Pediatrics

Exposure to arsenic and other metals in utero is associated with an elevated risk for atopic dermatitis in children, researchers report in a study published Oct. 27, 2021, in JAMA Network Open.

In this multicenter cohort study, led by epidemiologist Shu-Li Wang, PhD, of the National Institute of Environmental Health Sciences, in Taiwan, each twofold increase in prenatal arsenic level correlated with a 2.4-fold higher rate of atopic dermatitis in 4-year-olds.

Atopic diseases have been on the rise. Eczema (atopic dermatitis) is the first stage of the so-called atopic march, followed by food allergies, allergic rhinitis, and asthma later in childhood. Previous research has linked heavy metal exposure to allergic diseases in adults. In another study by Dr. Wang and colleagues that was published in 2021, prenatal and early-life arsenic exposure was found to correlate with higher rates of allergic rhinitis and asthma in children. In that study, the participants were followed every 2-3 years through the age of 14 as part of the Taiwan Maternal and Infant Cohort Study.

The new study included 370 mother and child pairs who were enrolled in that birth cohort study between October 2012 and May 2015. During their third trimester of pregnancy, women completed questionnaires about their lifestyle, diet, and living environment. In addition, their height, weight, and blood pressure were recorded, and urine samples were taken. In follow-up interviews 3-4 years later, the mothers were asked whether their child had ever been diagnosed with atopic dermatitis.

The researchers used an inductively coupled plasma mass spectrometer to analyze the participants’ urine samples. They assessed for exposures in utero to eight metals: arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc.

Each unit increase of an index that estimates the combined exposure to these metals during pregnancy was associated with 63% higher odds of atopic dermatitis in the children by age 4. The researchers adjusted for parental allergies (yes or no), mother’s educational level (<12 years, 13-16 years, or >16 years), geographic area (central or eastern Taiwan), exposure to tobacco smoke during pregnancy, and the child’s gender. Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal coexposure index.

A wealth of previous research links arsenic exposure during adulthood to skin disease and immune dysfunction. Early-life arsenic exposure has been linked with elevated risk for various adult disorders, including cancer, diabetes, and heart disease, years later. In light of such research, “the findings in this paper are not surprising,” J. Christopher States, PhD, director of the Center for Integrative Environmental Health Science at the University of Louisville (Ky.), told this news organization. “Low-level arsenic exposure does not cause disease immediately, but it does appear to have long-lasting effects, making individuals susceptible to ‘second hits’ with another environmental agent.”

Research into the molecular mechanisms for these links has shown that arsenic and cadmium exposure can promote allergic phenotypes in immune cells. “We think the toxic metals activate the alarmin pathway, thus inducing innate lymphoid cells, then activating T-helper 2 cells, which drive immunoglobulin E production and breakdown of the epithelium and promotion of allergies,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University. Dr. Nadeau led that study, published in 2017 in PLOS One, along with epidemiologist Margaret Karagas, PhD, of Geisel School of Medicine at Dartmouth, Hanover, N.H.

As for what pregnant women can do to minimize their exposure to heavy metals, “that is a difficult problem and primarily a function of where one lives,” said Dr. States.

Drinking water and food are major sources of arsenic exposure. Groundwater is naturally contaminated with arsenic deposits that seep in from bedrock, said Dr. States. The U.S. Environmental Protection Agency regulates arsenic levels in public drinking water that is supplied to more than a few thousand people. However, small water supplies and private wells are unregulated, he said, and having these water sources tested for arsenic or fitted with systems to reduce arsenic can be very expensive.

Among foods, rice can have high concentrations of arsenic, Dr. Karagas told this news organization. To minimize arsenic exposure through the diet, women can limit rice-based foods, according to a web-based tool developed by her and coworkers.

In addition, tobacco smoke is a major source of cadmium exposure and a moderate source of arsenic exposure, Dr. States noted. Women can reduce their exposure to these metals by avoiding tobacco and secondhand smoke.

The study was supported by grants from the National Health Research Institutes, Chung Shan Medical University Hospital, Taiwan Ministry of Science and Technology, and the Taiwan Environmental Protection Administration. The authors and quoted experts report no relevant financial relationships.

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

Exposure to arsenic and other metals in utero is associated with an elevated risk for atopic dermatitis in children, researchers report in a study published Oct. 27, 2021, in JAMA Network Open.

In this multicenter cohort study, led by epidemiologist Shu-Li Wang, PhD, of the National Institute of Environmental Health Sciences, in Taiwan, each twofold increase in prenatal arsenic level correlated with a 2.4-fold higher rate of atopic dermatitis in 4-year-olds.

Atopic diseases have been on the rise. Eczema (atopic dermatitis) is the first stage of the so-called atopic march, followed by food allergies, allergic rhinitis, and asthma later in childhood. Previous research has linked heavy metal exposure to allergic diseases in adults. In another study by Dr. Wang and colleagues that was published in 2021, prenatal and early-life arsenic exposure was found to correlate with higher rates of allergic rhinitis and asthma in children. In that study, the participants were followed every 2-3 years through the age of 14 as part of the Taiwan Maternal and Infant Cohort Study.

The new study included 370 mother and child pairs who were enrolled in that birth cohort study between October 2012 and May 2015. During their third trimester of pregnancy, women completed questionnaires about their lifestyle, diet, and living environment. In addition, their height, weight, and blood pressure were recorded, and urine samples were taken. In follow-up interviews 3-4 years later, the mothers were asked whether their child had ever been diagnosed with atopic dermatitis.

