDX.COM

Mites are not found near pruritic papules. Scrape the mite burrows, which are small, linear, serpiginous lines, to discover the mature scabies mite.

The classic presentation also varies across age groups and populations.² In children, vesicles, pustules, and nodular pruritic lesions may coexist with eczema and impetigo. Among homeless individuals, coinfection with impetigo and eczema is common. Elderly patients are more likely to exhibit atypical lesions.⁶ Immunocompromised patients present with atypical papular scabies, crusted scabies, or scabies that may be only mildly pruritic or nonpruritic. In underdeveloped countries, indigenous populations are more susceptible to endemic scabies, with a high risk of scabies superinfection with Streptococcus.

Scabies subtypes with varying presentations

Clinical manifestations of scabies subtypes may make it difficult to diagnose the disease. These subtypes include nodular, pustular, vesiculobullous, and crusted scabies (Norwegian scabies). Although rare, these subtypes merit acknowledgement, as atypical cases contribute to the high rate of misdiagnosis.

Nodular scabies is a clinical variant that accounts for about 7% of scabies cases.⁷ It can resist traditional scabies treatment (permethrin cream, ivermectin—which we’ll discuss in a bit) and often requires topical or intralesional corticosteroid management. Nodular scabies most commonly affects male genitalia. Patients may have multiple excoriated skin-colored erythematous papules and nodules in areas involving the classic distribution of scabies (web spaces of fingers, flexural areas [FIGURE 3], scrotum, and groin).⁸

IMAGE COURTESY OF VISUALDX.COM

Continue to: Pustular scabies...

Pustular scabies is commonly seen in children and adolescents but can occur in all age groups. Patients may present with vesicular pustular lesions (FIGURE 4A and 4B).⁷ In some cases, topical corticosteroids have modified the classic clinical presentation into a pustular variant. However, scabies alone can cause pustular lesions.

IMAGES COURTESY OF VISUALDX.COM

Vesiculobullous scabies (FIGURE 5A and 5B) is a clinical subtype that may be mistaken for pemphigus vulgaris⁹ or bullous pemphigoid¹⁰ because of its strikingly similar clinical presentation to those disorders.

IMAGES COURTESY OF VISUALDX.COM

Crusted scabies (Norwegian scabies) is a severe, disseminated form of scabies that commonly affects immunocompromised patients, although cases are also seen in immunocompetent hosts. Afflicted immunocompetent patients often have a history of diabetes mellitus, liver cirrhosis, malnutrition, or alcohol abuse.¹¹ Patients present with a thick powdery or crusted white or yellow scale involving the feet or hands (FIGURE 6) that sometimes extends onto the limbs. Severe ­cases can involve wide body surfaces. One unusual presentation also included a desquamating rash without pruritus.¹²

IMAGE COURTESY OF VISUALDX.COM

Highly atypical cases

Distal white or yellow, thick, scaly, or crusted plaques can suggest psoriasis or dermatitis, but you should include scabies in the differential diagnosis.

Atypical presentations include lesions that appear outside of the classic distribution areas of scabies, lesions with uncharacteristic morphology, cases with coinfections, and instances in which patients are immunocompromised.¹³ Examples include scabies of the scalp coexisting with seborrheic dermatitis or dermatomyositis,¹⁴ scabies mimicking mastocytoma,^15,16 and scabies with coinfections of impetigo or eczema.¹⁷ These coinfections and clinical variations can be particularly challenging. Other reports of atypical scabies leading to misdiagnosis include a case of crusted scabies mimicking erythrodermic psoriasis¹⁸ and a case initially attributed to suppurative folliculitis and prurigo nodularis.¹⁹

Decisive diagnostic measures

Identifying the mite’s burrow on clinical exam is essential to making the diagnosis of scabies. Microscopic examinations of burrow scrapings remain the diagnostic gold standard. Frequently, nondermatologists perform skin scrapings of the pruritic papules of scabies instead of the burrows. These papules are a hypersensitivity reaction to the mites, and no scabetic mites will be found there. Burrows appear on exam as small, linear, serpiginous lines (FIGURE 7A and 7B).

IMAGES COURTESY OF VISUALDX.COM

Continue to: Handheld illumination with a dermatoscope...

Handheld illumination with a dermatoscope will allow visualization of the mite ­(FIGURE 8). (See “How fast do scabies mites move? Dermoscopy video answers that question.”) Dermatoscope findings consistent with scabies include a “delta ­glider,” a dark triangular shape that is the mite’s head hidden in the burrow,²⁰ or the classic “jet with contrail” (FIGURE 8).²¹ Scrape the burrow to discover the mature scabies mite (FIGURE 9) and confirm the diagnosis.

COURTESY OF ROMAN BRONFENBRENER, MD

Microscopic examination of scrapings has a reported sensitivity and specificity of up to 90% and 100%, respectively, when collection of scrapings is performed accurately and contains ova, feces, or mites.^14,20,22 Dermatologists increasingly use dermatoscopes to diagnose scabies. Dermoscopy's sensitivity is 91% and specificity is 85% to 86%,¹⁴ which is a reassuring frame of reference for physicians who do not routinely use dermatoscopes and instead rely on scrapings.

Continue to: How fast do scabies mites move? Dermoscopy video answers that question

SIDEBAR
How fast do scabies mites move? Dermoscopy video answers that question

Richard Usatine, MD; Ashfaq Marghoob, MD
University of Texas Health San Antonio (Dr. Usatine); Memorial Sloan Kettering Skin Cancer Center, Hauppauge, NY (Dr. Marghoob).

Dr. Marghoob reported that he has received honoraria for speaking for 3GEN. Dr. Usatine reported no potential conflict of interest relevant to this article.

A 22-year-old man infected with human immunodeficiency virus presented to a clinic with a 6-month history of intense pruritus. Physical examination revealed scale crust on the hands and wrists (FIGURE) and in the pubic region.

Dermoscopic examination of the rash on the wrist revealed scabies mites actively crawling on the surface of the skin. A superficial skin scraping revealed the Sarcoptes scabiei mite, several eggs, and scybala under the microscope. The extensive infestation in this patient with crusted scabies was related to his immunocompromised state. (The patient was successfully treated with oral ivermectin and topical permethrin.)

Unprecedented documentation of mite speed a clue to infectivity. The 36-second VIDEO captured an adult mite travelling a distance of 3 mm, translating to a speed of 5 mm/ min. Six younger adults/larvae were moving more rapidly with a maximum distance of 6 mm in 36 seconds (1 cm/min). The movement of a mite within the epidermis is slower, as the mite consumes keratin in creating burrows. The more rapid rate of movement on the skin surface may help to explain the contagious nature of scabies.

Vidyard Video

In this case, the mites and larvae were viewed on the screen of a smartphone to which a dermatoscope was attached magnetically. The mites were first visualized in the standard photo mode. Video mode was then used to capture the motion using the maximum zoom feature of the phone, to a magnification factor of 13.3×.

Literature to date has been silent on mites’ rate of motion. A Medline search yielded only 3 papers that addressed the issue of in vivo movement of scabies mites. None viewed the mites other than in their burrows and none calculated a rate of motion.

• In one study using videodermotoscopy, Micali stated that in most of the 16 cases identified, it was possible to observe the mites moving inside the burrows.1 No video images were published, and there was no mention of speed or characterization of the movement.¹
• A second study used reflectance confocal microscopy (RCM) to examine a single patient with crusted scabies. The authors claim to have viewed the ectoparasite's motion within the human host but provided no details of that motion.²
• In the third study, videodermoscopy showed a slightly higher sensitivity for scabies detection than RCM (95% vs. 92%).³ The authors did not mention visualization of movement of mites in their work but did quote the Micali paper for its mention of movements of the mite.

Applying digital dermoscopy in practice. It appears that this is the first published video documenting the movement of scabies mites and larvae in vivo using dermoscopy. This should pave the way for additional observations of scabies movement on and below the skin using dermoscopy with video. We recommend using the maximum zoom capability of the device along with the dermatoscope to view this movement. What has been surmised before—that the mite must move above the skin to infect human contacts—has now been captured in vivo using the power of dermoscopy.

CORRESPONDENCE
Richard P. Usatine, MD, 903 West Martin Street, San Antonio, TX 78207; [email protected].

REFERENCES
1. Micali G, Lacarrubba F, Lo Guzzo G. Scraping versus videodermatoscopy for the diagnosis of scabies: a comparative study. Acta Derm Venereol. 1999; 79:396.

2. Gürel MS, Turgut Erdemir AV, Tekin B. A case report of real-time in vivo demonstration of Sarcoptes scabiei. Turkiye Parazitol Derg. 2017; 41:229-232.

3. Cinotti E, Labeille B, Cambazard F, et al. Videodermoscopy compared to reflectance confocal microscopy for the diagnosis of scabies. J Eur Acad Dermatol Venereol. 2016; 30:1573-1577.

Continue to: 3 diagnostic missteps to avoid

 

 

3 diagnostic missteps to avoid

Misdiagnosis is often due to an overreliance on the clinical history without performing an adequate physical exam. In such cases, the physician often diagnoses a form of dermatitis as the cause of pruritic rash. (Admittedly, diagnostic error can result in either false-­positive or false-negative findings, and many patients are diagnosed with scabies when they have dermatitis.)

A second misstep? Scabies may be overlooked in a patient whose lesions are nonpruritic, such as someone with an immunocompromising condition.

And finally, crusted scabies is frequently mistaken for psoriasis or chronic dermatitis.⁸

Diagnostic errors are exceedingly troublesome for patients and caregivers. It is not unusual for a hospital or long-term care facility to lose significant employee work hours due to a scabies epidemic or fear of a scabies epidemic. In a 2003 outbreak of scabies in a Canadian long-term care facility, an estimated $200,000 was needed to control disease spread.²³

A topical agent is a mainstay of treatment

Watch the video of a scabies mite on the skin surface.

Permethrin cream is usually the first-line treatment choice.²⁴ Ivermectin, topical (cream) or systemic (pill), is the commonly used alternative for patients who do not respond to, or cannot tolerate, permethrin cream. A recent meta-analysis examined the effectiveness of 5% permethrin cream, 1% ivermectin cream, and oral ivermectin (200 mcg/kg single or double dose).²⁴ Overall, findings suggested there was no difference in the efficacy or in adverse effects of permethrin cream compared with ivermectin (topical or systemic) among adults. One study reported that permethrin cream was slightly more effective than ivermectin (cream or oral) because of the more rapid treatment response (approximately 94% clearance within 2 weeks of treatment, compared with 90%).²⁵

Continue to: Adjust treatment for special populations

 

 

Adjust treatment for special populations. Treatment of severe cases, such as crusted scabies, calls for combination therapy with oral ivermectin (200 mcg/kg) and 5% permethrin cream.²⁶

Five percent permethrin cream is the preferred treatment for children weighing < 15 kg and pregnant women; oral ivermectin has not been studied for efficacy and safety in these populations.²⁷

Effective response to treatment in these studies was measured by resolution of active scabies lesions and improvement in pruritus 1 to 2 weeks after treatment.

 

Anticipate these 3 clinical scenarios

The classic appearance of scabies usually triggers suspicion of its presence, leading to prompt identification of mite burrows and a correct diagnosis. Unfortunately, though, this is not always the case. And atypical presentations heighten the chance of diagnostic error, which overall occurs in nearly half of cases.¹ Keep in mind the following common scenarios, to help improve diagnosis.

1. When a patient presents with a severe pruritic eruption, the clinician may be tempted to settle early on a form of dermatitis and not consider the possibility of scabies. When the patient is later seen by an expert, the burrows are easily identified. Solution: Whenever a patient complains of severe pruritus, use a dermatoscope to carefully examine the digits, web spaces, proximal palms, wrists, and ankles for burrows.

Continue to: A patient with distal white or yellow, thick, scaly, or crusted plaques

 

 

2. A patient with distal white or yellow, thick, scaly, or crusted plaques is often thought to have psoriasis or dermatitis. But scabies should be included in the differential diagnosis. In particular, worsening thick, scaly plaques in an immunocompromised patient should prompt consideration of scabies.

3. Smooth nodules of the genitals in males, or pruritic smooth papules and plaques in other locations, should lead to the consideration of scabies. These presentations can be mistaken for lichen planus, folliculitis, papular urticaria, insect bites, or atopic dermatitis.

Due to the limited amount of mite burrows early in the disease process of scabies, and the gross similarities to a patient with dermatitis with skin excoriations, a thorough exam is needed—one that goes beyond the traditional web spaces and includes hidden/atypical locations such as margins of the feet and hands, the scalp, and neck creases. Careful and deliberate inspection for burrows is critical before ruling out the diagnosis.

CORRESPONDENCE
Art Papier, MD, 400 Red Creek Drive, Suite 200, Rochester, NY 14623; [email protected].

ACKNOWLEDGEMENT
We thank Angela Delacenserie, MA, for reviewing the manuscript and providing editing suggestions.

It is estimated that up to 45% of cases of scabies are misdiagnosed as another condition.¹ This can occur when common clinical features are overlooked, a skin exam is rushed (and the rash is chalked up to dermatitis), or the wrong part of the pruritic lesion is scraped (the papule, rather than the burrow). There are also atypical presentations of scabies, which can confound even the most astute clinician.¹ Misdiagnosis can increase health care costs due to repeat office visits or multiple referrals. In this article, we review the typical and atypical presentations of scabies and provide recommendations to aid physicians in its early recognition and correct diagnosis.

The scope of scabies infection, and its clinical stages

The prevalence of scabies, a common skin infection caused by the mite Sarcoptes scabiei, is estimated at 300 million cases worldwide annually, with the greatest incidence occurring in children and adolescents.¹ In the developing world, its clinical burden is highest among the homeless, those of lower socioeconomic status, and those with poor hygiene. In the developed world, the clinical burden is highest among hospitalized patients and residents of long-term living facilities.

The S scabiei mite is an obligate parasite that elicits an adaptive immune response in susceptible hosts. The female mite lays 60 to 90 eggs that mature into adult mites after completing the mite life cycle in human hosts. In immunocompetent patients, roughly 10 to 15 surviving mites can be found at any given point in the disease process.² In crusted or disseminated scabies, which often occur in immunocompromised patients, thousands of mites may be found at any given point in the disease process. ²

Scabies infection has 2 stages: the latent primary infection and the symptomatic secondary infection.

The primary infection starts with the initial mite invasion, typically with the transfer of impregnated females during person-to-person contact. Females deposit eggs as they burrow into the epidermis at the level of the stratum corneum with the use of proteolytic enzymes (creating the mite burrow). Surviving eggs hatch into larvae that then mature into nymphs and adult mites. After these adult mites mate, the impregnated females create new burrows and lay additional eggs.³ Patients may be asymptomatic during this initial stage and the infection may be transmitted from person to person through direct skin contact.

In children with scabies, vesicles, pustules, and nodular pruritic lesions may coexist with eczema and impetigo.

The second stage of infection is when patients experience severe pruritus with inflammatory papules seen on exam. The pruritus associated with scabies results from a delayed type IV hypersensitivity reaction to mite infestation. This requires host sensitization to the scabies mite. Clinically, there is a delayed onset (weeks) of numerous erythematous papules and, later, excoriated papules.

Conditions that scabies can mimic

The differential of typical scabies includes diagnoses manifesting with moderate to severe pruritus. In the immunocompetent adult, conditions to consider are atopic dermatitis, tinea corporis, papular urticaria, seborrheic dermatitis, poison ivy and other causes of contact dermatitis, drug eruptions, and irritant dermatitis. In immunocompetent infants, think of seborrheic dermatitis, atopic dermatitis, acropustulosis, and viral exanthems.

Continue to: Nodular scabies variants...

Nodular scabies variants can masquerade as pseudolymphoma, lymphoma, or leukemia cutis. In immunocompromised and elderly individuals, crusted scabies is often mistaken for psoriasis, atopic dermatitis, keratoderma, and lichen planus.^2,4,5

Scabies’ classic presentation

Typically, scabies causes intensely pruritic erythematous papules. Areas commonly affected are the webs and sides of fingers ­(FIGURE 1A and 1B), proximal palm and wrist flexors, extensor aspects of the arms and legs, axillary folds, periumbilical areas, the peri-areolar region in women, buttocks and thigh creases, and, in males, the genitals. The head may also be affected in children (FIGURE 1C), but seldom in adults. Interestingly, the back is usually spared across all age groups, though not always (FIGURE 2).

IMAGE COURTESY OF VISUALDX.COM

Mites are not found near pruritic papules. Scrape the mite burrows, which are small, linear, serpiginous lines, to discover the mature scabies mite.

