Practice Gap

Frictional, symmetric, asymptomatic, erythematous macules of the hands and feet can be mistaken for perniolike lesions associated with COVID-19, commonly known as COVID toes. However, in a low-risk setting without other associated symptoms or concerning findings on examination, consider and inquire about frequent use of a swimming pool. This activity can lead to localized pressure- and friction-induced erythema on palmar and plantar surfaces, called “pool palms and feet,” expanding on the already-named lesion “pool palms”—an entity that is distinct from COVID toes.

Technique for Diagnosis

We evaluated 4 patients in the outpatient setting who presented with localized, patterned, erythematous lesions of the hands or feet, or both, during the COVID-19 pandemic. The parents of our patients were concerned that the rash represented “COVID fingers and toes,” which are perniolike lesions seen in patients with suspected or confirmed current or prior COVID-19.¹

Pernio, also known as chilblains, is a superficial inflammatory vascular response, usually in the setting of exposure to cold.² This phenomenon usually appears as erythematous or violaceous macules and papules on acral skin, particularly on the dorsum and sides of the fingers and toes, with edema, vesiculation, and ulceration in more severe cases. Initially, it is pruritic and painful at times.

With COVID toes, there often is a delayed presentation of perniolike lesions after the onset of other COVID-19 symptoms, such as fever, cough, headache, and sore throat.^2,3 It has been described more often in younger patients and those with milder disease. However, because our patients had no known exposure to SARS-CoV-2 or other associated symptoms, our suspicion was low.

The 4 patients we evaluated—aged 4 to 12 years and in their usual good health—had blanchable erythema of the palmar fingers, palmar eminences of both hands, and plantar surfaces of both feet (Figure). There was no swelling or tenderness, and the lesions had no violaceous coloration, vesiculation, or ulceration. There was no associated pruritus or pain. One patient reported rough texture and mild peeling of the hands.

Upon further inquiry, the patients reported a history of extended time spent in home swimming pools, including holding on to the edge of the pool, due to limitation of activities because of COVID restrictions. One parent noted that the pool that caused the rash had a rough nonslip surface, whereas other pools that the children used, which had a smoother surface, caused no problems.

The morphology of symmetric blanching erythema in areas of pressure and friction, in the absence of a notable medical history, signs, or symptoms, was consistent with a diagnosis of pool palms, which has been described in the medical literature.^4-9 Pool palms can affect the palms and soles, which are subject to substantial friction, especially when a person is getting in and out of the pool. There is a general consensus that pool palms is a frictional dermatitis affecting children because the greater fragility of their skin is exacerbated by immersion in water.^4-9

Pool palms and feet is benign. Only supportive care, with cessation of swimming and application of emollients, is necessary.

Apart from COVID-19, other conditions to consider in a patient with erythematous lesions of the palms and soles include eczematous dermatitis; neutrophilic eccrine hidradenitis; and, if lesions are vesicular, hand-foot-and-mouth disease. Juvenile plantar dermatosis, which is thought to be due to moisture with occlusion in shoes, also might be considered but is distinguished by more scales and fissures that can be painful.

Location of the lesions is a critical variable. The patients we evaluated had lesions primarily on palmar and plantar surfaces where contact with pool surfaces was greatest, such as at bony prominences, which supported a diagnosis of frictional dermatitis, such as pool palms and feet. A thorough history and physical examination are helpful in determining the diagnosis.

Practical Implications

It is important to consider and recognize this localized pressure phenomenon of pool palms and feet, thus obviating an unnecessary workup or therapeutic interventions. Specifically, a finding of erythematous asymptomatic macules, with or without scaling, on bony prominences of the palms and soles is more consistent with pool palms and feet.

Pernio and COVID toes both present as erythematous to violaceous papules and macules, with edema, vesiculation, and ulceration in severe cases, often on the dorsum and sides of fingers and toes; typically the conditions are pruritic and painful at times.

Explaining the diagnosis of pool palms and feet and sharing one’s experience with similar cases might help alleviate parental fear and anxiety during the COVID-19 pandemic.

Practice Gap

Frictional, symmetric, asymptomatic, erythematous macules of the hands and feet can be mistaken for perniolike lesions associated with COVID-19, commonly known as COVID toes. However, in a low-risk setting without other associated symptoms or concerning findings on examination, consider and inquire about frequent use of a swimming pool. This activity can lead to localized pressure- and friction-induced erythema on palmar and plantar surfaces, called “pool palms and feet,” expanding on the already-named lesion “pool palms”—an entity that is distinct from COVID toes.

Technique for Diagnosis

We evaluated 4 patients in the outpatient setting who presented with localized, patterned, erythematous lesions of the hands or feet, or both, during the COVID-19 pandemic. The parents of our patients were concerned that the rash represented “COVID fingers and toes,” which are perniolike lesions seen in patients with suspected or confirmed current or prior COVID-19.¹

Pernio, also known as chilblains, is a superficial inflammatory vascular response, usually in the setting of exposure to cold.² This phenomenon usually appears as erythematous or violaceous macules and papules on acral skin, particularly on the dorsum and sides of the fingers and toes, with edema, vesiculation, and ulceration in more severe cases. Initially, it is pruritic and painful at times.

With COVID toes, there often is a delayed presentation of perniolike lesions after the onset of other COVID-19 symptoms, such as fever, cough, headache, and sore throat.^2,3 It has been described more often in younger patients and those with milder disease. However, because our patients had no known exposure to SARS-CoV-2 or other associated symptoms, our suspicion was low.

The 4 patients we evaluated—aged 4 to 12 years and in their usual good health—had blanchable erythema of the palmar fingers, palmar eminences of both hands, and plantar surfaces of both feet (Figure). There was no swelling or tenderness, and the lesions had no violaceous coloration, vesiculation, or ulceration. There was no associated pruritus or pain. One patient reported rough texture and mild peeling of the hands.

Upon further inquiry, the patients reported a history of extended time spent in home swimming pools, including holding on to the edge of the pool, due to limitation of activities because of COVID restrictions. One parent noted that the pool that caused the rash had a rough nonslip surface, whereas other pools that the children used, which had a smoother surface, caused no problems.

The morphology of symmetric blanching erythema in areas of pressure and friction, in the absence of a notable medical history, signs, or symptoms, was consistent with a diagnosis of pool palms, which has been described in the medical literature.^4-9 Pool palms can affect the palms and soles, which are subject to substantial friction, especially when a person is getting in and out of the pool. There is a general consensus that pool palms is a frictional dermatitis affecting children because the greater fragility of their skin is exacerbated by immersion in water.^4-9

Pool palms and feet is benign. Only supportive care, with cessation of swimming and application of emollients, is necessary.

Apart from COVID-19, other conditions to consider in a patient with erythematous lesions of the palms and soles include eczematous dermatitis; neutrophilic eccrine hidradenitis; and, if lesions are vesicular, hand-foot-and-mouth disease. Juvenile plantar dermatosis, which is thought to be due to moisture with occlusion in shoes, also might be considered but is distinguished by more scales and fissures that can be painful.

Location of the lesions is a critical variable. The patients we evaluated had lesions primarily on palmar and plantar surfaces where contact with pool surfaces was greatest, such as at bony prominences, which supported a diagnosis of frictional dermatitis, such as pool palms and feet. A thorough history and physical examination are helpful in determining the diagnosis.

Practical Implications

It is important to consider and recognize this localized pressure phenomenon of pool palms and feet, thus obviating an unnecessary workup or therapeutic interventions. Specifically, a finding of erythematous asymptomatic macules, with or without scaling, on bony prominences of the palms and soles is more consistent with pool palms and feet.

Pernio and COVID toes both present as erythematous to violaceous papules and macules, with edema, vesiculation, and ulceration in severe cases, often on the dorsum and sides of fingers and toes; typically the conditions are pruritic and painful at times.

Explaining the diagnosis of pool palms and feet and sharing one’s experience with similar cases might help alleviate parental fear and anxiety during the COVID-19 pandemic.

Practice Gap

Frictional, symmetric, asymptomatic, erythematous macules of the hands and feet can be mistaken for perniolike lesions associated with COVID-19, commonly known as COVID toes. However, in a low-risk setting without other associated symptoms or concerning findings on examination, consider and inquire about frequent use of a swimming pool. This activity can lead to localized pressure- and friction-induced erythema on palmar and plantar surfaces, called “pool palms and feet,” expanding on the already-named lesion “pool palms”—an entity that is distinct from COVID toes.

Technique for Diagnosis

We evaluated 4 patients in the outpatient setting who presented with localized, patterned, erythematous lesions of the hands or feet, or both, during the COVID-19 pandemic. The parents of our patients were concerned that the rash represented “COVID fingers and toes,” which are perniolike lesions seen in patients with suspected or confirmed current or prior COVID-19.¹

Pernio, also known as chilblains, is a superficial inflammatory vascular response, usually in the setting of exposure to cold.² This phenomenon usually appears as erythematous or violaceous macules and papules on acral skin, particularly on the dorsum and sides of the fingers and toes, with edema, vesiculation, and ulceration in more severe cases. Initially, it is pruritic and painful at times.

With COVID toes, there often is a delayed presentation of perniolike lesions after the onset of other COVID-19 symptoms, such as fever, cough, headache, and sore throat.^2,3 It has been described more often in younger patients and those with milder disease. However, because our patients had no known exposure to SARS-CoV-2 or other associated symptoms, our suspicion was low.

The 4 patients we evaluated—aged 4 to 12 years and in their usual good health—had blanchable erythema of the palmar fingers, palmar eminences of both hands, and plantar surfaces of both feet (Figure). There was no swelling or tenderness, and the lesions had no violaceous coloration, vesiculation, or ulceration. There was no associated pruritus or pain. One patient reported rough texture and mild peeling of the hands.

Upon further inquiry, the patients reported a history of extended time spent in home swimming pools, including holding on to the edge of the pool, due to limitation of activities because of COVID restrictions. One parent noted that the pool that caused the rash had a rough nonslip surface, whereas other pools that the children used, which had a smoother surface, caused no problems.

The morphology of symmetric blanching erythema in areas of pressure and friction, in the absence of a notable medical history, signs, or symptoms, was consistent with a diagnosis of pool palms, which has been described in the medical literature.^4-9 Pool palms can affect the palms and soles, which are subject to substantial friction, especially when a person is getting in and out of the pool. There is a general consensus that pool palms is a frictional dermatitis affecting children because the greater fragility of their skin is exacerbated by immersion in water.^4-9

Pool palms and feet is benign. Only supportive care, with cessation of swimming and application of emollients, is necessary.

Apart from COVID-19, other conditions to consider in a patient with erythematous lesions of the palms and soles include eczematous dermatitis; neutrophilic eccrine hidradenitis; and, if lesions are vesicular, hand-foot-and-mouth disease. Juvenile plantar dermatosis, which is thought to be due to moisture with occlusion in shoes, also might be considered but is distinguished by more scales and fissures that can be painful.

Location of the lesions is a critical variable. The patients we evaluated had lesions primarily on palmar and plantar surfaces where contact with pool surfaces was greatest, such as at bony prominences, which supported a diagnosis of frictional dermatitis, such as pool palms and feet. A thorough history and physical examination are helpful in determining the diagnosis.

Practical Implications

It is important to consider and recognize this localized pressure phenomenon of pool palms and feet, thus obviating an unnecessary workup or therapeutic interventions. Specifically, a finding of erythematous asymptomatic macules, with or without scaling, on bony prominences of the palms and soles is more consistent with pool palms and feet.

Pernio and COVID toes both present as erythematous to violaceous papules and macules, with edema, vesiculation, and ulceration in severe cases, often on the dorsum and sides of fingers and toes; typically the conditions are pruritic and painful at times.

Explaining the diagnosis of pool palms and feet and sharing one’s experience with similar cases might help alleviate parental fear and anxiety during the COVID-19 pandemic.

In a new scientific statement on diet and lifestyle recommendations, the American Heart Association is highlighting, for the first time, structural challenges that impede the adoption of heart-healthy dietary patterns.

American Heart Association

This is in addition to stressing aspects of diet that improve cardiovascular health and reduce cardiovascular risk, with an emphasis on dietary patterns and food-based guidance beyond naming individual foods or nutrients.

The 2021 Dietary Guidance to Improve Cardiovascular Health scientific statement, developed under Alice H. Lichtenstein, DSc, chair of the AHA writing group, provides 10 evidence-based guidance recommendations to promote cardiometabolic health.

“The way to make heart-healthy choices every day,” said Dr. Lichtenstein, of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, in a statement, “is to step back, look at the environment in which you eat, whether it be at home, at work, during social interaction, and then identify what the best choices are. And if there are no good choices, then think about how you can modify your environment so that there are good choices.”

The statement, published in Circulation, underscores growing evidence that nutrition-related chronic diseases have maternal-nutritional origins, and that prevention of pediatric obesity is a key to preserving and prolonging ideal cardiovascular health.

The features are as follows:

• Adjust energy intake and expenditure to achieve and maintain a healthy body weight. To counter the shift toward higher energy intake and more sedentary lifestyles over the past 3 decades, the statement recommends at least 150 minutes of moderate physical activity per week, adjusted for individual’s age, activity level, sex, and size.
• Eat plenty of fruits and vegetables; choose a wide variety. Observational and intervention studies document that dietary patterns rich in varied fruits and vegetables, with the exception of white potatoes, are linked to a lower risk of cardiovascular disease (CVD). Also, whole fruits and vegetables, which more readily provide fiber and satiety, are preferred over juices.
• Choose whole grain foods and products made mostly with whole grains rather than refined grains. Evidence from observational, interventional, and clinical studies confirm the benefits of frequent consumption of whole grains over infrequent consumption or over refined grains in terms of CVD risk, coronary heart disease (CHD), stroke, metabolic syndrome, cardiometabolic risk factors, laxation, and gut microbiota.
• Choose healthy sources of protein, mostly from plants (legumes and nuts).
• Higher intake of legumes, which are rich in protein and fiber, is associated with lower CVD risk, while higher nut intake is associated with lower risks of CVD, CHD, and stroke mortality/incidence. Replacing animal-source foods with plant-source whole foods, beyond health benefits, lowers the diet’s carbon footprint. Meat alternatives are often ultraprocessed and evidence on their short- and long-term health effects is limited. Unsaturated fats are preferred, as are lean, nonprocessed meats.
• Use liquid plant oils rather than tropical oils (coconut, palm, and palm kernel), animal fats (butter and lard), and partially hydrogenated fats. Saturated and trans fats (animal and dairy fats, and partially hydrogenated fat) should be replaced with nontropical liquid plant oils. Evidence supports cardiovascular benefits of dietary unsaturated fats, especially polyunsaturated fats primarily from plant oils (e.g. soybean, corn, safflower and sunflower oils, walnuts, and flax seeds).
• Choose minimally processed foods instead of ultraprocessed foods. Because of their proven association with adverse health outcomes, including overweight and obesity, cardiometabolic disorders (type 2 diabetes, CVD), and all-cause mortality, the consumption of many ultraprocessed foods is of concern. Ultraprocessed foods include artificial colors and flavors and preservatives that promote shelf stability, preserve texture, and increase palatability. A general principle is to emphasize unprocessed or minimally processed foods.
• Minimize intake of beverages and foods with added sugars. Added sugars (commonly glucose, dextrose, sucrose, corn syrup, honey, maple syrup, and concentrated fruit juice) are tied to elevated risk for type 2 diabetes, high cholesterol, and excess body weight. Findings from meta-analyses on body weight and metabolic outcomes for replacing added sugars with low-energy sweeteners are mixed, and the possibility of reverse causality has been raised.
• Choose and prepare foods with little or no salt. In general, the effects of sodium reduction on blood pressure tend to be higher in Black people, middle-aged and older people, and those with hypertension. In the United States, the main combined sources of sodium intake are processed foods, those prepared outside the home, packaged foods, and restaurant foods. Potassium-enriched salts are a promising alternative.
• If you don’t drink alcohol, don’t start; if you choose to drink, limit intake.
• While relationships between alcohol intake and cardiovascular outcomes are complex, the 2020 Dietary Guidelines Advisory Committee recently concluded that those who do drink should consume no more than one drink per day and should not drink alcohol in binges; the 2020 Dietary Guidelines for Americans con­tinues to recommend no more than one drink per day for women and two drinks per day for men.
• Adhere to the guidance regardless in all settings. Food-based dietary guidance applies to all foods and beverages, regardless of where prepared, procured, and consumed. Policies should be enacted that encourage healthier default options (for example, whole grains, minimized sodium and sugar content).

Recognizing impediments

The AHA/ASA scientific statement closes with the declaration: “Creating an environment that facilitates, rather than impedes, adherence to heart-healthy dietary patterns among all individuals is a public health imperative.” It points to the National Institutes of Health’s 2020-2030 Strategic Plan for National Institutes of Health Nutrition Research, which focuses on precision nutrition as a means “to determine the impact on health of not only what individuals eat, but also of why, when, and how they eat throughout the life course.”

Ultimately, precision nutrition may provide personalized diets for CVD prevention. But the “food environment,” often conditioned by “rampant nutrition misinformation” through local, state, and federal practices and policies, may impede the adoption of heart-healthy dietary patterns. Factors such as targeted food marketing (for example, of processed food and beverages in minority neighborhoods), structural racism, neighborhood segregation, unhealthy built environments, and food insecurity create environments in which unhealthy foods are the default option.”

These factors compound adverse dietary and health effects, and underscore a need to “directly combat nutrition misinformation among the public and health care professionals.” They also explain why, despite widespread knowledge of heart-healthy dietary pattern components, little progress has been made in achieving dietary goals in the United States.

Dr. Lichtenstein’s office, in response to a request regarding AHA advocacy and consumer programs, provided the following links: Voices for Healthy Kids initiative site and choosing healthier processed foods and one on fresh, frozen, and canned fruits and vegetables.

Dr. Lichtenstein had no disclosures. Disclosures for the writing group members are included in the statement.

In a new scientific statement on diet and lifestyle recommendations, the American Heart Association is highlighting, for the first time, structural challenges that impede the adoption of heart-healthy dietary patterns.

American Heart Association

This is in addition to stressing aspects of diet that improve cardiovascular health and reduce cardiovascular risk, with an emphasis on dietary patterns and food-based guidance beyond naming individual foods or nutrients.

The 2021 Dietary Guidance to Improve Cardiovascular Health scientific statement, developed under Alice H. Lichtenstein, DSc, chair of the AHA writing group, provides 10 evidence-based guidance recommendations to promote cardiometabolic health.

“The way to make heart-healthy choices every day,” said Dr. Lichtenstein, of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, in a statement, “is to step back, look at the environment in which you eat, whether it be at home, at work, during social interaction, and then identify what the best choices are. And if there are no good choices, then think about how you can modify your environment so that there are good choices.”

The statement, published in Circulation, underscores growing evidence that nutrition-related chronic diseases have maternal-nutritional origins, and that prevention of pediatric obesity is a key to preserving and prolonging ideal cardiovascular health.

The features are as follows:

• Adjust energy intake and expenditure to achieve and maintain a healthy body weight. To counter the shift toward higher energy intake and more sedentary lifestyles over the past 3 decades, the statement recommends at least 150 minutes of moderate physical activity per week, adjusted for individual’s age, activity level, sex, and size.
• Eat plenty of fruits and vegetables; choose a wide variety. Observational and intervention studies document that dietary patterns rich in varied fruits and vegetables, with the exception of white potatoes, are linked to a lower risk of cardiovascular disease (CVD). Also, whole fruits and vegetables, which more readily provide fiber and satiety, are preferred over juices.
• Choose whole grain foods and products made mostly with whole grains rather than refined grains. Evidence from observational, interventional, and clinical studies confirm the benefits of frequent consumption of whole grains over infrequent consumption or over refined grains in terms of CVD risk, coronary heart disease (CHD), stroke, metabolic syndrome, cardiometabolic risk factors, laxation, and gut microbiota.
• Choose healthy sources of protein, mostly from plants (legumes and nuts).
• Higher intake of legumes, which are rich in protein and fiber, is associated with lower CVD risk, while higher nut intake is associated with lower risks of CVD, CHD, and stroke mortality/incidence. Replacing animal-source foods with plant-source whole foods, beyond health benefits, lowers the diet’s carbon footprint. Meat alternatives are often ultraprocessed and evidence on their short- and long-term health effects is limited. Unsaturated fats are preferred, as are lean, nonprocessed meats.
• Use liquid plant oils rather than tropical oils (coconut, palm, and palm kernel), animal fats (butter and lard), and partially hydrogenated fats. Saturated and trans fats (animal and dairy fats, and partially hydrogenated fat) should be replaced with nontropical liquid plant oils. Evidence supports cardiovascular benefits of dietary unsaturated fats, especially polyunsaturated fats primarily from plant oils (e.g. soybean, corn, safflower and sunflower oils, walnuts, and flax seeds).
• Choose minimally processed foods instead of ultraprocessed foods. Because of their proven association with adverse health outcomes, including overweight and obesity, cardiometabolic disorders (type 2 diabetes, CVD), and all-cause mortality, the consumption of many ultraprocessed foods is of concern. Ultraprocessed foods include artificial colors and flavors and preservatives that promote shelf stability, preserve texture, and increase palatability. A general principle is to emphasize unprocessed or minimally processed foods.
• Minimize intake of beverages and foods with added sugars. Added sugars (commonly glucose, dextrose, sucrose, corn syrup, honey, maple syrup, and concentrated fruit juice) are tied to elevated risk for type 2 diabetes, high cholesterol, and excess body weight. Findings from meta-analyses on body weight and metabolic outcomes for replacing added sugars with low-energy sweeteners are mixed, and the possibility of reverse causality has been raised.
• Choose and prepare foods with little or no salt. In general, the effects of sodium reduction on blood pressure tend to be higher in Black people, middle-aged and older people, and those with hypertension. In the United States, the main combined sources of sodium intake are processed foods, those prepared outside the home, packaged foods, and restaurant foods. Potassium-enriched salts are a promising alternative.
• If you don’t drink alcohol, don’t start; if you choose to drink, limit intake.
• While relationships between alcohol intake and cardiovascular outcomes are complex, the 2020 Dietary Guidelines Advisory Committee recently concluded that those who do drink should consume no more than one drink per day and should not drink alcohol in binges; the 2020 Dietary Guidelines for Americans con­tinues to recommend no more than one drink per day for women and two drinks per day for men.
• Adhere to the guidance regardless in all settings. Food-based dietary guidance applies to all foods and beverages, regardless of where prepared, procured, and consumed. Policies should be enacted that encourage healthier default options (for example, whole grains, minimized sodium and sugar content).

Recognizing impediments

The AHA/ASA scientific statement closes with the declaration: “Creating an environment that facilitates, rather than impedes, adherence to heart-healthy dietary patterns among all individuals is a public health imperative.” It points to the National Institutes of Health’s 2020-2030 Strategic Plan for National Institutes of Health Nutrition Research, which focuses on precision nutrition as a means “to determine the impact on health of not only what individuals eat, but also of why, when, and how they eat throughout the life course.”