The researchers used an inductively coupled plasma mass spectrometer to analyze the participants’ urine samples. They assessed for exposures in utero to eight metals: arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc.

Each unit increase of an index that estimates the combined exposure to these metals during pregnancy was associated with 63% higher odds of atopic dermatitis in the children by age 4. The researchers adjusted for parental allergies (yes or no), mother’s educational level (<12 years, 13-16 years, or >16 years), geographic area (central or eastern Taiwan), exposure to tobacco smoke during pregnancy, and the child’s gender. Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal coexposure index.

A wealth of previous research links arsenic exposure during adulthood to skin disease and immune dysfunction. Early-life arsenic exposure has been linked with elevated risk for various adult disorders, including cancer, diabetes, and heart disease, years later. In light of such research, “the findings in this paper are not surprising,” J. Christopher States, PhD, director of the Center for Integrative Environmental Health Science at the University of Louisville (Ky.), told this news organization. “Low-level arsenic exposure does not cause disease immediately, but it does appear to have long-lasting effects, making individuals susceptible to ‘second hits’ with another environmental agent.”

Research into the molecular mechanisms for these links has shown that arsenic and cadmium exposure can promote allergic phenotypes in immune cells. “We think the toxic metals activate the alarmin pathway, thus inducing innate lymphoid cells, then activating T-helper 2 cells, which drive immunoglobulin E production and breakdown of the epithelium and promotion of allergies,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University. Dr. Nadeau led that study, published in 2017 in PLOS One, along with epidemiologist Margaret Karagas, PhD, of Geisel School of Medicine at Dartmouth, Hanover, N.H.

As for what pregnant women can do to minimize their exposure to heavy metals, “that is a difficult problem and primarily a function of where one lives,” said Dr. States.

Drinking water and food are major sources of arsenic exposure. Groundwater is naturally contaminated with arsenic deposits that seep in from bedrock, said Dr. States. The U.S. Environmental Protection Agency regulates arsenic levels in public drinking water that is supplied to more than a few thousand people. However, small water supplies and private wells are unregulated, he said, and having these water sources tested for arsenic or fitted with systems to reduce arsenic can be very expensive.

Among foods, rice can have high concentrations of arsenic, Dr. Karagas told this news organization. To minimize arsenic exposure through the diet, women can limit rice-based foods, according to a web-based tool developed by her and coworkers.

In addition, tobacco smoke is a major source of cadmium exposure and a moderate source of arsenic exposure, Dr. States noted. Women can reduce their exposure to these metals by avoiding tobacco and secondhand smoke.

The study was supported by grants from the National Health Research Institutes, Chung Shan Medical University Hospital, Taiwan Ministry of Science and Technology, and the Taiwan Environmental Protection Administration. The authors and quoted experts report no relevant financial relationships.

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

Exposure to arsenic and other metals in utero is associated with an elevated risk for atopic dermatitis in children, researchers report in a study published Oct. 27, 2021, in JAMA Network Open.

In this multicenter cohort study, led by epidemiologist Shu-Li Wang, PhD, of the National Institute of Environmental Health Sciences, in Taiwan, each twofold increase in prenatal arsenic level correlated with a 2.4-fold higher rate of atopic dermatitis in 4-year-olds.

Atopic diseases have been on the rise. Eczema (atopic dermatitis) is the first stage of the so-called atopic march, followed by food allergies, allergic rhinitis, and asthma later in childhood. Previous research has linked heavy metal exposure to allergic diseases in adults. In another study by Dr. Wang and colleagues that was published in 2021, prenatal and early-life arsenic exposure was found to correlate with higher rates of allergic rhinitis and asthma in children. In that study, the participants were followed every 2-3 years through the age of 14 as part of the Taiwan Maternal and Infant Cohort Study.

The new study included 370 mother and child pairs who were enrolled in that birth cohort study between October 2012 and May 2015. During their third trimester of pregnancy, women completed questionnaires about their lifestyle, diet, and living environment. In addition, their height, weight, and blood pressure were recorded, and urine samples were taken. In follow-up interviews 3-4 years later, the mothers were asked whether their child had ever been diagnosed with atopic dermatitis.

The researchers used an inductively coupled plasma mass spectrometer to analyze the participants’ urine samples. They assessed for exposures in utero to eight metals: arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc.

Each unit increase of an index that estimates the combined exposure to these metals during pregnancy was associated with 63% higher odds of atopic dermatitis in the children by age 4. The researchers adjusted for parental allergies (yes or no), mother’s educational level (<12 years, 13-16 years, or >16 years), geographic area (central or eastern Taiwan), exposure to tobacco smoke during pregnancy, and the child’s gender. Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal coexposure index.

A wealth of previous research links arsenic exposure during adulthood to skin disease and immune dysfunction. Early-life arsenic exposure has been linked with elevated risk for various adult disorders, including cancer, diabetes, and heart disease, years later. In light of such research, “the findings in this paper are not surprising,” J. Christopher States, PhD, director of the Center for Integrative Environmental Health Science at the University of Louisville (Ky.), told this news organization. “Low-level arsenic exposure does not cause disease immediately, but it does appear to have long-lasting effects, making individuals susceptible to ‘second hits’ with another environmental agent.”

Research into the molecular mechanisms for these links has shown that arsenic and cadmium exposure can promote allergic phenotypes in immune cells. “We think the toxic metals activate the alarmin pathway, thus inducing innate lymphoid cells, then activating T-helper 2 cells, which drive immunoglobulin E production and breakdown of the epithelium and promotion of allergies,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University. Dr. Nadeau led that study, published in 2017 in PLOS One, along with epidemiologist Margaret Karagas, PhD, of Geisel School of Medicine at Dartmouth, Hanover, N.H.