The classic presentation also varies across age groups and populations.² In children, vesicles, pustules, and nodular pruritic lesions may coexist with eczema and impetigo. Among homeless individuals, coinfection with impetigo and eczema is common. Elderly patients are more likely to exhibit atypical lesions.⁶ Immunocompromised patients present with atypical papular scabies, crusted scabies, or scabies that may be only mildly pruritic or nonpruritic. In underdeveloped countries, indigenous populations are more susceptible to endemic scabies, with a high risk of scabies superinfection with Streptococcus.

Scabies subtypes with varying presentations

Clinical manifestations of scabies subtypes may make it difficult to diagnose the disease. These subtypes include nodular, pustular, vesiculobullous, and crusted scabies (Norwegian scabies). Although rare, these subtypes merit acknowledgement, as atypical cases contribute to the high rate of misdiagnosis.

Nodular scabies is a clinical variant that accounts for about 7% of scabies cases.⁷ It can resist traditional scabies treatment (permethrin cream, ivermectin—which we’ll discuss in a bit) and often requires topical or intralesional corticosteroid management. Nodular scabies most commonly affects male genitalia. Patients may have multiple excoriated skin-colored erythematous papules and nodules in areas involving the classic distribution of scabies (web spaces of fingers, flexural areas [FIGURE 3], scrotum, and groin).⁸

IMAGE COURTESY OF VISUALDX.COM

Continue to: Pustular scabies...

Pustular scabies is commonly seen in children and adolescents but can occur in all age groups. Patients may present with vesicular pustular lesions (FIGURE 4A and 4B).⁷ In some cases, topical corticosteroids have modified the classic clinical presentation into a pustular variant. However, scabies alone can cause pustular lesions.

IMAGES COURTESY OF VISUALDX.COM

Vesiculobullous scabies (FIGURE 5A and 5B) is a clinical subtype that may be mistaken for pemphigus vulgaris⁹ or bullous pemphigoid¹⁰ because of its strikingly similar clinical presentation to those disorders.

IMAGES COURTESY OF VISUALDX.COM

Crusted scabies (Norwegian scabies) is a severe, disseminated form of scabies that commonly affects immunocompromised patients, although cases are also seen in immunocompetent hosts. Afflicted immunocompetent patients often have a history of diabetes mellitus, liver cirrhosis, malnutrition, or alcohol abuse.¹¹ Patients present with a thick powdery or crusted white or yellow scale involving the feet or hands (FIGURE 6) that sometimes extends onto the limbs. Severe ­cases can involve wide body surfaces. One unusual presentation also included a desquamating rash without pruritus.¹²

IMAGE COURTESY OF VISUALDX.COM

Highly atypical cases

Distal white or yellow, thick, scaly, or crusted plaques can suggest psoriasis or dermatitis, but you should include scabies in the differential diagnosis.

Atypical presentations include lesions that appear outside of the classic distribution areas of scabies, lesions with uncharacteristic morphology, cases with coinfections, and instances in which patients are immunocompromised.¹³ Examples include scabies of the scalp coexisting with seborrheic dermatitis or dermatomyositis,¹⁴ scabies mimicking mastocytoma,^15,16 and scabies with coinfections of impetigo or eczema.¹⁷ These coinfections and clinical variations can be particularly challenging. Other reports of atypical scabies leading to misdiagnosis include a case of crusted scabies mimicking erythrodermic psoriasis¹⁸ and a case initially attributed to suppurative folliculitis and prurigo nodularis.¹⁹

Decisive diagnostic measures

Identifying the mite’s burrow on clinical exam is essential to making the diagnosis of scabies. Microscopic examinations of burrow scrapings remain the diagnostic gold standard. Frequently, nondermatologists perform skin scrapings of the pruritic papules of scabies instead of the burrows. These papules are a hypersensitivity reaction to the mites, and no scabetic mites will be found there. Burrows appear on exam as small, linear, serpiginous lines (FIGURE 7A and 7B).

IMAGES COURTESY OF VISUALDX.COM

Continue to: Handheld illumination with a dermatoscope...

Handheld illumination with a dermatoscope will allow visualization of the mite ­(FIGURE 8). (See “How fast do scabies mites move? Dermoscopy video answers that question.”) Dermatoscope findings consistent with scabies include a “delta ­glider,” a dark triangular shape that is the mite’s head hidden in the burrow,²⁰ or the classic “jet with contrail” (FIGURE 8).²¹ Scrape the burrow to discover the mature scabies mite (FIGURE 9) and confirm the diagnosis.

COURTESY OF ROMAN BRONFENBRENER, MD

Microscopic examination of scrapings has a reported sensitivity and specificity of up to 90% and 100%, respectively, when collection of scrapings is performed accurately and contains ova, feces, or mites.^14,20,22 Dermatologists increasingly use dermatoscopes to diagnose scabies. Dermoscopy's sensitivity is 91% and specificity is 85% to 86%,¹⁴ which is a reassuring frame of reference for physicians who do not routinely use dermatoscopes and instead rely on scrapings.

Continue to: How fast do scabies mites move? Dermoscopy video answers that question

SIDEBAR
How fast do scabies mites move? Dermoscopy video answers that question

Richard Usatine, MD; Ashfaq Marghoob, MD
University of Texas Health San Antonio (Dr. Usatine); Memorial Sloan Kettering Skin Cancer Center, Hauppauge, NY (Dr. Marghoob).

Dr. Marghoob reported that he has received honoraria for speaking for 3GEN. Dr. Usatine reported no potential conflict of interest relevant to this article.

A 22-year-old man infected with human immunodeficiency virus presented to a clinic with a 6-month history of intense pruritus. Physical examination revealed scale crust on the hands and wrists (FIGURE) and in the pubic region.

Dermoscopic examination of the rash on the wrist revealed scabies mites actively crawling on the surface of the skin. A superficial skin scraping revealed the Sarcoptes scabiei mite, several eggs, and scybala under the microscope. The extensive infestation in this patient with crusted scabies was related to his immunocompromised state. (The patient was successfully treated with oral ivermectin and topical permethrin.)

Unprecedented documentation of mite speed a clue to infectivity. The 36-second VIDEO captured an adult mite travelling a distance of 3 mm, translating to a speed of 5 mm/ min. Six younger adults/larvae were moving more rapidly with a maximum distance of 6 mm in 36 seconds (1 cm/min). The movement of a mite within the epidermis is slower, as the mite consumes keratin in creating burrows. The more rapid rate of movement on the skin surface may help to explain the contagious nature of scabies.

Vidyard Video

In this case, the mites and larvae were viewed on the screen of a smartphone to which a dermatoscope was attached magnetically. The mites were first visualized in the standard photo mode. Video mode was then used to capture the motion using the maximum zoom feature of the phone, to a magnification factor of 13.3×.

Literature to date has been silent on mites’ rate of motion. A Medline search yielded only 3 papers that addressed the issue of in vivo movement of scabies mites. None viewed the mites other than in their burrows and none calculated a rate of motion.

• In one study using videodermotoscopy, Micali stated that in most of the 16 cases identified, it was possible to observe the mites moving inside the burrows.1 No video images were published, and there was no mention of speed or characterization of the movement.¹
• A second study used reflectance confocal microscopy (RCM) to examine a single patient with crusted scabies. The authors claim to have viewed the ectoparasite's motion within the human host but provided no details of that motion.²
• In the third study, videodermoscopy showed a slightly higher sensitivity for scabies detection than RCM (95% vs. 92%).³ The authors did not mention visualization of movement of mites in their work but did quote the Micali paper for its mention of movements of the mite.

Applying digital dermoscopy in practice. It appears that this is the first published video documenting the movement of scabies mites and larvae in vivo using dermoscopy. This should pave the way for additional observations of scabies movement on and below the skin using dermoscopy with video. We recommend using the maximum zoom capability of the device along with the dermatoscope to view this movement. What has been surmised before—that the mite must move above the skin to infect human contacts—has now been captured in vivo using the power of dermoscopy.

CORRESPONDENCE
Richard P. Usatine, MD, 903 West Martin Street, San Antonio, TX 78207; [email protected].

REFERENCES
1. Micali G, Lacarrubba F, Lo Guzzo G. Scraping versus videodermatoscopy for the diagnosis of scabies: a comparative study. Acta Derm Venereol. 1999; 79:396.

2. Gürel MS, Turgut Erdemir AV, Tekin B. A case report of real-time in vivo demonstration of Sarcoptes scabiei. Turkiye Parazitol Derg. 2017; 41:229-232.

3. Cinotti E, Labeille B, Cambazard F, et al. Videodermoscopy compared to reflectance confocal microscopy for the diagnosis of scabies. J Eur Acad Dermatol Venereol. 2016; 30:1573-1577.

Continue to: 3 diagnostic missteps to avoid

 

 

3 diagnostic missteps to avoid

Misdiagnosis is often due to an overreliance on the clinical history without performing an adequate physical exam. In such cases, the physician often diagnoses a form of dermatitis as the cause of pruritic rash. (Admittedly, diagnostic error can result in either false-­positive or false-negative findings, and many patients are diagnosed with scabies when they have dermatitis.)

A second misstep? Scabies may be overlooked in a patient whose lesions are nonpruritic, such as someone with an immunocompromising condition.

And finally, crusted scabies is frequently mistaken for psoriasis or chronic dermatitis.⁸

Diagnostic errors are exceedingly troublesome for patients and caregivers. It is not unusual for a hospital or long-term care facility to lose significant employee work hours due to a scabies epidemic or fear of a scabies epidemic. In a 2003 outbreak of scabies in a Canadian long-term care facility, an estimated $200,000 was needed to control disease spread.²³

A topical agent is a mainstay of treatment

Watch the video of a scabies mite on the skin surface.

Permethrin cream is usually the first-line treatment choice.²⁴ Ivermectin, topical (cream) or systemic (pill), is the commonly used alternative for patients who do not respond to, or cannot tolerate, permethrin cream. A recent meta-analysis examined the effectiveness of 5% permethrin cream, 1% ivermectin cream, and oral ivermectin (200 mcg/kg single or double dose).²⁴ Overall, findings suggested there was no difference in the efficacy or in adverse effects of permethrin cream compared with ivermectin (topical or systemic) among adults. One study reported that permethrin cream was slightly more effective than ivermectin (cream or oral) because of the more rapid treatment response (approximately 94% clearance within 2 weeks of treatment, compared with 90%).²⁵

Continue to: Adjust treatment for special populations

 

 

Adjust treatment for special populations. Treatment of severe cases, such as crusted scabies, calls for combination therapy with oral ivermectin (200 mcg/kg) and 5% permethrin cream.²⁶

Five percent permethrin cream is the preferred treatment for children weighing < 15 kg and pregnant women; oral ivermectin has not been studied for efficacy and safety in these populations.²⁷

Effective response to treatment in these studies was measured by resolution of active scabies lesions and improvement in pruritus 1 to 2 weeks after treatment.

 

Anticipate these 3 clinical scenarios

The classic appearance of scabies usually triggers suspicion of its presence, leading to prompt identification of mite burrows and a correct diagnosis. Unfortunately, though, this is not always the case. And atypical presentations heighten the chance of diagnostic error, which overall occurs in nearly half of cases.¹ Keep in mind the following common scenarios, to help improve diagnosis.

1. When a patient presents with a severe pruritic eruption, the clinician may be tempted to settle early on a form of dermatitis and not consider the possibility of scabies. When the patient is later seen by an expert, the burrows are easily identified. Solution: Whenever a patient complains of severe pruritus, use a dermatoscope to carefully examine the digits, web spaces, proximal palms, wrists, and ankles for burrows.

Continue to: A patient with distal white or yellow, thick, scaly, or crusted plaques

 

 

2. A patient with distal white or yellow, thick, scaly, or crusted plaques is often thought to have psoriasis or dermatitis. But scabies should be included in the differential diagnosis. In particular, worsening thick, scaly plaques in an immunocompromised patient should prompt consideration of scabies.

3. Smooth nodules of the genitals in males, or pruritic smooth papules and plaques in other locations, should lead to the consideration of scabies. These presentations can be mistaken for lichen planus, folliculitis, papular urticaria, insect bites, or atopic dermatitis.

Due to the limited amount of mite burrows early in the disease process of scabies, and the gross similarities to a patient with dermatitis with skin excoriations, a thorough exam is needed—one that goes beyond the traditional web spaces and includes hidden/atypical locations such as margins of the feet and hands, the scalp, and neck creases. Careful and deliberate inspection for burrows is critical before ruling out the diagnosis.

CORRESPONDENCE
Art Papier, MD, 400 Red Creek Drive, Suite 200, Rochester, NY 14623; [email protected].

ACKNOWLEDGEMENT
We thank Angela Delacenserie, MA, for reviewing the manuscript and providing editing suggestions.

It is estimated that up to 45% of cases of scabies are misdiagnosed as another condition.¹ This can occur when common clinical features are overlooked, a skin exam is rushed (and the rash is chalked up to dermatitis), or the wrong part of the pruritic lesion is scraped (the papule, rather than the burrow). There are also atypical presentations of scabies, which can confound even the most astute clinician.¹ Misdiagnosis can increase health care costs due to repeat office visits or multiple referrals. In this article, we review the typical and atypical presentations of scabies and provide recommendations to aid physicians in its early recognition and correct diagnosis.

The scope of scabies infection, and its clinical stages

The prevalence of scabies, a common skin infection caused by the mite Sarcoptes scabiei, is estimated at 300 million cases worldwide annually, with the greatest incidence occurring in children and adolescents.¹ In the developing world, its clinical burden is highest among the homeless, those of lower socioeconomic status, and those with poor hygiene. In the developed world, the clinical burden is highest among hospitalized patients and residents of long-term living facilities.

The S scabiei mite is an obligate parasite that elicits an adaptive immune response in susceptible hosts. The female mite lays 60 to 90 eggs that mature into adult mites after completing the mite life cycle in human hosts. In immunocompetent patients, roughly 10 to 15 surviving mites can be found at any given point in the disease process.² In crusted or disseminated scabies, which often occur in immunocompromised patients, thousands of mites may be found at any given point in the disease process. ²

Scabies infection has 2 stages: the latent primary infection and the symptomatic secondary infection.

The primary infection starts with the initial mite invasion, typically with the transfer of impregnated females during person-to-person contact. Females deposit eggs as they burrow into the epidermis at the level of the stratum corneum with the use of proteolytic enzymes (creating the mite burrow). Surviving eggs hatch into larvae that then mature into nymphs and adult mites. After these adult mites mate, the impregnated females create new burrows and lay additional eggs.³ Patients may be asymptomatic during this initial stage and the infection may be transmitted from person to person through direct skin contact.

In children with scabies, vesicles, pustules, and nodular pruritic lesions may coexist with eczema and impetigo.

The second stage of infection is when patients experience severe pruritus with inflammatory papules seen on exam. The pruritus associated with scabies results from a delayed type IV hypersensitivity reaction to mite infestation. This requires host sensitization to the scabies mite. Clinically, there is a delayed onset (weeks) of numerous erythematous papules and, later, excoriated papules.

Conditions that scabies can mimic

The differential of typical scabies includes diagnoses manifesting with moderate to severe pruritus. In the immunocompetent adult, conditions to consider are atopic dermatitis, tinea corporis, papular urticaria, seborrheic dermatitis, poison ivy and other causes of contact dermatitis, drug eruptions, and irritant dermatitis. In immunocompetent infants, think of seborrheic dermatitis, atopic dermatitis, acropustulosis, and viral exanthems.

Continue to: Nodular scabies variants...

Nodular scabies variants can masquerade as pseudolymphoma, lymphoma, or leukemia cutis. In immunocompromised and elderly individuals, crusted scabies is often mistaken for psoriasis, atopic dermatitis, keratoderma, and lichen planus.^2,4,5

Scabies’ classic presentation

Typically, scabies causes intensely pruritic erythematous papules. Areas commonly affected are the webs and sides of fingers ­(FIGURE 1A and 1B), proximal palm and wrist flexors, extensor aspects of the arms and legs, axillary folds, periumbilical areas, the peri-areolar region in women, buttocks and thigh creases, and, in males, the genitals. The head may also be affected in children (FIGURE 1C), but seldom in adults. Interestingly, the back is usually spared across all age groups, though not always (FIGURE 2).

IMAGE COURTESY OF VISUALDX.COM

Mites are not found near pruritic papules. Scrape the mite burrows, which are small, linear, serpiginous lines, to discover the mature scabies mite.

The classic presentation also varies across age groups and populations.² In children, vesicles, pustules, and nodular pruritic lesions may coexist with eczema and impetigo. Among homeless individuals, coinfection with impetigo and eczema is common. Elderly patients are more likely to exhibit atypical lesions.⁶ Immunocompromised patients present with atypical papular scabies, crusted scabies, or scabies that may be only mildly pruritic or nonpruritic. In underdeveloped countries, indigenous populations are more susceptible to endemic scabies, with a high risk of scabies superinfection with Streptococcus.