Ultimately, precision nutrition may provide personalized diets for CVD prevention. But the “food environment,” often conditioned by “rampant nutrition misinformation” through local, state, and federal practices and policies, may impede the adoption of heart-healthy dietary patterns. Factors such as targeted food marketing (for example, of processed food and beverages in minority neighborhoods), structural racism, neighborhood segregation, unhealthy built environments, and food insecurity create environments in which unhealthy foods are the default option.”

These factors compound adverse dietary and health effects, and underscore a need to “directly combat nutrition misinformation among the public and health care professionals.” They also explain why, despite widespread knowledge of heart-healthy dietary pattern components, little progress has been made in achieving dietary goals in the United States.

Dr. Lichtenstein’s office, in response to a request regarding AHA advocacy and consumer programs, provided the following links: Voices for Healthy Kids initiative site and choosing healthier processed foods and one on fresh, frozen, and canned fruits and vegetables.

Dr. Lichtenstein had no disclosures. Disclosures for the writing group members are included in the statement.

In a new scientific statement on diet and lifestyle recommendations, the American Heart Association is highlighting, for the first time, structural challenges that impede the adoption of heart-healthy dietary patterns.

American Heart Association

This is in addition to stressing aspects of diet that improve cardiovascular health and reduce cardiovascular risk, with an emphasis on dietary patterns and food-based guidance beyond naming individual foods or nutrients.

The 2021 Dietary Guidance to Improve Cardiovascular Health scientific statement, developed under Alice H. Lichtenstein, DSc, chair of the AHA writing group, provides 10 evidence-based guidance recommendations to promote cardiometabolic health.

“The way to make heart-healthy choices every day,” said Dr. Lichtenstein, of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, in a statement, “is to step back, look at the environment in which you eat, whether it be at home, at work, during social interaction, and then identify what the best choices are. And if there are no good choices, then think about how you can modify your environment so that there are good choices.”

The statement, published in Circulation, underscores growing evidence that nutrition-related chronic diseases have maternal-nutritional origins, and that prevention of pediatric obesity is a key to preserving and prolonging ideal cardiovascular health.

The features are as follows:

• Adjust energy intake and expenditure to achieve and maintain a healthy body weight. To counter the shift toward higher energy intake and more sedentary lifestyles over the past 3 decades, the statement recommends at least 150 minutes of moderate physical activity per week, adjusted for individual’s age, activity level, sex, and size.
• Eat plenty of fruits and vegetables; choose a wide variety. Observational and intervention studies document that dietary patterns rich in varied fruits and vegetables, with the exception of white potatoes, are linked to a lower risk of cardiovascular disease (CVD). Also, whole fruits and vegetables, which more readily provide fiber and satiety, are preferred over juices.
• Choose whole grain foods and products made mostly with whole grains rather than refined grains. Evidence from observational, interventional, and clinical studies confirm the benefits of frequent consumption of whole grains over infrequent consumption or over refined grains in terms of CVD risk, coronary heart disease (CHD), stroke, metabolic syndrome, cardiometabolic risk factors, laxation, and gut microbiota.
• Choose healthy sources of protein, mostly from plants (legumes and nuts).
• Higher intake of legumes, which are rich in protein and fiber, is associated with lower CVD risk, while higher nut intake is associated with lower risks of CVD, CHD, and stroke mortality/incidence. Replacing animal-source foods with plant-source whole foods, beyond health benefits, lowers the diet’s carbon footprint. Meat alternatives are often ultraprocessed and evidence on their short- and long-term health effects is limited. Unsaturated fats are preferred, as are lean, nonprocessed meats.
• Use liquid plant oils rather than tropical oils (coconut, palm, and palm kernel), animal fats (butter and lard), and partially hydrogenated fats. Saturated and trans fats (animal and dairy fats, and partially hydrogenated fat) should be replaced with nontropical liquid plant oils. Evidence supports cardiovascular benefits of dietary unsaturated fats, especially polyunsaturated fats primarily from plant oils (e.g. soybean, corn, safflower and sunflower oils, walnuts, and flax seeds).
• Choose minimally processed foods instead of ultraprocessed foods. Because of their proven association with adverse health outcomes, including overweight and obesity, cardiometabolic disorders (type 2 diabetes, CVD), and all-cause mortality, the consumption of many ultraprocessed foods is of concern. Ultraprocessed foods include artificial colors and flavors and preservatives that promote shelf stability, preserve texture, and increase palatability. A general principle is to emphasize unprocessed or minimally processed foods.
• Minimize intake of beverages and foods with added sugars. Added sugars (commonly glucose, dextrose, sucrose, corn syrup, honey, maple syrup, and concentrated fruit juice) are tied to elevated risk for type 2 diabetes, high cholesterol, and excess body weight. Findings from meta-analyses on body weight and metabolic outcomes for replacing added sugars with low-energy sweeteners are mixed, and the possibility of reverse causality has been raised.
• Choose and prepare foods with little or no salt. In general, the effects of sodium reduction on blood pressure tend to be higher in Black people, middle-aged and older people, and those with hypertension. In the United States, the main combined sources of sodium intake are processed foods, those prepared outside the home, packaged foods, and restaurant foods. Potassium-enriched salts are a promising alternative.
• If you don’t drink alcohol, don’t start; if you choose to drink, limit intake.
• While relationships between alcohol intake and cardiovascular outcomes are complex, the 2020 Dietary Guidelines Advisory Committee recently concluded that those who do drink should consume no more than one drink per day and should not drink alcohol in binges; the 2020 Dietary Guidelines for Americans con­tinues to recommend no more than one drink per day for women and two drinks per day for men.
• Adhere to the guidance regardless in all settings. Food-based dietary guidance applies to all foods and beverages, regardless of where prepared, procured, and consumed. Policies should be enacted that encourage healthier default options (for example, whole grains, minimized sodium and sugar content).

Recognizing impediments

The AHA/ASA scientific statement closes with the declaration: “Creating an environment that facilitates, rather than impedes, adherence to heart-healthy dietary patterns among all individuals is a public health imperative.” It points to the National Institutes of Health’s 2020-2030 Strategic Plan for National Institutes of Health Nutrition Research, which focuses on precision nutrition as a means “to determine the impact on health of not only what individuals eat, but also of why, when, and how they eat throughout the life course.”

Ultimately, precision nutrition may provide personalized diets for CVD prevention. But the “food environment,” often conditioned by “rampant nutrition misinformation” through local, state, and federal practices and policies, may impede the adoption of heart-healthy dietary patterns. Factors such as targeted food marketing (for example, of processed food and beverages in minority neighborhoods), structural racism, neighborhood segregation, unhealthy built environments, and food insecurity create environments in which unhealthy foods are the default option.”

These factors compound adverse dietary and health effects, and underscore a need to “directly combat nutrition misinformation among the public and health care professionals.” They also explain why, despite widespread knowledge of heart-healthy dietary pattern components, little progress has been made in achieving dietary goals in the United States.

Dr. Lichtenstein’s office, in response to a request regarding AHA advocacy and consumer programs, provided the following links: Voices for Healthy Kids initiative site and choosing healthier processed foods and one on fresh, frozen, and canned fruits and vegetables.

Dr. Lichtenstein had no disclosures. Disclosures for the writing group members are included in the statement.

Pediatric nail psoriasis is a condition that has not been extensively studied. The prevalence of nail alterations in pediatric patients with psoriasis varies among different studies, ranging from 17% to 39.2%.¹ Nail pitting, onycholysis associated with subungual hyperkeratosis, paronychia, and pachyonychia are the most frequent features of psoriatic nail involvement in children.^2,3 The management of nail psoriasis in children and adolescents is critical due to the quality-of-life impact, from potential functional impairment issues to the obvious cosmetic problems, which can aggravate the psychologic distress and social embarrassment of patients with psoriasis. Despite the emergence of modern potent systemic agents to treat chronic plaque psoriasis, nail psoriasis often is refractory to treatment.⁴ Coupled with the limited on-label options for psoriasis treatment in children, the management of nail psoriasis in this special patient group constitutes an even greater therapeutic challenge. This report aims to summarize the limited existing data on the successful management of nail psoriasis in the pediatric population.

Reviewing the Literature on Nail Psoriasis

We conducted a search of PubMed articles indexed for MEDLINE, Embase, and Scopus using the following Medical Subject Headings key terms: nail psoriasis and children, juvenile, pediatric. Additional articles were identified from the reference lists of the retrieved articles and citations. Our search included reports in the English language published from 2000 to 2019. The selection process included the following 2 steps: screening of the titles and abstracts, followed by evaluation of the selected full-text articles.

Topical Treatments for Nail Psoriasis

Because most systemic antipsoriatic treatments that can be administered in adult patients have not yet been granted an official license for administration in children, topical treatments are considered by many physicians as the preferred first-line therapy for psoriatic nail involvement in pediatric patients.^5,6 However, only scarce data are available in the literature concerning the successful use of local agents in pediatric patients with psoriasis.

The main limitation of local treatments relates mostly to their impaired penetration into the affected area (nails). To optimize drug penetration, some authors suggest the use of potent keratolytic topical preparations to reduce the nail volume and facilitate drug absorption.⁷ A popular suggestion is trimming the onycholytic nail plate followed by 40% urea avulsion to treat subungual hyperkeratosis⁸ or simply the use of occlusive 40% urea in petroleum jelly.⁹ Other approaches include clipping the onycholytic nail over the diseased nail bed or processing the nail plate through grinding or even drilling holes with the use of mechanical burrs or ablative lasers to enhance the penetration of the topical agent.⁷

A frequent approach in pediatric patients is clipping the detached nails combined with daily application of calcipotriene (calcipotriol) and steroids, such as betamethasone dipropionate.^5,8 Reports on the use of regimens with clobetasol propionate ointment 0.05% under occlusion, with or without the concomitant use of calcipotriol solution 0.005%, also are present in the literature but not always with satisfactory results.^10,11 Another successfully administered topical steroid is mometasone furoate cream 0.1%.¹² Although the use of intralesional triamcinolone acetonide also has demonstrated encouraging outcomes in isolated reports,¹³ associated adverse events, such as pain and hematomas, can result in tolerability issues for pediatric patients.⁷

Piraccini et al¹⁴ described the case of an 8-year-old patient with pustular nail psoriasis who showed improvement within 3 to 6 months of treatment with topical calcipotriol 5 μg/g as monotherapy applied to the nail and periungual tissues twice daily. Another approach, described by Diluvio et al,¹⁵ is the use of tazarotene gel 0.05% applied once daily to the affected nail plates, nail folds, and periungual skin without occlusion. In a 6-year-old patient with isolated nail psoriasis, this treatment regimen demonstrated notable improvement within 8 weeks.¹⁵

Systemic Treatments for Nail Psoriasis

Data on the successful administration of systemic agents in pediatric patients also are extremely scarce. Due to the lack of clinical trials, everyday practice is mostly based on isolated case series and case reports.

Methotrexate—Lee¹¹ described the case of an 11-year-old girl with severe, symptomatic, 20-nail psoriatic onychodystrophy who showed a complete response to oral methotrexate 5 mg/wk after topical clobetasol propionate and calcipotriol failed. Improvement was seen as early as 4 weeks after therapy initiation, and complete resolution of the lesions was documented after 9 and 13 months of methotrexate therapy for the fingers and toes, respectively.¹¹ The successful use of methotrexate in the improvement of psoriatic nail dystrophy in a pediatric patient also was documented by Teran et al.¹⁶ In this case, a 9-year-old girl with erythrodermic psoriasis, psoriatic arthritis, and severe onychodystrophy showed notable amelioration of all psoriatic manifestations, including the nail findings, with systemic methotrexate therapy (dose not specified).¹⁶ Notably, the authors reported that the improvement of onychodystrophy occurred with considerable delay compared to the other psoriatic lesions,¹⁶ indicating the already-known refractoriness of nail psoriasis to the various therapeutic attempts.^9-15

Acitretin—Another agent that has been linked with partial improvement of acrodermatitis continua of Hallopeau (ACH)–associated onychodystrophy is acitretin. In a case series of 15 pediatric patients with pustular psoriasis, a 5-year-old boy with severe nail involvement presented with partial amelioration of nail changes with acitretin within the first 6 weeks of treatment using the following regimen: initial dosage of 0.8 mg/kg/d for 6 weeks, followed by 0.3 mg/kg/d for 4 weeks.¹⁷

Biologics—The emerging use of biologics in pediatric psoriasis also has brought important advances in the successful management of nail psoriasis in children and adolescents.^18-21 Wells et al¹⁸ presented the case of an 8-year-old girl with nail psoriasis, psoriatic arthritis, and plaque psoriasis who showed complete resolution of all psoriatic manifestations, including nail involvement, within 3 months of treatment with secukinumab 150 mg subcutaneously every 4 weeks. Prior failed treatments included various systemic agents (ie, subcutaneous methotrexate 20 mg/m², etanercept 0.8 mg/kg weekly, adalimumab 40 mg every 2 weeks) as well as topical agents (ie, urea, tazarotene, corticosteroids) and intralesional triamcinolone.¹⁸

Infliximab also has been successfully used for pediatric nail psoriasis. Watabe et al¹⁹ presented the case of an 8-year-old girl with psoriatic onychodystrophy in addition to psoriatic onycho-pachydermo-periostitis. Prior therapy with adalimumab 20 mg every other week combined with methotrexate 10 mg weekly failed. She experienced notable amelioration of the nail dystrophy within 3 months of using a combination of infliximab and methotrexate (infliximab 5 mg/kg intravenously on weeks 0, 2, and 6, and every 8 weeks thereafter; methotrexate 10 mg/wk).¹⁹

Cases in which infliximab has resulted in rapid yet only transient restoration of psoriatic onychodystrophy also are present in the literature. Pereira et al²⁰ reported that a 3-year-old patient with severe 20-digit onychodystrophy in addition to pustular psoriasis had complete resolution of nail lesions within 2 weeks of treatment with infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 7 weeks thereafter), which was sustained over the course of 1 year. The therapy had to be discontinued because of exacerbation of the cutaneous symptoms; thereafter, etanercept was initiated. Although the patient noted major improvement of all skin lesions under etanercept, only moderate amelioration of the psoriatic nail lesions was demonstrated.²⁰

Dini et al²¹ described a 9-year-old girl with severe ACH-associated psoriatic onychodystrophy who showed complete clearance of all lesions within 8 weeks of treatment with adalimumab (initially 80 mg, followed by 40 mg after 1 week and then 40 mg every other week). Prior treatment with potent topical corticosteroids, cyclosporine (3 mg/kg/d for 6 months), and etanercept (0.4 mg/kg twice weekly for 3 months) was ineffective.²¹

Phototherapy—Other systemic agents with reported satisfactory outcomes in the treatment of psoriatic onychodystrophy include thalidomide combined with UVB phototherapy. Kiszewski et al²² described a 2-year-old patient with ACH and severe 19-digit onychodystrophy. Prior failed therapies included occluded clobetasol ointment 0.05%, occluded pimecrolimus 0.1%, and systemic methotrexate, while systemic acitretin (0.8 mg⁄kg⁄d) resulted in elevated cholesterol levels and therefore had to be interrupted. Improvement was seen 2 months after the initiation of a combined broadband UVB and thalidomide (50 mg⁄d) treatment, with no documented relapses after discontinuation of therapy.²²

Narrowband UVB (311 nm) also has been used as monotherapy for ACH-associated onychodystrophy, as demonstrated by Bordignon et al.²³ They reported a 9-year-old patient who showed partial improvement of isolated onychodystrophy of the fourth nail plate of the left hand after 36 sessions of narrowband UVB using a 311-nm filtering handpiece with a square spot size of 19×19 mm.²³

Conclusion

Nail psoriasis constitutes a type of psoriasis that is not only refractory to most treatments but is accompanied by substantial psychological and occasionally functional burden for the affected individuals.²⁴ Data concerning therapeutic options in the pediatric population are extremely limited, and therefore the everyday practice often involves administration of off-label medications, which can constitute a dilemma for many physicians, especially for safety.¹⁰ We suggest a simple therapeutic algorithm for the management of pediatric nail psoriasis based on the summarized data that are currently available in the literature. This algorithm is shown in the eFigure.

As progressively more agents—especially biologics—receive approval for use in plaque psoriasis in pediatric patients,²⁵ it is expected that gradually more real-life data on their side efficacy for plaque psoriasis of the nails in children also will come to light. Furthermore, their on-label use in pediatric psoriasis patients will facilitate further relevant clinical trials to this target group so that the potential of these medications in the management of nail psoriasis can be fully explored.

Pediatric nail psoriasis is a condition that has not been extensively studied. The prevalence of nail alterations in pediatric patients with psoriasis varies among different studies, ranging from 17% to 39.2%.¹ Nail pitting, onycholysis associated with subungual hyperkeratosis, paronychia, and pachyonychia are the most frequent features of psoriatic nail involvement in children.^2,3 The management of nail psoriasis in children and adolescents is critical due to the quality-of-life impact, from potential functional impairment issues to the obvious cosmetic problems, which can aggravate the psychologic distress and social embarrassment of patients with psoriasis. Despite the emergence of modern potent systemic agents to treat chronic plaque psoriasis, nail psoriasis often is refractory to treatment.⁴ Coupled with the limited on-label options for psoriasis treatment in children, the management of nail psoriasis in this special patient group constitutes an even greater therapeutic challenge. This report aims to summarize the limited existing data on the successful management of nail psoriasis in the pediatric population.

Reviewing the Literature on Nail Psoriasis

We conducted a search of PubMed articles indexed for MEDLINE, Embase, and Scopus using the following Medical Subject Headings key terms: nail psoriasis and children, juvenile, pediatric. Additional articles were identified from the reference lists of the retrieved articles and citations. Our search included reports in the English language published from 2000 to 2019. The selection process included the following 2 steps: screening of the titles and abstracts, followed by evaluation of the selected full-text articles.

Topical Treatments for Nail Psoriasis

Because most systemic antipsoriatic treatments that can be administered in adult patients have not yet been granted an official license for administration in children, topical treatments are considered by many physicians as the preferred first-line therapy for psoriatic nail involvement in pediatric patients.^5,6 However, only scarce data are available in the literature concerning the successful use of local agents in pediatric patients with psoriasis.

The main limitation of local treatments relates mostly to their impaired penetration into the affected area (nails). To optimize drug penetration, some authors suggest the use of potent keratolytic topical preparations to reduce the nail volume and facilitate drug absorption.⁷ A popular suggestion is trimming the onycholytic nail plate followed by 40% urea avulsion to treat subungual hyperkeratosis⁸ or simply the use of occlusive 40% urea in petroleum jelly.⁹ Other approaches include clipping the onycholytic nail over the diseased nail bed or processing the nail plate through grinding or even drilling holes with the use of mechanical burrs or ablative lasers to enhance the penetration of the topical agent.⁷

A frequent approach in pediatric patients is clipping the detached nails combined with daily application of calcipotriene (calcipotriol) and steroids, such as betamethasone dipropionate.^5,8 Reports on the use of regimens with clobetasol propionate ointment 0.05% under occlusion, with or without the concomitant use of calcipotriol solution 0.005%, also are present in the literature but not always with satisfactory results.^10,11 Another successfully administered topical steroid is mometasone furoate cream 0.1%.¹² Although the use of intralesional triamcinolone acetonide also has demonstrated encouraging outcomes in isolated reports,¹³ associated adverse events, such as pain and hematomas, can result in tolerability issues for pediatric patients.⁷

Piraccini et al¹⁴ described the case of an 8-year-old patient with pustular nail psoriasis who showed improvement within 3 to 6 months of treatment with topical calcipotriol 5 μg/g as monotherapy applied to the nail and periungual tissues twice daily. Another approach, described by Diluvio et al,¹⁵ is the use of tazarotene gel 0.05% applied once daily to the affected nail plates, nail folds, and periungual skin without occlusion. In a 6-year-old patient with isolated nail psoriasis, this treatment regimen demonstrated notable improvement within 8 weeks.¹⁵

Systemic Treatments for Nail Psoriasis

Data on the successful administration of systemic agents in pediatric patients also are extremely scarce. Due to the lack of clinical trials, everyday practice is mostly based on isolated case series and case reports.

Methotrexate—Lee¹¹ described the case of an 11-year-old girl with severe, symptomatic, 20-nail psoriatic onychodystrophy who showed a complete response to oral methotrexate 5 mg/wk after topical clobetasol propionate and calcipotriol failed. Improvement was seen as early as 4 weeks after therapy initiation, and complete resolution of the lesions was documented after 9 and 13 months of methotrexate therapy for the fingers and toes, respectively.¹¹ The successful use of methotrexate in the improvement of psoriatic nail dystrophy in a pediatric patient also was documented by Teran et al.¹⁶ In this case, a 9-year-old girl with erythrodermic psoriasis, psoriatic arthritis, and severe onychodystrophy showed notable amelioration of all psoriatic manifestations, including the nail findings, with systemic methotrexate therapy (dose not specified).¹⁶ Notably, the authors reported that the improvement of onychodystrophy occurred with considerable delay compared to the other psoriatic lesions,¹⁶ indicating the already-known refractoriness of nail psoriasis to the various therapeutic attempts.^9-15

Acitretin—Another agent that has been linked with partial improvement of acrodermatitis continua of Hallopeau (ACH)–associated onychodystrophy is acitretin. In a case series of 15 pediatric patients with pustular psoriasis, a 5-year-old boy with severe nail involvement presented with partial amelioration of nail changes with acitretin within the first 6 weeks of treatment using the following regimen: initial dosage of 0.8 mg/kg/d for 6 weeks, followed by 0.3 mg/kg/d for 4 weeks.¹⁷

Biologics—The emerging use of biologics in pediatric psoriasis also has brought important advances in the successful management of nail psoriasis in children and adolescents.^18-21 Wells et al¹⁸ presented the case of an 8-year-old girl with nail psoriasis, psoriatic arthritis, and plaque psoriasis who showed complete resolution of all psoriatic manifestations, including nail involvement, within 3 months of treatment with secukinumab 150 mg subcutaneously every 4 weeks. Prior failed treatments included various systemic agents (ie, subcutaneous methotrexate 20 mg/m², etanercept 0.8 mg/kg weekly, adalimumab 40 mg every 2 weeks) as well as topical agents (ie, urea, tazarotene, corticosteroids) and intralesional triamcinolone.¹⁸

Infliximab also has been successfully used for pediatric nail psoriasis. Watabe et al¹⁹ presented the case of an 8-year-old girl with psoriatic onychodystrophy in addition to psoriatic onycho-pachydermo-periostitis. Prior therapy with adalimumab 20 mg every other week combined with methotrexate 10 mg weekly failed. She experienced notable amelioration of the nail dystrophy within 3 months of using a combination of infliximab and methotrexate (infliximab 5 mg/kg intravenously on weeks 0, 2, and 6, and every 8 weeks thereafter; methotrexate 10 mg/wk).¹⁹

Cases in which infliximab has resulted in rapid yet only transient restoration of psoriatic onychodystrophy also are present in the literature. Pereira et al²⁰ reported that a 3-year-old patient with severe 20-digit onychodystrophy in addition to pustular psoriasis had complete resolution of nail lesions within 2 weeks of treatment with infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 7 weeks thereafter), which was sustained over the course of 1 year. The therapy had to be discontinued because of exacerbation of the cutaneous symptoms; thereafter, etanercept was initiated. Although the patient noted major improvement of all skin lesions under etanercept, only moderate amelioration of the psoriatic nail lesions was demonstrated.²⁰

Dini et al²¹ described a 9-year-old girl with severe ACH-associated psoriatic onychodystrophy who showed complete clearance of all lesions within 8 weeks of treatment with adalimumab (initially 80 mg, followed by 40 mg after 1 week and then 40 mg every other week). Prior treatment with potent topical corticosteroids, cyclosporine (3 mg/kg/d for 6 months), and etanercept (0.4 mg/kg twice weekly for 3 months) was ineffective.²¹

Phototherapy—Other systemic agents with reported satisfactory outcomes in the treatment of psoriatic onychodystrophy include thalidomide combined with UVB phototherapy. Kiszewski et al²² described a 2-year-old patient with ACH and severe 19-digit onychodystrophy. Prior failed therapies included occluded clobetasol ointment 0.05%, occluded pimecrolimus 0.1%, and systemic methotrexate, while systemic acitretin (0.8 mg⁄kg⁄d) resulted in elevated cholesterol levels and therefore had to be interrupted. Improvement was seen 2 months after the initiation of a combined broadband UVB and thalidomide (50 mg⁄d) treatment, with no documented relapses after discontinuation of therapy.²²

Narrowband UVB (311 nm) also has been used as monotherapy for ACH-associated onychodystrophy, as demonstrated by Bordignon et al.²³ They reported a 9-year-old patient who showed partial improvement of isolated onychodystrophy of the fourth nail plate of the left hand after 36 sessions of narrowband UVB using a 311-nm filtering handpiece with a square spot size of 19×19 mm.²³

Conclusion

Nail psoriasis constitutes a type of psoriasis that is not only refractory to most treatments but is accompanied by substantial psychological and occasionally functional burden for the affected individuals.²⁴ Data concerning therapeutic options in the pediatric population are extremely limited, and therefore the everyday practice often involves administration of off-label medications, which can constitute a dilemma for many physicians, especially for safety.¹⁰ We suggest a simple therapeutic algorithm for the management of pediatric nail psoriasis based on the summarized data that are currently available in the literature. This algorithm is shown in the eFigure.