As for what pregnant women can do to minimize their exposure to heavy metals, “that is a difficult problem and primarily a function of where one lives,” said Dr. States.

Drinking water and food are major sources of arsenic exposure. Groundwater is naturally contaminated with arsenic deposits that seep in from bedrock, said Dr. States. The U.S. Environmental Protection Agency regulates arsenic levels in public drinking water that is supplied to more than a few thousand people. However, small water supplies and private wells are unregulated, he said, and having these water sources tested for arsenic or fitted with systems to reduce arsenic can be very expensive.

Among foods, rice can have high concentrations of arsenic, Dr. Karagas told this news organization. To minimize arsenic exposure through the diet, women can limit rice-based foods, according to a web-based tool developed by her and coworkers.

In addition, tobacco smoke is a major source of cadmium exposure and a moderate source of arsenic exposure, Dr. States noted. Women can reduce their exposure to these metals by avoiding tobacco and secondhand smoke.

The study was supported by grants from the National Health Research Institutes, Chung Shan Medical University Hospital, Taiwan Ministry of Science and Technology, and the Taiwan Environmental Protection Administration. The authors and quoted experts report no relevant financial relationships.

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

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

The anticipated biennial peak in acute flaccid myelitis cases did not occur in 2020, possibly because of “nonpharmaceutical interventions implemented during the COVID-19 pandemic,” suggested researchers at the Centers for Disease Control and Prevention.

Acute flaccid myelitis (AFM) is an uncommon but serious complication of some viral infections, including West Nile virus and nonpolio enteroviruses. It is “characterized by sudden onset of limb weakness and lesions in the gray matter of the spinal cord,” they said, and more than 90% of cases occur in young children.

Cases of AFM, which can lead to respiratory insufficiency and permanent paralysis, spiked during the late summer and early fall in 2014, 2016, and 2018 and were expected to do so again in 2020, Sarah Kidd, MD, and associates at the division of viral diseases at the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta, said in the Morbidity and Mortality Weekly Report.

Monthly peaks in those previous years – each occurring in September – reached 51 cases in 2014, 43 cases in 2016, and 88 cases in 2018, but in 2020 there was only 1 case reported in September, with a high of 4 coming in May, CDC data show. The total number of cases for 2020 (32) was, in fact, lower than in 2019, when 47 were reported.

The investigators’ main objective was to see if there were any differences between the 2018 and 2019-2020 cases. Reports from state health departments to the CDC showed that, in 2019-2020, “patients were older; more likely to have lower limb involvement; and less likely to have upper limb involvement, prodromal illness, [cerebrospinal fluid] pleocytosis, or specimens that tested positive for EV [enterovirus]-D68” than patients from 2018, Dr. Kidd and associates said.

Mask wearing and reduced in-school attendance may have decreased circulation of EV-D68 – the enterovirus type most often detected in the stool and respiratory specimens of AFM patients – as was seen with other respiratory viruses, such as influenza and respiratory syncytial virus, in 2020. Previous studies have suggested that EV-D68 drives the increases in cases during peak years, the researchers noted.

The absence of such an increase “in 2020 reflects a deviation from the previously observed biennial pattern, and it is unclear when the next increase in AFM should be expected. Clinicians should continue to maintain vigilance and suspect AFM in any child with acute flaccid limb weakness, particularly in the setting of recent febrile or respiratory illness,” they wrote.
 

[email protected]

The anticipated biennial peak in acute flaccid myelitis cases did not occur in 2020, possibly because of “nonpharmaceutical interventions implemented during the COVID-19 pandemic,” suggested researchers at the Centers for Disease Control and Prevention.

Acute flaccid myelitis (AFM) is an uncommon but serious complication of some viral infections, including West Nile virus and nonpolio enteroviruses. It is “characterized by sudden onset of limb weakness and lesions in the gray matter of the spinal cord,” they said, and more than 90% of cases occur in young children.

Cases of AFM, which can lead to respiratory insufficiency and permanent paralysis, spiked during the late summer and early fall in 2014, 2016, and 2018 and were expected to do so again in 2020, Sarah Kidd, MD, and associates at the division of viral diseases at the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta, said in the Morbidity and Mortality Weekly Report.

Monthly peaks in those previous years – each occurring in September – reached 51 cases in 2014, 43 cases in 2016, and 88 cases in 2018, but in 2020 there was only 1 case reported in September, with a high of 4 coming in May, CDC data show. The total number of cases for 2020 (32) was, in fact, lower than in 2019, when 47 were reported.

The investigators’ main objective was to see if there were any differences between the 2018 and 2019-2020 cases. Reports from state health departments to the CDC showed that, in 2019-2020, “patients were older; more likely to have lower limb involvement; and less likely to have upper limb involvement, prodromal illness, [cerebrospinal fluid] pleocytosis, or specimens that tested positive for EV [enterovirus]-D68” than patients from 2018, Dr. Kidd and associates said.

Mask wearing and reduced in-school attendance may have decreased circulation of EV-D68 – the enterovirus type most often detected in the stool and respiratory specimens of AFM patients – as was seen with other respiratory viruses, such as influenza and respiratory syncytial virus, in 2020. Previous studies have suggested that EV-D68 drives the increases in cases during peak years, the researchers noted.

The absence of such an increase “in 2020 reflects a deviation from the previously observed biennial pattern, and it is unclear when the next increase in AFM should be expected. Clinicians should continue to maintain vigilance and suspect AFM in any child with acute flaccid limb weakness, particularly in the setting of recent febrile or respiratory illness,” they wrote.
 