Scabies subtypes with varying presentations

Clinical manifestations of scabies subtypes may make it difficult to diagnose the disease. These subtypes include nodular, pustular, vesiculobullous, and crusted scabies (Norwegian scabies). Although rare, these subtypes merit acknowledgement, as atypical cases contribute to the high rate of misdiagnosis.

Nodular scabies is a clinical variant that accounts for about 7% of scabies cases.⁷ It can resist traditional scabies treatment (permethrin cream, ivermectin—which we’ll discuss in a bit) and often requires topical or intralesional corticosteroid management. Nodular scabies most commonly affects male genitalia. Patients may have multiple excoriated skin-colored erythematous papules and nodules in areas involving the classic distribution of scabies (web spaces of fingers, flexural areas [FIGURE 3], scrotum, and groin).⁸

IMAGE COURTESY OF VISUALDX.COM

Continue to: Pustular scabies...

Pustular scabies is commonly seen in children and adolescents but can occur in all age groups. Patients may present with vesicular pustular lesions (FIGURE 4A and 4B).⁷ In some cases, topical corticosteroids have modified the classic clinical presentation into a pustular variant. However, scabies alone can cause pustular lesions.

IMAGES COURTESY OF VISUALDX.COM

Vesiculobullous scabies (FIGURE 5A and 5B) is a clinical subtype that may be mistaken for pemphigus vulgaris⁹ or bullous pemphigoid¹⁰ because of its strikingly similar clinical presentation to those disorders.

IMAGES COURTESY OF VISUALDX.COM

Crusted scabies (Norwegian scabies) is a severe, disseminated form of scabies that commonly affects immunocompromised patients, although cases are also seen in immunocompetent hosts. Afflicted immunocompetent patients often have a history of diabetes mellitus, liver cirrhosis, malnutrition, or alcohol abuse.¹¹ Patients present with a thick powdery or crusted white or yellow scale involving the feet or hands (FIGURE 6) that sometimes extends onto the limbs. Severe ­cases can involve wide body surfaces. One unusual presentation also included a desquamating rash without pruritus.¹²

IMAGE COURTESY OF VISUALDX.COM

Highly atypical cases

Distal white or yellow, thick, scaly, or crusted plaques can suggest psoriasis or dermatitis, but you should include scabies in the differential diagnosis.

Atypical presentations include lesions that appear outside of the classic distribution areas of scabies, lesions with uncharacteristic morphology, cases with coinfections, and instances in which patients are immunocompromised.¹³ Examples include scabies of the scalp coexisting with seborrheic dermatitis or dermatomyositis,¹⁴ scabies mimicking mastocytoma,^15,16 and scabies with coinfections of impetigo or eczema.¹⁷ These coinfections and clinical variations can be particularly challenging. Other reports of atypical scabies leading to misdiagnosis include a case of crusted scabies mimicking erythrodermic psoriasis¹⁸ and a case initially attributed to suppurative folliculitis and prurigo nodularis.¹⁹

Decisive diagnostic measures

Identifying the mite’s burrow on clinical exam is essential to making the diagnosis of scabies. Microscopic examinations of burrow scrapings remain the diagnostic gold standard. Frequently, nondermatologists perform skin scrapings of the pruritic papules of scabies instead of the burrows. These papules are a hypersensitivity reaction to the mites, and no scabetic mites will be found there. Burrows appear on exam as small, linear, serpiginous lines (FIGURE 7A and 7B).

IMAGES COURTESY OF VISUALDX.COM

Continue to: Handheld illumination with a dermatoscope...

Handheld illumination with a dermatoscope will allow visualization of the mite ­(FIGURE 8). (See “How fast do scabies mites move? Dermoscopy video answers that question.”) Dermatoscope findings consistent with scabies include a “delta ­glider,” a dark triangular shape that is the mite’s head hidden in the burrow,²⁰ or the classic “jet with contrail” (FIGURE 8).²¹ Scrape the burrow to discover the mature scabies mite (FIGURE 9) and confirm the diagnosis.

COURTESY OF ROMAN BRONFENBRENER, MD

Microscopic examination of scrapings has a reported sensitivity and specificity of up to 90% and 100%, respectively, when collection of scrapings is performed accurately and contains ova, feces, or mites.^14,20,22 Dermatologists increasingly use dermatoscopes to diagnose scabies. Dermoscopy's sensitivity is 91% and specificity is 85% to 86%,¹⁴ which is a reassuring frame of reference for physicians who do not routinely use dermatoscopes and instead rely on scrapings.

Continue to: How fast do scabies mites move? Dermoscopy video answers that question

SIDEBAR
How fast do scabies mites move? Dermoscopy video answers that question

Richard Usatine, MD; Ashfaq Marghoob, MD
University of Texas Health San Antonio (Dr. Usatine); Memorial Sloan Kettering Skin Cancer Center, Hauppauge, NY (Dr. Marghoob).

Dr. Marghoob reported that he has received honoraria for speaking for 3GEN. Dr. Usatine reported no potential conflict of interest relevant to this article.

A 22-year-old man infected with human immunodeficiency virus presented to a clinic with a 6-month history of intense pruritus. Physical examination revealed scale crust on the hands and wrists (FIGURE) and in the pubic region.

Dermoscopic examination of the rash on the wrist revealed scabies mites actively crawling on the surface of the skin. A superficial skin scraping revealed the Sarcoptes scabiei mite, several eggs, and scybala under the microscope. The extensive infestation in this patient with crusted scabies was related to his immunocompromised state. (The patient was successfully treated with oral ivermectin and topical permethrin.)

Unprecedented documentation of mite speed a clue to infectivity. The 36-second VIDEO captured an adult mite travelling a distance of 3 mm, translating to a speed of 5 mm/ min. Six younger adults/larvae were moving more rapidly with a maximum distance of 6 mm in 36 seconds (1 cm/min). The movement of a mite within the epidermis is slower, as the mite consumes keratin in creating burrows. The more rapid rate of movement on the skin surface may help to explain the contagious nature of scabies.

Vidyard Video

In this case, the mites and larvae were viewed on the screen of a smartphone to which a dermatoscope was attached magnetically. The mites were first visualized in the standard photo mode. Video mode was then used to capture the motion using the maximum zoom feature of the phone, to a magnification factor of 13.3×.

Literature to date has been silent on mites’ rate of motion. A Medline search yielded only 3 papers that addressed the issue of in vivo movement of scabies mites. None viewed the mites other than in their burrows and none calculated a rate of motion.

• In one study using videodermotoscopy, Micali stated that in most of the 16 cases identified, it was possible to observe the mites moving inside the burrows.1 No video images were published, and there was no mention of speed or characterization of the movement.¹
• A second study used reflectance confocal microscopy (RCM) to examine a single patient with crusted scabies. The authors claim to have viewed the ectoparasite's motion within the human host but provided no details of that motion.²
• In the third study, videodermoscopy showed a slightly higher sensitivity for scabies detection than RCM (95% vs. 92%).³ The authors did not mention visualization of movement of mites in their work but did quote the Micali paper for its mention of movements of the mite.

Applying digital dermoscopy in practice. It appears that this is the first published video documenting the movement of scabies mites and larvae in vivo using dermoscopy. This should pave the way for additional observations of scabies movement on and below the skin using dermoscopy with video. We recommend using the maximum zoom capability of the device along with the dermatoscope to view this movement. What has been surmised before—that the mite must move above the skin to infect human contacts—has now been captured in vivo using the power of dermoscopy.

CORRESPONDENCE
Richard P. Usatine, MD, 903 West Martin Street, San Antonio, TX 78207; [email protected].

REFERENCES
1. Micali G, Lacarrubba F, Lo Guzzo G. Scraping versus videodermatoscopy for the diagnosis of scabies: a comparative study. Acta Derm Venereol. 1999; 79:396.

2. Gürel MS, Turgut Erdemir AV, Tekin B. A case report of real-time in vivo demonstration of Sarcoptes scabiei. Turkiye Parazitol Derg. 2017; 41:229-232.

3. Cinotti E, Labeille B, Cambazard F, et al. Videodermoscopy compared to reflectance confocal microscopy for the diagnosis of scabies. J Eur Acad Dermatol Venereol. 2016; 30:1573-1577.

Continue to: 3 diagnostic missteps to avoid

 

 

3 diagnostic missteps to avoid

Misdiagnosis is often due to an overreliance on the clinical history without performing an adequate physical exam. In such cases, the physician often diagnoses a form of dermatitis as the cause of pruritic rash. (Admittedly, diagnostic error can result in either false-­positive or false-negative findings, and many patients are diagnosed with scabies when they have dermatitis.)

A second misstep? Scabies may be overlooked in a patient whose lesions are nonpruritic, such as someone with an immunocompromising condition.

And finally, crusted scabies is frequently mistaken for psoriasis or chronic dermatitis.⁸

Diagnostic errors are exceedingly troublesome for patients and caregivers. It is not unusual for a hospital or long-term care facility to lose significant employee work hours due to a scabies epidemic or fear of a scabies epidemic. In a 2003 outbreak of scabies in a Canadian long-term care facility, an estimated $200,000 was needed to control disease spread.²³

A topical agent is a mainstay of treatment

Watch the video of a scabies mite on the skin surface.

Permethrin cream is usually the first-line treatment choice.²⁴ Ivermectin, topical (cream) or systemic (pill), is the commonly used alternative for patients who do not respond to, or cannot tolerate, permethrin cream. A recent meta-analysis examined the effectiveness of 5% permethrin cream, 1% ivermectin cream, and oral ivermectin (200 mcg/kg single or double dose).²⁴ Overall, findings suggested there was no difference in the efficacy or in adverse effects of permethrin cream compared with ivermectin (topical or systemic) among adults. One study reported that permethrin cream was slightly more effective than ivermectin (cream or oral) because of the more rapid treatment response (approximately 94% clearance within 2 weeks of treatment, compared with 90%).²⁵

Continue to: Adjust treatment for special populations

 

 

Adjust treatment for special populations. Treatment of severe cases, such as crusted scabies, calls for combination therapy with oral ivermectin (200 mcg/kg) and 5% permethrin cream.²⁶

Five percent permethrin cream is the preferred treatment for children weighing < 15 kg and pregnant women; oral ivermectin has not been studied for efficacy and safety in these populations.²⁷

Effective response to treatment in these studies was measured by resolution of active scabies lesions and improvement in pruritus 1 to 2 weeks after treatment.

 

Anticipate these 3 clinical scenarios

The classic appearance of scabies usually triggers suspicion of its presence, leading to prompt identification of mite burrows and a correct diagnosis. Unfortunately, though, this is not always the case. And atypical presentations heighten the chance of diagnostic error, which overall occurs in nearly half of cases.¹ Keep in mind the following common scenarios, to help improve diagnosis.

1. When a patient presents with a severe pruritic eruption, the clinician may be tempted to settle early on a form of dermatitis and not consider the possibility of scabies. When the patient is later seen by an expert, the burrows are easily identified. Solution: Whenever a patient complains of severe pruritus, use a dermatoscope to carefully examine the digits, web spaces, proximal palms, wrists, and ankles for burrows.

Continue to: A patient with distal white or yellow, thick, scaly, or crusted plaques

 

 

2. A patient with distal white or yellow, thick, scaly, or crusted plaques is often thought to have psoriasis or dermatitis. But scabies should be included in the differential diagnosis. In particular, worsening thick, scaly plaques in an immunocompromised patient should prompt consideration of scabies.

3. Smooth nodules of the genitals in males, or pruritic smooth papules and plaques in other locations, should lead to the consideration of scabies. These presentations can be mistaken for lichen planus, folliculitis, papular urticaria, insect bites, or atopic dermatitis.

Due to the limited amount of mite burrows early in the disease process of scabies, and the gross similarities to a patient with dermatitis with skin excoriations, a thorough exam is needed—one that goes beyond the traditional web spaces and includes hidden/atypical locations such as margins of the feet and hands, the scalp, and neck creases. Careful and deliberate inspection for burrows is critical before ruling out the diagnosis.

CORRESPONDENCE
Art Papier, MD, 400 Red Creek Drive, Suite 200, Rochester, NY 14623; [email protected].

ACKNOWLEDGEMENT
We thank Angela Delacenserie, MA, for reviewing the manuscript and providing editing suggestions.

New studies show that many people who lose weight can maintain that loss for longer than a few months by utilizing strategies that can be undertaken upon your recommendation and with your ongoing support. In this article, I review the evidence that supports the effectiveness of those interventions and activities for helping patients keep off the weight they’ve lost.

Prolonging the duration of weight maintenance

Until recently, most studies that focused on weight maintenance after weight loss followed subjects for only a few months or a year after the goal was achieved. With that limited window of follow-up, the belief arose in weight-loss medicine that most people gain back lost weight within 2 years. Findings that are emerging from recent studies with longer follow-up, however, suggest that weight loss can be maintained for as long as 8 years.¹

The National Health and Nutrition Examination Survey² and the Action in Health for Diabetes (Look AHEAD) trial^3,4 reported that, among adults who lost 10% or more of body weight, approximately 60% maintained that weight loss at 1 year. Look AHEAD had a much longer duration: 42% of participants who lost at least 10% of body weight by the end of Year 1 maintained at least that 10% loss by the end of Year 4.⁵ In addition, Look AHEAD demonstrated that extended provision of maintenance interventions after weight loss can facilitate clinically meaningful weight loss for as long as 8 years—2 or 3 times longer than what was reported in earlier randomized trials.⁴

We have evidence-based guidance for achieving long-term weight maintenance and good reason to believe that success is achievable for patients. The 10 strategies that follow can help you to guide patients to become successful “maintainers.”

IMAGE: @JOE GORMAN

1. Emphasize more weight loss in the first 3 months of a program

Losing more weight initially seems to point to more success in relation to maintenance. This suggests that more intensive help, such as more frequent visits with a physician and a dietitian during the first 3 months might be an important step to help patients lose and maintain weight.

These 10 strategies can help guide patients to become successful "maintainers."

Much of our information on successful maintainers comes from the National Weight Control Registry (NWCR) at the Warren Alpert Medical School at Brown University.¹ This research study has gathered information from more than 10,000 people who successfully lost ≥ 30 lb (average, 60 lb) and kept it off for at least 1 year. To challenge the widespread belief that only a few people who attempt weight loss succeed long term, the NWCR identifies and investigates the characteristics of individuals who have succeeded.

A new and encouraging finding is from a small study that showed that people can maintain weight loss brought about by either medical or surgical means: Those who lost > 15% of their starting weight and were followed closely by health care professionals maintained their weight loss at 1 year.⁵

Continue to: 2. Advise patients to consume fewer calories and eat more nonglycemic fruits and vegetables

2. Advise patients to consume fewer calories and eat more nonglycemic fruits and vegetables

When a person loses weight, their basal metabolic rate drops; to maintain their new weight, they need to consume fewer calories. That person must continue to have a calorie deficit, which varies individually but is often about 500 kcal/d. There is no formula for this; at our clinic, when a patient achieves goal weight, we have them increase intake by 100 kcal/d/wk in nutritious food until they start to gain weight. When they start to gain weight, we have them decrease intake by 100 kcal/d until they do not gain any longer.

Many patients complain of hunger after they lose weight because of an increase in the body’s level of ghrelin, the hunger hormone, and a decrease in the level of leptin, which is associated with satiety. Many achieve a lower calorie count and fight hunger by increasing fiber intake.

In a 24-year study that looked at weight change, researchers noted a strong inverse association between increased intake of higher-fiber, lower-glycemic fruits and vegetables and weight change.⁶ Lower-glycemic vegetables include most vegetables (exceptions are corn, potatoes, and peas, which are associated with weight gain). Benefit was strongest with berries, apples, pears, tofu or soy, cauliflower, and cruciferous and green leafy vegetables.⁶ Adding 1 serving a day of nonstarchy fruits and vegetables was associated with less weight gain over time.

The order in which food is eaten might be important, as evidenced by a small study⁷ that ­focused on patients with diabetes. ­Investigators found that subjects who ate vegetables first, protein second, and grain third had fewer fluctuations in blood glucose level than those who ate carbohydrates first—­suggesting that this order might be a good way for patients to eat at least some of their meals. The reduced insulin excursions observed in this experimental setting suggest that the vegetable–protein–grain meal pattern can improve insulin sensitivity and help with blood glucose control.