As progressively more agents—especially biologics—receive approval for use in plaque psoriasis in pediatric patients,²⁵ it is expected that gradually more real-life data on their side efficacy for plaque psoriasis of the nails in children also will come to light. Furthermore, their on-label use in pediatric psoriasis patients will facilitate further relevant clinical trials to this target group so that the potential of these medications in the management of nail psoriasis can be fully explored.

Pediatric nail psoriasis is a condition that has not been extensively studied. The prevalence of nail alterations in pediatric patients with psoriasis varies among different studies, ranging from 17% to 39.2%.¹ Nail pitting, onycholysis associated with subungual hyperkeratosis, paronychia, and pachyonychia are the most frequent features of psoriatic nail involvement in children.^2,3 The management of nail psoriasis in children and adolescents is critical due to the quality-of-life impact, from potential functional impairment issues to the obvious cosmetic problems, which can aggravate the psychologic distress and social embarrassment of patients with psoriasis. Despite the emergence of modern potent systemic agents to treat chronic plaque psoriasis, nail psoriasis often is refractory to treatment.⁴ Coupled with the limited on-label options for psoriasis treatment in children, the management of nail psoriasis in this special patient group constitutes an even greater therapeutic challenge. This report aims to summarize the limited existing data on the successful management of nail psoriasis in the pediatric population.

Reviewing the Literature on Nail Psoriasis

We conducted a search of PubMed articles indexed for MEDLINE, Embase, and Scopus using the following Medical Subject Headings key terms: nail psoriasis and children, juvenile, pediatric. Additional articles were identified from the reference lists of the retrieved articles and citations. Our search included reports in the English language published from 2000 to 2019. The selection process included the following 2 steps: screening of the titles and abstracts, followed by evaluation of the selected full-text articles.

Topical Treatments for Nail Psoriasis

Because most systemic antipsoriatic treatments that can be administered in adult patients have not yet been granted an official license for administration in children, topical treatments are considered by many physicians as the preferred first-line therapy for psoriatic nail involvement in pediatric patients.^5,6 However, only scarce data are available in the literature concerning the successful use of local agents in pediatric patients with psoriasis.

The main limitation of local treatments relates mostly to their impaired penetration into the affected area (nails). To optimize drug penetration, some authors suggest the use of potent keratolytic topical preparations to reduce the nail volume and facilitate drug absorption.⁷ A popular suggestion is trimming the onycholytic nail plate followed by 40% urea avulsion to treat subungual hyperkeratosis⁸ or simply the use of occlusive 40% urea in petroleum jelly.⁹ Other approaches include clipping the onycholytic nail over the diseased nail bed or processing the nail plate through grinding or even drilling holes with the use of mechanical burrs or ablative lasers to enhance the penetration of the topical agent.⁷

A frequent approach in pediatric patients is clipping the detached nails combined with daily application of calcipotriene (calcipotriol) and steroids, such as betamethasone dipropionate.^5,8 Reports on the use of regimens with clobetasol propionate ointment 0.05% under occlusion, with or without the concomitant use of calcipotriol solution 0.005%, also are present in the literature but not always with satisfactory results.^10,11 Another successfully administered topical steroid is mometasone furoate cream 0.1%.¹² Although the use of intralesional triamcinolone acetonide also has demonstrated encouraging outcomes in isolated reports,¹³ associated adverse events, such as pain and hematomas, can result in tolerability issues for pediatric patients.⁷

Piraccini et al¹⁴ described the case of an 8-year-old patient with pustular nail psoriasis who showed improvement within 3 to 6 months of treatment with topical calcipotriol 5 μg/g as monotherapy applied to the nail and periungual tissues twice daily. Another approach, described by Diluvio et al,¹⁵ is the use of tazarotene gel 0.05% applied once daily to the affected nail plates, nail folds, and periungual skin without occlusion. In a 6-year-old patient with isolated nail psoriasis, this treatment regimen demonstrated notable improvement within 8 weeks.¹⁵

Systemic Treatments for Nail Psoriasis

Data on the successful administration of systemic agents in pediatric patients also are extremely scarce. Due to the lack of clinical trials, everyday practice is mostly based on isolated case series and case reports.

Methotrexate—Lee¹¹ described the case of an 11-year-old girl with severe, symptomatic, 20-nail psoriatic onychodystrophy who showed a complete response to oral methotrexate 5 mg/wk after topical clobetasol propionate and calcipotriol failed. Improvement was seen as early as 4 weeks after therapy initiation, and complete resolution of the lesions was documented after 9 and 13 months of methotrexate therapy for the fingers and toes, respectively.¹¹ The successful use of methotrexate in the improvement of psoriatic nail dystrophy in a pediatric patient also was documented by Teran et al.¹⁶ In this case, a 9-year-old girl with erythrodermic psoriasis, psoriatic arthritis, and severe onychodystrophy showed notable amelioration of all psoriatic manifestations, including the nail findings, with systemic methotrexate therapy (dose not specified).¹⁶ Notably, the authors reported that the improvement of onychodystrophy occurred with considerable delay compared to the other psoriatic lesions,¹⁶ indicating the already-known refractoriness of nail psoriasis to the various therapeutic attempts.^9-15

Acitretin—Another agent that has been linked with partial improvement of acrodermatitis continua of Hallopeau (ACH)–associated onychodystrophy is acitretin. In a case series of 15 pediatric patients with pustular psoriasis, a 5-year-old boy with severe nail involvement presented with partial amelioration of nail changes with acitretin within the first 6 weeks of treatment using the following regimen: initial dosage of 0.8 mg/kg/d for 6 weeks, followed by 0.3 mg/kg/d for 4 weeks.¹⁷

Biologics—The emerging use of biologics in pediatric psoriasis also has brought important advances in the successful management of nail psoriasis in children and adolescents.^18-21 Wells et al¹⁸ presented the case of an 8-year-old girl with nail psoriasis, psoriatic arthritis, and plaque psoriasis who showed complete resolution of all psoriatic manifestations, including nail involvement, within 3 months of treatment with secukinumab 150 mg subcutaneously every 4 weeks. Prior failed treatments included various systemic agents (ie, subcutaneous methotrexate 20 mg/m², etanercept 0.8 mg/kg weekly, adalimumab 40 mg every 2 weeks) as well as topical agents (ie, urea, tazarotene, corticosteroids) and intralesional triamcinolone.¹⁸

Infliximab also has been successfully used for pediatric nail psoriasis. Watabe et al¹⁹ presented the case of an 8-year-old girl with psoriatic onychodystrophy in addition to psoriatic onycho-pachydermo-periostitis. Prior therapy with adalimumab 20 mg every other week combined with methotrexate 10 mg weekly failed. She experienced notable amelioration of the nail dystrophy within 3 months of using a combination of infliximab and methotrexate (infliximab 5 mg/kg intravenously on weeks 0, 2, and 6, and every 8 weeks thereafter; methotrexate 10 mg/wk).¹⁹

Cases in which infliximab has resulted in rapid yet only transient restoration of psoriatic onychodystrophy also are present in the literature. Pereira et al²⁰ reported that a 3-year-old patient with severe 20-digit onychodystrophy in addition to pustular psoriasis had complete resolution of nail lesions within 2 weeks of treatment with infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 7 weeks thereafter), which was sustained over the course of 1 year. The therapy had to be discontinued because of exacerbation of the cutaneous symptoms; thereafter, etanercept was initiated. Although the patient noted major improvement of all skin lesions under etanercept, only moderate amelioration of the psoriatic nail lesions was demonstrated.²⁰

Dini et al²¹ described a 9-year-old girl with severe ACH-associated psoriatic onychodystrophy who showed complete clearance of all lesions within 8 weeks of treatment with adalimumab (initially 80 mg, followed by 40 mg after 1 week and then 40 mg every other week). Prior treatment with potent topical corticosteroids, cyclosporine (3 mg/kg/d for 6 months), and etanercept (0.4 mg/kg twice weekly for 3 months) was ineffective.²¹

Phototherapy—Other systemic agents with reported satisfactory outcomes in the treatment of psoriatic onychodystrophy include thalidomide combined with UVB phototherapy. Kiszewski et al²² described a 2-year-old patient with ACH and severe 19-digit onychodystrophy. Prior failed therapies included occluded clobetasol ointment 0.05%, occluded pimecrolimus 0.1%, and systemic methotrexate, while systemic acitretin (0.8 mg⁄kg⁄d) resulted in elevated cholesterol levels and therefore had to be interrupted. Improvement was seen 2 months after the initiation of a combined broadband UVB and thalidomide (50 mg⁄d) treatment, with no documented relapses after discontinuation of therapy.²²

Narrowband UVB (311 nm) also has been used as monotherapy for ACH-associated onychodystrophy, as demonstrated by Bordignon et al.²³ They reported a 9-year-old patient who showed partial improvement of isolated onychodystrophy of the fourth nail plate of the left hand after 36 sessions of narrowband UVB using a 311-nm filtering handpiece with a square spot size of 19×19 mm.²³

Conclusion

Nail psoriasis constitutes a type of psoriasis that is not only refractory to most treatments but is accompanied by substantial psychological and occasionally functional burden for the affected individuals.²⁴ Data concerning therapeutic options in the pediatric population are extremely limited, and therefore the everyday practice often involves administration of off-label medications, which can constitute a dilemma for many physicians, especially for safety.¹⁰ We suggest a simple therapeutic algorithm for the management of pediatric nail psoriasis based on the summarized data that are currently available in the literature. This algorithm is shown in the eFigure.

As progressively more agents—especially biologics—receive approval for use in plaque psoriasis in pediatric patients,²⁵ it is expected that gradually more real-life data on their side efficacy for plaque psoriasis of the nails in children also will come to light. Furthermore, their on-label use in pediatric psoriasis patients will facilitate further relevant clinical trials to this target group so that the potential of these medications in the management of nail psoriasis can be fully explored.

Annular erythemas of infancy (AEIs) are rare benign skin eruptions characterized by annular or circinate, erythematous patches and plaques that arise in patients younger than 1 year.¹ Annular erythemas of infancy originally were described by Peterson and Jarratt² in 1981. Relatively few cases of AEIs have been reported in the literature (eTable).^2-15

Case Report

An 11-month-old girl presented to dermatology for a rash characterized by annular erythematous patches and plaques on the back, arms, and legs (Figure 1). Three months prior, the rash was more diffuse, monomorphic, and papular. Based on physical examination, the differential diagnosis included a gyrate erythema such as erythema annulare centrifugum (EAC), neonatal lupus, a viral exanthem, leukemia cutis, and AEI. A skin punch biopsy was performed.

Histologically, the biopsy revealed a superficial to mid dermal, tight, coat sleeve–like, perivascular lymphohistiocytic infiltrate admixed with rare neutrophils in eosinophils within the dermis (Figure 2A). The infiltrate also contained numerous large mononuclear cells with enlarged nuclei, fine loose chromatin, rare nucleoli, and a thin rim of cytoplasm (Figure 2B). There were associated apoptotic bodies with karyorrhectic debris. Immunohistochemistry exhibited enlarged cells that were strong staining with CD3 and CD4, which was consistent with reactive helper T cells (Figure 3). A myeloperoxidase stain highlighted few neutrophils. Stains for terminal deoxynucleotidyl transferase, CD1a, CD117, and CD34 were negative. These findings along with the clinical presentation yielded a diagnosis of AEI with reactive helper T cells.

Comment

Clinical Presentation of AEIs—Annular erythemas of infancy are rare benign skin eruptions that develop in the first few months of life.^1,16 Few cases have been reported (eTable). Clinically, AEIs are characterized by annular or circinate, erythematous patches and plaques. They can occur on the face, trunk, and extremities, and they completely resolve by 1 year of age in most cases. One case was reported to persist in a patient from birth until 15 years of age.⁹ It is thought that AEIs may occur as a hypersensitivity reaction to an unrecognized antigen.

Histopathology—Histologically, AEIs demonstrate a superficial and deep, perivascular, inflammatory infiltrate in the dermis composed of small lymphocytes, some neutrophils, and eosinophils.¹⁶ Less common variants of AEI include eosinophilic annular erythema, characterized by a diffuse dermal infiltrate of eosinophils and some lymphocytes, and neutrophilic figurate erythema of infancy, characterized by a dermal infiltrate with neutrophils and leukocytoclasis without vasculitis.¹

Our patient’s skin rash was unusual in that the biopsy demonstrated few neutrophils, rare eosinophils, and larger mononuclear cells consistent with reactive helper T lymphocytes. Although these cells may raise concern for an atypical lymphoid infiltrate, recognition of areas with more conventional histopathology of AEIs can facilitate the correct diagnosis.

Differential Diagnosis—The main considerations in the differential diagnosis for AEIs include the following: EAC, familial annular erythema, erythema gyratum atrophicans transiens neonatale, erythema chronicum migrans, urticaria, tinea corporis, neonatal lupus erythematosus, viral exanthems, and leukemia cutis.¹⁶

Erythema annulare centrifugum typically begins in middle age and follows a course of 2 or more years.² It occurs in association with an underlying infection or neoplasm, and it can develop on the trunk and proximal extremities. Morphologically, EAC can present with arcuate or polycyclic lesions with trailing scale. Histologically, a skin biopsy shows a tight, coat sleeve–like, perivascular, lymphohistiocytic infiltrate in the dermis, with variable epidermal spongiosis and parakeratosis.¹⁶ Our patient’s biopsy did show a tight perivascular infiltrate, raising suspicion for EAC. However, the eruption occurred in infancy, and she had no clinical evidence of infection or neoplasm.

Familial annular erythemas can arise within a few days after birth and can present on any part of the body, including the tongue.² Individual lesions can persist for 4 to 5 days and can accompany congenital malformations. Morphologically, they can present as papules that slowly enlarge to form arcuate lesions with central hyperpigmentation. Histologically, there can be a mild, perivascular, lymphocytic infiltrate in the dermis.¹⁶ Our patient’s lesions showed no scale or pigmentation and occurred without a family history or associated malformations.

Erythema gyratum atrophicans transiens neonatale also can arise in the first few days of life and can affect the trunk, neck, and lips.¹⁶ Morphologically, the skin lesions can present as arcuate erythematous patches (3–20 mm) with raised borders and central atrophy. Histologically, there is epidermal atrophy with a dermal perivascular mononuclear cell infiltrate with edema. Our patient’s clinical presentation was not classic for this condition, and the lesions showed no atrophy.

Erythema chronicum migrans can arise in children, often with a history of an arthropod bite.¹³ Morphologically, lesions can evolve over weeks to months and rarely are multiple. Erythema chronicum migrans most commonly occurs in the United States in association with Lyme disease from infection with Borrelia burgdorferi. Histologically, erythema chronicum migrans shows a superficial and deep, perivascular lymphocytic infiltrate in the dermis with plasma cells and eosinophils. A silver stain can demonstrate dermal spirochetes. Our patient had no history of an arthropod bite. A Warthin-Starry stain performed on the biopsy was negative for spirochetes, and serologies for Lyme disease were negative.

Urticaria is rare in neonates and can occur on any part of the body.² Morphologically, the skin lesions can present as arcuate, erythematous, and polycyclic plaques that wax and wane. Histologically, there is dermal edema with a mild, perivascular and interstitial, mixed inflammatory infiltrate.¹⁶ Our patient’s biopsy did not reveal notable edema, and the perivascular infiltrate was coat sleeve–like with few neutrophils and eosinophils. The patient did not respond to initial treatment with antihistamines, making urticaria less likely.

Tinea corporis is rare in neonates and can occur on any part of the body.¹³ Morphologically, it can present as scaly annular lesions that are fixed and more persistent. Histologically, there are fungal hyphae and/or yeast in the stratum corneum with spongiotic dermatitis and parakeratosis. Our patient’s lesions were not scaly, and the biopsy demonstrated minimal spongiosis. A periodic acid–Schiff special stain was negative for fungal microorganisms.

Neonatal lupus erythematosus can arise at birth or during the first few weeks of life.¹⁶ Morphologically, the skin lesions occur on the scalp, forehead, or neck in a periorbital or malar distribution. They can present as erythematous, annular, scaly patches and plaques. Transplacental transmission of material autoantibodies has been implicated in the etiology, and a complication is infantile heart block. Histologically, a skin biopsy typically shows interface/lichenoid dermatitis. However, our patient’s biopsy did not demonstrate interface changes, and serologically she was negative for autoantibodies.

Viral exanthems are skin eruptions that accompany underlying viral infections.¹⁷ Morphologically, patients can present with an erythematous maculopapular rash, sometimes with vesicular, petechial, and urticarial lesions. Laboratory confirmation is made by virus-specific serologies. Histologically, viral exanthems can show a superficial, perivascular, lymphocytic infiltrate in the dermis, with reactive T cells and epidermal spongiosis. Our patient was afebrile and had no known sick contacts. A cytomegalovirus immunohistochemical study on the biopsy was negative, and an Epstein-Barr encoding region in situ hybridization study was negative.

Leukemia cutis is the infiltration of the skin by leukemic cells, most often in conjunction with systemic leukemia.¹⁸ In infants and children, the most common leukemia is B-cell acute lymphoblastic leukemia. Morphologically, the skin lesions are characterized by single or multiple violaceous papules, nodules, and plaques. Histologically, there is a perivascular to interstitial infiltrate of atypical mononuclear cells in the dermis and sometimes subcutis. The leukemic cells demonstrate enlarged nuclei with coarse chromatin and prominent nucleoli. Increased mitotic activity may be seen with karyorrhectic debris. Immunohistochemically, the tumor cells can be positive for myeloperoxidase, CD43, CD68, CD34, and CD117.¹⁸ Although our patient’s biopsy demonstrated mononuclear cells with karyorrhexis, the cells did not have striking atypia and were negative for blast markers. A recent complete blood cell count on the patient was normal.

Conclusion

We report an unusual case of AEI with mononuclear cells consistent with helper T cells. One must keep these cells in mind when evaluating a biopsy of AEI, as they are benign and not suggestive of an atypical lymphoid infiltrate or leukemia cutis. This will prevent misdiagnosis and ensure that the patient receives appropriate management.

Annular erythemas of infancy (AEIs) are rare benign skin eruptions characterized by annular or circinate, erythematous patches and plaques that arise in patients younger than 1 year.¹ Annular erythemas of infancy originally were described by Peterson and Jarratt² in 1981. Relatively few cases of AEIs have been reported in the literature (eTable).^2-15

Case Report

An 11-month-old girl presented to dermatology for a rash characterized by annular erythematous patches and plaques on the back, arms, and legs (Figure 1). Three months prior, the rash was more diffuse, monomorphic, and papular. Based on physical examination, the differential diagnosis included a gyrate erythema such as erythema annulare centrifugum (EAC), neonatal lupus, a viral exanthem, leukemia cutis, and AEI. A skin punch biopsy was performed.

Histologically, the biopsy revealed a superficial to mid dermal, tight, coat sleeve–like, perivascular lymphohistiocytic infiltrate admixed with rare neutrophils in eosinophils within the dermis (Figure 2A). The infiltrate also contained numerous large mononuclear cells with enlarged nuclei, fine loose chromatin, rare nucleoli, and a thin rim of cytoplasm (Figure 2B). There were associated apoptotic bodies with karyorrhectic debris. Immunohistochemistry exhibited enlarged cells that were strong staining with CD3 and CD4, which was consistent with reactive helper T cells (Figure 3). A myeloperoxidase stain highlighted few neutrophils. Stains for terminal deoxynucleotidyl transferase, CD1a, CD117, and CD34 were negative. These findings along with the clinical presentation yielded a diagnosis of AEI with reactive helper T cells.

Comment

Clinical Presentation of AEIs—Annular erythemas of infancy are rare benign skin eruptions that develop in the first few months of life.^1,16 Few cases have been reported (eTable). Clinically, AEIs are characterized by annular or circinate, erythematous patches and plaques. They can occur on the face, trunk, and extremities, and they completely resolve by 1 year of age in most cases. One case was reported to persist in a patient from birth until 15 years of age.⁹ It is thought that AEIs may occur as a hypersensitivity reaction to an unrecognized antigen.

Histopathology—Histologically, AEIs demonstrate a superficial and deep, perivascular, inflammatory infiltrate in the dermis composed of small lymphocytes, some neutrophils, and eosinophils.¹⁶ Less common variants of AEI include eosinophilic annular erythema, characterized by a diffuse dermal infiltrate of eosinophils and some lymphocytes, and neutrophilic figurate erythema of infancy, characterized by a dermal infiltrate with neutrophils and leukocytoclasis without vasculitis.¹

Our patient’s skin rash was unusual in that the biopsy demonstrated few neutrophils, rare eosinophils, and larger mononuclear cells consistent with reactive helper T lymphocytes. Although these cells may raise concern for an atypical lymphoid infiltrate, recognition of areas with more conventional histopathology of AEIs can facilitate the correct diagnosis.