[email protected]

The anticipated biennial peak in acute flaccid myelitis cases did not occur in 2020, possibly because of “nonpharmaceutical interventions implemented during the COVID-19 pandemic,” suggested researchers at the Centers for Disease Control and Prevention.

Acute flaccid myelitis (AFM) is an uncommon but serious complication of some viral infections, including West Nile virus and nonpolio enteroviruses. It is “characterized by sudden onset of limb weakness and lesions in the gray matter of the spinal cord,” they said, and more than 90% of cases occur in young children.

Cases of AFM, which can lead to respiratory insufficiency and permanent paralysis, spiked during the late summer and early fall in 2014, 2016, and 2018 and were expected to do so again in 2020, Sarah Kidd, MD, and associates at the division of viral diseases at the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta, said in the Morbidity and Mortality Weekly Report.

Monthly peaks in those previous years – each occurring in September – reached 51 cases in 2014, 43 cases in 2016, and 88 cases in 2018, but in 2020 there was only 1 case reported in September, with a high of 4 coming in May, CDC data show. The total number of cases for 2020 (32) was, in fact, lower than in 2019, when 47 were reported.

The investigators’ main objective was to see if there were any differences between the 2018 and 2019-2020 cases. Reports from state health departments to the CDC showed that, in 2019-2020, “patients were older; more likely to have lower limb involvement; and less likely to have upper limb involvement, prodromal illness, [cerebrospinal fluid] pleocytosis, or specimens that tested positive for EV [enterovirus]-D68” than patients from 2018, Dr. Kidd and associates said.

Mask wearing and reduced in-school attendance may have decreased circulation of EV-D68 – the enterovirus type most often detected in the stool and respiratory specimens of AFM patients – as was seen with other respiratory viruses, such as influenza and respiratory syncytial virus, in 2020. Previous studies have suggested that EV-D68 drives the increases in cases during peak years, the researchers noted.

The absence of such an increase “in 2020 reflects a deviation from the previously observed biennial pattern, and it is unclear when the next increase in AFM should be expected. Clinicians should continue to maintain vigilance and suspect AFM in any child with acute flaccid limb weakness, particularly in the setting of recent febrile or respiratory illness,” they wrote.
 

[email protected]

The Diagnosis: Infantile Digital Fibromatosis

Infantile digital fibromatosis (IDF) is a rare benign neoplasm of infancy prone to recurrence after resection but not to metastasis. It usually is limited to the fingers and toes.¹ One-third of cases occur at birth. Most patients develop clinical symptoms within the first year of life, but presentation can occur in adolescents and adults. The exact etiology and pathogenesis of IDF remain unclear, but trauma is thought to be a trigger.

Physical examination reveals single or multiple smooth, round, pink papules or nodules confined to the sides and backs of the fingers, sparing the thumb and first toe.^2,3 The nodules typically are firm, less than 2 cm in diameter, and often painless. Infantile digital fibromatosis exhibits an indolent progression followed by a rapid growth phase during several months, which may lead to functional impairment and joint deformities.^4,5 Histopathology displays spindle cells with eosinophilic cytoplasmic inclusions that range from round to oval with uneven distribution, lack of refraction, and a large size difference (3–15 μm).6 The inclusions are deep red with Masson trichrome staining and can express smooth muscle actin and calponin. Tumor cells usually express vimentin, smooth muscle actin, calponin, and desmin but fail to express S-100 protein. The Ki67 proliferation index is 2% to 15%.^6,7

Nonsurgical treatments for IDF include topical imiquimod, topical or intradermal injection of glucocorticoids, and intradermal injection of 5-fluorouracil. Complete resection should be reserved for cases with invasive growth that may lead to joint deformities, tendon or ligament involvement, digit or contracture deformity, and complications such as decreased joint mobility. Although there is a recurrence rate of up to 50% after excision, most lesions eventually will spontaneously regress and will leave no scar.^8-10

The clinical and histopathologic differential diagnoses of IDF include other cutaneous diseases that occur in the digits. A dermatofibroma is a round, firm, fibrohistiocytic nodule that mainly occurs on the extensor limbs. Histopathology includes both fibrous and cellular types.¹¹ Histologic analysis shows an ill-defined dermal proliferation of spindled fibroblasts with pale eosinophilic cytoplasm and bland fusiform nuclei growing in bands or fascicles that trap collagen fibers at the periphery (Figure 1). Generally, dermatofibromas have marked epidermal hyperplasia, which differs from IDF.

A digital myxoid cyst is characterized by a fleshcolored, hemispherical, and translucent cystic nodule that arises from the dorsum of the distal interphalangeal joint.¹² It commonly is associated with injury and chronic pressure. Translucent viscous liquid may flow out when the cyst is punctured, a hallmark feature of this entity. Clinical variants of myxoid cyst include myxomatous and ganglion types. Histopathology reveals excessive mucin deposited in the dermis, and the surrounding collagen is compressed to form the pseudocyst (Figure 2).

A giant cell tumor of the tendon sheath presents with asymptomatic nodules or lumps. Lesions frequently are localized to the tendon sheath, especially on the fingers and wrists, with no malignant tendency or propensity for spontaneous regression.¹³ The local recurrence rate is as high as 45%, which is related to surgical resection insufficiency.¹⁴ Histopathologic examination shows lobulated tumor tissue surrounded by dense fibrosis. The tumor cells are histiocytic with scattered giant cells (Figure 3). The characteristic osteoclastlike giant cells have eosinophilic cytoplasm and irregularly arranged nuclei in varying numbers.