3. Encourage patients to eat at home and to avoid processed foods

In a small, randomized controlled study⁸ in 2019 at the National Institutes of Health, 20 inpatients were fed an ultraprocessed diet that was matched, in calories and macronutrients, in an unprocessed diet fed to controls. Subjects in the ultraprocessed food group ate, on average, 500 kcal/d more and gained 2 lbs in 2 weeks. An ultraprocessed breakfast might consist of a bagel with cream cheese and turkey bacon; the unprocessed breakfast was oatmeal with bananas, walnuts, and skim milk. Notably, the ultraprocessed diet was cheaper; nonprocessed foods cost 50% more.

Continue to: A retrospective review...

Losing the most weight and making frequent office visits to a physician and dietitian early in weight loss can determine the success of maintenance later.

A retrospective review of a sample of US adults’ caloric and nutritional intake determined that eating at a full-service restaurant is not associated with consumption of fewer calories than eating at a fast food restaurant: Eating at either type of restaurant was associated with excess (approximately 200 kcal/meal) caloric intake.⁹

4. Emphasize the importance of eating breakfast and increasing protein intake

Increased protein throughout the day, particularly at breakfast, has been suggested to help with weight maintenance. In a large European study,¹⁰ even slightly increased protein intake (approximately 1.2 g/kg of body weight and of low glycemic index food) was associated with weight maintenance. In another review,¹¹ researchers concluded that 25 to 30 g of protein at each meal can provide improvement in appetite and weight management, although they cautioned that further research is needed. A study that looked at increasing intake of protein at breakfast to 35 g in adolescent females resulted in less snacking later in the day.¹²

In the NWCR, successful maintainers had breakfast daily, a lower fat diet, and fewer calories (approximately 1500 kcal/d)— routines that were all associated with greater success.¹ Therefore, eating protein at approximately 1.2 g/kg of body weight (possibly, even more [35 g] at breakfast) and ingesting less fat and fewer calories all contributed to successful maintenance. Eating nuts and legume-based proteins, such as beans and tofu, should be encouraged.

Only a few studies have looked at dairy protein intake and weight maintenance. In one study, consumption of dairy proteins was not associated with a change in body weight or other metabolic risk markers during weight maintenance.¹³ Yogurt, because of its probiotic content, might be good for weight maintenance, but this has not been studied well, and studies that have been conducted are inconclusive.¹⁴

Another study looked at consumption of protein supplements. It found no improvement in body composition over a 24-week period when protein intake was increased to 1.45 g/kg when compared to 1.16 g/kg in controls. Although subjects felt less hungry, this was not reflected in a reduction in caloric intake.¹⁵

Continue to: Most patients do need counseling...

Most patients do need counseling on whole grain intake: Explaining that a bagel is the same as 4 servings of toast and that a cup (ie, a fistful) of cooked pasta is 3 servings of grains is helpful. Patients should aim for 1 serving of grain at each meal; when shopping for grains, they should choose those that have the “whole” first on the list of ingredients because whole grain, rather than refined grain, intake is associated with less diabetes and colon cancer.¹⁶

5. Underscore the importance of self-monitoring

Self-monitoring is key to weight maintenance. This can mean weighing oneself or tracking one’s food intake (or both). Daily weighing is important: A study showed that patients who decrease how often they weigh themselves were likely to eat more and thus gain weight.¹⁷

Monitoring intake is also important. Recommended online calorie counters (eg, ­myfitnesspal.com, loseit.com), tools such as a Fitbit, or even keeping a food diary to help patients track intake. In a review of technology-based interventions to maintain weight loss, the use of apps was variable and effectiveness of devices was mixed. The authors recommended that physicians complement Web-based applications with personal contact.¹⁸

6. Encourage patients to spend more time exercising

After weight loss is achieved, maintaining a high level of activity is important. Recommendations focus on moving about 1 hr/d or 200 to 300 min/wk.¹⁹ A program of several daily “bouts,” or episodes of moderate-to-vigorous physical activity, is recommended in the new Centers for Disease Control and Prevention guidelines¹⁹ and might be preferable, or equivalent, to a concentrated expenditure of energy. Patients might consider, for example, a 10-minute session, 4 times a day, 5 days a week, instead of a ­single, 40-minute session, 5 days a week.¹⁹ Furthermore, to sustain weight loss, moderate exercise might be more effective than exercise of vigorous intensity or extended duration.¹⁹ Most patients in the NWCR report that walking is their principal form of activity.¹

Resistance training, which improves muscle strength and endurance, with or without diet restriction, has not been shown to be effective for weight loss but might help with weight maintenance and might improve a patient’s lipid profile, insulin resistance, and blood pressure. In obese adolescents, resistance weight training led to positive changes in body composition, such as decreased waist circumference.²⁰ Resistance training likely enhances weight maintenance and should be encouraged because of its effect on increasing lean muscle mass, the most important factor in determining basal metabolic rate.

Continue to: 7. Work with patients to ensure sound sleep hygiene

7. Work with patients to ensure sound sleep hygiene

Short sleep duration (< 6 hours a night) is associated with obesity. There are few studies on weight maintenance and sleep; a study that was reviewed by the NWCR found that people who are highly successful at both weight loss and long-term maintenance are more likely to (1) be categorized as a “morning-type” chronotype (ie, getting up early), and (2) report longer sleep duration and better sleep quality, compared to treatment-seeking overweight and obese subjects. Furthermore, these NWCR subjects were more likely to report shorter sleep latency (time required to fall asleep) and were less likely to report short sleep, defined as < 6 to 7 hours a night.²¹

Counsel patients to eat fewer calories, avoid highly processed foods, and increase protein intake—preferably by preparing food at home.

Patients should strive for 7 to 8 hours of sleep a night; sleep apnea should be addressed as necessary.¹⁷ It is important for doctors to encourage patients to go to bed and get up at the same times every day (eg, 10 pm to 6 am daily).

8. Start a trial of medical therapy

Weight-loss medicines are beyond the scope of this article but worth discussing. In accordance with obesity guidelines, if a patient responds well to a weight-loss medication and loses ≥ 5% of body weight after 3 months, continue prescribing the medication. If the medication is ineffective or the patient experiences adverse effects, stop the prescription and consider an alternative medication or approach to maintenance.

The US Food and Drug Administration has approved 5 medications for long-term use in weight maintenance: the 2 combination formulations bupropion–naltrexone and phentermine–topiramate, as well as liraglutide, lorcaserin, and orlistat. A review of the use of these drugs over 1 year showed that they provide a modest favorable effect on cardiometabolic outcomes that vary by drug class.²² In particular, liraglutide has been shown to reduce the risk of cardiovascular disease outcomes in patients with diabetes who have a history of atherosclerotic disease or heart attack and stroke.²³ Further research is needed to evaluate the long-term impact of these drugs on cardiovascular risk.

9. Address mental health challenges

Certain personal traits and behaviors appear to help people lose weight: In a study, maintainers were more likely to be characterized as being good problem-solvers, having hope, and having a more positive mood.^24,25

Continue to: Addressing mental health issues...

Addressing mental health issues, especially depression, is paramount in patients with obesity. Treating patients with depression and hopelessness, as well as helping them with problem-solving, should be the focus of weight-management care.

A retrospective review determined that eating at a full-service restaurant is not associated with consumption of fewer calories than eating at a fast food restaurant.

Choosing an antidepressant not associated with the adverse effect of weight gain is important. Almost all selective serotonin reuptake inhibitors and tricyclic antidepressants are associated with weight gain; bupropion is weight neutral and should be first-line treatment for patients who are overweight and obese.²⁶ If using an antidepressant associated with weight gain, initiate weight monitoring if the patient gains 3% of body weight in the first month of therapy. When caring for a patient who takes an antipsychotic, consider consulting with their mental health professional to determine the value of prescribing metformin, which has been shown to decrease weight gain associated with antipsychotics.²⁷

Because depression, anxiety, and attention deficit-hyperactivity disorder are all associated with obesity, it is important to work with obese patients’ mental health care providers to design ways to improve their care.

10. Encourage patients to modify old habits and adopt new ones

Focusing on establishing good habits can be helpful. In Great Britain, a program focused on forming new healthy habits and breaking old unhealthy habits by restructuring daily routines and increasing mindfulness was successful in keeping weight off in 65% of participants—an impressive degree of success.²⁴ Successful maintainers were sent daily text messages requesting that they interrupt their routines, which shifted their attention away from eating. Some of these distracting tasks included driving to work by a different route or volunteering for a charity. Such small changes helped improve weight maintenance.

Intuitive eating and mindfulness can help. New concepts that focus on healthy eating without caloric restriction are also emerging; one such approach is intuitive eating, which promotes eating that is based not only on cues connected to hunger and fullness, but also on enjoyment of food, such as eating slowly and savoring every bite.²⁸ Techniques such as sipping water or resting the fork between bites of food has been helpful with some patients. More research in the area of intuitive eating is needed.

Continue to: Recognizing true physiologic hunger...

Recognizing true physiologic hunger distinct from emotional hunger can improve with mindfulness training. This practice might provide a better way to help the so-called yo-yo dieter and binge eater to reach metabolic health. Interestingly, successful weight maintainers who allow themselves less restriction on weekends maintain weight better than those who try to restrict diet every day, according to a recent study.²⁹

Recommend a support group. Accountability is important: Group therapy in obesity treatment may be more effective than individual treatment.³⁰

The support of a group and the regular attendance at group meetings are connected to further significant weight loss in the weight-loss period and, later, during maintenance. Monthly meetings seem to help patients with weight maintenance but more research is needed to determine what interval of support-group meeting attendance is most effective.

CORRESPONDENCE
Marijane Hynes, MD, The George Washington University Medical Faculty Associates, Fifth Floor/Internal Medicine, 2150 Pennsylvania Avenue NW, Washington, DC 20037; [email protected].

New studies show that many people who lose weight can maintain that loss for longer than a few months by utilizing strategies that can be undertaken upon your recommendation and with your ongoing support. In this article, I review the evidence that supports the effectiveness of those interventions and activities for helping patients keep off the weight they’ve lost.

Prolonging the duration of weight maintenance

Until recently, most studies that focused on weight maintenance after weight loss followed subjects for only a few months or a year after the goal was achieved. With that limited window of follow-up, the belief arose in weight-loss medicine that most people gain back lost weight within 2 years. Findings that are emerging from recent studies with longer follow-up, however, suggest that weight loss can be maintained for as long as 8 years.¹

The National Health and Nutrition Examination Survey² and the Action in Health for Diabetes (Look AHEAD) trial^3,4 reported that, among adults who lost 10% or more of body weight, approximately 60% maintained that weight loss at 1 year. Look AHEAD had a much longer duration: 42% of participants who lost at least 10% of body weight by the end of Year 1 maintained at least that 10% loss by the end of Year 4.⁵ In addition, Look AHEAD demonstrated that extended provision of maintenance interventions after weight loss can facilitate clinically meaningful weight loss for as long as 8 years—2 or 3 times longer than what was reported in earlier randomized trials.⁴

We have evidence-based guidance for achieving long-term weight maintenance and good reason to believe that success is achievable for patients. The 10 strategies that follow can help you to guide patients to become successful “maintainers.”

IMAGE: @JOE GORMAN

1. Emphasize more weight loss in the first 3 months of a program

Losing more weight initially seems to point to more success in relation to maintenance. This suggests that more intensive help, such as more frequent visits with a physician and a dietitian during the first 3 months might be an important step to help patients lose and maintain weight.

These 10 strategies can help guide patients to become successful "maintainers."

Much of our information on successful maintainers comes from the National Weight Control Registry (NWCR) at the Warren Alpert Medical School at Brown University.¹ This research study has gathered information from more than 10,000 people who successfully lost ≥ 30 lb (average, 60 lb) and kept it off for at least 1 year. To challenge the widespread belief that only a few people who attempt weight loss succeed long term, the NWCR identifies and investigates the characteristics of individuals who have succeeded.

A new and encouraging finding is from a small study that showed that people can maintain weight loss brought about by either medical or surgical means: Those who lost > 15% of their starting weight and were followed closely by health care professionals maintained their weight loss at 1 year.⁵

Continue to: 2. Advise patients to consume fewer calories and eat more nonglycemic fruits and vegetables

2. Advise patients to consume fewer calories and eat more nonglycemic fruits and vegetables

When a person loses weight, their basal metabolic rate drops; to maintain their new weight, they need to consume fewer calories. That person must continue to have a calorie deficit, which varies individually but is often about 500 kcal/d. There is no formula for this; at our clinic, when a patient achieves goal weight, we have them increase intake by 100 kcal/d/wk in nutritious food until they start to gain weight. When they start to gain weight, we have them decrease intake by 100 kcal/d until they do not gain any longer.

Many patients complain of hunger after they lose weight because of an increase in the body’s level of ghrelin, the hunger hormone, and a decrease in the level of leptin, which is associated with satiety. Many achieve a lower calorie count and fight hunger by increasing fiber intake.

In a 24-year study that looked at weight change, researchers noted a strong inverse association between increased intake of higher-fiber, lower-glycemic fruits and vegetables and weight change.⁶ Lower-glycemic vegetables include most vegetables (exceptions are corn, potatoes, and peas, which are associated with weight gain). Benefit was strongest with berries, apples, pears, tofu or soy, cauliflower, and cruciferous and green leafy vegetables.⁶ Adding 1 serving a day of nonstarchy fruits and vegetables was associated with less weight gain over time.

The order in which food is eaten might be important, as evidenced by a small study⁷ that ­focused on patients with diabetes. ­Investigators found that subjects who ate vegetables first, protein second, and grain third had fewer fluctuations in blood glucose level than those who ate carbohydrates first—­suggesting that this order might be a good way for patients to eat at least some of their meals. The reduced insulin excursions observed in this experimental setting suggest that the vegetable–protein–grain meal pattern can improve insulin sensitivity and help with blood glucose control.

3. Encourage patients to eat at home and to avoid processed foods

In a small, randomized controlled study⁸ in 2019 at the National Institutes of Health, 20 inpatients were fed an ultraprocessed diet that was matched, in calories and macronutrients, in an unprocessed diet fed to controls. Subjects in the ultraprocessed food group ate, on average, 500 kcal/d more and gained 2 lbs in 2 weeks. An ultraprocessed breakfast might consist of a bagel with cream cheese and turkey bacon; the unprocessed breakfast was oatmeal with bananas, walnuts, and skim milk. Notably, the ultraprocessed diet was cheaper; nonprocessed foods cost 50% more.

Continue to: A retrospective review...

Losing the most weight and making frequent office visits to a physician and dietitian early in weight loss can determine the success of maintenance later.

A retrospective review of a sample of US adults’ caloric and nutritional intake determined that eating at a full-service restaurant is not associated with consumption of fewer calories than eating at a fast food restaurant: Eating at either type of restaurant was associated with excess (approximately 200 kcal/meal) caloric intake.⁹

4. Emphasize the importance of eating breakfast and increasing protein intake

Increased protein throughout the day, particularly at breakfast, has been suggested to help with weight maintenance. In a large European study,¹⁰ even slightly increased protein intake (approximately 1.2 g/kg of body weight and of low glycemic index food) was associated with weight maintenance. In another review,¹¹ researchers concluded that 25 to 30 g of protein at each meal can provide improvement in appetite and weight management, although they cautioned that further research is needed. A study that looked at increasing intake of protein at breakfast to 35 g in adolescent females resulted in less snacking later in the day.¹²

In the NWCR, successful maintainers had breakfast daily, a lower fat diet, and fewer calories (approximately 1500 kcal/d)— routines that were all associated with greater success.¹ Therefore, eating protein at approximately 1.2 g/kg of body weight (possibly, even more [35 g] at breakfast) and ingesting less fat and fewer calories all contributed to successful maintenance. Eating nuts and legume-based proteins, such as beans and tofu, should be encouraged.

Only a few studies have looked at dairy protein intake and weight maintenance. In one study, consumption of dairy proteins was not associated with a change in body weight or other metabolic risk markers during weight maintenance.¹³ Yogurt, because of its probiotic content, might be good for weight maintenance, but this has not been studied well, and studies that have been conducted are inconclusive.¹⁴

Another study looked at consumption of protein supplements. It found no improvement in body composition over a 24-week period when protein intake was increased to 1.45 g/kg when compared to 1.16 g/kg in controls. Although subjects felt less hungry, this was not reflected in a reduction in caloric intake.¹⁵

Continue to: Most patients do need counseling...