Differential Diagnosis—The main considerations in the differential diagnosis for AEIs include the following: EAC, familial annular erythema, erythema gyratum atrophicans transiens neonatale, erythema chronicum migrans, urticaria, tinea corporis, neonatal lupus erythematosus, viral exanthems, and leukemia cutis.¹⁶

Erythema annulare centrifugum typically begins in middle age and follows a course of 2 or more years.² It occurs in association with an underlying infection or neoplasm, and it can develop on the trunk and proximal extremities. Morphologically, EAC can present with arcuate or polycyclic lesions with trailing scale. Histologically, a skin biopsy shows a tight, coat sleeve–like, perivascular, lymphohistiocytic infiltrate in the dermis, with variable epidermal spongiosis and parakeratosis.¹⁶ Our patient’s biopsy did show a tight perivascular infiltrate, raising suspicion for EAC. However, the eruption occurred in infancy, and she had no clinical evidence of infection or neoplasm.

Familial annular erythemas can arise within a few days after birth and can present on any part of the body, including the tongue.² Individual lesions can persist for 4 to 5 days and can accompany congenital malformations. Morphologically, they can present as papules that slowly enlarge to form arcuate lesions with central hyperpigmentation. Histologically, there can be a mild, perivascular, lymphocytic infiltrate in the dermis.¹⁶ Our patient’s lesions showed no scale or pigmentation and occurred without a family history or associated malformations.

Erythema gyratum atrophicans transiens neonatale also can arise in the first few days of life and can affect the trunk, neck, and lips.¹⁶ Morphologically, the skin lesions can present as arcuate erythematous patches (3–20 mm) with raised borders and central atrophy. Histologically, there is epidermal atrophy with a dermal perivascular mononuclear cell infiltrate with edema. Our patient’s clinical presentation was not classic for this condition, and the lesions showed no atrophy.

Erythema chronicum migrans can arise in children, often with a history of an arthropod bite.¹³ Morphologically, lesions can evolve over weeks to months and rarely are multiple. Erythema chronicum migrans most commonly occurs in the United States in association with Lyme disease from infection with Borrelia burgdorferi. Histologically, erythema chronicum migrans shows a superficial and deep, perivascular lymphocytic infiltrate in the dermis with plasma cells and eosinophils. A silver stain can demonstrate dermal spirochetes. Our patient had no history of an arthropod bite. A Warthin-Starry stain performed on the biopsy was negative for spirochetes, and serologies for Lyme disease were negative.

Urticaria is rare in neonates and can occur on any part of the body.² Morphologically, the skin lesions can present as arcuate, erythematous, and polycyclic plaques that wax and wane. Histologically, there is dermal edema with a mild, perivascular and interstitial, mixed inflammatory infiltrate.¹⁶ Our patient’s biopsy did not reveal notable edema, and the perivascular infiltrate was coat sleeve–like with few neutrophils and eosinophils. The patient did not respond to initial treatment with antihistamines, making urticaria less likely.

Tinea corporis is rare in neonates and can occur on any part of the body.¹³ Morphologically, it can present as scaly annular lesions that are fixed and more persistent. Histologically, there are fungal hyphae and/or yeast in the stratum corneum with spongiotic dermatitis and parakeratosis. Our patient’s lesions were not scaly, and the biopsy demonstrated minimal spongiosis. A periodic acid–Schiff special stain was negative for fungal microorganisms.

Neonatal lupus erythematosus can arise at birth or during the first few weeks of life.¹⁶ Morphologically, the skin lesions occur on the scalp, forehead, or neck in a periorbital or malar distribution. They can present as erythematous, annular, scaly patches and plaques. Transplacental transmission of material autoantibodies has been implicated in the etiology, and a complication is infantile heart block. Histologically, a skin biopsy typically shows interface/lichenoid dermatitis. However, our patient’s biopsy did not demonstrate interface changes, and serologically she was negative for autoantibodies.

Viral exanthems are skin eruptions that accompany underlying viral infections.¹⁷ Morphologically, patients can present with an erythematous maculopapular rash, sometimes with vesicular, petechial, and urticarial lesions. Laboratory confirmation is made by virus-specific serologies. Histologically, viral exanthems can show a superficial, perivascular, lymphocytic infiltrate in the dermis, with reactive T cells and epidermal spongiosis. Our patient was afebrile and had no known sick contacts. A cytomegalovirus immunohistochemical study on the biopsy was negative, and an Epstein-Barr encoding region in situ hybridization study was negative.

Leukemia cutis is the infiltration of the skin by leukemic cells, most often in conjunction with systemic leukemia.¹⁸ In infants and children, the most common leukemia is B-cell acute lymphoblastic leukemia. Morphologically, the skin lesions are characterized by single or multiple violaceous papules, nodules, and plaques. Histologically, there is a perivascular to interstitial infiltrate of atypical mononuclear cells in the dermis and sometimes subcutis. The leukemic cells demonstrate enlarged nuclei with coarse chromatin and prominent nucleoli. Increased mitotic activity may be seen with karyorrhectic debris. Immunohistochemically, the tumor cells can be positive for myeloperoxidase, CD43, CD68, CD34, and CD117.¹⁸ Although our patient’s biopsy demonstrated mononuclear cells with karyorrhexis, the cells did not have striking atypia and were negative for blast markers. A recent complete blood cell count on the patient was normal.

Conclusion

We report an unusual case of AEI with mononuclear cells consistent with helper T cells. One must keep these cells in mind when evaluating a biopsy of AEI, as they are benign and not suggestive of an atypical lymphoid infiltrate or leukemia cutis. This will prevent misdiagnosis and ensure that the patient receives appropriate management.

Annular erythemas of infancy (AEIs) are rare benign skin eruptions characterized by annular or circinate, erythematous patches and plaques that arise in patients younger than 1 year.¹ Annular erythemas of infancy originally were described by Peterson and Jarratt² in 1981. Relatively few cases of AEIs have been reported in the literature (eTable).^2-15

Case Report

An 11-month-old girl presented to dermatology for a rash characterized by annular erythematous patches and plaques on the back, arms, and legs (Figure 1). Three months prior, the rash was more diffuse, monomorphic, and papular. Based on physical examination, the differential diagnosis included a gyrate erythema such as erythema annulare centrifugum (EAC), neonatal lupus, a viral exanthem, leukemia cutis, and AEI. A skin punch biopsy was performed.

Histologically, the biopsy revealed a superficial to mid dermal, tight, coat sleeve–like, perivascular lymphohistiocytic infiltrate admixed with rare neutrophils in eosinophils within the dermis (Figure 2A). The infiltrate also contained numerous large mononuclear cells with enlarged nuclei, fine loose chromatin, rare nucleoli, and a thin rim of cytoplasm (Figure 2B). There were associated apoptotic bodies with karyorrhectic debris. Immunohistochemistry exhibited enlarged cells that were strong staining with CD3 and CD4, which was consistent with reactive helper T cells (Figure 3). A myeloperoxidase stain highlighted few neutrophils. Stains for terminal deoxynucleotidyl transferase, CD1a, CD117, and CD34 were negative. These findings along with the clinical presentation yielded a diagnosis of AEI with reactive helper T cells.

Comment

Clinical Presentation of AEIs—Annular erythemas of infancy are rare benign skin eruptions that develop in the first few months of life.^1,16 Few cases have been reported (eTable). Clinically, AEIs are characterized by annular or circinate, erythematous patches and plaques. They can occur on the face, trunk, and extremities, and they completely resolve by 1 year of age in most cases. One case was reported to persist in a patient from birth until 15 years of age.⁹ It is thought that AEIs may occur as a hypersensitivity reaction to an unrecognized antigen.

Histopathology—Histologically, AEIs demonstrate a superficial and deep, perivascular, inflammatory infiltrate in the dermis composed of small lymphocytes, some neutrophils, and eosinophils.¹⁶ Less common variants of AEI include eosinophilic annular erythema, characterized by a diffuse dermal infiltrate of eosinophils and some lymphocytes, and neutrophilic figurate erythema of infancy, characterized by a dermal infiltrate with neutrophils and leukocytoclasis without vasculitis.¹

Our patient’s skin rash was unusual in that the biopsy demonstrated few neutrophils, rare eosinophils, and larger mononuclear cells consistent with reactive helper T lymphocytes. Although these cells may raise concern for an atypical lymphoid infiltrate, recognition of areas with more conventional histopathology of AEIs can facilitate the correct diagnosis.

Differential Diagnosis—The main considerations in the differential diagnosis for AEIs include the following: EAC, familial annular erythema, erythema gyratum atrophicans transiens neonatale, erythema chronicum migrans, urticaria, tinea corporis, neonatal lupus erythematosus, viral exanthems, and leukemia cutis.¹⁶

Erythema annulare centrifugum typically begins in middle age and follows a course of 2 or more years.² It occurs in association with an underlying infection or neoplasm, and it can develop on the trunk and proximal extremities. Morphologically, EAC can present with arcuate or polycyclic lesions with trailing scale. Histologically, a skin biopsy shows a tight, coat sleeve–like, perivascular, lymphohistiocytic infiltrate in the dermis, with variable epidermal spongiosis and parakeratosis.¹⁶ Our patient’s biopsy did show a tight perivascular infiltrate, raising suspicion for EAC. However, the eruption occurred in infancy, and she had no clinical evidence of infection or neoplasm.

Familial annular erythemas can arise within a few days after birth and can present on any part of the body, including the tongue.² Individual lesions can persist for 4 to 5 days and can accompany congenital malformations. Morphologically, they can present as papules that slowly enlarge to form arcuate lesions with central hyperpigmentation. Histologically, there can be a mild, perivascular, lymphocytic infiltrate in the dermis.¹⁶ Our patient’s lesions showed no scale or pigmentation and occurred without a family history or associated malformations.

Erythema gyratum atrophicans transiens neonatale also can arise in the first few days of life and can affect the trunk, neck, and lips.¹⁶ Morphologically, the skin lesions can present as arcuate erythematous patches (3–20 mm) with raised borders and central atrophy. Histologically, there is epidermal atrophy with a dermal perivascular mononuclear cell infiltrate with edema. Our patient’s clinical presentation was not classic for this condition, and the lesions showed no atrophy.

Erythema chronicum migrans can arise in children, often with a history of an arthropod bite.¹³ Morphologically, lesions can evolve over weeks to months and rarely are multiple. Erythema chronicum migrans most commonly occurs in the United States in association with Lyme disease from infection with Borrelia burgdorferi. Histologically, erythema chronicum migrans shows a superficial and deep, perivascular lymphocytic infiltrate in the dermis with plasma cells and eosinophils. A silver stain can demonstrate dermal spirochetes. Our patient had no history of an arthropod bite. A Warthin-Starry stain performed on the biopsy was negative for spirochetes, and serologies for Lyme disease were negative.

Urticaria is rare in neonates and can occur on any part of the body.² Morphologically, the skin lesions can present as arcuate, erythematous, and polycyclic plaques that wax and wane. Histologically, there is dermal edema with a mild, perivascular and interstitial, mixed inflammatory infiltrate.¹⁶ Our patient’s biopsy did not reveal notable edema, and the perivascular infiltrate was coat sleeve–like with few neutrophils and eosinophils. The patient did not respond to initial treatment with antihistamines, making urticaria less likely.

Tinea corporis is rare in neonates and can occur on any part of the body.¹³ Morphologically, it can present as scaly annular lesions that are fixed and more persistent. Histologically, there are fungal hyphae and/or yeast in the stratum corneum with spongiotic dermatitis and parakeratosis. Our patient’s lesions were not scaly, and the biopsy demonstrated minimal spongiosis. A periodic acid–Schiff special stain was negative for fungal microorganisms.

Neonatal lupus erythematosus can arise at birth or during the first few weeks of life.¹⁶ Morphologically, the skin lesions occur on the scalp, forehead, or neck in a periorbital or malar distribution. They can present as erythematous, annular, scaly patches and plaques. Transplacental transmission of material autoantibodies has been implicated in the etiology, and a complication is infantile heart block. Histologically, a skin biopsy typically shows interface/lichenoid dermatitis. However, our patient’s biopsy did not demonstrate interface changes, and serologically she was negative for autoantibodies.

Viral exanthems are skin eruptions that accompany underlying viral infections.¹⁷ Morphologically, patients can present with an erythematous maculopapular rash, sometimes with vesicular, petechial, and urticarial lesions. Laboratory confirmation is made by virus-specific serologies. Histologically, viral exanthems can show a superficial, perivascular, lymphocytic infiltrate in the dermis, with reactive T cells and epidermal spongiosis. Our patient was afebrile and had no known sick contacts. A cytomegalovirus immunohistochemical study on the biopsy was negative, and an Epstein-Barr encoding region in situ hybridization study was negative.

Leukemia cutis is the infiltration of the skin by leukemic cells, most often in conjunction with systemic leukemia.¹⁸ In infants and children, the most common leukemia is B-cell acute lymphoblastic leukemia. Morphologically, the skin lesions are characterized by single or multiple violaceous papules, nodules, and plaques. Histologically, there is a perivascular to interstitial infiltrate of atypical mononuclear cells in the dermis and sometimes subcutis. The leukemic cells demonstrate enlarged nuclei with coarse chromatin and prominent nucleoli. Increased mitotic activity may be seen with karyorrhectic debris. Immunohistochemically, the tumor cells can be positive for myeloperoxidase, CD43, CD68, CD34, and CD117.¹⁸ Although our patient’s biopsy demonstrated mononuclear cells with karyorrhexis, the cells did not have striking atypia and were negative for blast markers. A recent complete blood cell count on the patient was normal.

Conclusion

We report an unusual case of AEI with mononuclear cells consistent with helper T cells. One must keep these cells in mind when evaluating a biopsy of AEI, as they are benign and not suggestive of an atypical lymphoid infiltrate or leukemia cutis. This will prevent misdiagnosis and ensure that the patient receives appropriate management.

Exostosis is a type of benign bone tumor in which trabecular (spongy) bone overgrows its normal border in a nodular pattern. ^1,2 Histologically, it usually is surrounded by a fibrocartilaginous cap. ³ It is most commonly found on the lateral or medial aspect of the foot and is thought to be caused by trauma, either physical pressure or infection. ⁴ When this lesion is found under the nail bed, it is termed subungual exostosis ( Dupuytren exostosis ) . ³ Sequelae of a subungual exostosis include nail dystrophy and lifting of the nail away from the toe, in addition to infection and possible loss of the toenail (onycholysis). There are only 2 genetic conditions related to exostosis: hereditary multiple exostosis and multiple exostoses-mental retardation syndrome.

An exostosis may appear to be a wart on first inspection. It may present similar to osteochondromas, and the only way to get a true diagnosis is by biopsy of the lesion. The treatment for an exostosis is surgery. The surgeon must remove the lesion at the base of the bone from which it grows to prevent recurrence of the lesion.⁵

Because exostosis may cause nail bed disruption, the differential diagnosis may include nail deformities, such as traumatic onycholysis, onychogryphosis, verrucae, subungual infection, or nail trauma.^6,7

Case Report

A 7-year-old boy presented with changes of the right great toenail over the last 4 months. The patient noted that the affected nail was discolored, dystrophic, painful, and thickened. He did not recall prior trauma to the affected nail, and his mother stated that the lesion was growing and becoming more painful with a throbbing sensation at times. He described the pain as stabbing, which was exacerbated while walking and playing sports. Neither the patient nor his family had ever had any similar condition. He was not taking any medications, only a daily multivitamin. He had a history of eczematous dermatitis and keratosis pilaris without any other medical illnesses. He had a family history of psoriasis; however, no prior instances of exostosis had been reported. He had no medication allergies.

A full-body cutaneous and nail examination showed a well-developed, well-nourished boy who was in no acute distress. A firm, subungual, pink, pearly,hyperkeratotic nodule was appreciated on the right great toe (Figure 1). The lesion was tender to palpation. The rest of the examination and review of systems were normal.

From the clinical findings, a differential diagnosis of glomus tumor, hemangioma, and infection was considered. Periodic acid–Schiff stain was negative, which ruled out fungal infection. Nail avulsion and a shave biopsy were performed under general anesthesia. There was an exostosis arising from the dorsal aspect of the great toe measuring approximately 5 mm in width at the base and approximately 1 mm in height, which endorsed a diagnosis of distal phalanx subungual exostosis. A postsurgery radiograph (Figure 2) showed residual bone below the level of shave removal at the nail bed.

Comment

Exostosis is most commonly found on the lateral or medial aspect of the hallux (great toe) in patients younger than 18 years.⁸ Diagnosis often is obvious, even without a radiograph or biopsy, because the exostosis comes out from under the tip of the nail. Our case was interesting because the patient was a child, and the exostosis did not lift the nail or extrude from the distal tip of the nail bed. Evidence suggests that a greater-than-expected genetic influence contributes to an exostosis, though further investigation is needed to determine all of the causes and risk factors for subungual bony exostosis. Timely diagnosis and treatment are essential to the prevention of sequelae of the disease, such as toe infection or chronic pain.

Exostosis is a type of benign bone tumor in which trabecular (spongy) bone overgrows its normal border in a nodular pattern. ^1,2 Histologically, it usually is surrounded by a fibrocartilaginous cap. ³ It is most commonly found on the lateral or medial aspect of the foot and is thought to be caused by trauma, either physical pressure or infection. ⁴ When this lesion is found under the nail bed, it is termed subungual exostosis ( Dupuytren exostosis ) . ³ Sequelae of a subungual exostosis include nail dystrophy and lifting of the nail away from the toe, in addition to infection and possible loss of the toenail (onycholysis). There are only 2 genetic conditions related to exostosis: hereditary multiple exostosis and multiple exostoses-mental retardation syndrome.

An exostosis may appear to be a wart on first inspection. It may present similar to osteochondromas, and the only way to get a true diagnosis is by biopsy of the lesion. The treatment for an exostosis is surgery. The surgeon must remove the lesion at the base of the bone from which it grows to prevent recurrence of the lesion.⁵

Because exostosis may cause nail bed disruption, the differential diagnosis may include nail deformities, such as traumatic onycholysis, onychogryphosis, verrucae, subungual infection, or nail trauma.^6,7

Case Report

A 7-year-old boy presented with changes of the right great toenail over the last 4 months. The patient noted that the affected nail was discolored, dystrophic, painful, and thickened. He did not recall prior trauma to the affected nail, and his mother stated that the lesion was growing and becoming more painful with a throbbing sensation at times. He described the pain as stabbing, which was exacerbated while walking and playing sports. Neither the patient nor his family had ever had any similar condition. He was not taking any medications, only a daily multivitamin. He had a history of eczematous dermatitis and keratosis pilaris without any other medical illnesses. He had a family history of psoriasis; however, no prior instances of exostosis had been reported. He had no medication allergies.

A full-body cutaneous and nail examination showed a well-developed, well-nourished boy who was in no acute distress. A firm, subungual, pink, pearly,hyperkeratotic nodule was appreciated on the right great toe (Figure 1). The lesion was tender to palpation. The rest of the examination and review of systems were normal.

From the clinical findings, a differential diagnosis of glomus tumor, hemangioma, and infection was considered. Periodic acid–Schiff stain was negative, which ruled out fungal infection. Nail avulsion and a shave biopsy were performed under general anesthesia. There was an exostosis arising from the dorsal aspect of the great toe measuring approximately 5 mm in width at the base and approximately 1 mm in height, which endorsed a diagnosis of distal phalanx subungual exostosis. A postsurgery radiograph (Figure 2) showed residual bone below the level of shave removal at the nail bed.

Comment

Exostosis is most commonly found on the lateral or medial aspect of the hallux (great toe) in patients younger than 18 years.⁸ Diagnosis often is obvious, even without a radiograph or biopsy, because the exostosis comes out from under the tip of the nail. Our case was interesting because the patient was a child, and the exostosis did not lift the nail or extrude from the distal tip of the nail bed. Evidence suggests that a greater-than-expected genetic influence contributes to an exostosis, though further investigation is needed to determine all of the causes and risk factors for subungual bony exostosis. Timely diagnosis and treatment are essential to the prevention of sequelae of the disease, such as toe infection or chronic pain.

Exostosis is a type of benign bone tumor in which trabecular (spongy) bone overgrows its normal border in a nodular pattern. ^1,2 Histologically, it usually is surrounded by a fibrocartilaginous cap. ³ It is most commonly found on the lateral or medial aspect of the foot and is thought to be caused by trauma, either physical pressure or infection. ⁴ When this lesion is found under the nail bed, it is termed subungual exostosis ( Dupuytren exostosis ) . ³ Sequelae of a subungual exostosis include nail dystrophy and lifting of the nail away from the toe, in addition to infection and possible loss of the toenail (onycholysis). There are only 2 genetic conditions related to exostosis: hereditary multiple exostosis and multiple exostoses-mental retardation syndrome.

An exostosis may appear to be a wart on first inspection. It may present similar to osteochondromas, and the only way to get a true diagnosis is by biopsy of the lesion. The treatment for an exostosis is surgery. The surgeon must remove the lesion at the base of the bone from which it grows to prevent recurrence of the lesion.⁵

Because exostosis may cause nail bed disruption, the differential diagnosis may include nail deformities, such as traumatic onycholysis, onychogryphosis, verrucae, subungual infection, or nail trauma.^6,7

Case Report

A 7-year-old boy presented with changes of the right great toenail over the last 4 months. The patient noted that the affected nail was discolored, dystrophic, painful, and thickened. He did not recall prior trauma to the affected nail, and his mother stated that the lesion was growing and becoming more painful with a throbbing sensation at times. He described the pain as stabbing, which was exacerbated while walking and playing sports. Neither the patient nor his family had ever had any similar condition. He was not taking any medications, only a daily multivitamin. He had a history of eczematous dermatitis and keratosis pilaris without any other medical illnesses. He had a family history of psoriasis; however, no prior instances of exostosis had been reported. He had no medication allergies.

A full-body cutaneous and nail examination showed a well-developed, well-nourished boy who was in no acute distress. A firm, subungual, pink, pearly,hyperkeratotic nodule was appreciated on the right great toe (Figure 1). The lesion was tender to palpation. The rest of the examination and review of systems were normal.

From the clinical findings, a differential diagnosis of glomus tumor, hemangioma, and infection was considered. Periodic acid–Schiff stain was negative, which ruled out fungal infection. Nail avulsion and a shave biopsy were performed under general anesthesia. There was an exostosis arising from the dorsal aspect of the great toe measuring approximately 5 mm in width at the base and approximately 1 mm in height, which endorsed a diagnosis of distal phalanx subungual exostosis. A postsurgery radiograph (Figure 2) showed residual bone below the level of shave removal at the nail bed.

Comment

Exostosis is most commonly found on the lateral or medial aspect of the hallux (great toe) in patients younger than 18 years.⁸ Diagnosis often is obvious, even without a radiograph or biopsy, because the exostosis comes out from under the tip of the nail. Our case was interesting because the patient was a child, and the exostosis did not lift the nail or extrude from the distal tip of the nail bed. Evidence suggests that a greater-than-expected genetic influence contributes to an exostosis, though further investigation is needed to determine all of the causes and risk factors for subungual bony exostosis. Timely diagnosis and treatment are essential to the prevention of sequelae of the disease, such as toe infection or chronic pain.