Keloids are connective tissue hyperplasias caused by skin injury. Histopathologically, keloids are characterized by nodules of thick hyalinized collagen bundles and whorled fibroblasts (Figure 4). No inclusions in the fibroblasts and a history of trauma can differentiate keloids from IDF.

The Diagnosis: Infantile Digital Fibromatosis

Infantile digital fibromatosis (IDF) is a rare benign neoplasm of infancy prone to recurrence after resection but not to metastasis. It usually is limited to the fingers and toes.¹ One-third of cases occur at birth. Most patients develop clinical symptoms within the first year of life, but presentation can occur in adolescents and adults. The exact etiology and pathogenesis of IDF remain unclear, but trauma is thought to be a trigger.

Physical examination reveals single or multiple smooth, round, pink papules or nodules confined to the sides and backs of the fingers, sparing the thumb and first toe.^2,3 The nodules typically are firm, less than 2 cm in diameter, and often painless. Infantile digital fibromatosis exhibits an indolent progression followed by a rapid growth phase during several months, which may lead to functional impairment and joint deformities.^4,5 Histopathology displays spindle cells with eosinophilic cytoplasmic inclusions that range from round to oval with uneven distribution, lack of refraction, and a large size difference (3–15 μm).6 The inclusions are deep red with Masson trichrome staining and can express smooth muscle actin and calponin. Tumor cells usually express vimentin, smooth muscle actin, calponin, and desmin but fail to express S-100 protein. The Ki67 proliferation index is 2% to 15%.^6,7

Nonsurgical treatments for IDF include topical imiquimod, topical or intradermal injection of glucocorticoids, and intradermal injection of 5-fluorouracil. Complete resection should be reserved for cases with invasive growth that may lead to joint deformities, tendon or ligament involvement, digit or contracture deformity, and complications such as decreased joint mobility. Although there is a recurrence rate of up to 50% after excision, most lesions eventually will spontaneously regress and will leave no scar.^8-10

The clinical and histopathologic differential diagnoses of IDF include other cutaneous diseases that occur in the digits. A dermatofibroma is a round, firm, fibrohistiocytic nodule that mainly occurs on the extensor limbs. Histopathology includes both fibrous and cellular types.¹¹ Histologic analysis shows an ill-defined dermal proliferation of spindled fibroblasts with pale eosinophilic cytoplasm and bland fusiform nuclei growing in bands or fascicles that trap collagen fibers at the periphery (Figure 1). Generally, dermatofibromas have marked epidermal hyperplasia, which differs from IDF.

A digital myxoid cyst is characterized by a fleshcolored, hemispherical, and translucent cystic nodule that arises from the dorsum of the distal interphalangeal joint.¹² It commonly is associated with injury and chronic pressure. Translucent viscous liquid may flow out when the cyst is punctured, a hallmark feature of this entity. Clinical variants of myxoid cyst include myxomatous and ganglion types. Histopathology reveals excessive mucin deposited in the dermis, and the surrounding collagen is compressed to form the pseudocyst (Figure 2).

A giant cell tumor of the tendon sheath presents with asymptomatic nodules or lumps. Lesions frequently are localized to the tendon sheath, especially on the fingers and wrists, with no malignant tendency or propensity for spontaneous regression.¹³ The local recurrence rate is as high as 45%, which is related to surgical resection insufficiency.¹⁴ Histopathologic examination shows lobulated tumor tissue surrounded by dense fibrosis. The tumor cells are histiocytic with scattered giant cells (Figure 3). The characteristic osteoclastlike giant cells have eosinophilic cytoplasm and irregularly arranged nuclei in varying numbers.

Keloids are connective tissue hyperplasias caused by skin injury. Histopathologically, keloids are characterized by nodules of thick hyalinized collagen bundles and whorled fibroblasts (Figure 4). No inclusions in the fibroblasts and a history of trauma can differentiate keloids from IDF.

The Diagnosis: Infantile Digital Fibromatosis

Infantile digital fibromatosis (IDF) is a rare benign neoplasm of infancy prone to recurrence after resection but not to metastasis. It usually is limited to the fingers and toes.¹ One-third of cases occur at birth. Most patients develop clinical symptoms within the first year of life, but presentation can occur in adolescents and adults. The exact etiology and pathogenesis of IDF remain unclear, but trauma is thought to be a trigger.

Physical examination reveals single or multiple smooth, round, pink papules or nodules confined to the sides and backs of the fingers, sparing the thumb and first toe.^2,3 The nodules typically are firm, less than 2 cm in diameter, and often painless. Infantile digital fibromatosis exhibits an indolent progression followed by a rapid growth phase during several months, which may lead to functional impairment and joint deformities.^4,5 Histopathology displays spindle cells with eosinophilic cytoplasmic inclusions that range from round to oval with uneven distribution, lack of refraction, and a large size difference (3–15 μm).6 The inclusions are deep red with Masson trichrome staining and can express smooth muscle actin and calponin. Tumor cells usually express vimentin, smooth muscle actin, calponin, and desmin but fail to express S-100 protein. The Ki67 proliferation index is 2% to 15%.^6,7

Nonsurgical treatments for IDF include topical imiquimod, topical or intradermal injection of glucocorticoids, and intradermal injection of 5-fluorouracil. Complete resection should be reserved for cases with invasive growth that may lead to joint deformities, tendon or ligament involvement, digit or contracture deformity, and complications such as decreased joint mobility. Although there is a recurrence rate of up to 50% after excision, most lesions eventually will spontaneously regress and will leave no scar.^8-10

The clinical and histopathologic differential diagnoses of IDF include other cutaneous diseases that occur in the digits. A dermatofibroma is a round, firm, fibrohistiocytic nodule that mainly occurs on the extensor limbs. Histopathology includes both fibrous and cellular types.¹¹ Histologic analysis shows an ill-defined dermal proliferation of spindled fibroblasts with pale eosinophilic cytoplasm and bland fusiform nuclei growing in bands or fascicles that trap collagen fibers at the periphery (Figure 1). Generally, dermatofibromas have marked epidermal hyperplasia, which differs from IDF.