Most patients do need counseling on whole grain intake: Explaining that a bagel is the same as 4 servings of toast and that a cup (ie, a fistful) of cooked pasta is 3 servings of grains is helpful. Patients should aim for 1 serving of grain at each meal; when shopping for grains, they should choose those that have the “whole” first on the list of ingredients because whole grain, rather than refined grain, intake is associated with less diabetes and colon cancer.¹⁶

5. Underscore the importance of self-monitoring

Self-monitoring is key to weight maintenance. This can mean weighing oneself or tracking one’s food intake (or both). Daily weighing is important: A study showed that patients who decrease how often they weigh themselves were likely to eat more and thus gain weight.¹⁷

Monitoring intake is also important. Recommended online calorie counters (eg, ­myfitnesspal.com, loseit.com), tools such as a Fitbit, or even keeping a food diary to help patients track intake. In a review of technology-based interventions to maintain weight loss, the use of apps was variable and effectiveness of devices was mixed. The authors recommended that physicians complement Web-based applications with personal contact.¹⁸

6. Encourage patients to spend more time exercising

After weight loss is achieved, maintaining a high level of activity is important. Recommendations focus on moving about 1 hr/d or 200 to 300 min/wk.¹⁹ A program of several daily “bouts,” or episodes of moderate-to-vigorous physical activity, is recommended in the new Centers for Disease Control and Prevention guidelines¹⁹ and might be preferable, or equivalent, to a concentrated expenditure of energy. Patients might consider, for example, a 10-minute session, 4 times a day, 5 days a week, instead of a ­single, 40-minute session, 5 days a week.¹⁹ Furthermore, to sustain weight loss, moderate exercise might be more effective than exercise of vigorous intensity or extended duration.¹⁹ Most patients in the NWCR report that walking is their principal form of activity.¹

Resistance training, which improves muscle strength and endurance, with or without diet restriction, has not been shown to be effective for weight loss but might help with weight maintenance and might improve a patient’s lipid profile, insulin resistance, and blood pressure. In obese adolescents, resistance weight training led to positive changes in body composition, such as decreased waist circumference.²⁰ Resistance training likely enhances weight maintenance and should be encouraged because of its effect on increasing lean muscle mass, the most important factor in determining basal metabolic rate.

Continue to: 7. Work with patients to ensure sound sleep hygiene

7. Work with patients to ensure sound sleep hygiene

Short sleep duration (< 6 hours a night) is associated with obesity. There are few studies on weight maintenance and sleep; a study that was reviewed by the NWCR found that people who are highly successful at both weight loss and long-term maintenance are more likely to (1) be categorized as a “morning-type” chronotype (ie, getting up early), and (2) report longer sleep duration and better sleep quality, compared to treatment-seeking overweight and obese subjects. Furthermore, these NWCR subjects were more likely to report shorter sleep latency (time required to fall asleep) and were less likely to report short sleep, defined as < 6 to 7 hours a night.²¹

Counsel patients to eat fewer calories, avoid highly processed foods, and increase protein intake—preferably by preparing food at home.

Patients should strive for 7 to 8 hours of sleep a night; sleep apnea should be addressed as necessary.¹⁷ It is important for doctors to encourage patients to go to bed and get up at the same times every day (eg, 10 pm to 6 am daily).

8. Start a trial of medical therapy

Weight-loss medicines are beyond the scope of this article but worth discussing. In accordance with obesity guidelines, if a patient responds well to a weight-loss medication and loses ≥ 5% of body weight after 3 months, continue prescribing the medication. If the medication is ineffective or the patient experiences adverse effects, stop the prescription and consider an alternative medication or approach to maintenance.

The US Food and Drug Administration has approved 5 medications for long-term use in weight maintenance: the 2 combination formulations bupropion–naltrexone and phentermine–topiramate, as well as liraglutide, lorcaserin, and orlistat. A review of the use of these drugs over 1 year showed that they provide a modest favorable effect on cardiometabolic outcomes that vary by drug class.²² In particular, liraglutide has been shown to reduce the risk of cardiovascular disease outcomes in patients with diabetes who have a history of atherosclerotic disease or heart attack and stroke.²³ Further research is needed to evaluate the long-term impact of these drugs on cardiovascular risk.

9. Address mental health challenges

Certain personal traits and behaviors appear to help people lose weight: In a study, maintainers were more likely to be characterized as being good problem-solvers, having hope, and having a more positive mood.^24,25

Continue to: Addressing mental health issues...

Addressing mental health issues, especially depression, is paramount in patients with obesity. Treating patients with depression and hopelessness, as well as helping them with problem-solving, should be the focus of weight-management care.

A retrospective review determined that eating at a full-service restaurant is not associated with consumption of fewer calories than eating at a fast food restaurant.

Choosing an antidepressant not associated with the adverse effect of weight gain is important. Almost all selective serotonin reuptake inhibitors and tricyclic antidepressants are associated with weight gain; bupropion is weight neutral and should be first-line treatment for patients who are overweight and obese.²⁶ If using an antidepressant associated with weight gain, initiate weight monitoring if the patient gains 3% of body weight in the first month of therapy. When caring for a patient who takes an antipsychotic, consider consulting with their mental health professional to determine the value of prescribing metformin, which has been shown to decrease weight gain associated with antipsychotics.²⁷

Because depression, anxiety, and attention deficit-hyperactivity disorder are all associated with obesity, it is important to work with obese patients’ mental health care providers to design ways to improve their care.

10. Encourage patients to modify old habits and adopt new ones

Focusing on establishing good habits can be helpful. In Great Britain, a program focused on forming new healthy habits and breaking old unhealthy habits by restructuring daily routines and increasing mindfulness was successful in keeping weight off in 65% of participants—an impressive degree of success.²⁴ Successful maintainers were sent daily text messages requesting that they interrupt their routines, which shifted their attention away from eating. Some of these distracting tasks included driving to work by a different route or volunteering for a charity. Such small changes helped improve weight maintenance.

Intuitive eating and mindfulness can help. New concepts that focus on healthy eating without caloric restriction are also emerging; one such approach is intuitive eating, which promotes eating that is based not only on cues connected to hunger and fullness, but also on enjoyment of food, such as eating slowly and savoring every bite.²⁸ Techniques such as sipping water or resting the fork between bites of food has been helpful with some patients. More research in the area of intuitive eating is needed.

Continue to: Recognizing true physiologic hunger...

Recognizing true physiologic hunger distinct from emotional hunger can improve with mindfulness training. This practice might provide a better way to help the so-called yo-yo dieter and binge eater to reach metabolic health. Interestingly, successful weight maintainers who allow themselves less restriction on weekends maintain weight better than those who try to restrict diet every day, according to a recent study.²⁹

Recommend a support group. Accountability is important: Group therapy in obesity treatment may be more effective than individual treatment.³⁰

The support of a group and the regular attendance at group meetings are connected to further significant weight loss in the weight-loss period and, later, during maintenance. Monthly meetings seem to help patients with weight maintenance but more research is needed to determine what interval of support-group meeting attendance is most effective.

CORRESPONDENCE
Marijane Hynes, MD, The George Washington University Medical Faculty Associates, Fifth Floor/Internal Medicine, 2150 Pennsylvania Avenue NW, Washington, DC 20037; [email protected].

New studies show that many people who lose weight can maintain that loss for longer than a few months by utilizing strategies that can be undertaken upon your recommendation and with your ongoing support. In this article, I review the evidence that supports the effectiveness of those interventions and activities for helping patients keep off the weight they’ve lost.

Prolonging the duration of weight maintenance

Until recently, most studies that focused on weight maintenance after weight loss followed subjects for only a few months or a year after the goal was achieved. With that limited window of follow-up, the belief arose in weight-loss medicine that most people gain back lost weight within 2 years. Findings that are emerging from recent studies with longer follow-up, however, suggest that weight loss can be maintained for as long as 8 years.¹

The National Health and Nutrition Examination Survey² and the Action in Health for Diabetes (Look AHEAD) trial^3,4 reported that, among adults who lost 10% or more of body weight, approximately 60% maintained that weight loss at 1 year. Look AHEAD had a much longer duration: 42% of participants who lost at least 10% of body weight by the end of Year 1 maintained at least that 10% loss by the end of Year 4.⁵ In addition, Look AHEAD demonstrated that extended provision of maintenance interventions after weight loss can facilitate clinically meaningful weight loss for as long as 8 years—2 or 3 times longer than what was reported in earlier randomized trials.⁴

We have evidence-based guidance for achieving long-term weight maintenance and good reason to believe that success is achievable for patients. The 10 strategies that follow can help you to guide patients to become successful “maintainers.”

IMAGE: @JOE GORMAN

1. Emphasize more weight loss in the first 3 months of a program

Losing more weight initially seems to point to more success in relation to maintenance. This suggests that more intensive help, such as more frequent visits with a physician and a dietitian during the first 3 months might be an important step to help patients lose and maintain weight.

These 10 strategies can help guide patients to become successful "maintainers."

Much of our information on successful maintainers comes from the National Weight Control Registry (NWCR) at the Warren Alpert Medical School at Brown University.¹ This research study has gathered information from more than 10,000 people who successfully lost ≥ 30 lb (average, 60 lb) and kept it off for at least 1 year. To challenge the widespread belief that only a few people who attempt weight loss succeed long term, the NWCR identifies and investigates the characteristics of individuals who have succeeded.

A new and encouraging finding is from a small study that showed that people can maintain weight loss brought about by either medical or surgical means: Those who lost > 15% of their starting weight and were followed closely by health care professionals maintained their weight loss at 1 year.⁵

Continue to: 2. Advise patients to consume fewer calories and eat more nonglycemic fruits and vegetables

2. Advise patients to consume fewer calories and eat more nonglycemic fruits and vegetables

When a person loses weight, their basal metabolic rate drops; to maintain their new weight, they need to consume fewer calories. That person must continue to have a calorie deficit, which varies individually but is often about 500 kcal/d. There is no formula for this; at our clinic, when a patient achieves goal weight, we have them increase intake by 100 kcal/d/wk in nutritious food until they start to gain weight. When they start to gain weight, we have them decrease intake by 100 kcal/d until they do not gain any longer.

Many patients complain of hunger after they lose weight because of an increase in the body’s level of ghrelin, the hunger hormone, and a decrease in the level of leptin, which is associated with satiety. Many achieve a lower calorie count and fight hunger by increasing fiber intake.

In a 24-year study that looked at weight change, researchers noted a strong inverse association between increased intake of higher-fiber, lower-glycemic fruits and vegetables and weight change.⁶ Lower-glycemic vegetables include most vegetables (exceptions are corn, potatoes, and peas, which are associated with weight gain). Benefit was strongest with berries, apples, pears, tofu or soy, cauliflower, and cruciferous and green leafy vegetables.⁶ Adding 1 serving a day of nonstarchy fruits and vegetables was associated with less weight gain over time.

The order in which food is eaten might be important, as evidenced by a small study⁷ that ­focused on patients with diabetes. ­Investigators found that subjects who ate vegetables first, protein second, and grain third had fewer fluctuations in blood glucose level than those who ate carbohydrates first—­suggesting that this order might be a good way for patients to eat at least some of their meals. The reduced insulin excursions observed in this experimental setting suggest that the vegetable–protein–grain meal pattern can improve insulin sensitivity and help with blood glucose control.

3. Encourage patients to eat at home and to avoid processed foods

In a small, randomized controlled study⁸ in 2019 at the National Institutes of Health, 20 inpatients were fed an ultraprocessed diet that was matched, in calories and macronutrients, in an unprocessed diet fed to controls. Subjects in the ultraprocessed food group ate, on average, 500 kcal/d more and gained 2 lbs in 2 weeks. An ultraprocessed breakfast might consist of a bagel with cream cheese and turkey bacon; the unprocessed breakfast was oatmeal with bananas, walnuts, and skim milk. Notably, the ultraprocessed diet was cheaper; nonprocessed foods cost 50% more.

Continue to: A retrospective review...

Losing the most weight and making frequent office visits to a physician and dietitian early in weight loss can determine the success of maintenance later.

A retrospective review of a sample of US adults’ caloric and nutritional intake determined that eating at a full-service restaurant is not associated with consumption of fewer calories than eating at a fast food restaurant: Eating at either type of restaurant was associated with excess (approximately 200 kcal/meal) caloric intake.⁹

4. Emphasize the importance of eating breakfast and increasing protein intake

Increased protein throughout the day, particularly at breakfast, has been suggested to help with weight maintenance. In a large European study,¹⁰ even slightly increased protein intake (approximately 1.2 g/kg of body weight and of low glycemic index food) was associated with weight maintenance. In another review,¹¹ researchers concluded that 25 to 30 g of protein at each meal can provide improvement in appetite and weight management, although they cautioned that further research is needed. A study that looked at increasing intake of protein at breakfast to 35 g in adolescent females resulted in less snacking later in the day.¹²

In the NWCR, successful maintainers had breakfast daily, a lower fat diet, and fewer calories (approximately 1500 kcal/d)— routines that were all associated with greater success.¹ Therefore, eating protein at approximately 1.2 g/kg of body weight (possibly, even more [35 g] at breakfast) and ingesting less fat and fewer calories all contributed to successful maintenance. Eating nuts and legume-based proteins, such as beans and tofu, should be encouraged.

Only a few studies have looked at dairy protein intake and weight maintenance. In one study, consumption of dairy proteins was not associated with a change in body weight or other metabolic risk markers during weight maintenance.¹³ Yogurt, because of its probiotic content, might be good for weight maintenance, but this has not been studied well, and studies that have been conducted are inconclusive.¹⁴

Another study looked at consumption of protein supplements. It found no improvement in body composition over a 24-week period when protein intake was increased to 1.45 g/kg when compared to 1.16 g/kg in controls. Although subjects felt less hungry, this was not reflected in a reduction in caloric intake.¹⁵

Continue to: Most patients do need counseling...

Most patients do need counseling on whole grain intake: Explaining that a bagel is the same as 4 servings of toast and that a cup (ie, a fistful) of cooked pasta is 3 servings of grains is helpful. Patients should aim for 1 serving of grain at each meal; when shopping for grains, they should choose those that have the “whole” first on the list of ingredients because whole grain, rather than refined grain, intake is associated with less diabetes and colon cancer.¹⁶

5. Underscore the importance of self-monitoring

Self-monitoring is key to weight maintenance. This can mean weighing oneself or tracking one’s food intake (or both). Daily weighing is important: A study showed that patients who decrease how often they weigh themselves were likely to eat more and thus gain weight.¹⁷

Monitoring intake is also important. Recommended online calorie counters (eg, ­myfitnesspal.com, loseit.com), tools such as a Fitbit, or even keeping a food diary to help patients track intake. In a review of technology-based interventions to maintain weight loss, the use of apps was variable and effectiveness of devices was mixed. The authors recommended that physicians complement Web-based applications with personal contact.¹⁸

6. Encourage patients to spend more time exercising

After weight loss is achieved, maintaining a high level of activity is important. Recommendations focus on moving about 1 hr/d or 200 to 300 min/wk.¹⁹ A program of several daily “bouts,” or episodes of moderate-to-vigorous physical activity, is recommended in the new Centers for Disease Control and Prevention guidelines¹⁹ and might be preferable, or equivalent, to a concentrated expenditure of energy. Patients might consider, for example, a 10-minute session, 4 times a day, 5 days a week, instead of a ­single, 40-minute session, 5 days a week.¹⁹ Furthermore, to sustain weight loss, moderate exercise might be more effective than exercise of vigorous intensity or extended duration.¹⁹ Most patients in the NWCR report that walking is their principal form of activity.¹

Resistance training, which improves muscle strength and endurance, with or without diet restriction, has not been shown to be effective for weight loss but might help with weight maintenance and might improve a patient’s lipid profile, insulin resistance, and blood pressure. In obese adolescents, resistance weight training led to positive changes in body composition, such as decreased waist circumference.²⁰ Resistance training likely enhances weight maintenance and should be encouraged because of its effect on increasing lean muscle mass, the most important factor in determining basal metabolic rate.

Continue to: 7. Work with patients to ensure sound sleep hygiene

7. Work with patients to ensure sound sleep hygiene

Short sleep duration (< 6 hours a night) is associated with obesity. There are few studies on weight maintenance and sleep; a study that was reviewed by the NWCR found that people who are highly successful at both weight loss and long-term maintenance are more likely to (1) be categorized as a “morning-type” chronotype (ie, getting up early), and (2) report longer sleep duration and better sleep quality, compared to treatment-seeking overweight and obese subjects. Furthermore, these NWCR subjects were more likely to report shorter sleep latency (time required to fall asleep) and were less likely to report short sleep, defined as < 6 to 7 hours a night.²¹

Counsel patients to eat fewer calories, avoid highly processed foods, and increase protein intake—preferably by preparing food at home.

Patients should strive for 7 to 8 hours of sleep a night; sleep apnea should be addressed as necessary.¹⁷ It is important for doctors to encourage patients to go to bed and get up at the same times every day (eg, 10 pm to 6 am daily).