High genetic risk for a range of psychiatric illnesses appears to influence individuals’ choice of urban or rural life, new research suggests.

Individuals with a genetic predisposition to schizophrenia, bipolar disorder (BD), autism spectrum disorder (ASD), or anorexia nervosa (AN) are significantly more likely to move from a rural to an urban setting, whereas those at high genetic risk for attention-deficit/hyperactivity disorder were more likely to do the opposite.

The findings held even in those at high genetic risk who had never been diagnosed with a psychiatric disorder, highlighting a genetic factor that previous research linking urban living to mental illness has not explored.

“It’s not as simple as saying that urban environment is responsible for schizophrenia and everyone should move out of urban environments and they will be safe,” study investigator Evangelos Vassos, MD, PhD, senior clinical research fellow at King’s College London, and a consulting psychiatrist, said in an interview. “If you are genetically predisposed to schizophrenia, you will still be predisposed to schizophrenia even if you move.”

The study was published online in JAMA Psychiatry.
 

Genetic influence

The study results don’t rule out environmental influence, but offer evidence that the migration pattern researchers have tracked for years may have a multifactorial explanation.

“Our research shows that, at some level, an individual’s genes select their environment and that the relationship between environmental and genetic influences on mental health is interrelated,” Jessye Maxwell, MSc, lead author and a PhD candidate in psychiatry at King’s College, said in a statement. “This overlap needs to be considered when developing models to predict the risk of people developing mental health conditions in the future.”

For the study, the investigators calculated polygenic risk scores (PRS) of different psychiatric illnesses for 385,793 U.K. Biobank participants aged 37-73. PRS analyzes genetic information across a person’s entire genome, rather than by individual genes.

They used address history and U.K. census records from 1931 to 2011 to map population density over time.

PRS analyses showed significant associations with higher population density throughout adulthood, reaching highest significance between age 45 and 55 years for schizophrenia (88 people/km²; 95% confidence interval, 65-98 people/km²), BD (44 people/km²; 95%CI, 34-54 people/km²), AN (36 people/km²; 95%CI, 22-50 people/km²), and ASD (35 people/km²; 95%CI, 25-45 people/km²).

When they compared those who were born and stayed in rural or suburban areas to their counterparts who moved from those areas to cities, they found the odds of moving to urban areas ranged from 5% among people at high genetic risk for schizophrenia to 13% of those with a high risk for BD. Only people at high risk for ADHD were more likely to move to rural areas.

However, the study is not without its limitations. Only people of European descent were included, family medical history was unavailable for some participants, and only about 50,000 people had a lifetime diagnosis of mental illness, which is not representative of the general population.
 

‘Convincing evidence’

Still, the research adds another piece of the puzzle scientists seek to solve about where people live and mental illness risk, said Jordan DeVylder, PhD, associate professor of social work at Fordham University, New York, who commented on the study for this news organization.

Dr. DeVylder, who has also published research on the topic but was not part of the current study, noted that urban living has long been thought to be among the most consistent environmental risk factors for psychosis. However, he noted, “this association can also be explained by genetic selection, in which the same genes that predispose one to schizophrenia also predispose one to choose urban living.”

“This study presents the most convincing evidence to date that genetics have a major role in this association, at least in the countries where this association between urban living and psychosis exists,” he said.

The study was funded by National Institute for Health Research, Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. The authors and Dr. DeVylder have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

High genetic risk for a range of psychiatric illnesses appears to influence individuals’ choice of urban or rural life, new research suggests.

Individuals with a genetic predisposition to schizophrenia, bipolar disorder (BD), autism spectrum disorder (ASD), or anorexia nervosa (AN) are significantly more likely to move from a rural to an urban setting, whereas those at high genetic risk for attention-deficit/hyperactivity disorder were more likely to do the opposite.

The findings held even in those at high genetic risk who had never been diagnosed with a psychiatric disorder, highlighting a genetic factor that previous research linking urban living to mental illness has not explored.

“It’s not as simple as saying that urban environment is responsible for schizophrenia and everyone should move out of urban environments and they will be safe,” study investigator Evangelos Vassos, MD, PhD, senior clinical research fellow at King’s College London, and a consulting psychiatrist, said in an interview. “If you are genetically predisposed to schizophrenia, you will still be predisposed to schizophrenia even if you move.”

The study was published online in JAMA Psychiatry.
 

Genetic influence

The study results don’t rule out environmental influence, but offer evidence that the migration pattern researchers have tracked for years may have a multifactorial explanation.

“Our research shows that, at some level, an individual’s genes select their environment and that the relationship between environmental and genetic influences on mental health is interrelated,” Jessye Maxwell, MSc, lead author and a PhD candidate in psychiatry at King’s College, said in a statement. “This overlap needs to be considered when developing models to predict the risk of people developing mental health conditions in the future.”

For the study, the investigators calculated polygenic risk scores (PRS) of different psychiatric illnesses for 385,793 U.K. Biobank participants aged 37-73. PRS analyzes genetic information across a person’s entire genome, rather than by individual genes.

They used address history and U.K. census records from 1931 to 2011 to map population density over time.

PRS analyses showed significant associations with higher population density throughout adulthood, reaching highest significance between age 45 and 55 years for schizophrenia (88 people/km²; 95% confidence interval, 65-98 people/km²), BD (44 people/km²; 95%CI, 34-54 people/km²), AN (36 people/km²; 95%CI, 22-50 people/km²), and ASD (35 people/km²; 95%CI, 25-45 people/km²).

When they compared those who were born and stayed in rural or suburban areas to their counterparts who moved from those areas to cities, they found the odds of moving to urban areas ranged from 5% among people at high genetic risk for schizophrenia to 13% of those with a high risk for BD. Only people at high risk for ADHD were more likely to move to rural areas.

However, the study is not without its limitations. Only people of European descent were included, family medical history was unavailable for some participants, and only about 50,000 people had a lifetime diagnosis of mental illness, which is not representative of the general population.
 

‘Convincing evidence’

Still, the research adds another piece of the puzzle scientists seek to solve about where people live and mental illness risk, said Jordan DeVylder, PhD, associate professor of social work at Fordham University, New York, who commented on the study for this news organization.

Dr. DeVylder, who has also published research on the topic but was not part of the current study, noted that urban living has long been thought to be among the most consistent environmental risk factors for psychosis. However, he noted, “this association can also be explained by genetic selection, in which the same genes that predispose one to schizophrenia also predispose one to choose urban living.”

“This study presents the most convincing evidence to date that genetics have a major role in this association, at least in the countries where this association between urban living and psychosis exists,” he said.

The study was funded by National Institute for Health Research, Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. The authors and Dr. DeVylder have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

High genetic risk for a range of psychiatric illnesses appears to influence individuals’ choice of urban or rural life, new research suggests.

Individuals with a genetic predisposition to schizophrenia, bipolar disorder (BD), autism spectrum disorder (ASD), or anorexia nervosa (AN) are significantly more likely to move from a rural to an urban setting, whereas those at high genetic risk for attention-deficit/hyperactivity disorder were more likely to do the opposite.

The findings held even in those at high genetic risk who had never been diagnosed with a psychiatric disorder, highlighting a genetic factor that previous research linking urban living to mental illness has not explored.

“It’s not as simple as saying that urban environment is responsible for schizophrenia and everyone should move out of urban environments and they will be safe,” study investigator Evangelos Vassos, MD, PhD, senior clinical research fellow at King’s College London, and a consulting psychiatrist, said in an interview. “If you are genetically predisposed to schizophrenia, you will still be predisposed to schizophrenia even if you move.”

The study was published online in JAMA Psychiatry.
 

Genetic influence

The study results don’t rule out environmental influence, but offer evidence that the migration pattern researchers have tracked for years may have a multifactorial explanation.

“Our research shows that, at some level, an individual’s genes select their environment and that the relationship between environmental and genetic influences on mental health is interrelated,” Jessye Maxwell, MSc, lead author and a PhD candidate in psychiatry at King’s College, said in a statement. “This overlap needs to be considered when developing models to predict the risk of people developing mental health conditions in the future.”

For the study, the investigators calculated polygenic risk scores (PRS) of different psychiatric illnesses for 385,793 U.K. Biobank participants aged 37-73. PRS analyzes genetic information across a person’s entire genome, rather than by individual genes.

They used address history and U.K. census records from 1931 to 2011 to map population density over time.

PRS analyses showed significant associations with higher population density throughout adulthood, reaching highest significance between age 45 and 55 years for schizophrenia (88 people/km²; 95% confidence interval, 65-98 people/km²), BD (44 people/km²; 95%CI, 34-54 people/km²), AN (36 people/km²; 95%CI, 22-50 people/km²), and ASD (35 people/km²; 95%CI, 25-45 people/km²).

When they compared those who were born and stayed in rural or suburban areas to their counterparts who moved from those areas to cities, they found the odds of moving to urban areas ranged from 5% among people at high genetic risk for schizophrenia to 13% of those with a high risk for BD. Only people at high risk for ADHD were more likely to move to rural areas.

However, the study is not without its limitations. Only people of European descent were included, family medical history was unavailable for some participants, and only about 50,000 people had a lifetime diagnosis of mental illness, which is not representative of the general population.
 

‘Convincing evidence’

Still, the research adds another piece of the puzzle scientists seek to solve about where people live and mental illness risk, said Jordan DeVylder, PhD, associate professor of social work at Fordham University, New York, who commented on the study for this news organization.

Dr. DeVylder, who has also published research on the topic but was not part of the current study, noted that urban living has long been thought to be among the most consistent environmental risk factors for psychosis. However, he noted, “this association can also be explained by genetic selection, in which the same genes that predispose one to schizophrenia also predispose one to choose urban living.”

“This study presents the most convincing evidence to date that genetics have a major role in this association, at least in the countries where this association between urban living and psychosis exists,” he said.

The study was funded by National Institute for Health Research, Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. The authors and Dr. DeVylder have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In early 2020, Justin Bullock, MD, MPH, did what few, if any, resident physicians have done: He published an honest account in the New England Journal of Medicine of a would-be suicide attempt during medical training.

In the article, Dr. Bullock matter-of-factly laid out how, in 2019, intern-year night shifts contributed to a depressive episode. For Dr. Bullock, who has a bipolar disorder, sleep dysregulation can be deadly. He had a plan for completing suicide, and this wouldn’t have been his first attempt. Thanks to his history and openness about his condition, Dr. Bullock had an experienced care team that helped him get to a psychiatric hospital before anything happened. While there for around 5 days, he wrote the bulk of the NEJM article.

The article took Dr. Bullock’s impact nationwide. In the medical world, where mental illness is a serious problem but still deeply stigmatized, Dr. Bullock’s unblinking honesty on the issue is still radical to many. On Twitter and in interviews, Dr. Bullock is an unapologetic advocate for accommodations for people in medicine with mental illness. “One of the things that inspired me to speak out early on is that I feel I stand in a place of so much privilege,” Dr. Bullock told this news organization. “I often feel this sense of ... ‘you have to speak up, Justin; no one else can.’ ”

Dr. Bullock’s activism is especially noteworthy, given that he is still establishing his career. In August, while an internal medicine resident at the University of California, San Francisco, he received a lifetime teaching award from UCSF because he had received three prior teaching awards; a recognition like this is considered rare someone so early in their career. Now in his final year of residency, he actively researches medical education, advocates for mental health support, and is working to become a leading voice on related issues.

“It seems to be working,” his older sister, Jacquis Mahoney, RN, said during a visit to the UCSF campus. Instead of any awkwardness, everyone is thrilled to learn that she is Justin’s sister. “There’s a lot of pride and excitement.”
 

Suicide attempts during medical training

Now 28, Dr. Bullock grew up in Detroit, with his mom and two older sisters. His father was incarcerated for much of Dr. Bullock’s childhood, in part because of his own bipolar disorder not being well controlled, Dr. Bullock said.

When he was younger, Dr. Bullock was the peacekeeper in the house between his two sisters, said Ms. Mahoney: “Justin was always very delicate and kind.”

He played soccer and ran track but also loved math and science. While outwardly accumulating an impressive resume, Dr. Bullock was internally struggling. In high school, he made what he now calls an “immature” attempt at suicide after coming out as gay to his family. While Dr. Bullock said he doesn’t necessarily dwell on the discrimination he has faced as a gay, Black man, his awareness of how others perceive and treat him because of his identity increases the background stress present in his daily life.

After high school, Dr. Bullock went to MIT in Boston, where he continued running and studied chemical-biological engineering. During college, Dr. Bullock thought he was going to have to withdraw from MIT because of his depression. Thankfully, he received counseling from student services and advice from a track coach who sat him down and talked about pragmatic solutions, like medication. “That was life-changing,” said Dr. Bullock.

When trying to decide between engineering and medicine, Dr. Bullock realized he preferred contemplating medical problems to engineering ones. So he applied to medical school. Dr. Bullock eventually ended up at UCSF, where he was selected to participate in the Program in Medical Education for the Urban Underserved, a 5-year track at the college for students committed to working with underserved communities.

By the time Dr. Bullock got to medical school, he was feeling good. In consultation with his psychiatrist, he thought it worthwhile to take a break from his medications. At that time, his diagnosis was major depressive disorder and he had only had one serious depressive episode, which didn’t necessarily indicate that he would need medication long-term, he said. 

Dr. Bullock loved everything about medical school. “One day when I was in my first year of med school, I called my mom and said: ‘It’s like science summer camp but every day!’” he recalled.

Despite his enthusiasm, though, he began feeling something troubling. Recognizing the symptoms of early depression, Dr. Bullock restarted his medication. But this time, the same SSRI only made things worse. He went from sleeping 8 hours to 90 minutes a night. He felt angry. One day, he went on a furious 22-mile run. Plus, within the first 6 months of moving to San Francisco, Dr. Bullock was stopped by the police three different times while riding his bike. He attributes this to his race, which has only further added to his stress. In September 2015, during his second year of medical school, Dr. Bullock attempted suicide again. This time, he was intubated in the ED and rushed to the ICU.

He was given a new diagnosis: bipolar disorder. He changed medications and lived for a time with Ms. Mahoney and his other sister, who moved from Chicago to California to be with him. “My family has helped me a lot,” he said.

Dr. Bullock was initially not sure whether he would be able to return to school after his attempted suicide. Overall, UCSF was extremely supportive, he said. That came as a relief. Medical school was a grounding force in his life, not a destabilizing one: “If I had been pushed out, it would have been really harmful to me.”

Then Dr. Bullock started residency. The sleep disruption that comes with the night shift – the resident rite of passage – triggered another episode. At first, Dr. Bullock was overly productive; his mind was active and alert after staying up all night. He worked on new research during the day instead of sleeping. 

Sleep disturbance is a hallmark symptom of bipolar disorder. “Justin should never be on a 24-hour call,” said Lisa Meeks, PhD, associate professor of psychiatry and family medicine at the University of Colorado at Denver, Aurora, and a leading scholar on disability advocacy for medical trainees. When he started residency, Dr. Bullock was open with his program director about his diagnosis and sought accommodations to go to therapy each week. But he didn’t try to get out of night shifts or 24-hour calls, despite his care team urging him to do so. “I have this sense of wanting to tough it out,” he said. He also felt guilty making his peers take on his share of those challenging shifts.

In December 2019, Dr. Bullock was voluntarily hospitalized for a few days and started writing the article that would later appear in NEJM. In January, a friend and UCSF medical student completed suicide. In March, the same month his NEJM article came out, Dr. Bullock attempted suicide again. This time, he quickly recognized that he was making a mistake and called an ambulance. “For me, as far as suicide attempts go, it’s the most positive one.”
 

Advocating for changes in medical training

Throughout his medical training, Dr. Bullock was always open about his struggles with his peers and with the administration. He shared his suicidal thoughts at a Mental Illness Among Us event during medical school. His story resonated with peers who were surprised that Dr. Bullock, who was thriving academically, could be struggling emotionally. 

During residency, he led small group discussions and gave lectures at the medical school, including a talk about his attempts to create institutional change at UCSF, such as his public fight against the college’s Fitness for Duty (FFD) assessment process. That discussion earned him an Outstanding Lecturer award. Because it was the third award he had received from the medical school, Dr. Bullock also automatically earned a lifetime teaching award. When he told his mom, a teacher herself, about the award, she joked: “Are you old enough for ‘lifetime’ anything?”

Dr. Bullock has also spoken out and actively fought against the processes within the medical community that prevent people from coming forward until it is too late. Physicians and trainees often fear that if they seek mental health treatment, they will have to disclose that treatment to a potential employer or licensing board and then be barred from practicing medicine. Because he has been open about his mental health for so long, Dr. Bullock feels that he is in a position to push back against these norms. For example, in June he coauthored another article, this time for the Journal of Hospital Medicine, describing the traumatizing FFD assessment that followed his March 2020 suicide attempt.

In that article, Dr. Bullock wrote how no mental health professional served on the UCSF Physician Well Being Committee – comprising physicians and lawyers who evaluate physician impairment or potential physician impairment – that evaluated him. Dr. Bullock was referred to an outside psychiatrist. He also describes how he was forced to release all of his psychiatric records and undergo extensive drug testing, despite having no history of substance abuse. To return to work, he had to sign a contract, agreeing to be monitored and to attend a specific kind of therapy.

While steps like these can, in the right circumstances, protect both the public and doctors-in-training in important ways, they can also “be very punitive and isolating for someone going through a mental health crisis,” said Dr. Meeks. There were also no Black physicians or lawyers on the committee evaluating Dr. Bullock. “That was really egregious, when you look back.” Dr. Meeks is a coauthor on Dr. Bullock’s JHM article and a mentor and previous student disability officer at UCSF. 

Dr. Bullock raised objections to UCSF administrators about how he felt that the committee was discriminating against him because of his mental illness despite assurances from the director of his program that there have never been any performance or professionalism concerns with him. He said the administrators told him he was the first person to question the FFD process. This isn’t surprising, given that all the power in such situations usually lies with the hospital and the administrators, whereas the resident or physician is worried about losing their job and their license, said Dr. Meeks.

Dr. Bullock contends that he’s in a unique position to speak out, considering his stellar academic and work records, openness about his mental illness before a crisis, access to quality mental health care, and extensive personal network among the UCSF administration. “I know that I hold power within my institution; I spoke out because I could,” Dr. Bullock said. In addition to writing an article about his experience, Dr. Bullock shared his story with a task force appointed by the medical staff president to review the Physician Well-Being Committee and the overall FFD process. Even before Dr. Bullock shared his story with the public, the task force had already been appointed as a result of the increased concern about physician mental health during the ongoing COVID-19 pandemic, Michelle Guy, MD, clinical professor of medicine at UCSF, told this news organization. 

Elizabeth Fernandez, a UCSF senior public information representative, declined to comment on Dr. Bullock’s specific experience as reported in the JHM. “As with every hospital accredited by the Joint Commission, UCSF Medical Center has a Physician Well Being Committee that provides resources for physicians who may need help with chemical dependency or mental illness,” Ms. Fernandez said.

“Our goal through this program is always, first, to provide the compassion and assistance our physicians need to address the issues they face and continue to pursue their careers. This program is entirely voluntary and is bound by federal and state laws and regulations to protect the confidentiality of its participants, while ensuring that – first and foremost – no one is harmed by the situation, including the participant.”
 

Overcoming stigma to change the system

All of the attention – from national media outlets such as Vox to struggling peers and others – is fulfilling, Dr. Bullock said. But it can also be overwhelming. “I have definitely been praised as ‘Black excellence,’ and that definitely has added to the pressure to keep going ... to keep pushing at times,” he said.

Ms. Mahoney added: “He’s willing to sacrifice himself in order to make a difference. He would be a sacrificial lamb” for the Black community, the gay community, or any minority community.

Despite these concerns and his past suicide attempts, colleagues feel that Dr. Bullock is in a strong place to make decisions. “I trust Justin to put the boundaries up when they are needed and to engage in a way that feels comfortable for him,” said Ms. Meeks. “He is someone who has incredible self-awareness.”

Dr. Bullock’s history isn’t just something he overcame: It’s something that makes him a better, more empathetic doctor, said Ms. Mahoney. He knows what it’s like to be hospitalized, to deal with the frustration of insurance, to navigate the complexity of the health care system as a patient, or to be facing a deep internal darkness. He “can genuinely hold that person’s hand and say: ‘I know what you’re going through and we’re going to work through this day by day,’ ” she said. “That is something he can bring that no other physician can bring.”

In his advocacy on Twitter, in lectures, and in conversations with UCSF administrators, Dr. Bullock is pushing for board licensing questions to be reformed so physicians are no longer penalized for seeking mental health treatment. He would also like residency programs to make it easier and less stigmatizing for trainees to receive accommodations for a disability or mental illness.

“They say one person can’t change a system,” said Dr. Meeks, “but I do think Justin is calling an awful lot of attention to the system and I do think there will be changes because of his advocacy.”

A version of this article first appeared on Medscape.com.

In early 2020, Justin Bullock, MD, MPH, did what few, if any, resident physicians have done: He published an honest account in the New England Journal of Medicine of a would-be suicide attempt during medical training.

In the article, Dr. Bullock matter-of-factly laid out how, in 2019, intern-year night shifts contributed to a depressive episode. For Dr. Bullock, who has a bipolar disorder, sleep dysregulation can be deadly. He had a plan for completing suicide, and this wouldn’t have been his first attempt. Thanks to his history and openness about his condition, Dr. Bullock had an experienced care team that helped him get to a psychiatric hospital before anything happened. While there for around 5 days, he wrote the bulk of the NEJM article.

The article took Dr. Bullock’s impact nationwide. In the medical world, where mental illness is a serious problem but still deeply stigmatized, Dr. Bullock’s unblinking honesty on the issue is still radical to many. On Twitter and in interviews, Dr. Bullock is an unapologetic advocate for accommodations for people in medicine with mental illness. “One of the things that inspired me to speak out early on is that I feel I stand in a place of so much privilege,” Dr. Bullock told this news organization. “I often feel this sense of ... ‘you have to speak up, Justin; no one else can.’ ”

Dr. Bullock’s activism is especially noteworthy, given that he is still establishing his career. In August, while an internal medicine resident at the University of California, San Francisco, he received a lifetime teaching award from UCSF because he had received three prior teaching awards; a recognition like this is considered rare someone so early in their career. Now in his final year of residency, he actively researches medical education, advocates for mental health support, and is working to become a leading voice on related issues.

“It seems to be working,” his older sister, Jacquis Mahoney, RN, said during a visit to the UCSF campus. Instead of any awkwardness, everyone is thrilled to learn that she is Justin’s sister. “There’s a lot of pride and excitement.”
 

Suicide attempts during medical training

Now 28, Dr. Bullock grew up in Detroit, with his mom and two older sisters. His father was incarcerated for much of Dr. Bullock’s childhood, in part because of his own bipolar disorder not being well controlled, Dr. Bullock said.

When he was younger, Dr. Bullock was the peacekeeper in the house between his two sisters, said Ms. Mahoney: “Justin was always very delicate and kind.”

He played soccer and ran track but also loved math and science. While outwardly accumulating an impressive resume, Dr. Bullock was internally struggling. In high school, he made what he now calls an “immature” attempt at suicide after coming out as gay to his family. While Dr. Bullock said he doesn’t necessarily dwell on the discrimination he has faced as a gay, Black man, his awareness of how others perceive and treat him because of his identity increases the background stress present in his daily life.