A digital myxoid cyst is characterized by a fleshcolored, hemispherical, and translucent cystic nodule that arises from the dorsum of the distal interphalangeal joint.¹² It commonly is associated with injury and chronic pressure. Translucent viscous liquid may flow out when the cyst is punctured, a hallmark feature of this entity. Clinical variants of myxoid cyst include myxomatous and ganglion types. Histopathology reveals excessive mucin deposited in the dermis, and the surrounding collagen is compressed to form the pseudocyst (Figure 2).

A giant cell tumor of the tendon sheath presents with asymptomatic nodules or lumps. Lesions frequently are localized to the tendon sheath, especially on the fingers and wrists, with no malignant tendency or propensity for spontaneous regression.¹³ The local recurrence rate is as high as 45%, which is related to surgical resection insufficiency.¹⁴ Histopathologic examination shows lobulated tumor tissue surrounded by dense fibrosis. The tumor cells are histiocytic with scattered giant cells (Figure 3). The characteristic osteoclastlike giant cells have eosinophilic cytoplasm and irregularly arranged nuclei in varying numbers.

Keloids are connective tissue hyperplasias caused by skin injury. Histopathologically, keloids are characterized by nodules of thick hyalinized collagen bundles and whorled fibroblasts (Figure 4). No inclusions in the fibroblasts and a history of trauma can differentiate keloids from IDF.

Naila Makhani, MD completed medical school training at the University of British Columbia (Vancouver, Canada). This was followed by a residency in child neurology and fellowship in MS and other demyelinating diseases at the University of Toronto and The Hospital for Sick Children (Toronto, Canada). Concurrent with fellowship training, Dr. Makhani obtained a Masters’ degree in public health from Harvard University. Dr. Makhani is the Director of the Pediatric MS Program at Yale and the lead investigator of a multi-center international study examining outcomes following the radiologically isolated syndrome in children.

Q1. Could you please provide an overview of Radiologically Isolated Syndrome ?

A1. Radiologically Isolated Syndrome (RIS) was first described in adults in 2009. Since then it has also been increasingly recognized and diagnosed in children. RIS is diagnosed after an MRI of the brain that the patient has sought for reasons other than suspected multiple sclerosis-- for instance, for evaluation of head trauma or headache. However, unexpectedly or incidentally, the patient’s MRI shows the typical findings that we see in multiple sclerosis, even in the absence of any typical clinical symptoms. RIS is generally considered a rare syndrome.

Q2. You created Yale Medicine’s Pediatric Multiple Sclerosis program which advocates for the eradication of MS. What  criteria defines a rare disease? Does RIS meet these criteria? And if so, how?

A2. The criteria for a rare disease vary, depending on the reference. In the US, a rare disease is defined as a condition that affects fewer than 200,000 people, in total, across the country.  By contrast, in Europe, a disease is considered rare if it affects fewer than one in every 2,000 people within the country’s population.

In the case of RIS, especially in children, we suspect that this is a rare condition, but we don't know for sure, as there have been very few population-based studies. There is one large study that was conducted in Europe that found one case of RIS among approximately 5,000 otherwise healthy children, who were between 7 and 14 years of age.  I think that's our best estimate of the overall prevalence of RIS in children. Using that finding, it likely would qualify as a rare condition, although, as I said, we really don't know for sure, as the prevalence may vary among different populations or age groups.

Q3. How do you investigate and manage RIS in children? What are some of the challenges?  

A3. For children with radiologically isolated syndrome, we usually undertake a comprehensive workup. This includes a detailed clinical neurological exam to ensure that there are no abnormalities that would, for instance, suggest a misdiagnosis of multiple sclerosis or an alternative diagnosis. In addition to the brain MRI, we usually obtain an MRI of the spinal cord to determine whether there is any spinal cord involvement. We also obtain blood tests. We often analyze spinal fluid as well, primarily to exclude other alternative processes that may explain the  MRI findings. A key challenge in this field is that there are currently no formal guidelines for the investigation and management of children with RIS. Collaborations within the pediatric MS community are needed to develop such consensus approaches to standardize care.

Q4. What are the most significant risk factors that indicate children with RIS could one day develop multiple sclerosis?

A4.This is an area of active research within our group. So far, we've found that approximately 42% of children with RIS develop multiple sclerosis in the future; on average, two years following their first abnormal MRI. Therefore, this is a high-risk group for developing  multiple sclerosis in the future. Thus far, we've determined that in children with RIS, it is the presence of abnormal spinal cord imaging and an abnormality in spinal fluid – namely, the presence of oligoclonal bands – that are likely the predictors of whether these children could develop MS in the future. a child’s possible development 

Q5. Based on your recent studies, are there data in children highlighting the potential for higher prevalence  in one population over another?

A5. Thus far, population-based studies assessing RIS, especially in children, have been rare and thus far have not identified particular subgroups with increased prevalence. We do know that the prevalence of multiple sclerosis varies across different age groups and across gender. Whether such associations are also present for RIS is an area of active research.