8. Start a trial of medical therapy

Weight-loss medicines are beyond the scope of this article but worth discussing. In accordance with obesity guidelines, if a patient responds well to a weight-loss medication and loses ≥ 5% of body weight after 3 months, continue prescribing the medication. If the medication is ineffective or the patient experiences adverse effects, stop the prescription and consider an alternative medication or approach to maintenance.

The US Food and Drug Administration has approved 5 medications for long-term use in weight maintenance: the 2 combination formulations bupropion–naltrexone and phentermine–topiramate, as well as liraglutide, lorcaserin, and orlistat. A review of the use of these drugs over 1 year showed that they provide a modest favorable effect on cardiometabolic outcomes that vary by drug class.²² In particular, liraglutide has been shown to reduce the risk of cardiovascular disease outcomes in patients with diabetes who have a history of atherosclerotic disease or heart attack and stroke.²³ Further research is needed to evaluate the long-term impact of these drugs on cardiovascular risk.

9. Address mental health challenges

Certain personal traits and behaviors appear to help people lose weight: In a study, maintainers were more likely to be characterized as being good problem-solvers, having hope, and having a more positive mood.^24,25

Continue to: Addressing mental health issues...

Addressing mental health issues, especially depression, is paramount in patients with obesity. Treating patients with depression and hopelessness, as well as helping them with problem-solving, should be the focus of weight-management care.

A retrospective review determined that eating at a full-service restaurant is not associated with consumption of fewer calories than eating at a fast food restaurant.

Choosing an antidepressant not associated with the adverse effect of weight gain is important. Almost all selective serotonin reuptake inhibitors and tricyclic antidepressants are associated with weight gain; bupropion is weight neutral and should be first-line treatment for patients who are overweight and obese.²⁶ If using an antidepressant associated with weight gain, initiate weight monitoring if the patient gains 3% of body weight in the first month of therapy. When caring for a patient who takes an antipsychotic, consider consulting with their mental health professional to determine the value of prescribing metformin, which has been shown to decrease weight gain associated with antipsychotics.²⁷

Because depression, anxiety, and attention deficit-hyperactivity disorder are all associated with obesity, it is important to work with obese patients’ mental health care providers to design ways to improve their care.

10. Encourage patients to modify old habits and adopt new ones

Focusing on establishing good habits can be helpful. In Great Britain, a program focused on forming new healthy habits and breaking old unhealthy habits by restructuring daily routines and increasing mindfulness was successful in keeping weight off in 65% of participants—an impressive degree of success.²⁴ Successful maintainers were sent daily text messages requesting that they interrupt their routines, which shifted their attention away from eating. Some of these distracting tasks included driving to work by a different route or volunteering for a charity. Such small changes helped improve weight maintenance.

Intuitive eating and mindfulness can help. New concepts that focus on healthy eating without caloric restriction are also emerging; one such approach is intuitive eating, which promotes eating that is based not only on cues connected to hunger and fullness, but also on enjoyment of food, such as eating slowly and savoring every bite.²⁸ Techniques such as sipping water or resting the fork between bites of food has been helpful with some patients. More research in the area of intuitive eating is needed.

Continue to: Recognizing true physiologic hunger...

Recognizing true physiologic hunger distinct from emotional hunger can improve with mindfulness training. This practice might provide a better way to help the so-called yo-yo dieter and binge eater to reach metabolic health. Interestingly, successful weight maintainers who allow themselves less restriction on weekends maintain weight better than those who try to restrict diet every day, according to a recent study.²⁹

Recommend a support group. Accountability is important: Group therapy in obesity treatment may be more effective than individual treatment.³⁰

The support of a group and the regular attendance at group meetings are connected to further significant weight loss in the weight-loss period and, later, during maintenance. Monthly meetings seem to help patients with weight maintenance but more research is needed to determine what interval of support-group meeting attendance is most effective.

CORRESPONDENCE
Marijane Hynes, MD, The George Washington University Medical Faculty Associates, Fifth Floor/Internal Medicine, 2150 Pennsylvania Avenue NW, Washington, DC 20037; [email protected].

Overall adolescent vaccination coverage is improving in the United States.¹ But for adolescents up to 15 years of age, there’s a large gap between the rate of vaccination for human papillomavirus (HPV) and the higher rates of coverage for tetanus, diphtheria, and acellular pertussis (Tdap) and meningococcal conjugate (MenACWY) vaccines.¹ Adopting or refining practice customs reviewed in this article can increase HPV vaccination rates and continue to improve coverage of all vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) for adolescents between the ages of 11 and 12.

The evolution of ACIP’s HPV vaccine recommendations

Before December 2016, ACIP recommended a 3-dose HPV series for all adolescents between the ages of 11 and 12, given on a 0, 1-2, and 6-month schedule.² The series could be started at 9 years of age. It could be administered to females as old as 26 years, and to males through 21 years (or ages 22-26 years for those who wish to be vaccinated, who have certain medical conditions, or who are included in special populations—ie, gay and bisexual men, men who have sex with men, immunocompromised men, men with human immunodeficiency virus [HIV], and transgender men).

In 2016, ACIP revised its recommendation for adolescents who initiate vaccination before their 15th birthday: a 2-dose schedule is adequate, with the second dose given 6 to 12 months after the first dose. For those who initiate vaccination on or after their 15th birthday, and for those with certain medical conditions, the recommendation remains 3 doses on a 0, 1-2, and 6-month schedule.³

As of August 2019,⁴ ACIP now recommends that all women and men receive catch-up HPV vaccination through age 26. For individuals 27 to 45 years of age who have not been adequately vaccinated, HPV vaccine may be given based on shared clinical decision making with their physician.

How are we doing?

Overall, adolescent vaccination coverage is improving in the United States (see “Vaccination goals from ACIP and Healthy People 2020”^1,5,6), but the rate of improvement of HPV coverage is lower than that for Tdap and MenACWY coverage by age 15 years (although completion of the ­MenACWY vaccine series is low). From 2015 to 2016, coverage increased for 1 or more doses of Tdap, from 86.4% to 88% among 17-year olds (87.9% for 15-year olds), and coverage for 1 or more doses of MenACWY increased from 81.7% to 83.5% among 17-year olds (80.4% among 15-year olds).¹ Both Tdap and MenACWY coverage rates have surpassed Healthy People 2020 goals of 80%, and the focus now is on maintenance of coverage. Data from the 2016 National Immunization Survey ­(NIS)-Teen show that completion of the HPV vaccine series (applying updated HPV vaccine recommendations retrospectively) increased to 45.4% for 15-year-olds,¹ still far below the Healthy People 2020 goal of 80%. Completion rates for 2 or more doses of MenACWY also increased from 33.3% to 39.1%.¹

Common barriers to improved vaccine coverage

Barriers to improved vaccination rates include a lack of regular assessment of vaccine status; limited use of electronic records, tools, and immunization registries; lack of health care provider knowledge on current vaccine recommendations; vaccine costs; missed opportunities; and patient/parent refusals.^7,8 The Community Preventive Services Task Force outlines several well-established evidence-based ways that administrators and physicians can counter these barriers:

• give a strong recommendation to vaccinate,^9,10
• incorporate an audit/feedback mechanism for health care providers who vaccinate,^9,11
• use electronic alerts to remind health care providers to vaccinate,^9,12
• use your state’s electronic immunization information systems (IIS),^7,13
• appoint a vaccine practice team/­vaccine champion,^9,14 and
• implement standing orders and ­reminder/recall systems.^7,9,15

In 2016, 45.4% of 15-year-olds had completed the HPV vaccine series—far below the Healthy People 2020 goal of 80%.

The passage of the Affordable Care Act (ACA)—which mandates that certain preventive services, including ACIP-recommended immunizations, be covered as part of basic care at no cost-sharing—reduces the once-common financial barrier to vaccine uptake.¹⁶ A key contributor to low uptake of HPV vaccination by adolescents is parental refusal.¹⁷

Continue to: The threats posed by HPV

HPV infections are the most commonly transmitted infections in the United States and nearly all men and women will be exposed to one or more types of HPV at some point in their lives. Current data show that 79 million Americans, most in their late teens and early 20s, are infected with HPV, and about 14 million people in the United States become newly infected each year.¹⁸ HPV is a DNA tumor virus that causes epithelial proliferation at cutaneous and mucosal surfaces.

There are more than 100 types of the virus,¹⁹ including more than 40 strains that infect the human genital tract. Of the latter 40 strains, there are oncogenic or high-risk types and non-oncogenic or low-risk types.²⁰ HPV infection with high-risk types causes cervical, vaginal, and vulvar cancers in women; penile cancers in men; and oropharyngeal and anal cancers in both men and women. Low-risk HPV types cause genital warts in both men and women.²¹ The current available HPV vaccine in the United States is a 9-valent vaccine (9vHPV) that replaces the former 2- and 4-valent HPV vaccines and includes immunogenic coverage against high-risk HPV types 16, 18, 31, 33, 45, 52, and 58; and low-risk types 6 and 11.²²

Centers for Disease Control and Prevention (CDC) data from 2010 to 2014 show that approximately 23,700 women and approximately 17,300 men in the United States developed HPV-associated cancer. Most common in women are cervical cancers and in men, oropharyngeal cancers (cancers of the back of the throat, base of the tongue, and tonsils). Using population-based data to genotype HPV types from cancer tissues, the CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.²³ A significant percentage of these cancers could potentially be prevented by receipt of 9vHPV.^23,24

Make adolescent immunization a high priority

Anticipate opportunities to vaccinate and take steps to make your immunization and scheduling processes more prominent. With HPV specifically, you can strongly advocate for vaccination, address parental misgivings and educate them using clear communication styles, and acquire knowledge to answer concerns about potential vaccine adverse ­effects.

Every visit is an opportunity to vaccinate. The American Academy of Family Physicians and The American Academy of Pediatrics recommend that adolescents have annual preventive visits for screening, immunizations, and assessment and counseling for risky behaviors. However, many adolescents do not present annually for preventive visits, and fewer than half of adolescents receive regular preventive care.²⁵ In a study of 425 family physicians and pediatricians, almost all pediatricians endorsed the importance of annual well visits, while less than three-quarters of family physicians did.²⁶ An analysis of national surveillance systems shows rates for preventive health care visits range from 43% to 74% among adolescents 10 to 17 years of age, and 26% to 58% among young adults 18 to 25 years of age.²⁷ Overall, 67% of adolescent health care visits are for acute care, and 10% are for follow-up care.²⁸

Continue to: Missed opportunities for the HPV vaccine

Missed opportunities for the HPV vaccine. One study showed that at least 86% of unvaccinated adolescents had missed opportunities to receive HPV vaccine.²⁹ A study of 14,588 adolescent girls from January 2010 through August 2015 showed that HPV vaccine was given at only 37.1% of visits in which MenACWY or Tdap vaccines were administered.³⁰ The rate of HPV vaccination was just 26% during well adolescent visits, and 41.8% during all other primary care visits.³⁰ Every adolescent health care visit—including visits for acute care, chronic care, follow-up, or office-based procedures—is an opportunity to review vaccination status.

Give vaccines concomitantly (simultaneously or same-day). ACIP counsels that minor illnesses, such as mild upper respiratory infections with or without low-grade fever, are not contraindications to routine vaccination.³⁰ Also, the safety of simultaneous vaccine administration, often a concern of both parents and health care providers, has been well established. Each vaccine’s immunogenicity and safety profile are maintained when given concomitantly with other vaccines, and fewer visits are needed to complete an adolescent’s vaccination status.^31,32

Immediately schedule follow up visits and use reminder/recall systems. Parents of adolescents who opt for HPV vaccination are not always aware of the timing of the 2- or 3-dose schedule and may not even be aware that more than 1 dose of vaccine is recommended.

In a study of 14,588 adolescent girls who had vaccinations at an office visit, only 37.1% also received the HPV vaccine.

A qualitative study of pediatric primary care providers and parents/guardians of adolescent patients showed that for HPV vaccination series completion, 65% of parents/guardians expected to be reminded of any needed doses, while 52% of the pediatric primary care providers relied on parents to schedule subsequent immunizations, and often the HPV series was not completed.³³ Higher completion rates of the HPV vaccination series were achieved when follow-up appointments were scheduled at checkout for the 2nd or 3rd vaccine dose after initiation of HPV vaccination.³³ The use of patient reminder/recall systems using telephone calls or mailings (phone usage is more effective than mailings) is also shown to improve vaccination completion rates.³⁴

Recommend HPV vaccination clearly and resolutely

In a cross-sectional survey of 800 parents of adolescents ages 9 to 14 years, HPV vaccine was deemed the least likely vaccine to have been “very strongly” recommended by their health care provider, compared with the strength of recommendations for influenza, Tdap, and MenACWY vaccines.³⁵ The strength of a health care provider’s recommendation to vaccinate is the single most influential factor in vaccine uptake.^10,36,37 Most family physicians self-report “always recommending standard pediatric vaccines”; however, only a minority are following ACIP recommendations.³⁸ A national study reported that only about two-thirds of parents who received HPV vaccine recommendations perceived a high level of health care provider endorsement.³⁹ The takeaway point: Give a clear, unambiguous, strong recommendation to vaccinate with HPV to prevent infection; cervical, oropharyngeal, and other cancers; and genital warts.

Continue to: Tell parents why the timing is important

Tell parents why the timing is important. Inform parents that the HPV vaccine must be administered while their child is young (before the adolescent’s first sexual contact) to ensure the most robust immune response to the vaccine.⁴⁰ Unsolicited explanations about sexual activity need not be offered when discussing HPV vaccination, as it is fair to assume that sexual contact is a reality for nearly all people in their adolescent or adult life; and by extension, most sexually active people will likely have exposure to HPV at some time in their lives. By adulthood, sexual activity is nearly universal: The National Longitudinal Study of Adolescent Health showed that only about 3% of participants tracked since adolescence reported no sexual experience by (average age) 28.5 years.⁴¹

How you say it matters. Many pediatricians and family physicians report recommending HPV vaccine inconsistently, behind schedule, or without urgency,⁴² sending mixed messages by failing to endorse HPV vaccination strongly, failing to differentiate it from other vaccines, and presenting it as an “optional” vaccine that could be delayed.⁴³ Physicians and other health care providers who begin conversations about HPV vaccine by saying that the adolescent is “due” for the vaccine show higher vaccine recommendation quality scores than those who give unsolicited information about the vaccine, elicit questions before recommendation, or present the vaccine as an “option.”⁴² Parents who are “on the fence” may hesitate and decline HPV vaccination with a halfhearted recommendation.⁴⁴

The CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.

“Your child is due for his/her Tdap, HPV, influenza, and meningococcal vaccinations to prevent potentially devastating disease and several cancers. I highly recommend all 4 vaccinations today” is more persuasive than, “I recommend your child receive his/her Tdap, meningococcal, and influenza vaccines. And we can also discuss the HPV vaccine.”