After high school, Dr. Bullock went to MIT in Boston, where he continued running and studied chemical-biological engineering. During college, Dr. Bullock thought he was going to have to withdraw from MIT because of his depression. Thankfully, he received counseling from student services and advice from a track coach who sat him down and talked about pragmatic solutions, like medication. “That was life-changing,” said Dr. Bullock.

When trying to decide between engineering and medicine, Dr. Bullock realized he preferred contemplating medical problems to engineering ones. So he applied to medical school. Dr. Bullock eventually ended up at UCSF, where he was selected to participate in the Program in Medical Education for the Urban Underserved, a 5-year track at the college for students committed to working with underserved communities.

By the time Dr. Bullock got to medical school, he was feeling good. In consultation with his psychiatrist, he thought it worthwhile to take a break from his medications. At that time, his diagnosis was major depressive disorder and he had only had one serious depressive episode, which didn’t necessarily indicate that he would need medication long-term, he said. 

Dr. Bullock loved everything about medical school. “One day when I was in my first year of med school, I called my mom and said: ‘It’s like science summer camp but every day!’” he recalled.

Despite his enthusiasm, though, he began feeling something troubling. Recognizing the symptoms of early depression, Dr. Bullock restarted his medication. But this time, the same SSRI only made things worse. He went from sleeping 8 hours to 90 minutes a night. He felt angry. One day, he went on a furious 22-mile run. Plus, within the first 6 months of moving to San Francisco, Dr. Bullock was stopped by the police three different times while riding his bike. He attributes this to his race, which has only further added to his stress. In September 2015, during his second year of medical school, Dr. Bullock attempted suicide again. This time, he was intubated in the ED and rushed to the ICU.

He was given a new diagnosis: bipolar disorder. He changed medications and lived for a time with Ms. Mahoney and his other sister, who moved from Chicago to California to be with him. “My family has helped me a lot,” he said.

Dr. Bullock was initially not sure whether he would be able to return to school after his attempted suicide. Overall, UCSF was extremely supportive, he said. That came as a relief. Medical school was a grounding force in his life, not a destabilizing one: “If I had been pushed out, it would have been really harmful to me.”

Then Dr. Bullock started residency. The sleep disruption that comes with the night shift – the resident rite of passage – triggered another episode. At first, Dr. Bullock was overly productive; his mind was active and alert after staying up all night. He worked on new research during the day instead of sleeping. 

Sleep disturbance is a hallmark symptom of bipolar disorder. “Justin should never be on a 24-hour call,” said Lisa Meeks, PhD, associate professor of psychiatry and family medicine at the University of Colorado at Denver, Aurora, and a leading scholar on disability advocacy for medical trainees. When he started residency, Dr. Bullock was open with his program director about his diagnosis and sought accommodations to go to therapy each week. But he didn’t try to get out of night shifts or 24-hour calls, despite his care team urging him to do so. “I have this sense of wanting to tough it out,” he said. He also felt guilty making his peers take on his share of those challenging shifts.

In December 2019, Dr. Bullock was voluntarily hospitalized for a few days and started writing the article that would later appear in NEJM. In January, a friend and UCSF medical student completed suicide. In March, the same month his NEJM article came out, Dr. Bullock attempted suicide again. This time, he quickly recognized that he was making a mistake and called an ambulance. “For me, as far as suicide attempts go, it’s the most positive one.”
 

Advocating for changes in medical training

Throughout his medical training, Dr. Bullock was always open about his struggles with his peers and with the administration. He shared his suicidal thoughts at a Mental Illness Among Us event during medical school. His story resonated with peers who were surprised that Dr. Bullock, who was thriving academically, could be struggling emotionally. 

During residency, he led small group discussions and gave lectures at the medical school, including a talk about his attempts to create institutional change at UCSF, such as his public fight against the college’s Fitness for Duty (FFD) assessment process. That discussion earned him an Outstanding Lecturer award. Because it was the third award he had received from the medical school, Dr. Bullock also automatically earned a lifetime teaching award. When he told his mom, a teacher herself, about the award, she joked: “Are you old enough for ‘lifetime’ anything?”

Dr. Bullock has also spoken out and actively fought against the processes within the medical community that prevent people from coming forward until it is too late. Physicians and trainees often fear that if they seek mental health treatment, they will have to disclose that treatment to a potential employer or licensing board and then be barred from practicing medicine. Because he has been open about his mental health for so long, Dr. Bullock feels that he is in a position to push back against these norms. For example, in June he coauthored another article, this time for the Journal of Hospital Medicine, describing the traumatizing FFD assessment that followed his March 2020 suicide attempt.

In that article, Dr. Bullock wrote how no mental health professional served on the UCSF Physician Well Being Committee – comprising physicians and lawyers who evaluate physician impairment or potential physician impairment – that evaluated him. Dr. Bullock was referred to an outside psychiatrist. He also describes how he was forced to release all of his psychiatric records and undergo extensive drug testing, despite having no history of substance abuse. To return to work, he had to sign a contract, agreeing to be monitored and to attend a specific kind of therapy.

While steps like these can, in the right circumstances, protect both the public and doctors-in-training in important ways, they can also “be very punitive and isolating for someone going through a mental health crisis,” said Dr. Meeks. There were also no Black physicians or lawyers on the committee evaluating Dr. Bullock. “That was really egregious, when you look back.” Dr. Meeks is a coauthor on Dr. Bullock’s JHM article and a mentor and previous student disability officer at UCSF. 

Dr. Bullock raised objections to UCSF administrators about how he felt that the committee was discriminating against him because of his mental illness despite assurances from the director of his program that there have never been any performance or professionalism concerns with him. He said the administrators told him he was the first person to question the FFD process. This isn’t surprising, given that all the power in such situations usually lies with the hospital and the administrators, whereas the resident or physician is worried about losing their job and their license, said Dr. Meeks.

Dr. Bullock contends that he’s in a unique position to speak out, considering his stellar academic and work records, openness about his mental illness before a crisis, access to quality mental health care, and extensive personal network among the UCSF administration. “I know that I hold power within my institution; I spoke out because I could,” Dr. Bullock said. In addition to writing an article about his experience, Dr. Bullock shared his story with a task force appointed by the medical staff president to review the Physician Well-Being Committee and the overall FFD process. Even before Dr. Bullock shared his story with the public, the task force had already been appointed as a result of the increased concern about physician mental health during the ongoing COVID-19 pandemic, Michelle Guy, MD, clinical professor of medicine at UCSF, told this news organization. 

Elizabeth Fernandez, a UCSF senior public information representative, declined to comment on Dr. Bullock’s specific experience as reported in the JHM. “As with every hospital accredited by the Joint Commission, UCSF Medical Center has a Physician Well Being Committee that provides resources for physicians who may need help with chemical dependency or mental illness,” Ms. Fernandez said.

“Our goal through this program is always, first, to provide the compassion and assistance our physicians need to address the issues they face and continue to pursue their careers. This program is entirely voluntary and is bound by federal and state laws and regulations to protect the confidentiality of its participants, while ensuring that – first and foremost – no one is harmed by the situation, including the participant.”
 

Overcoming stigma to change the system

All of the attention – from national media outlets such as Vox to struggling peers and others – is fulfilling, Dr. Bullock said. But it can also be overwhelming. “I have definitely been praised as ‘Black excellence,’ and that definitely has added to the pressure to keep going ... to keep pushing at times,” he said.

Ms. Mahoney added: “He’s willing to sacrifice himself in order to make a difference. He would be a sacrificial lamb” for the Black community, the gay community, or any minority community.

Despite these concerns and his past suicide attempts, colleagues feel that Dr. Bullock is in a strong place to make decisions. “I trust Justin to put the boundaries up when they are needed and to engage in a way that feels comfortable for him,” said Ms. Meeks. “He is someone who has incredible self-awareness.”

Dr. Bullock’s history isn’t just something he overcame: It’s something that makes him a better, more empathetic doctor, said Ms. Mahoney. He knows what it’s like to be hospitalized, to deal with the frustration of insurance, to navigate the complexity of the health care system as a patient, or to be facing a deep internal darkness. He “can genuinely hold that person’s hand and say: ‘I know what you’re going through and we’re going to work through this day by day,’ ” she said. “That is something he can bring that no other physician can bring.”

In his advocacy on Twitter, in lectures, and in conversations with UCSF administrators, Dr. Bullock is pushing for board licensing questions to be reformed so physicians are no longer penalized for seeking mental health treatment. He would also like residency programs to make it easier and less stigmatizing for trainees to receive accommodations for a disability or mental illness.

“They say one person can’t change a system,” said Dr. Meeks, “but I do think Justin is calling an awful lot of attention to the system and I do think there will be changes because of his advocacy.”

A version of this article first appeared on Medscape.com.

In early 2020, Justin Bullock, MD, MPH, did what few, if any, resident physicians have done: He published an honest account in the New England Journal of Medicine of a would-be suicide attempt during medical training.

In the article, Dr. Bullock matter-of-factly laid out how, in 2019, intern-year night shifts contributed to a depressive episode. For Dr. Bullock, who has a bipolar disorder, sleep dysregulation can be deadly. He had a plan for completing suicide, and this wouldn’t have been his first attempt. Thanks to his history and openness about his condition, Dr. Bullock had an experienced care team that helped him get to a psychiatric hospital before anything happened. While there for around 5 days, he wrote the bulk of the NEJM article.

The article took Dr. Bullock’s impact nationwide. In the medical world, where mental illness is a serious problem but still deeply stigmatized, Dr. Bullock’s unblinking honesty on the issue is still radical to many. On Twitter and in interviews, Dr. Bullock is an unapologetic advocate for accommodations for people in medicine with mental illness. “One of the things that inspired me to speak out early on is that I feel I stand in a place of so much privilege,” Dr. Bullock told this news organization. “I often feel this sense of ... ‘you have to speak up, Justin; no one else can.’ ”

Dr. Bullock’s activism is especially noteworthy, given that he is still establishing his career. In August, while an internal medicine resident at the University of California, San Francisco, he received a lifetime teaching award from UCSF because he had received three prior teaching awards; a recognition like this is considered rare someone so early in their career. Now in his final year of residency, he actively researches medical education, advocates for mental health support, and is working to become a leading voice on related issues.

“It seems to be working,” his older sister, Jacquis Mahoney, RN, said during a visit to the UCSF campus. Instead of any awkwardness, everyone is thrilled to learn that she is Justin’s sister. “There’s a lot of pride and excitement.”
 

Suicide attempts during medical training

Now 28, Dr. Bullock grew up in Detroit, with his mom and two older sisters. His father was incarcerated for much of Dr. Bullock’s childhood, in part because of his own bipolar disorder not being well controlled, Dr. Bullock said.

When he was younger, Dr. Bullock was the peacekeeper in the house between his two sisters, said Ms. Mahoney: “Justin was always very delicate and kind.”

He played soccer and ran track but also loved math and science. While outwardly accumulating an impressive resume, Dr. Bullock was internally struggling. In high school, he made what he now calls an “immature” attempt at suicide after coming out as gay to his family. While Dr. Bullock said he doesn’t necessarily dwell on the discrimination he has faced as a gay, Black man, his awareness of how others perceive and treat him because of his identity increases the background stress present in his daily life.

After high school, Dr. Bullock went to MIT in Boston, where he continued running and studied chemical-biological engineering. During college, Dr. Bullock thought he was going to have to withdraw from MIT because of his depression. Thankfully, he received counseling from student services and advice from a track coach who sat him down and talked about pragmatic solutions, like medication. “That was life-changing,” said Dr. Bullock.

When trying to decide between engineering and medicine, Dr. Bullock realized he preferred contemplating medical problems to engineering ones. So he applied to medical school. Dr. Bullock eventually ended up at UCSF, where he was selected to participate in the Program in Medical Education for the Urban Underserved, a 5-year track at the college for students committed to working with underserved communities.

By the time Dr. Bullock got to medical school, he was feeling good. In consultation with his psychiatrist, he thought it worthwhile to take a break from his medications. At that time, his diagnosis was major depressive disorder and he had only had one serious depressive episode, which didn’t necessarily indicate that he would need medication long-term, he said. 

Dr. Bullock loved everything about medical school. “One day when I was in my first year of med school, I called my mom and said: ‘It’s like science summer camp but every day!’” he recalled.

Despite his enthusiasm, though, he began feeling something troubling. Recognizing the symptoms of early depression, Dr. Bullock restarted his medication. But this time, the same SSRI only made things worse. He went from sleeping 8 hours to 90 minutes a night. He felt angry. One day, he went on a furious 22-mile run. Plus, within the first 6 months of moving to San Francisco, Dr. Bullock was stopped by the police three different times while riding his bike. He attributes this to his race, which has only further added to his stress. In September 2015, during his second year of medical school, Dr. Bullock attempted suicide again. This time, he was intubated in the ED and rushed to the ICU.

He was given a new diagnosis: bipolar disorder. He changed medications and lived for a time with Ms. Mahoney and his other sister, who moved from Chicago to California to be with him. “My family has helped me a lot,” he said.

Dr. Bullock was initially not sure whether he would be able to return to school after his attempted suicide. Overall, UCSF was extremely supportive, he said. That came as a relief. Medical school was a grounding force in his life, not a destabilizing one: “If I had been pushed out, it would have been really harmful to me.”

Then Dr. Bullock started residency. The sleep disruption that comes with the night shift – the resident rite of passage – triggered another episode. At first, Dr. Bullock was overly productive; his mind was active and alert after staying up all night. He worked on new research during the day instead of sleeping. 

Sleep disturbance is a hallmark symptom of bipolar disorder. “Justin should never be on a 24-hour call,” said Lisa Meeks, PhD, associate professor of psychiatry and family medicine at the University of Colorado at Denver, Aurora, and a leading scholar on disability advocacy for medical trainees. When he started residency, Dr. Bullock was open with his program director about his diagnosis and sought accommodations to go to therapy each week. But he didn’t try to get out of night shifts or 24-hour calls, despite his care team urging him to do so. “I have this sense of wanting to tough it out,” he said. He also felt guilty making his peers take on his share of those challenging shifts.

In December 2019, Dr. Bullock was voluntarily hospitalized for a few days and started writing the article that would later appear in NEJM. In January, a friend and UCSF medical student completed suicide. In March, the same month his NEJM article came out, Dr. Bullock attempted suicide again. This time, he quickly recognized that he was making a mistake and called an ambulance. “For me, as far as suicide attempts go, it’s the most positive one.”
 

Advocating for changes in medical training

Throughout his medical training, Dr. Bullock was always open about his struggles with his peers and with the administration. He shared his suicidal thoughts at a Mental Illness Among Us event during medical school. His story resonated with peers who were surprised that Dr. Bullock, who was thriving academically, could be struggling emotionally. 

During residency, he led small group discussions and gave lectures at the medical school, including a talk about his attempts to create institutional change at UCSF, such as his public fight against the college’s Fitness for Duty (FFD) assessment process. That discussion earned him an Outstanding Lecturer award. Because it was the third award he had received from the medical school, Dr. Bullock also automatically earned a lifetime teaching award. When he told his mom, a teacher herself, about the award, she joked: “Are you old enough for ‘lifetime’ anything?”

Dr. Bullock has also spoken out and actively fought against the processes within the medical community that prevent people from coming forward until it is too late. Physicians and trainees often fear that if they seek mental health treatment, they will have to disclose that treatment to a potential employer or licensing board and then be barred from practicing medicine. Because he has been open about his mental health for so long, Dr. Bullock feels that he is in a position to push back against these norms. For example, in June he coauthored another article, this time for the Journal of Hospital Medicine, describing the traumatizing FFD assessment that followed his March 2020 suicide attempt.

In that article, Dr. Bullock wrote how no mental health professional served on the UCSF Physician Well Being Committee – comprising physicians and lawyers who evaluate physician impairment or potential physician impairment – that evaluated him. Dr. Bullock was referred to an outside psychiatrist. He also describes how he was forced to release all of his psychiatric records and undergo extensive drug testing, despite having no history of substance abuse. To return to work, he had to sign a contract, agreeing to be monitored and to attend a specific kind of therapy.

While steps like these can, in the right circumstances, protect both the public and doctors-in-training in important ways, they can also “be very punitive and isolating for someone going through a mental health crisis,” said Dr. Meeks. There were also no Black physicians or lawyers on the committee evaluating Dr. Bullock. “That was really egregious, when you look back.” Dr. Meeks is a coauthor on Dr. Bullock’s JHM article and a mentor and previous student disability officer at UCSF. 

Dr. Bullock raised objections to UCSF administrators about how he felt that the committee was discriminating against him because of his mental illness despite assurances from the director of his program that there have never been any performance or professionalism concerns with him. He said the administrators told him he was the first person to question the FFD process. This isn’t surprising, given that all the power in such situations usually lies with the hospital and the administrators, whereas the resident or physician is worried about losing their job and their license, said Dr. Meeks.

Dr. Bullock contends that he’s in a unique position to speak out, considering his stellar academic and work records, openness about his mental illness before a crisis, access to quality mental health care, and extensive personal network among the UCSF administration. “I know that I hold power within my institution; I spoke out because I could,” Dr. Bullock said. In addition to writing an article about his experience, Dr. Bullock shared his story with a task force appointed by the medical staff president to review the Physician Well-Being Committee and the overall FFD process. Even before Dr. Bullock shared his story with the public, the task force had already been appointed as a result of the increased concern about physician mental health during the ongoing COVID-19 pandemic, Michelle Guy, MD, clinical professor of medicine at UCSF, told this news organization. 

Elizabeth Fernandez, a UCSF senior public information representative, declined to comment on Dr. Bullock’s specific experience as reported in the JHM. “As with every hospital accredited by the Joint Commission, UCSF Medical Center has a Physician Well Being Committee that provides resources for physicians who may need help with chemical dependency or mental illness,” Ms. Fernandez said.

“Our goal through this program is always, first, to provide the compassion and assistance our physicians need to address the issues they face and continue to pursue their careers. This program is entirely voluntary and is bound by federal and state laws and regulations to protect the confidentiality of its participants, while ensuring that – first and foremost – no one is harmed by the situation, including the participant.”
 

Overcoming stigma to change the system

All of the attention – from national media outlets such as Vox to struggling peers and others – is fulfilling, Dr. Bullock said. But it can also be overwhelming. “I have definitely been praised as ‘Black excellence,’ and that definitely has added to the pressure to keep going ... to keep pushing at times,” he said.

Ms. Mahoney added: “He’s willing to sacrifice himself in order to make a difference. He would be a sacrificial lamb” for the Black community, the gay community, or any minority community.

Despite these concerns and his past suicide attempts, colleagues feel that Dr. Bullock is in a strong place to make decisions. “I trust Justin to put the boundaries up when they are needed and to engage in a way that feels comfortable for him,” said Ms. Meeks. “He is someone who has incredible self-awareness.”

Dr. Bullock’s history isn’t just something he overcame: It’s something that makes him a better, more empathetic doctor, said Ms. Mahoney. He knows what it’s like to be hospitalized, to deal with the frustration of insurance, to navigate the complexity of the health care system as a patient, or to be facing a deep internal darkness. He “can genuinely hold that person’s hand and say: ‘I know what you’re going through and we’re going to work through this day by day,’ ” she said. “That is something he can bring that no other physician can bring.”

In his advocacy on Twitter, in lectures, and in conversations with UCSF administrators, Dr. Bullock is pushing for board licensing questions to be reformed so physicians are no longer penalized for seeking mental health treatment. He would also like residency programs to make it easier and less stigmatizing for trainees to receive accommodations for a disability or mental illness.

“They say one person can’t change a system,” said Dr. Meeks, “but I do think Justin is calling an awful lot of attention to the system and I do think there will be changes because of his advocacy.”

A version of this article first appeared on Medscape.com.

The Biden administration on Nov. 4 unveiled its rule to require most of the country’s larger employers to mandate workers be fully vaccinated against COVID-19, but set a Jan. 4 deadline, avoiding the busy holiday season.

The White House also shifted the time lines for earlier mandates applying to federal workers and contractors to Jan. 4. And the same deadline applies to a new separate rule for health care workers.

The new rules are meant to preempt “any inconsistent state or local laws,” including bans and limits on employers’ authority to require vaccination, masks, or testing, the White House said in a statement.

The rule on employers from the Occupational Safety and Health Administration will apply to organizations with 100 or more employees. These employers will need to make sure each worker is fully vaccinated or tests for COVID-19 on at least a weekly basis. The OSHA rule will also require that employers provide paid time for employees to get vaccinated and ensure that all unvaccinated workers wear a face mask in the workplace. This rule will cover 84 million employees. The OSHA rule will not apply to workplaces covered by either the Centers for Medicare & Medicaid Services rule or the federal contractor vaccination requirement

“The virus will not go away by itself, or because we wish it away: We have to act,” President Joe Biden said in a statement. “Vaccination is the single best pathway out of this pandemic.”

Mandates were not the preferred route to managing the pandemic, he said.

“Too many people remain unvaccinated for us to get out of this pandemic for good,” he said. “So I instituted requirements – and they are working.”

The White House said 70% percent of U.S. adults are now fully vaccinated – up from less than 1% when Mr. Biden took office in January.

The CMS vaccine rule is meant to cover more than 17 million workers and about 76,000 medical care sites, including hospitals, ambulatory surgery centers, nursing homes, dialysis facilities, home health agencies, and long-term care facilities. The rule will apply to employees whether their positions involve patient care or not.

Unlike the OSHA mandate, the one for health care workers will not offer the option of frequent COVID-19 testing instead of vaccination. There is a “higher bar” for health care workers, given their role in treating patients, so the mandate allows only for vaccination or limited exemptions, a senior administration official said on Nov. 3 during a call with reporters.

The CMS rule includes a “range of remedies,” including penalties and denial of payment for health care facilities that fail to meet the vaccine mandate. CMS could theoretically cut off hospitals and other medical organizations for failure to comply, but that would be a “last resort,” a senior administration official said. CMS will instead work with health care facilities to help them comply with the federal rule on vaccination of medical workers.

The new CMS rules apply only to Medicare- and Medicaid-certified centers and organizations. The rule does not directly apply to other health care entities, such as doctor’s offices, that are not regulated by CMS.

“Most states have separate licensing requirements for health care staff and health care providers that would be applicable to physician office staff and other staff in small health care entities that are not subject to vaccination requirements under this IFC,” CMS said in the rule.

A version of this article first appeared on WebMD.com.

The Biden administration on Nov. 4 unveiled its rule to require most of the country’s larger employers to mandate workers be fully vaccinated against COVID-19, but set a Jan. 4 deadline, avoiding the busy holiday season.

The White House also shifted the time lines for earlier mandates applying to federal workers and contractors to Jan. 4. And the same deadline applies to a new separate rule for health care workers.

The new rules are meant to preempt “any inconsistent state or local laws,” including bans and limits on employers’ authority to require vaccination, masks, or testing, the White House said in a statement.