Naila Makhani, MD completed medical school training at the University of British Columbia (Vancouver, Canada). This was followed by a residency in child neurology and fellowship in MS and other demyelinating diseases at the University of Toronto and The Hospital for Sick Children (Toronto, Canada). Concurrent with fellowship training, Dr. Makhani obtained a Masters’ degree in public health from Harvard University. Dr. Makhani is the Director of the Pediatric MS Program at Yale and the lead investigator of a multi-center international study examining outcomes following the radiologically isolated syndrome in children.

Q1. Could you please provide an overview of Radiologically Isolated Syndrome ?

A1. Radiologically Isolated Syndrome (RIS) was first described in adults in 2009. Since then it has also been increasingly recognized and diagnosed in children. RIS is diagnosed after an MRI of the brain that the patient has sought for reasons other than suspected multiple sclerosis-- for instance, for evaluation of head trauma or headache. However, unexpectedly or incidentally, the patient’s MRI shows the typical findings that we see in multiple sclerosis, even in the absence of any typical clinical symptoms. RIS is generally considered a rare syndrome.

Q2. You created Yale Medicine’s Pediatric Multiple Sclerosis program which advocates for the eradication of MS. What  criteria defines a rare disease? Does RIS meet these criteria? And if so, how?

A2. The criteria for a rare disease vary, depending on the reference. In the US, a rare disease is defined as a condition that affects fewer than 200,000 people, in total, across the country.  By contrast, in Europe, a disease is considered rare if it affects fewer than one in every 2,000 people within the country’s population.

In the case of RIS, especially in children, we suspect that this is a rare condition, but we don't know for sure, as there have been very few population-based studies. There is one large study that was conducted in Europe that found one case of RIS among approximately 5,000 otherwise healthy children, who were between 7 and 14 years of age.  I think that's our best estimate of the overall prevalence of RIS in children. Using that finding, it likely would qualify as a rare condition, although, as I said, we really don't know for sure, as the prevalence may vary among different populations or age groups.

Q3. How do you investigate and manage RIS in children? What are some of the challenges?  

A3. For children with radiologically isolated syndrome, we usually undertake a comprehensive workup. This includes a detailed clinical neurological exam to ensure that there are no abnormalities that would, for instance, suggest a misdiagnosis of multiple sclerosis or an alternative diagnosis. In addition to the brain MRI, we usually obtain an MRI of the spinal cord to determine whether there is any spinal cord involvement. We also obtain blood tests. We often analyze spinal fluid as well, primarily to exclude other alternative processes that may explain the  MRI findings. A key challenge in this field is that there are currently no formal guidelines for the investigation and management of children with RIS. Collaborations within the pediatric MS community are needed to develop such consensus approaches to standardize care.

Q4. What are the most significant risk factors that indicate children with RIS could one day develop multiple sclerosis?

A4.This is an area of active research within our group. So far, we've found that approximately 42% of children with RIS develop multiple sclerosis in the future; on average, two years following their first abnormal MRI. Therefore, this is a high-risk group for developing  multiple sclerosis in the future. Thus far, we've determined that in children with RIS, it is the presence of abnormal spinal cord imaging and an abnormality in spinal fluid – namely, the presence of oligoclonal bands – that are likely the predictors of whether these children could develop MS in the future. a child’s possible development 

Q5. Based on your recent studies, are there data in children highlighting the potential for higher prevalence  in one population over another?

A5. Thus far, population-based studies assessing RIS, especially in children, have been rare and thus far have not identified particular subgroups with increased prevalence. We do know that the prevalence of multiple sclerosis varies across different age groups and across gender. Whether such associations are also present for RIS is an area of active research.

Naila Makhani, MD completed medical school training at the University of British Columbia (Vancouver, Canada). This was followed by a residency in child neurology and fellowship in MS and other demyelinating diseases at the University of Toronto and The Hospital for Sick Children (Toronto, Canada). Concurrent with fellowship training, Dr. Makhani obtained a Masters’ degree in public health from Harvard University. Dr. Makhani is the Director of the Pediatric MS Program at Yale and the lead investigator of a multi-center international study examining outcomes following the radiologically isolated syndrome in children.

Q1. Could you please provide an overview of Radiologically Isolated Syndrome ?

A1. Radiologically Isolated Syndrome (RIS) was first described in adults in 2009. Since then it has also been increasingly recognized and diagnosed in children. RIS is diagnosed after an MRI of the brain that the patient has sought for reasons other than suspected multiple sclerosis-- for instance, for evaluation of head trauma or headache. However, unexpectedly or incidentally, the patient’s MRI shows the typical findings that we see in multiple sclerosis, even in the absence of any typical clinical symptoms. RIS is generally considered a rare syndrome.

Q2. You created Yale Medicine’s Pediatric Multiple Sclerosis program which advocates for the eradication of MS. What  criteria defines a rare disease? Does RIS meet these criteria? And if so, how?

A2. The criteria for a rare disease vary, depending on the reference. In the US, a rare disease is defined as a condition that affects fewer than 200,000 people, in total, across the country.  By contrast, in Europe, a disease is considered rare if it affects fewer than one in every 2,000 people within the country’s population.

In the case of RIS, especially in children, we suspect that this is a rare condition, but we don't know for sure, as there have been very few population-based studies. There is one large study that was conducted in Europe that found one case of RIS among approximately 5,000 otherwise healthy children, who were between 7 and 14 years of age.  I think that's our best estimate of the overall prevalence of RIS in children. Using that finding, it likely would qualify as a rare condition, although, as I said, we really don't know for sure, as the prevalence may vary among different populations or age groups.