Direct presumptive language that assumes vaccine delivery is associated with higher odds of HPV vaccine acceptance and same-day agreement to vaccination than is an open-ended participatory conversational style.⁴⁵ Saying, “I believe in the importance of this cancer-preventing vaccine for your child” is more persuasive than saying, “What do you think about starting the HPV vaccination series today?”⁴⁶

Don’t give up when parents initially refuse HPV vaccinations for their adolescents. Parents’ decisions about HPV vaccination may change over time. Repeated positive recommendations and counseling for HPV vaccination over multiple visits have been shown in a large multivariable analysis to increase parent acceptance of HPV vaccination: 45% of parents reported secondary acceptance of HPV vaccination, and an additional 24% intended to vaccinate in the next 12 months.⁴⁷ Combining a presumptive communication style with motivational interviewing and a fact sheet has contributed to higher clinician-perceived levels of parental HPV vaccine acceptance and increased vaccination rates.⁴⁸

Continue to: Know how to address parents' concerns about safety

Know how to address parents’ concerns about safety

Be prepared to discuss and answer parents’ questions or concerns regarding any vaccine, especially the HPV vaccine. Social networks are important in parents’ vaccination decision-making,⁴⁹ and they may seek information from such sources as Twitter, Facebook, Google, and YouTube, where misinformation may be disseminated. A quantitative analysis of 560 YouTube videos relaying a false link between vaccines and autism or other serious adverse effects on children were uploaded between December 2007 and July 2017, with a peak of 224 videos uploaded in the first 7 months of 2017.⁵⁰ Most were negative in tone and dispensed misinformation.⁵⁰

The National Vaccine Information Center (NVIC) is an organization that takes a skeptical view of the US government and pharmaceutical companies. NVIC is widely criticized by scientists and leaders in vaccine science and public health as spreading false information on the risks of vaccines and, specifically, that HPV vaccination causes chronic disease. NVIC reports that receipt of HPV vaccine may increase the risk for cervical cancer and death.⁵¹ Pediatrician and vaccine researcher Dr. Paul Offit, interviewed by The Lancet in response to NVIC and other anti-vaccine groups’ messages, stated: “anti-vaccination organizations are unequivocally threatening public health.”⁵²

Describe the robust safety-monitoring system. The CDC is aware of public concern about the safety of HPV vaccine. Ongoing monitoring of vaccine safety and studies conducted by the CDC, the Food and Drug Administration (FDA), and other organizations has documented a reassuring safety record since the vaccine’s introduction in 2006.⁵³ Assure parents that the Vaccine Adverse Event Reporting System (VAERS) summary of 7244 reports following 9vHPV vaccination (December 1, 2014 – December 31, 2017) showed that most (97%) reports were nonserious: No new safety signals or unexpected patterns were observed, confirming consistency of the safety profile of 9vHPV with data from pre-licensure trials and post-licensure data on 4vHPV.⁵⁴

Acknowledge the usually mild, transient potential risks of HPV vaccination as reported to VAERS: local injection site symptoms such as pain, redness, or swelling in the arm where the injection was given (most common adverse effect), dizziness, fainting, headache, nausea, and fever.⁵³ Point out that fainting after vaccination is common in adolescents⁵⁵ and that the CDC and ACIP recommend observation of adolescents for 15 minutes following HPV vaccination.⁵⁶ Consider this 15-minute observation period after adolescent receipt of any vaccine to be part of standard practice in your vaccination setting.⁵⁶

Contest unfounded views. Other common parental concerns about effects of HPV vaccine include supposed promotion of promiscuity, increased incidence of premature ovarian failure or insufficiency (POI), and increased risk of Guillain-Barré Syndrome (GBS), often propagated through published reports, media coverage, Web sites, and social media. Assure worried parents that many studies have shown that receipt of the vaccine is safe and does not lead to initiation of sexual activity or promiscuity, and, in fact, safer sexual health practices have been observed following vaccination.^57-59

Continue to: A large longitudinal...

In one study, 65% of parents expected to be reminded of any needed HPV vaccine doses, while 52% of the pediatric PCPs relied on parents to schedule subsequent immunizations.

A large longitudinal adolescent health survey administered in British Columbia looked at sexual health behaviors and risk factors in adolescent girls before and after receipt of HPV vaccination (2003, 2008, 2013).⁵⁹ Results showed no significant change in the reported number of sexual partners (2003-2013), increased reported use of contraception and condoms, and lower pregnancy rates.⁵⁹ There is no evidence that HPV vaccines cause reproductive problems in women⁵³; a review of VAERS reports from 2009 through 2015 did not detect any safety concerns for POI or other reproductive problems in females.⁶⁰ A 2018 population-based study of nearly 200,000 women observed no increase of POI following receipt of HPV vaccination.⁶¹ In addition, several recent studies have shown no increased risk for GBS following receipt of HPV vaccine.^62-64

CORRESPONDENCE
Pamela G. Rockwell, DO, FAAFP, 24 Frank Lloyd Wright Drive, SPC 5795, Room 2300, Lobby H, Ann Arbor, MI 48105; [email protected].

Overall adolescent vaccination coverage is improving in the United States.¹ But for adolescents up to 15 years of age, there’s a large gap between the rate of vaccination for human papillomavirus (HPV) and the higher rates of coverage for tetanus, diphtheria, and acellular pertussis (Tdap) and meningococcal conjugate (MenACWY) vaccines.¹ Adopting or refining practice customs reviewed in this article can increase HPV vaccination rates and continue to improve coverage of all vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) for adolescents between the ages of 11 and 12.

The evolution of ACIP’s HPV vaccine recommendations

Before December 2016, ACIP recommended a 3-dose HPV series for all adolescents between the ages of 11 and 12, given on a 0, 1-2, and 6-month schedule.² The series could be started at 9 years of age. It could be administered to females as old as 26 years, and to males through 21 years (or ages 22-26 years for those who wish to be vaccinated, who have certain medical conditions, or who are included in special populations—ie, gay and bisexual men, men who have sex with men, immunocompromised men, men with human immunodeficiency virus [HIV], and transgender men).

In 2016, ACIP revised its recommendation for adolescents who initiate vaccination before their 15th birthday: a 2-dose schedule is adequate, with the second dose given 6 to 12 months after the first dose. For those who initiate vaccination on or after their 15th birthday, and for those with certain medical conditions, the recommendation remains 3 doses on a 0, 1-2, and 6-month schedule.³

As of August 2019,⁴ ACIP now recommends that all women and men receive catch-up HPV vaccination through age 26. For individuals 27 to 45 years of age who have not been adequately vaccinated, HPV vaccine may be given based on shared clinical decision making with their physician.

How are we doing?

Overall, adolescent vaccination coverage is improving in the United States (see “Vaccination goals from ACIP and Healthy People 2020”^1,5,6), but the rate of improvement of HPV coverage is lower than that for Tdap and MenACWY coverage by age 15 years (although completion of the ­MenACWY vaccine series is low). From 2015 to 2016, coverage increased for 1 or more doses of Tdap, from 86.4% to 88% among 17-year olds (87.9% for 15-year olds), and coverage for 1 or more doses of MenACWY increased from 81.7% to 83.5% among 17-year olds (80.4% among 15-year olds).¹ Both Tdap and MenACWY coverage rates have surpassed Healthy People 2020 goals of 80%, and the focus now is on maintenance of coverage. Data from the 2016 National Immunization Survey ­(NIS)-Teen show that completion of the HPV vaccine series (applying updated HPV vaccine recommendations retrospectively) increased to 45.4% for 15-year-olds,¹ still far below the Healthy People 2020 goal of 80%. Completion rates for 2 or more doses of MenACWY also increased from 33.3% to 39.1%.¹

Common barriers to improved vaccine coverage

Barriers to improved vaccination rates include a lack of regular assessment of vaccine status; limited use of electronic records, tools, and immunization registries; lack of health care provider knowledge on current vaccine recommendations; vaccine costs; missed opportunities; and patient/parent refusals.^7,8 The Community Preventive Services Task Force outlines several well-established evidence-based ways that administrators and physicians can counter these barriers:

• give a strong recommendation to vaccinate,^9,10
• incorporate an audit/feedback mechanism for health care providers who vaccinate,^9,11
• use electronic alerts to remind health care providers to vaccinate,^9,12
• use your state’s electronic immunization information systems (IIS),^7,13
• appoint a vaccine practice team/­vaccine champion,^9,14 and
• implement standing orders and ­reminder/recall systems.^7,9,15

In 2016, 45.4% of 15-year-olds had completed the HPV vaccine series—far below the Healthy People 2020 goal of 80%.

The passage of the Affordable Care Act (ACA)—which mandates that certain preventive services, including ACIP-recommended immunizations, be covered as part of basic care at no cost-sharing—reduces the once-common financial barrier to vaccine uptake.¹⁶ A key contributor to low uptake of HPV vaccination by adolescents is parental refusal.¹⁷

Continue to: The threats posed by HPV

HPV infections are the most commonly transmitted infections in the United States and nearly all men and women will be exposed to one or more types of HPV at some point in their lives. Current data show that 79 million Americans, most in their late teens and early 20s, are infected with HPV, and about 14 million people in the United States become newly infected each year.¹⁸ HPV is a DNA tumor virus that causes epithelial proliferation at cutaneous and mucosal surfaces.

There are more than 100 types of the virus,¹⁹ including more than 40 strains that infect the human genital tract. Of the latter 40 strains, there are oncogenic or high-risk types and non-oncogenic or low-risk types.²⁰ HPV infection with high-risk types causes cervical, vaginal, and vulvar cancers in women; penile cancers in men; and oropharyngeal and anal cancers in both men and women. Low-risk HPV types cause genital warts in both men and women.²¹ The current available HPV vaccine in the United States is a 9-valent vaccine (9vHPV) that replaces the former 2- and 4-valent HPV vaccines and includes immunogenic coverage against high-risk HPV types 16, 18, 31, 33, 45, 52, and 58; and low-risk types 6 and 11.²²

Centers for Disease Control and Prevention (CDC) data from 2010 to 2014 show that approximately 23,700 women and approximately 17,300 men in the United States developed HPV-associated cancer. Most common in women are cervical cancers and in men, oropharyngeal cancers (cancers of the back of the throat, base of the tongue, and tonsils). Using population-based data to genotype HPV types from cancer tissues, the CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.²³ A significant percentage of these cancers could potentially be prevented by receipt of 9vHPV.^23,24

Make adolescent immunization a high priority

Anticipate opportunities to vaccinate and take steps to make your immunization and scheduling processes more prominent. With HPV specifically, you can strongly advocate for vaccination, address parental misgivings and educate them using clear communication styles, and acquire knowledge to answer concerns about potential vaccine adverse ­effects.

Every visit is an opportunity to vaccinate. The American Academy of Family Physicians and The American Academy of Pediatrics recommend that adolescents have annual preventive visits for screening, immunizations, and assessment and counseling for risky behaviors. However, many adolescents do not present annually for preventive visits, and fewer than half of adolescents receive regular preventive care.²⁵ In a study of 425 family physicians and pediatricians, almost all pediatricians endorsed the importance of annual well visits, while less than three-quarters of family physicians did.²⁶ An analysis of national surveillance systems shows rates for preventive health care visits range from 43% to 74% among adolescents 10 to 17 years of age, and 26% to 58% among young adults 18 to 25 years of age.²⁷ Overall, 67% of adolescent health care visits are for acute care, and 10% are for follow-up care.²⁸

Continue to: Missed opportunities for the HPV vaccine

Missed opportunities for the HPV vaccine. One study showed that at least 86% of unvaccinated adolescents had missed opportunities to receive HPV vaccine.²⁹ A study of 14,588 adolescent girls from January 2010 through August 2015 showed that HPV vaccine was given at only 37.1% of visits in which MenACWY or Tdap vaccines were administered.³⁰ The rate of HPV vaccination was just 26% during well adolescent visits, and 41.8% during all other primary care visits.³⁰ Every adolescent health care visit—including visits for acute care, chronic care, follow-up, or office-based procedures—is an opportunity to review vaccination status.

Give vaccines concomitantly (simultaneously or same-day). ACIP counsels that minor illnesses, such as mild upper respiratory infections with or without low-grade fever, are not contraindications to routine vaccination.³⁰ Also, the safety of simultaneous vaccine administration, often a concern of both parents and health care providers, has been well established. Each vaccine’s immunogenicity and safety profile are maintained when given concomitantly with other vaccines, and fewer visits are needed to complete an adolescent’s vaccination status.^31,32

Immediately schedule follow up visits and use reminder/recall systems. Parents of adolescents who opt for HPV vaccination are not always aware of the timing of the 2- or 3-dose schedule and may not even be aware that more than 1 dose of vaccine is recommended.

In a study of 14,588 adolescent girls who had vaccinations at an office visit, only 37.1% also received the HPV vaccine.

A qualitative study of pediatric primary care providers and parents/guardians of adolescent patients showed that for HPV vaccination series completion, 65% of parents/guardians expected to be reminded of any needed doses, while 52% of the pediatric primary care providers relied on parents to schedule subsequent immunizations, and often the HPV series was not completed.³³ Higher completion rates of the HPV vaccination series were achieved when follow-up appointments were scheduled at checkout for the 2nd or 3rd vaccine dose after initiation of HPV vaccination.³³ The use of patient reminder/recall systems using telephone calls or mailings (phone usage is more effective than mailings) is also shown to improve vaccination completion rates.³⁴

Recommend HPV vaccination clearly and resolutely

In a cross-sectional survey of 800 parents of adolescents ages 9 to 14 years, HPV vaccine was deemed the least likely vaccine to have been “very strongly” recommended by their health care provider, compared with the strength of recommendations for influenza, Tdap, and MenACWY vaccines.³⁵ The strength of a health care provider’s recommendation to vaccinate is the single most influential factor in vaccine uptake.^10,36,37 Most family physicians self-report “always recommending standard pediatric vaccines”; however, only a minority are following ACIP recommendations.³⁸ A national study reported that only about two-thirds of parents who received HPV vaccine recommendations perceived a high level of health care provider endorsement.³⁹ The takeaway point: Give a clear, unambiguous, strong recommendation to vaccinate with HPV to prevent infection; cervical, oropharyngeal, and other cancers; and genital warts.

Continue to: Tell parents why the timing is important

Tell parents why the timing is important. Inform parents that the HPV vaccine must be administered while their child is young (before the adolescent’s first sexual contact) to ensure the most robust immune response to the vaccine.⁴⁰ Unsolicited explanations about sexual activity need not be offered when discussing HPV vaccination, as it is fair to assume that sexual contact is a reality for nearly all people in their adolescent or adult life; and by extension, most sexually active people will likely have exposure to HPV at some time in their lives. By adulthood, sexual activity is nearly universal: The National Longitudinal Study of Adolescent Health showed that only about 3% of participants tracked since adolescence reported no sexual experience by (average age) 28.5 years.⁴¹

How you say it matters. Many pediatricians and family physicians report recommending HPV vaccine inconsistently, behind schedule, or without urgency,⁴² sending mixed messages by failing to endorse HPV vaccination strongly, failing to differentiate it from other vaccines, and presenting it as an “optional” vaccine that could be delayed.⁴³ Physicians and other health care providers who begin conversations about HPV vaccine by saying that the adolescent is “due” for the vaccine show higher vaccine recommendation quality scores than those who give unsolicited information about the vaccine, elicit questions before recommendation, or present the vaccine as an “option.”⁴² Parents who are “on the fence” may hesitate and decline HPV vaccination with a halfhearted recommendation.⁴⁴

The CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.

“Your child is due for his/her Tdap, HPV, influenza, and meningococcal vaccinations to prevent potentially devastating disease and several cancers. I highly recommend all 4 vaccinations today” is more persuasive than, “I recommend your child receive his/her Tdap, meningococcal, and influenza vaccines. And we can also discuss the HPV vaccine.”

Direct presumptive language that assumes vaccine delivery is associated with higher odds of HPV vaccine acceptance and same-day agreement to vaccination than is an open-ended participatory conversational style.⁴⁵ Saying, “I believe in the importance of this cancer-preventing vaccine for your child” is more persuasive than saying, “What do you think about starting the HPV vaccination series today?”⁴⁶

Don’t give up when parents initially refuse HPV vaccinations for their adolescents. Parents’ decisions about HPV vaccination may change over time. Repeated positive recommendations and counseling for HPV vaccination over multiple visits have been shown in a large multivariable analysis to increase parent acceptance of HPV vaccination: 45% of parents reported secondary acceptance of HPV vaccination, and an additional 24% intended to vaccinate in the next 12 months.⁴⁷ Combining a presumptive communication style with motivational interviewing and a fact sheet has contributed to higher clinician-perceived levels of parental HPV vaccine acceptance and increased vaccination rates.⁴⁸

Continue to: Know how to address parents' concerns about safety

Know how to address parents’ concerns about safety

Be prepared to discuss and answer parents’ questions or concerns regarding any vaccine, especially the HPV vaccine. Social networks are important in parents’ vaccination decision-making,⁴⁹ and they may seek information from such sources as Twitter, Facebook, Google, and YouTube, where misinformation may be disseminated. A quantitative analysis of 560 YouTube videos relaying a false link between vaccines and autism or other serious adverse effects on children were uploaded between December 2007 and July 2017, with a peak of 224 videos uploaded in the first 7 months of 2017.⁵⁰ Most were negative in tone and dispensed misinformation.⁵⁰

The National Vaccine Information Center (NVIC) is an organization that takes a skeptical view of the US government and pharmaceutical companies. NVIC is widely criticized by scientists and leaders in vaccine science and public health as spreading false information on the risks of vaccines and, specifically, that HPV vaccination causes chronic disease. NVIC reports that receipt of HPV vaccine may increase the risk for cervical cancer and death.⁵¹ Pediatrician and vaccine researcher Dr. Paul Offit, interviewed by The Lancet in response to NVIC and other anti-vaccine groups’ messages, stated: “anti-vaccination organizations are unequivocally threatening public health.”⁵²

Describe the robust safety-monitoring system. The CDC is aware of public concern about the safety of HPV vaccine. Ongoing monitoring of vaccine safety and studies conducted by the CDC, the Food and Drug Administration (FDA), and other organizations has documented a reassuring safety record since the vaccine’s introduction in 2006.⁵³ Assure parents that the Vaccine Adverse Event Reporting System (VAERS) summary of 7244 reports following 9vHPV vaccination (December 1, 2014 – December 31, 2017) showed that most (97%) reports were nonserious: No new safety signals or unexpected patterns were observed, confirming consistency of the safety profile of 9vHPV with data from pre-licensure trials and post-licensure data on 4vHPV.⁵⁴

Acknowledge the usually mild, transient potential risks of HPV vaccination as reported to VAERS: local injection site symptoms such as pain, redness, or swelling in the arm where the injection was given (most common adverse effect), dizziness, fainting, headache, nausea, and fever.⁵³ Point out that fainting after vaccination is common in adolescents⁵⁵ and that the CDC and ACIP recommend observation of adolescents for 15 minutes following HPV vaccination.⁵⁶ Consider this 15-minute observation period after adolescent receipt of any vaccine to be part of standard practice in your vaccination setting.⁵⁶

Contest unfounded views. Other common parental concerns about effects of HPV vaccine include supposed promotion of promiscuity, increased incidence of premature ovarian failure or insufficiency (POI), and increased risk of Guillain-Barré Syndrome (GBS), often propagated through published reports, media coverage, Web sites, and social media. Assure worried parents that many studies have shown that receipt of the vaccine is safe and does not lead to initiation of sexual activity or promiscuity, and, in fact, safer sexual health practices have been observed following vaccination.^57-59

Continue to: A large longitudinal...