The rule on employers from the Occupational Safety and Health Administration will apply to organizations with 100 or more employees. These employers will need to make sure each worker is fully vaccinated or tests for COVID-19 on at least a weekly basis. The OSHA rule will also require that employers provide paid time for employees to get vaccinated and ensure that all unvaccinated workers wear a face mask in the workplace. This rule will cover 84 million employees. The OSHA rule will not apply to workplaces covered by either the Centers for Medicare & Medicaid Services rule or the federal contractor vaccination requirement

“The virus will not go away by itself, or because we wish it away: We have to act,” President Joe Biden said in a statement. “Vaccination is the single best pathway out of this pandemic.”

Mandates were not the preferred route to managing the pandemic, he said.

“Too many people remain unvaccinated for us to get out of this pandemic for good,” he said. “So I instituted requirements – and they are working.”

The White House said 70% percent of U.S. adults are now fully vaccinated – up from less than 1% when Mr. Biden took office in January.

The CMS vaccine rule is meant to cover more than 17 million workers and about 76,000 medical care sites, including hospitals, ambulatory surgery centers, nursing homes, dialysis facilities, home health agencies, and long-term care facilities. The rule will apply to employees whether their positions involve patient care or not.

Unlike the OSHA mandate, the one for health care workers will not offer the option of frequent COVID-19 testing instead of vaccination. There is a “higher bar” for health care workers, given their role in treating patients, so the mandate allows only for vaccination or limited exemptions, a senior administration official said on Nov. 3 during a call with reporters.

The CMS rule includes a “range of remedies,” including penalties and denial of payment for health care facilities that fail to meet the vaccine mandate. CMS could theoretically cut off hospitals and other medical organizations for failure to comply, but that would be a “last resort,” a senior administration official said. CMS will instead work with health care facilities to help them comply with the federal rule on vaccination of medical workers.

The new CMS rules apply only to Medicare- and Medicaid-certified centers and organizations. The rule does not directly apply to other health care entities, such as doctor’s offices, that are not regulated by CMS.

“Most states have separate licensing requirements for health care staff and health care providers that would be applicable to physician office staff and other staff in small health care entities that are not subject to vaccination requirements under this IFC,” CMS said in the rule.

A version of this article first appeared on WebMD.com.

The Biden administration on Nov. 4 unveiled its rule to require most of the country’s larger employers to mandate workers be fully vaccinated against COVID-19, but set a Jan. 4 deadline, avoiding the busy holiday season.

The White House also shifted the time lines for earlier mandates applying to federal workers and contractors to Jan. 4. And the same deadline applies to a new separate rule for health care workers.

The new rules are meant to preempt “any inconsistent state or local laws,” including bans and limits on employers’ authority to require vaccination, masks, or testing, the White House said in a statement.

The rule on employers from the Occupational Safety and Health Administration will apply to organizations with 100 or more employees. These employers will need to make sure each worker is fully vaccinated or tests for COVID-19 on at least a weekly basis. The OSHA rule will also require that employers provide paid time for employees to get vaccinated and ensure that all unvaccinated workers wear a face mask in the workplace. This rule will cover 84 million employees. The OSHA rule will not apply to workplaces covered by either the Centers for Medicare & Medicaid Services rule or the federal contractor vaccination requirement

“The virus will not go away by itself, or because we wish it away: We have to act,” President Joe Biden said in a statement. “Vaccination is the single best pathway out of this pandemic.”

Mandates were not the preferred route to managing the pandemic, he said.

“Too many people remain unvaccinated for us to get out of this pandemic for good,” he said. “So I instituted requirements – and they are working.”

The White House said 70% percent of U.S. adults are now fully vaccinated – up from less than 1% when Mr. Biden took office in January.

The CMS vaccine rule is meant to cover more than 17 million workers and about 76,000 medical care sites, including hospitals, ambulatory surgery centers, nursing homes, dialysis facilities, home health agencies, and long-term care facilities. The rule will apply to employees whether their positions involve patient care or not.

Unlike the OSHA mandate, the one for health care workers will not offer the option of frequent COVID-19 testing instead of vaccination. There is a “higher bar” for health care workers, given their role in treating patients, so the mandate allows only for vaccination or limited exemptions, a senior administration official said on Nov. 3 during a call with reporters.

The CMS rule includes a “range of remedies,” including penalties and denial of payment for health care facilities that fail to meet the vaccine mandate. CMS could theoretically cut off hospitals and other medical organizations for failure to comply, but that would be a “last resort,” a senior administration official said. CMS will instead work with health care facilities to help them comply with the federal rule on vaccination of medical workers.

The new CMS rules apply only to Medicare- and Medicaid-certified centers and organizations. The rule does not directly apply to other health care entities, such as doctor’s offices, that are not regulated by CMS.

“Most states have separate licensing requirements for health care staff and health care providers that would be applicable to physician office staff and other staff in small health care entities that are not subject to vaccination requirements under this IFC,” CMS said in the rule.

A version of this article first appeared on WebMD.com.

The prevalence of T2DM is on the rise in the United States, and T2DM is currently the 7th leading cause of death.¹ In a study of 28,143 participants in the US National Health and Nutrition Examination Survey (NHANES) who were 18 years or older, the prevalence of diabetes increased from 9.8% to 14.3% between 2000 and 2008.² About 24% of the participants had undiagnosed diabetes prior to the testing they received as a study participant.² People from minority groups have a higher rate of T2DM than non-Hispanic White people. Using data from 2018, the Centers for Disease Control and Prevention reported that the prevalence of diagnosed diabetes was highest among American Indians/Alaska Natives (14.7%), people of Hispanic origin (12.5%), and non-Hispanic Blacks (11.7%), followed by non-Hispanic Asians (9.2%) and non-Hispanic Whites (7.5%).¹ Diabetes is a major risk factor for myocardial infarction, stroke, renal failure, retinopathy, peripheral vascular disease, and neuropathy.¹ Early detection and treatment of both prediabetes and diabetes may improve health and reduce these preventable complications, saving lives, preventing heart and renal failure and blindness.

T2DM is caused by a combination of insulin resistance and insufficient pancreatic secretion of insulin to overcome the insulin resistance.³ In young adults with insulin resistance, pancreatic secretion of insulin is often sufficient to overcome the insulin resistance resulting in normal glucose levels and persistently increased insulin concentration. As individuals with insulin resistance age, pancreatic secretion of insulin may decline, resulting in insufficient production of insulin and rising glucose levels. Many individuals experience a prolonged stage of prediabetes that may be present for decades prior to transitioning to T2DM. In 2020, 35% of US adults were reported to have prediabetes.¹

Screening for diabetes mellitus

The US Preventive Services Task Force (USPSTF) recently recommended that all adults aged 35 to 70 years who are overweight or obese be screened for T2DM (B recommendation).⁴ Screening for diabetes will also result in detecting many people with prediabetes. The criteria for diagnosing diabetes and prediabetes are presented in the TABLE. Based on cohort studies, the USPSTF noted that screening every 3 years is a reasonable approach.⁴ They also recommended that people diagnosed with prediabetes should initiate preventive measures, including optimizing diet, weight loss, exercise, and in some cases, medication treatment such as metformin.⁵

Approaches to the diagnosis of diabetes and prediabetes

Three laboratory tests are widely utilized for the diagnosis of prediabetes and diabetes: measurement of a plasma glucose 2 hours following consumption of oral glucose 75 g (2-hr oral glucose tolerance test [OGTT]), measurement of a fasting plasma glucose, and measurement of hemoglobin A_1c (see Table).⁶In clinical practice, the best diabetes screening test is the test the patient will complete. Most evidence indicates that, compared with the 2-hr OGTT, a hemoglobin A_1c measurement is specific for diagnosing T2DM, but not sensitive. In other words, if the hemoglobin A_1c is ≥6.5%, the glucose measurement 2 hours following an OGTT will very likely be ≥200 mg/dL. But if the hemoglobin A_1c is between 5.7% and 6.5%, the person might be diagnosed with T2DM if they had a 2-hr OGTT.⁶

In one study, 1,241 nondiabetic, overweight, or obese participants had all 3 tests to diagnose T2DM.⁷ The 2-hr OGTT diagnosed T2DM in 148 participants (12%). However, the hemoglobin A_1c test only diagnosed T2DM in 78 of the 148 participants who were diagnosed with T2DM based on the 2-hr OGTT, missing 47% of the cases of T2DM. In this study, using the 2-hr OGTT as the “gold standard” reference test, the hemoglobin A_1c test had a sensitivity of 53% and specificity of 97%.⁷

In clinical practice one approach is to explain to the patient the pros and cons of the 3 tests for T2DM and ask them to select the test they prefer to complete. In a high-risk population, including people with obesity, completing any of the 3 tests is better than not testing for diabetes. It also should be noted that, among people who have a normal body mass index (BMI), a “prediabetes” diagnosis is controversial. Compared with obese persons with prediabetes, people with a normal BMI and prediabetes diagnosed by a blood test progress to diabetes at a much lower rate. The value of diagnosing prediabetes after 70 years of age is also controversial because few people in this situation progress to diabetes.⁸ Clinicians should be cautious about diagnosing prediabetes in lean or elderly people.

The reliability of the hemoglobin A_1c test is reduced in conditions associated with increased red blood cell turnover, including sickle cell disease, pregnancy (second and third trimesters), hemodialysis, recent blood transfusions or erythropoietin therapy. In these clinical situations, only blood glucose measurements should be used to diagnose prediabetes and T2DM.⁶ It should be noted that concordance among any of the 3 tests is not perfect.⁶

Continue to: A 2-step approach to diagnosing T2DM...

An alternative to relying on a single test for T2DM is to use a 2-step approach for screening. The first step is a hemoglobin A_1c measurement, which neither requires fasting nor waiting for 2 hours for post–glucose load blood draw. If the hemoglobin A_1c result is ≥6.5%, a T2DM diagnosis can be made, with no additional testing. If the hemoglobin A_1c result is 5.7% to 6.4%, the person probably has either prediabetes or diabetes and can be offered a 2-hr OGTT to definitively determine if T2DM is the proper diagnosis. If the hemoglobin A_1c test is <5.7%, it is unlikely that the person has T2DM or prediabetes at the time of the test. In this situation, the testing could be repeated in 3 years. Using a 2-step approach reduces the number of people who are tested with a 2-hr OGTT and detects more cases of T2DM than a 1-step approach that relies on a hemoglobin A_1c measurement alone.

Treatment of prediabetes is warranted in people at high risk for developing diabetes

It is better to prevent diabetes among people with a high risk of diabetes than to treat diabetes once it is established. People with prediabetes who are overweight or obese are at high risk for developing diabetes. Prediabetes is diagnosed by a fasting plasma glucose level of 100 to 125 mg/dL or a hemoglobin A_1c measurement of 5.7% to 6.4%.

High-quality randomized clinical trials have definitively demonstrated that, among people at high risk for developing diabetes, lifestyle modification and metformin treatment reduce the risk of developing diabetes. In the Diabetes Prevention Program (DPP) 3,234 people with a high risk of diabetes, mean BMI 34 kg/m², were randomly assigned to 1 of 3 groups⁹:

• a control group
• metformin (850 mg twice daily) or
• lifestyle modification that included exercise (moderate intensity exercise for 150 minutes per week and weight loss (7% of body weight using a low-calorie, low-fat diet).

At 2.8 years of follow-up the incidence of diabetes was 11%, 7.8%, and 4.8% per 100 person-years in the people assigned to the control, metformin, and lifestyle modification groups, respectively.⁹ In the DPP study, compared with the control group, metformin was most effective in decreasing the risk of transitioning to diabetes in people who had a BMI ≥35 kg/m² (53% reduction in risk) or a BMI from 30 to 35 kg/m² (16% reduction in risk).⁹ Metformin was not as effective at preventing the transition to diabetes in people who had a normal BMI or who were overweight (3% reduction).⁹

In the Finnish Diabetes Prevention Study, 522 obese people with impaired glucose tolerance were randomly assigned to lifestyle modification or a control group. After 4 years, the cumulative incidence of diabetes was 11% and 23% in the lifestyle modification and control groups, respectively.¹⁰ A meta-analysis of 23 randomized clinical trials reported that, among people with a high risk of developing diabetes, compared with no intervention (control group), lifestyle modification, including dieting, exercising, and weight loss significantly reduced the risk of developing diabetes (pooled relative risk [RR], 0.78; 95% confidence interval [CI], 0.69‒0.88).⁵

In clinical practice, offering a patient at high risk for diabetes a suite of options, including^5,9,10:

• a formal nutrition consult with the goal of targeting a 7% reduction in weight
• recommending moderate intensity exercise, 150 minutes weekly
• metformin treatment, if the patient is obese

would reduce the patient’s risk of developing diabetes.

Treatment of T2DM is complex

For people with T2DM, a widely recommended treatment goal is to reduce the hemoglobin A_1c measurement to ≤7%. Initial treatment includes a comprehensive diabetes self-management education program, weight loss using diet and exercise, and metformin treatment. Metformin may be associated with an increased risk of lactic acidosis, especially in people with renal insufficiency. The US Food and Drug Administration (FDA) recommends against initiating metformin therapy for people with an estimated glomerular filtration rate (eGFR) of 30 to 45 mL/min/1.73 m². The FDA determined that metformin is contraindicated in people with an eGFR of <30 mL/min/1.73 m².¹¹ Many people with T2DM will require treatment with multiple pharmacologic agents to achieve a hemoglobin A_1c ≤7%. In addition to metformin, pharmacologic agents used to treat T2DM include insulin, sulfonylureas, glucagon-like peptide-1(GLP-1) receptor agonists, a sodium glucose cotransporter (SGLT2) inhibitor, dipeptidyl peptidase-4 (DPP-4) inhibitors, or an alpha-glucosidase inhibitor. Given the complexity of managing T2DM over a lifetime, most individuals with T2DM receive their diabetes care from a primary care clinician or subspecialist in endocrinology.

Experts predict that, within the next 8 years, the prevalence of obesity among adults in the United States will be approximately 50%.¹² The US health care system has not been effective in controlling the obesity epidemic. Our failure to control the obesity epidemic will result in an increase in the prevalence of prediabetes and T2DM, leading to a rise in cardiovascular, renal, and eye disease. The diagnosis of prediabetes and diabetes is within the scope of practice of obstetrics and gynecology. The treatment of prediabetes is also within the scope of ObGyns, who have both expertise and familiarity in the diagnosis of gestational diabetes, a form of prediabetes. ●

The prevalence of T2DM is on the rise in the United States, and T2DM is currently the 7th leading cause of death.¹ In a study of 28,143 participants in the US National Health and Nutrition Examination Survey (NHANES) who were 18 years or older, the prevalence of diabetes increased from 9.8% to 14.3% between 2000 and 2008.² About 24% of the participants had undiagnosed diabetes prior to the testing they received as a study participant.² People from minority groups have a higher rate of T2DM than non-Hispanic White people. Using data from 2018, the Centers for Disease Control and Prevention reported that the prevalence of diagnosed diabetes was highest among American Indians/Alaska Natives (14.7%), people of Hispanic origin (12.5%), and non-Hispanic Blacks (11.7%), followed by non-Hispanic Asians (9.2%) and non-Hispanic Whites (7.5%).¹ Diabetes is a major risk factor for myocardial infarction, stroke, renal failure, retinopathy, peripheral vascular disease, and neuropathy.¹ Early detection and treatment of both prediabetes and diabetes may improve health and reduce these preventable complications, saving lives, preventing heart and renal failure and blindness.

T2DM is caused by a combination of insulin resistance and insufficient pancreatic secretion of insulin to overcome the insulin resistance.³ In young adults with insulin resistance, pancreatic secretion of insulin is often sufficient to overcome the insulin resistance resulting in normal glucose levels and persistently increased insulin concentration. As individuals with insulin resistance age, pancreatic secretion of insulin may decline, resulting in insufficient production of insulin and rising glucose levels. Many individuals experience a prolonged stage of prediabetes that may be present for decades prior to transitioning to T2DM. In 2020, 35% of US adults were reported to have prediabetes.¹

Screening for diabetes mellitus

The US Preventive Services Task Force (USPSTF) recently recommended that all adults aged 35 to 70 years who are overweight or obese be screened for T2DM (B recommendation).⁴ Screening for diabetes will also result in detecting many people with prediabetes. The criteria for diagnosing diabetes and prediabetes are presented in the TABLE. Based on cohort studies, the USPSTF noted that screening every 3 years is a reasonable approach.⁴ They also recommended that people diagnosed with prediabetes should initiate preventive measures, including optimizing diet, weight loss, exercise, and in some cases, medication treatment such as metformin.⁵

Approaches to the diagnosis of diabetes and prediabetes

Three laboratory tests are widely utilized for the diagnosis of prediabetes and diabetes: measurement of a plasma glucose 2 hours following consumption of oral glucose 75 g (2-hr oral glucose tolerance test [OGTT]), measurement of a fasting plasma glucose, and measurement of hemoglobin A_1c (see Table).⁶In clinical practice, the best diabetes screening test is the test the patient will complete. Most evidence indicates that, compared with the 2-hr OGTT, a hemoglobin A_1c measurement is specific for diagnosing T2DM, but not sensitive. In other words, if the hemoglobin A_1c is ≥6.5%, the glucose measurement 2 hours following an OGTT will very likely be ≥200 mg/dL. But if the hemoglobin A_1c is between 5.7% and 6.5%, the person might be diagnosed with T2DM if they had a 2-hr OGTT.⁶

In one study, 1,241 nondiabetic, overweight, or obese participants had all 3 tests to diagnose T2DM.⁷ The 2-hr OGTT diagnosed T2DM in 148 participants (12%). However, the hemoglobin A_1c test only diagnosed T2DM in 78 of the 148 participants who were diagnosed with T2DM based on the 2-hr OGTT, missing 47% of the cases of T2DM. In this study, using the 2-hr OGTT as the “gold standard” reference test, the hemoglobin A_1c test had a sensitivity of 53% and specificity of 97%.⁷

In clinical practice one approach is to explain to the patient the pros and cons of the 3 tests for T2DM and ask them to select the test they prefer to complete. In a high-risk population, including people with obesity, completing any of the 3 tests is better than not testing for diabetes. It also should be noted that, among people who have a normal body mass index (BMI), a “prediabetes” diagnosis is controversial. Compared with obese persons with prediabetes, people with a normal BMI and prediabetes diagnosed by a blood test progress to diabetes at a much lower rate. The value of diagnosing prediabetes after 70 years of age is also controversial because few people in this situation progress to diabetes.⁸ Clinicians should be cautious about diagnosing prediabetes in lean or elderly people.

The reliability of the hemoglobin A_1c test is reduced in conditions associated with increased red blood cell turnover, including sickle cell disease, pregnancy (second and third trimesters), hemodialysis, recent blood transfusions or erythropoietin therapy. In these clinical situations, only blood glucose measurements should be used to diagnose prediabetes and T2DM.⁶ It should be noted that concordance among any of the 3 tests is not perfect.⁶

Continue to: A 2-step approach to diagnosing T2DM...

An alternative to relying on a single test for T2DM is to use a 2-step approach for screening. The first step is a hemoglobin A_1c measurement, which neither requires fasting nor waiting for 2 hours for post–glucose load blood draw. If the hemoglobin A_1c result is ≥6.5%, a T2DM diagnosis can be made, with no additional testing. If the hemoglobin A_1c result is 5.7% to 6.4%, the person probably has either prediabetes or diabetes and can be offered a 2-hr OGTT to definitively determine if T2DM is the proper diagnosis. If the hemoglobin A_1c test is <5.7%, it is unlikely that the person has T2DM or prediabetes at the time of the test. In this situation, the testing could be repeated in 3 years. Using a 2-step approach reduces the number of people who are tested with a 2-hr OGTT and detects more cases of T2DM than a 1-step approach that relies on a hemoglobin A_1c measurement alone.

Treatment of prediabetes is warranted in people at high risk for developing diabetes

It is better to prevent diabetes among people with a high risk of diabetes than to treat diabetes once it is established. People with prediabetes who are overweight or obese are at high risk for developing diabetes. Prediabetes is diagnosed by a fasting plasma glucose level of 100 to 125 mg/dL or a hemoglobin A_1c measurement of 5.7% to 6.4%.

High-quality randomized clinical trials have definitively demonstrated that, among people at high risk for developing diabetes, lifestyle modification and metformin treatment reduce the risk of developing diabetes. In the Diabetes Prevention Program (DPP) 3,234 people with a high risk of diabetes, mean BMI 34 kg/m², were randomly assigned to 1 of 3 groups⁹:

• a control group
• metformin (850 mg twice daily) or
• lifestyle modification that included exercise (moderate intensity exercise for 150 minutes per week and weight loss (7% of body weight using a low-calorie, low-fat diet).

At 2.8 years of follow-up the incidence of diabetes was 11%, 7.8%, and 4.8% per 100 person-years in the people assigned to the control, metformin, and lifestyle modification groups, respectively.⁹ In the DPP study, compared with the control group, metformin was most effective in decreasing the risk of transitioning to diabetes in people who had a BMI ≥35 kg/m² (53% reduction in risk) or a BMI from 30 to 35 kg/m² (16% reduction in risk).⁹ Metformin was not as effective at preventing the transition to diabetes in people who had a normal BMI or who were overweight (3% reduction).⁹

In the Finnish Diabetes Prevention Study, 522 obese people with impaired glucose tolerance were randomly assigned to lifestyle modification or a control group. After 4 years, the cumulative incidence of diabetes was 11% and 23% in the lifestyle modification and control groups, respectively.¹⁰ A meta-analysis of 23 randomized clinical trials reported that, among people with a high risk of developing diabetes, compared with no intervention (control group), lifestyle modification, including dieting, exercising, and weight loss significantly reduced the risk of developing diabetes (pooled relative risk [RR], 0.78; 95% confidence interval [CI], 0.69‒0.88).⁵

In clinical practice, offering a patient at high risk for diabetes a suite of options, including^5,9,10:

• a formal nutrition consult with the goal of targeting a 7% reduction in weight
• recommending moderate intensity exercise, 150 minutes weekly
• metformin treatment, if the patient is obese

would reduce the patient’s risk of developing diabetes.

Treatment of T2DM is complex

For people with T2DM, a widely recommended treatment goal is to reduce the hemoglobin A_1c measurement to ≤7%. Initial treatment includes a comprehensive diabetes self-management education program, weight loss using diet and exercise, and metformin treatment. Metformin may be associated with an increased risk of lactic acidosis, especially in people with renal insufficiency. The US Food and Drug Administration (FDA) recommends against initiating metformin therapy for people with an estimated glomerular filtration rate (eGFR) of 30 to 45 mL/min/1.73 m². The FDA determined that metformin is contraindicated in people with an eGFR of <30 mL/min/1.73 m².¹¹ Many people with T2DM will require treatment with multiple pharmacologic agents to achieve a hemoglobin A_1c ≤7%. In addition to metformin, pharmacologic agents used to treat T2DM include insulin, sulfonylureas, glucagon-like peptide-1(GLP-1) receptor agonists, a sodium glucose cotransporter (SGLT2) inhibitor, dipeptidyl peptidase-4 (DPP-4) inhibitors, or an alpha-glucosidase inhibitor. Given the complexity of managing T2DM over a lifetime, most individuals with T2DM receive their diabetes care from a primary care clinician or subspecialist in endocrinology.