In one study, 65% of parents expected to be reminded of any needed HPV vaccine doses, while 52% of the pediatric PCPs relied on parents to schedule subsequent immunizations.

A large longitudinal adolescent health survey administered in British Columbia looked at sexual health behaviors and risk factors in adolescent girls before and after receipt of HPV vaccination (2003, 2008, 2013).⁵⁹ Results showed no significant change in the reported number of sexual partners (2003-2013), increased reported use of contraception and condoms, and lower pregnancy rates.⁵⁹ There is no evidence that HPV vaccines cause reproductive problems in women⁵³; a review of VAERS reports from 2009 through 2015 did not detect any safety concerns for POI or other reproductive problems in females.⁶⁰ A 2018 population-based study of nearly 200,000 women observed no increase of POI following receipt of HPV vaccination.⁶¹ In addition, several recent studies have shown no increased risk for GBS following receipt of HPV vaccine.^62-64

CORRESPONDENCE
Pamela G. Rockwell, DO, FAAFP, 24 Frank Lloyd Wright Drive, SPC 5795, Room 2300, Lobby H, Ann Arbor, MI 48105; [email protected].

Overall adolescent vaccination coverage is improving in the United States.¹ But for adolescents up to 15 years of age, there’s a large gap between the rate of vaccination for human papillomavirus (HPV) and the higher rates of coverage for tetanus, diphtheria, and acellular pertussis (Tdap) and meningococcal conjugate (MenACWY) vaccines.¹ Adopting or refining practice customs reviewed in this article can increase HPV vaccination rates and continue to improve coverage of all vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) for adolescents between the ages of 11 and 12.

The evolution of ACIP’s HPV vaccine recommendations

Before December 2016, ACIP recommended a 3-dose HPV series for all adolescents between the ages of 11 and 12, given on a 0, 1-2, and 6-month schedule.² The series could be started at 9 years of age. It could be administered to females as old as 26 years, and to males through 21 years (or ages 22-26 years for those who wish to be vaccinated, who have certain medical conditions, or who are included in special populations—ie, gay and bisexual men, men who have sex with men, immunocompromised men, men with human immunodeficiency virus [HIV], and transgender men).

In 2016, ACIP revised its recommendation for adolescents who initiate vaccination before their 15th birthday: a 2-dose schedule is adequate, with the second dose given 6 to 12 months after the first dose. For those who initiate vaccination on or after their 15th birthday, and for those with certain medical conditions, the recommendation remains 3 doses on a 0, 1-2, and 6-month schedule.³

As of August 2019,⁴ ACIP now recommends that all women and men receive catch-up HPV vaccination through age 26. For individuals 27 to 45 years of age who have not been adequately vaccinated, HPV vaccine may be given based on shared clinical decision making with their physician.

How are we doing?

Overall, adolescent vaccination coverage is improving in the United States (see “Vaccination goals from ACIP and Healthy People 2020”^1,5,6), but the rate of improvement of HPV coverage is lower than that for Tdap and MenACWY coverage by age 15 years (although completion of the ­MenACWY vaccine series is low). From 2015 to 2016, coverage increased for 1 or more doses of Tdap, from 86.4% to 88% among 17-year olds (87.9% for 15-year olds), and coverage for 1 or more doses of MenACWY increased from 81.7% to 83.5% among 17-year olds (80.4% among 15-year olds).¹ Both Tdap and MenACWY coverage rates have surpassed Healthy People 2020 goals of 80%, and the focus now is on maintenance of coverage. Data from the 2016 National Immunization Survey ­(NIS)-Teen show that completion of the HPV vaccine series (applying updated HPV vaccine recommendations retrospectively) increased to 45.4% for 15-year-olds,¹ still far below the Healthy People 2020 goal of 80%. Completion rates for 2 or more doses of MenACWY also increased from 33.3% to 39.1%.¹

Common barriers to improved vaccine coverage

Barriers to improved vaccination rates include a lack of regular assessment of vaccine status; limited use of electronic records, tools, and immunization registries; lack of health care provider knowledge on current vaccine recommendations; vaccine costs; missed opportunities; and patient/parent refusals.^7,8 The Community Preventive Services Task Force outlines several well-established evidence-based ways that administrators and physicians can counter these barriers:

• give a strong recommendation to vaccinate,^9,10
• incorporate an audit/feedback mechanism for health care providers who vaccinate,^9,11
• use electronic alerts to remind health care providers to vaccinate,^9,12
• use your state’s electronic immunization information systems (IIS),^7,13
• appoint a vaccine practice team/­vaccine champion,^9,14 and
• implement standing orders and ­reminder/recall systems.^7,9,15

In 2016, 45.4% of 15-year-olds had completed the HPV vaccine series—far below the Healthy People 2020 goal of 80%.

The passage of the Affordable Care Act (ACA)—which mandates that certain preventive services, including ACIP-recommended immunizations, be covered as part of basic care at no cost-sharing—reduces the once-common financial barrier to vaccine uptake.¹⁶ A key contributor to low uptake of HPV vaccination by adolescents is parental refusal.¹⁷

Continue to: The threats posed by HPV

HPV infections are the most commonly transmitted infections in the United States and nearly all men and women will be exposed to one or more types of HPV at some point in their lives. Current data show that 79 million Americans, most in their late teens and early 20s, are infected with HPV, and about 14 million people in the United States become newly infected each year.¹⁸ HPV is a DNA tumor virus that causes epithelial proliferation at cutaneous and mucosal surfaces.

There are more than 100 types of the virus,¹⁹ including more than 40 strains that infect the human genital tract. Of the latter 40 strains, there are oncogenic or high-risk types and non-oncogenic or low-risk types.²⁰ HPV infection with high-risk types causes cervical, vaginal, and vulvar cancers in women; penile cancers in men; and oropharyngeal and anal cancers in both men and women. Low-risk HPV types cause genital warts in both men and women.²¹ The current available HPV vaccine in the United States is a 9-valent vaccine (9vHPV) that replaces the former 2- and 4-valent HPV vaccines and includes immunogenic coverage against high-risk HPV types 16, 18, 31, 33, 45, 52, and 58; and low-risk types 6 and 11.²²

Centers for Disease Control and Prevention (CDC) data from 2010 to 2014 show that approximately 23,700 women and approximately 17,300 men in the United States developed HPV-associated cancer. Most common in women are cervical cancers and in men, oropharyngeal cancers (cancers of the back of the throat, base of the tongue, and tonsils). Using population-based data to genotype HPV types from cancer tissues, the CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.²³ A significant percentage of these cancers could potentially be prevented by receipt of 9vHPV.^23,24

Make adolescent immunization a high priority

Anticipate opportunities to vaccinate and take steps to make your immunization and scheduling processes more prominent. With HPV specifically, you can strongly advocate for vaccination, address parental misgivings and educate them using clear communication styles, and acquire knowledge to answer concerns about potential vaccine adverse ­effects.

Every visit is an opportunity to vaccinate. The American Academy of Family Physicians and The American Academy of Pediatrics recommend that adolescents have annual preventive visits for screening, immunizations, and assessment and counseling for risky behaviors. However, many adolescents do not present annually for preventive visits, and fewer than half of adolescents receive regular preventive care.²⁵ In a study of 425 family physicians and pediatricians, almost all pediatricians endorsed the importance of annual well visits, while less than three-quarters of family physicians did.²⁶ An analysis of national surveillance systems shows rates for preventive health care visits range from 43% to 74% among adolescents 10 to 17 years of age, and 26% to 58% among young adults 18 to 25 years of age.²⁷ Overall, 67% of adolescent health care visits are for acute care, and 10% are for follow-up care.²⁸

Continue to: Missed opportunities for the HPV vaccine

Missed opportunities for the HPV vaccine. One study showed that at least 86% of unvaccinated adolescents had missed opportunities to receive HPV vaccine.²⁹ A study of 14,588 adolescent girls from January 2010 through August 2015 showed that HPV vaccine was given at only 37.1% of visits in which MenACWY or Tdap vaccines were administered.³⁰ The rate of HPV vaccination was just 26% during well adolescent visits, and 41.8% during all other primary care visits.³⁰ Every adolescent health care visit—including visits for acute care, chronic care, follow-up, or office-based procedures—is an opportunity to review vaccination status.

Give vaccines concomitantly (simultaneously or same-day). ACIP counsels that minor illnesses, such as mild upper respiratory infections with or without low-grade fever, are not contraindications to routine vaccination.³⁰ Also, the safety of simultaneous vaccine administration, often a concern of both parents and health care providers, has been well established. Each vaccine’s immunogenicity and safety profile are maintained when given concomitantly with other vaccines, and fewer visits are needed to complete an adolescent’s vaccination status.^31,32

Immediately schedule follow up visits and use reminder/recall systems. Parents of adolescents who opt for HPV vaccination are not always aware of the timing of the 2- or 3-dose schedule and may not even be aware that more than 1 dose of vaccine is recommended.

In a study of 14,588 adolescent girls who had vaccinations at an office visit, only 37.1% also received the HPV vaccine.

A qualitative study of pediatric primary care providers and parents/guardians of adolescent patients showed that for HPV vaccination series completion, 65% of parents/guardians expected to be reminded of any needed doses, while 52% of the pediatric primary care providers relied on parents to schedule subsequent immunizations, and often the HPV series was not completed.³³ Higher completion rates of the HPV vaccination series were achieved when follow-up appointments were scheduled at checkout for the 2nd or 3rd vaccine dose after initiation of HPV vaccination.³³ The use of patient reminder/recall systems using telephone calls or mailings (phone usage is more effective than mailings) is also shown to improve vaccination completion rates.³⁴

Recommend HPV vaccination clearly and resolutely

In a cross-sectional survey of 800 parents of adolescents ages 9 to 14 years, HPV vaccine was deemed the least likely vaccine to have been “very strongly” recommended by their health care provider, compared with the strength of recommendations for influenza, Tdap, and MenACWY vaccines.³⁵ The strength of a health care provider’s recommendation to vaccinate is the single most influential factor in vaccine uptake.^10,36,37 Most family physicians self-report “always recommending standard pediatric vaccines”; however, only a minority are following ACIP recommendations.³⁸ A national study reported that only about two-thirds of parents who received HPV vaccine recommendations perceived a high level of health care provider endorsement.³⁹ The takeaway point: Give a clear, unambiguous, strong recommendation to vaccinate with HPV to prevent infection; cervical, oropharyngeal, and other cancers; and genital warts.

Continue to: Tell parents why the timing is important

Tell parents why the timing is important. Inform parents that the HPV vaccine must be administered while their child is young (before the adolescent’s first sexual contact) to ensure the most robust immune response to the vaccine.⁴⁰ Unsolicited explanations about sexual activity need not be offered when discussing HPV vaccination, as it is fair to assume that sexual contact is a reality for nearly all people in their adolescent or adult life; and by extension, most sexually active people will likely have exposure to HPV at some time in their lives. By adulthood, sexual activity is nearly universal: The National Longitudinal Study of Adolescent Health showed that only about 3% of participants tracked since adolescence reported no sexual experience by (average age) 28.5 years.⁴¹

How you say it matters. Many pediatricians and family physicians report recommending HPV vaccine inconsistently, behind schedule, or without urgency,⁴² sending mixed messages by failing to endorse HPV vaccination strongly, failing to differentiate it from other vaccines, and presenting it as an “optional” vaccine that could be delayed.⁴³ Physicians and other health care providers who begin conversations about HPV vaccine by saying that the adolescent is “due” for the vaccine show higher vaccine recommendation quality scores than those who give unsolicited information about the vaccine, elicit questions before recommendation, or present the vaccine as an “option.”⁴² Parents who are “on the fence” may hesitate and decline HPV vaccination with a halfhearted recommendation.⁴⁴

The CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.

“Your child is due for his/her Tdap, HPV, influenza, and meningococcal vaccinations to prevent potentially devastating disease and several cancers. I highly recommend all 4 vaccinations today” is more persuasive than, “I recommend your child receive his/her Tdap, meningococcal, and influenza vaccines. And we can also discuss the HPV vaccine.”

Direct presumptive language that assumes vaccine delivery is associated with higher odds of HPV vaccine acceptance and same-day agreement to vaccination than is an open-ended participatory conversational style.⁴⁵ Saying, “I believe in the importance of this cancer-preventing vaccine for your child” is more persuasive than saying, “What do you think about starting the HPV vaccination series today?”⁴⁶

Don’t give up when parents initially refuse HPV vaccinations for their adolescents. Parents’ decisions about HPV vaccination may change over time. Repeated positive recommendations and counseling for HPV vaccination over multiple visits have been shown in a large multivariable analysis to increase parent acceptance of HPV vaccination: 45% of parents reported secondary acceptance of HPV vaccination, and an additional 24% intended to vaccinate in the next 12 months.⁴⁷ Combining a presumptive communication style with motivational interviewing and a fact sheet has contributed to higher clinician-perceived levels of parental HPV vaccine acceptance and increased vaccination rates.⁴⁸

Continue to: Know how to address parents' concerns about safety

Know how to address parents’ concerns about safety

Be prepared to discuss and answer parents’ questions or concerns regarding any vaccine, especially the HPV vaccine. Social networks are important in parents’ vaccination decision-making,⁴⁹ and they may seek information from such sources as Twitter, Facebook, Google, and YouTube, where misinformation may be disseminated. A quantitative analysis of 560 YouTube videos relaying a false link between vaccines and autism or other serious adverse effects on children were uploaded between December 2007 and July 2017, with a peak of 224 videos uploaded in the first 7 months of 2017.⁵⁰ Most were negative in tone and dispensed misinformation.⁵⁰

The National Vaccine Information Center (NVIC) is an organization that takes a skeptical view of the US government and pharmaceutical companies. NVIC is widely criticized by scientists and leaders in vaccine science and public health as spreading false information on the risks of vaccines and, specifically, that HPV vaccination causes chronic disease. NVIC reports that receipt of HPV vaccine may increase the risk for cervical cancer and death.⁵¹ Pediatrician and vaccine researcher Dr. Paul Offit, interviewed by The Lancet in response to NVIC and other anti-vaccine groups’ messages, stated: “anti-vaccination organizations are unequivocally threatening public health.”⁵²

Describe the robust safety-monitoring system. The CDC is aware of public concern about the safety of HPV vaccine. Ongoing monitoring of vaccine safety and studies conducted by the CDC, the Food and Drug Administration (FDA), and other organizations has documented a reassuring safety record since the vaccine’s introduction in 2006.⁵³ Assure parents that the Vaccine Adverse Event Reporting System (VAERS) summary of 7244 reports following 9vHPV vaccination (December 1, 2014 – December 31, 2017) showed that most (97%) reports were nonserious: No new safety signals or unexpected patterns were observed, confirming consistency of the safety profile of 9vHPV with data from pre-licensure trials and post-licensure data on 4vHPV.⁵⁴

Acknowledge the usually mild, transient potential risks of HPV vaccination as reported to VAERS: local injection site symptoms such as pain, redness, or swelling in the arm where the injection was given (most common adverse effect), dizziness, fainting, headache, nausea, and fever.⁵³ Point out that fainting after vaccination is common in adolescents⁵⁵ and that the CDC and ACIP recommend observation of adolescents for 15 minutes following HPV vaccination.⁵⁶ Consider this 15-minute observation period after adolescent receipt of any vaccine to be part of standard practice in your vaccination setting.⁵⁶