Experts predict that, within the next 8 years, the prevalence of obesity among adults in the United States will be approximately 50%.¹² The US health care system has not been effective in controlling the obesity epidemic. Our failure to control the obesity epidemic will result in an increase in the prevalence of prediabetes and T2DM, leading to a rise in cardiovascular, renal, and eye disease. The diagnosis of prediabetes and diabetes is within the scope of practice of obstetrics and gynecology. The treatment of prediabetes is also within the scope of ObGyns, who have both expertise and familiarity in the diagnosis of gestational diabetes, a form of prediabetes. ●

The prevalence of T2DM is on the rise in the United States, and T2DM is currently the 7th leading cause of death.¹ In a study of 28,143 participants in the US National Health and Nutrition Examination Survey (NHANES) who were 18 years or older, the prevalence of diabetes increased from 9.8% to 14.3% between 2000 and 2008.² About 24% of the participants had undiagnosed diabetes prior to the testing they received as a study participant.² People from minority groups have a higher rate of T2DM than non-Hispanic White people. Using data from 2018, the Centers for Disease Control and Prevention reported that the prevalence of diagnosed diabetes was highest among American Indians/Alaska Natives (14.7%), people of Hispanic origin (12.5%), and non-Hispanic Blacks (11.7%), followed by non-Hispanic Asians (9.2%) and non-Hispanic Whites (7.5%).¹ Diabetes is a major risk factor for myocardial infarction, stroke, renal failure, retinopathy, peripheral vascular disease, and neuropathy.¹ Early detection and treatment of both prediabetes and diabetes may improve health and reduce these preventable complications, saving lives, preventing heart and renal failure and blindness.

T2DM is caused by a combination of insulin resistance and insufficient pancreatic secretion of insulin to overcome the insulin resistance.³ In young adults with insulin resistance, pancreatic secretion of insulin is often sufficient to overcome the insulin resistance resulting in normal glucose levels and persistently increased insulin concentration. As individuals with insulin resistance age, pancreatic secretion of insulin may decline, resulting in insufficient production of insulin and rising glucose levels. Many individuals experience a prolonged stage of prediabetes that may be present for decades prior to transitioning to T2DM. In 2020, 35% of US adults were reported to have prediabetes.¹

Screening for diabetes mellitus

The US Preventive Services Task Force (USPSTF) recently recommended that all adults aged 35 to 70 years who are overweight or obese be screened for T2DM (B recommendation).⁴ Screening for diabetes will also result in detecting many people with prediabetes. The criteria for diagnosing diabetes and prediabetes are presented in the TABLE. Based on cohort studies, the USPSTF noted that screening every 3 years is a reasonable approach.⁴ They also recommended that people diagnosed with prediabetes should initiate preventive measures, including optimizing diet, weight loss, exercise, and in some cases, medication treatment such as metformin.⁵

Approaches to the diagnosis of diabetes and prediabetes

Three laboratory tests are widely utilized for the diagnosis of prediabetes and diabetes: measurement of a plasma glucose 2 hours following consumption of oral glucose 75 g (2-hr oral glucose tolerance test [OGTT]), measurement of a fasting plasma glucose, and measurement of hemoglobin A_1c (see Table).⁶In clinical practice, the best diabetes screening test is the test the patient will complete. Most evidence indicates that, compared with the 2-hr OGTT, a hemoglobin A_1c measurement is specific for diagnosing T2DM, but not sensitive. In other words, if the hemoglobin A_1c is ≥6.5%, the glucose measurement 2 hours following an OGTT will very likely be ≥200 mg/dL. But if the hemoglobin A_1c is between 5.7% and 6.5%, the person might be diagnosed with T2DM if they had a 2-hr OGTT.⁶

In one study, 1,241 nondiabetic, overweight, or obese participants had all 3 tests to diagnose T2DM.⁷ The 2-hr OGTT diagnosed T2DM in 148 participants (12%). However, the hemoglobin A_1c test only diagnosed T2DM in 78 of the 148 participants who were diagnosed with T2DM based on the 2-hr OGTT, missing 47% of the cases of T2DM. In this study, using the 2-hr OGTT as the “gold standard” reference test, the hemoglobin A_1c test had a sensitivity of 53% and specificity of 97%.⁷

In clinical practice one approach is to explain to the patient the pros and cons of the 3 tests for T2DM and ask them to select the test they prefer to complete. In a high-risk population, including people with obesity, completing any of the 3 tests is better than not testing for diabetes. It also should be noted that, among people who have a normal body mass index (BMI), a “prediabetes” diagnosis is controversial. Compared with obese persons with prediabetes, people with a normal BMI and prediabetes diagnosed by a blood test progress to diabetes at a much lower rate. The value of diagnosing prediabetes after 70 years of age is also controversial because few people in this situation progress to diabetes.⁸ Clinicians should be cautious about diagnosing prediabetes in lean or elderly people.

The reliability of the hemoglobin A_1c test is reduced in conditions associated with increased red blood cell turnover, including sickle cell disease, pregnancy (second and third trimesters), hemodialysis, recent blood transfusions or erythropoietin therapy. In these clinical situations, only blood glucose measurements should be used to diagnose prediabetes and T2DM.⁶ It should be noted that concordance among any of the 3 tests is not perfect.⁶

Continue to: A 2-step approach to diagnosing T2DM...

An alternative to relying on a single test for T2DM is to use a 2-step approach for screening. The first step is a hemoglobin A_1c measurement, which neither requires fasting nor waiting for 2 hours for post–glucose load blood draw. If the hemoglobin A_1c result is ≥6.5%, a T2DM diagnosis can be made, with no additional testing. If the hemoglobin A_1c result is 5.7% to 6.4%, the person probably has either prediabetes or diabetes and can be offered a 2-hr OGTT to definitively determine if T2DM is the proper diagnosis. If the hemoglobin A_1c test is <5.7%, it is unlikely that the person has T2DM or prediabetes at the time of the test. In this situation, the testing could be repeated in 3 years. Using a 2-step approach reduces the number of people who are tested with a 2-hr OGTT and detects more cases of T2DM than a 1-step approach that relies on a hemoglobin A_1c measurement alone.

Treatment of prediabetes is warranted in people at high risk for developing diabetes

It is better to prevent diabetes among people with a high risk of diabetes than to treat diabetes once it is established. People with prediabetes who are overweight or obese are at high risk for developing diabetes. Prediabetes is diagnosed by a fasting plasma glucose level of 100 to 125 mg/dL or a hemoglobin A_1c measurement of 5.7% to 6.4%.

High-quality randomized clinical trials have definitively demonstrated that, among people at high risk for developing diabetes, lifestyle modification and metformin treatment reduce the risk of developing diabetes. In the Diabetes Prevention Program (DPP) 3,234 people with a high risk of diabetes, mean BMI 34 kg/m², were randomly assigned to 1 of 3 groups⁹:

• a control group
• metformin (850 mg twice daily) or
• lifestyle modification that included exercise (moderate intensity exercise for 150 minutes per week and weight loss (7% of body weight using a low-calorie, low-fat diet).

At 2.8 years of follow-up the incidence of diabetes was 11%, 7.8%, and 4.8% per 100 person-years in the people assigned to the control, metformin, and lifestyle modification groups, respectively.⁹ In the DPP study, compared with the control group, metformin was most effective in decreasing the risk of transitioning to diabetes in people who had a BMI ≥35 kg/m² (53% reduction in risk) or a BMI from 30 to 35 kg/m² (16% reduction in risk).⁹ Metformin was not as effective at preventing the transition to diabetes in people who had a normal BMI or who were overweight (3% reduction).⁹

In the Finnish Diabetes Prevention Study, 522 obese people with impaired glucose tolerance were randomly assigned to lifestyle modification or a control group. After 4 years, the cumulative incidence of diabetes was 11% and 23% in the lifestyle modification and control groups, respectively.¹⁰ A meta-analysis of 23 randomized clinical trials reported that, among people with a high risk of developing diabetes, compared with no intervention (control group), lifestyle modification, including dieting, exercising, and weight loss significantly reduced the risk of developing diabetes (pooled relative risk [RR], 0.78; 95% confidence interval [CI], 0.69‒0.88).⁵

In clinical practice, offering a patient at high risk for diabetes a suite of options, including^5,9,10:

• a formal nutrition consult with the goal of targeting a 7% reduction in weight
• recommending moderate intensity exercise, 150 minutes weekly
• metformin treatment, if the patient is obese

would reduce the patient’s risk of developing diabetes.

Treatment of T2DM is complex

For people with T2DM, a widely recommended treatment goal is to reduce the hemoglobin A_1c measurement to ≤7%. Initial treatment includes a comprehensive diabetes self-management education program, weight loss using diet and exercise, and metformin treatment. Metformin may be associated with an increased risk of lactic acidosis, especially in people with renal insufficiency. The US Food and Drug Administration (FDA) recommends against initiating metformin therapy for people with an estimated glomerular filtration rate (eGFR) of 30 to 45 mL/min/1.73 m². The FDA determined that metformin is contraindicated in people with an eGFR of <30 mL/min/1.73 m².¹¹ Many people with T2DM will require treatment with multiple pharmacologic agents to achieve a hemoglobin A_1c ≤7%. In addition to metformin, pharmacologic agents used to treat T2DM include insulin, sulfonylureas, glucagon-like peptide-1(GLP-1) receptor agonists, a sodium glucose cotransporter (SGLT2) inhibitor, dipeptidyl peptidase-4 (DPP-4) inhibitors, or an alpha-glucosidase inhibitor. Given the complexity of managing T2DM over a lifetime, most individuals with T2DM receive their diabetes care from a primary care clinician or subspecialist in endocrinology.

Experts predict that, within the next 8 years, the prevalence of obesity among adults in the United States will be approximately 50%.¹² The US health care system has not been effective in controlling the obesity epidemic. Our failure to control the obesity epidemic will result in an increase in the prevalence of prediabetes and T2DM, leading to a rise in cardiovascular, renal, and eye disease. The diagnosis of prediabetes and diabetes is within the scope of practice of obstetrics and gynecology. The treatment of prediabetes is also within the scope of ObGyns, who have both expertise and familiarity in the diagnosis of gestational diabetes, a form of prediabetes. ●

Li FG, Maheux-Lacroix S, Deans R, et al. Effect of fractional carbon dioxide laser vs sham treatment on symptom severity in women with postmenopausal vaginal symptoms: a randomized clinical trial. JAMA. 2021;326:1381-1389. doi: 10.1001/jama.2021.14892.

EXPERT COMMENTARY

Symptomatic vaginal atrophy, also referred to as genitourinary syndrome of menopause (GSM), is common and tends to progress without treatment. When use of over-the-counter lubricants and/or moisturizers are not sufficient to address symptoms, vaginal estrogen has represented the mainstay of treatment for this condition and effectively addresses GSM symptoms.¹ In recent years, some physicians have been offering vaginal carbon dioxide (CO2) laser therapy as an alternative to vaginal estrogen in the treatment of GSM; however, the efficacy of laser therapy in this setting has been uncertain.

Li and colleagues conducted a double-blind randomized trial in postmenopausal women with bothersome vaginal symptoms to compare the efficacy of the fractional CO2 vaginal laser with that of sham treatment.

Details of the study

Investigators (who received no funding from any relevant commercial entity) at a teaching hospital in Sydney, Australia, randomly assigned 85 women with menopausal symptoms suggestive of GSM to laser (n = 43) or sham (n = 42) treatment. Participants underwent 3 treatments at monthly intervals. Laser treatments were performed with standard settings (40-watt power), while sham treatments were conducted with low settings that have no tissue effect. Local anesthesia cream was employed for all procedures, and a plume evacuator was used to remove visual and olfactory effects from laser smoke.

To maintain blinding, different clinicians performed assessments and treatments. Symptom severity assessments were based on a visual analog scale (VAS) and the Vulvovaginal Symptom Questionnaire (VSQ), with a minimal clinically important difference specified as a 50% decrease in severity scores of both assessment tools. Change in severity of symptoms, including dyspareunia, dysuria, vaginal dryness, and burning and itching, was assessed at 12 months. Quality of life, the Vaginal Health Index (VHI) score, and vaginal histology were among the secondary outcomes. In addition, vaginal biopsies were performed at baseline and 6 months after study treatment.

Among the 78 women (91.7%) who completed the 12-month evaluations, the mean age was approximately 57, more than 95% were White, and approximately half were sexually active.

Results. For the laser and sham treatment groups, at 12 months no significant differences were noted for change in overall symptoms or in the most severe symptom. Many participants who received laser or sham treatment reported an improvement in vaginal symptoms 12 months following treatment.

The VAS score for a change in symptom severity in the laser-treated group compared with the sham-treated group was -17.2 versus -26.6, a difference of 9.4 (95% confidence interval [CI], -28.6 to 47.5), while the VAS score for the most severe symptom was -24.5 versus -20.4, a difference of -4.1 (95% CI, -32.5 to 24.3). The VSQ score was, respectively, -3.1 versus -1.6 (difference, -1.5 [95% CI, -5.9 to 3.0]). The mean quality of life score showed no significant differences between the laser and the sham group (6.3 vs 1.4, a difference of 4.8 [95% CI, -3.9 to 13.5]). The VHI score was 0.9 in the laser group versus 1.3 in the sham group, for a difference of -0.4 (95% CI, -4.3 to 3.6). Likewise, the proportion of participants who noted a reduction of more than 50% in bother from their most severe symptoms was similar in the 2 groups. Similarly, changes in vaginal histology were similar in the laser and sham groups.

The proportion of participants who reported adverse events, including transient vaginal discomfort, discharge, or urinary tract symptoms, was similar in the 2 groups.

Study strengths and limitations

Although other randomized studies of fractionated laser therapy for GSM have been reported, this Australian trial is the largest and longest to date and also is the first to have used sham-treated controls.

Breast cancer survivors represent a group of patients for whom treatment of GSM can be a major conundrum—induced menopause that often results when combination chemotherapy is employed in premenopausal survivors can result in severe GSM; use of aromatase inhibitors likewise can cause bothersome GSM symptoms. Since the US Food and Drug Administration lists a personal history of breast cancer as a contraindication to use of any estrogen formulation, breast cancer survivors represent a population targeted by physicians offering vaginal laser treatment. Accordingly, that approximately 50% of trial participants were breast cancer survivors means the investigators were assessing the impact of laser therapy in a population of particular clinical relevance. Of note, as with participants overall, laser therapy when employed in breast cancer survivors did not result in outcomes distinct from sham treatments.² ●

Li FG, Maheux-Lacroix S, Deans R, et al. Effect of fractional carbon dioxide laser vs sham treatment on symptom severity in women with postmenopausal vaginal symptoms: a randomized clinical trial. JAMA. 2021;326:1381-1389. doi: 10.1001/jama.2021.14892.

EXPERT COMMENTARY

Symptomatic vaginal atrophy, also referred to as genitourinary syndrome of menopause (GSM), is common and tends to progress without treatment. When use of over-the-counter lubricants and/or moisturizers are not sufficient to address symptoms, vaginal estrogen has represented the mainstay of treatment for this condition and effectively addresses GSM symptoms.¹ In recent years, some physicians have been offering vaginal carbon dioxide (CO2) laser therapy as an alternative to vaginal estrogen in the treatment of GSM; however, the efficacy of laser therapy in this setting has been uncertain.

Li and colleagues conducted a double-blind randomized trial in postmenopausal women with bothersome vaginal symptoms to compare the efficacy of the fractional CO2 vaginal laser with that of sham treatment.

Details of the study

Investigators (who received no funding from any relevant commercial entity) at a teaching hospital in Sydney, Australia, randomly assigned 85 women with menopausal symptoms suggestive of GSM to laser (n = 43) or sham (n = 42) treatment. Participants underwent 3 treatments at monthly intervals. Laser treatments were performed with standard settings (40-watt power), while sham treatments were conducted with low settings that have no tissue effect. Local anesthesia cream was employed for all procedures, and a plume evacuator was used to remove visual and olfactory effects from laser smoke.

To maintain blinding, different clinicians performed assessments and treatments. Symptom severity assessments were based on a visual analog scale (VAS) and the Vulvovaginal Symptom Questionnaire (VSQ), with a minimal clinically important difference specified as a 50% decrease in severity scores of both assessment tools. Change in severity of symptoms, including dyspareunia, dysuria, vaginal dryness, and burning and itching, was assessed at 12 months. Quality of life, the Vaginal Health Index (VHI) score, and vaginal histology were among the secondary outcomes. In addition, vaginal biopsies were performed at baseline and 6 months after study treatment.

Among the 78 women (91.7%) who completed the 12-month evaluations, the mean age was approximately 57, more than 95% were White, and approximately half were sexually active.

Results. For the laser and sham treatment groups, at 12 months no significant differences were noted for change in overall symptoms or in the most severe symptom. Many participants who received laser or sham treatment reported an improvement in vaginal symptoms 12 months following treatment.

The VAS score for a change in symptom severity in the laser-treated group compared with the sham-treated group was -17.2 versus -26.6, a difference of 9.4 (95% confidence interval [CI], -28.6 to 47.5), while the VAS score for the most severe symptom was -24.5 versus -20.4, a difference of -4.1 (95% CI, -32.5 to 24.3). The VSQ score was, respectively, -3.1 versus -1.6 (difference, -1.5 [95% CI, -5.9 to 3.0]). The mean quality of life score showed no significant differences between the laser and the sham group (6.3 vs 1.4, a difference of 4.8 [95% CI, -3.9 to 13.5]). The VHI score was 0.9 in the laser group versus 1.3 in the sham group, for a difference of -0.4 (95% CI, -4.3 to 3.6). Likewise, the proportion of participants who noted a reduction of more than 50% in bother from their most severe symptoms was similar in the 2 groups. Similarly, changes in vaginal histology were similar in the laser and sham groups.

The proportion of participants who reported adverse events, including transient vaginal discomfort, discharge, or urinary tract symptoms, was similar in the 2 groups.

Study strengths and limitations

Although other randomized studies of fractionated laser therapy for GSM have been reported, this Australian trial is the largest and longest to date and also is the first to have used sham-treated controls.

Breast cancer survivors represent a group of patients for whom treatment of GSM can be a major conundrum—induced menopause that often results when combination chemotherapy is employed in premenopausal survivors can result in severe GSM; use of aromatase inhibitors likewise can cause bothersome GSM symptoms. Since the US Food and Drug Administration lists a personal history of breast cancer as a contraindication to use of any estrogen formulation, breast cancer survivors represent a population targeted by physicians offering vaginal laser treatment. Accordingly, that approximately 50% of trial participants were breast cancer survivors means the investigators were assessing the impact of laser therapy in a population of particular clinical relevance. Of note, as with participants overall, laser therapy when employed in breast cancer survivors did not result in outcomes distinct from sham treatments.² ●

Li FG, Maheux-Lacroix S, Deans R, et al. Effect of fractional carbon dioxide laser vs sham treatment on symptom severity in women with postmenopausal vaginal symptoms: a randomized clinical trial. JAMA. 2021;326:1381-1389. doi: 10.1001/jama.2021.14892.

EXPERT COMMENTARY

Symptomatic vaginal atrophy, also referred to as genitourinary syndrome of menopause (GSM), is common and tends to progress without treatment. When use of over-the-counter lubricants and/or moisturizers are not sufficient to address symptoms, vaginal estrogen has represented the mainstay of treatment for this condition and effectively addresses GSM symptoms.¹ In recent years, some physicians have been offering vaginal carbon dioxide (CO2) laser therapy as an alternative to vaginal estrogen in the treatment of GSM; however, the efficacy of laser therapy in this setting has been uncertain.

Li and colleagues conducted a double-blind randomized trial in postmenopausal women with bothersome vaginal symptoms to compare the efficacy of the fractional CO2 vaginal laser with that of sham treatment.

Details of the study

Investigators (who received no funding from any relevant commercial entity) at a teaching hospital in Sydney, Australia, randomly assigned 85 women with menopausal symptoms suggestive of GSM to laser (n = 43) or sham (n = 42) treatment. Participants underwent 3 treatments at monthly intervals. Laser treatments were performed with standard settings (40-watt power), while sham treatments were conducted with low settings that have no tissue effect. Local anesthesia cream was employed for all procedures, and a plume evacuator was used to remove visual and olfactory effects from laser smoke.

To maintain blinding, different clinicians performed assessments and treatments. Symptom severity assessments were based on a visual analog scale (VAS) and the Vulvovaginal Symptom Questionnaire (VSQ), with a minimal clinically important difference specified as a 50% decrease in severity scores of both assessment tools. Change in severity of symptoms, including dyspareunia, dysuria, vaginal dryness, and burning and itching, was assessed at 12 months. Quality of life, the Vaginal Health Index (VHI) score, and vaginal histology were among the secondary outcomes. In addition, vaginal biopsies were performed at baseline and 6 months after study treatment.

Among the 78 women (91.7%) who completed the 12-month evaluations, the mean age was approximately 57, more than 95% were White, and approximately half were sexually active.

Results. For the laser and sham treatment groups, at 12 months no significant differences were noted for change in overall symptoms or in the most severe symptom. Many participants who received laser or sham treatment reported an improvement in vaginal symptoms 12 months following treatment.

The VAS score for a change in symptom severity in the laser-treated group compared with the sham-treated group was -17.2 versus -26.6, a difference of 9.4 (95% confidence interval [CI], -28.6 to 47.5), while the VAS score for the most severe symptom was -24.5 versus -20.4, a difference of -4.1 (95% CI, -32.5 to 24.3). The VSQ score was, respectively, -3.1 versus -1.6 (difference, -1.5 [95% CI, -5.9 to 3.0]). The mean quality of life score showed no significant differences between the laser and the sham group (6.3 vs 1.4, a difference of 4.8 [95% CI, -3.9 to 13.5]). The VHI score was 0.9 in the laser group versus 1.3 in the sham group, for a difference of -0.4 (95% CI, -4.3 to 3.6). Likewise, the proportion of participants who noted a reduction of more than 50% in bother from their most severe symptoms was similar in the 2 groups. Similarly, changes in vaginal histology were similar in the laser and sham groups.

The proportion of participants who reported adverse events, including transient vaginal discomfort, discharge, or urinary tract symptoms, was similar in the 2 groups.

Study strengths and limitations

Although other randomized studies of fractionated laser therapy for GSM have been reported, this Australian trial is the largest and longest to date and also is the first to have used sham-treated controls.

Breast cancer survivors represent a group of patients for whom treatment of GSM can be a major conundrum—induced menopause that often results when combination chemotherapy is employed in premenopausal survivors can result in severe GSM; use of aromatase inhibitors likewise can cause bothersome GSM symptoms. Since the US Food and Drug Administration lists a personal history of breast cancer as a contraindication to use of any estrogen formulation, breast cancer survivors represent a population targeted by physicians offering vaginal laser treatment. Accordingly, that approximately 50% of trial participants were breast cancer survivors means the investigators were assessing the impact of laser therapy in a population of particular clinical relevance. Of note, as with participants overall, laser therapy when employed in breast cancer survivors did not result in outcomes distinct from sham treatments.² ●