Q3. How do you investigate and manage RIS in children? What are some of the challenges?  

A3. For children with radiologically isolated syndrome, we usually undertake a comprehensive workup. This includes a detailed clinical neurological exam to ensure that there are no abnormalities that would, for instance, suggest a misdiagnosis of multiple sclerosis or an alternative diagnosis. In addition to the brain MRI, we usually obtain an MRI of the spinal cord to determine whether there is any spinal cord involvement. We also obtain blood tests. We often analyze spinal fluid as well, primarily to exclude other alternative processes that may explain the  MRI findings. A key challenge in this field is that there are currently no formal guidelines for the investigation and management of children with RIS. Collaborations within the pediatric MS community are needed to develop such consensus approaches to standardize care.

Q4. What are the most significant risk factors that indicate children with RIS could one day develop multiple sclerosis?

A4.This is an area of active research within our group. So far, we've found that approximately 42% of children with RIS develop multiple sclerosis in the future; on average, two years following their first abnormal MRI. Therefore, this is a high-risk group for developing  multiple sclerosis in the future. Thus far, we've determined that in children with RIS, it is the presence of abnormal spinal cord imaging and an abnormality in spinal fluid – namely, the presence of oligoclonal bands – that are likely the predictors of whether these children could develop MS in the future. a child’s possible development 

Q5. Based on your recent studies, are there data in children highlighting the potential for higher prevalence  in one population over another?

A5. Thus far, population-based studies assessing RIS, especially in children, have been rare and thus far have not identified particular subgroups with increased prevalence. We do know that the prevalence of multiple sclerosis varies across different age groups and across gender. Whether such associations are also present for RIS is an area of active research.

Naila Makhani, MD completed medical school training at the University of British Columbia (Vancouver, Canada). This was followed by a residency in child neurology and fellowship in MS and other demyelinating diseases at the University of Toronto and The Hospital for Sick Children (Toronto, Canada). Concurrent with fellowship training, Dr. Makhani obtained a Masters’ degree in public health from Harvard University. Dr. Makhani is the Director of the Pediatric MS Program at Yale and the lead investigator of a multi-center international study examining outcomes following the radiologically isolated syndrome in children.

Q1. Could you please provide an overview of Radiologically Isolated Syndrome ?

A1. Radiologically Isolated Syndrome (RIS) was first described in adults in 2009. Since then it has also been increasingly recognized and diagnosed in children. RIS is diagnosed after an MRI of the brain that the patient has sought for reasons other than suspected multiple sclerosis-- for instance, for evaluation of head trauma or headache. However, unexpectedly or incidentally, the patient’s MRI shows the typical findings that we see in multiple sclerosis, even in the absence of any typical clinical symptoms. RIS is generally considered a rare syndrome.

Q2. You created Yale Medicine’s Pediatric Multiple Sclerosis program which advocates for the eradication of MS. What  criteria defines a rare disease? Does RIS meet these criteria? And if so, how?

A2. The criteria for a rare disease vary, depending on the reference. In the US, a rare disease is defined as a condition that affects fewer than 200,000 people, in total, across the country.  By contrast, in Europe, a disease is considered rare if it affects fewer than one in every 2,000 people within the country’s population.

In the case of RIS, especially in children, we suspect that this is a rare condition, but we don't know for sure, as there have been very few population-based studies. There is one large study that was conducted in Europe that found one case of RIS among approximately 5,000 otherwise healthy children, who were between 7 and 14 years of age.  I think that's our best estimate of the overall prevalence of RIS in children. Using that finding, it likely would qualify as a rare condition, although, as I said, we really don't know for sure, as the prevalence may vary among different populations or age groups.

Q3. How do you investigate and manage RIS in children? What are some of the challenges?  

A3. For children with radiologically isolated syndrome, we usually undertake a comprehensive workup. This includes a detailed clinical neurological exam to ensure that there are no abnormalities that would, for instance, suggest a misdiagnosis of multiple sclerosis or an alternative diagnosis. In addition to the brain MRI, we usually obtain an MRI of the spinal cord to determine whether there is any spinal cord involvement. We also obtain blood tests. We often analyze spinal fluid as well, primarily to exclude other alternative processes that may explain the  MRI findings. A key challenge in this field is that there are currently no formal guidelines for the investigation and management of children with RIS. Collaborations within the pediatric MS community are needed to develop such consensus approaches to standardize care.

Q4. What are the most significant risk factors that indicate children with RIS could one day develop multiple sclerosis?

A4.This is an area of active research within our group. So far, we've found that approximately 42% of children with RIS develop multiple sclerosis in the future; on average, two years following their first abnormal MRI. Therefore, this is a high-risk group for developing  multiple sclerosis in the future. Thus far, we've determined that in children with RIS, it is the presence of abnormal spinal cord imaging and an abnormality in spinal fluid – namely, the presence of oligoclonal bands – that are likely the predictors of whether these children could develop MS in the future. a child’s possible development 

Q5. Based on your recent studies, are there data in children highlighting the potential for higher prevalence  in one population over another?

A5. Thus far, population-based studies assessing RIS, especially in children, have been rare and thus far have not identified particular subgroups with increased prevalence. We do know that the prevalence of multiple sclerosis varies across different age groups and across gender. Whether such associations are also present for RIS is an area of active research.

Naila Makhani, MD completed medical school training at the University of British Columbia (Vancouver, Canada). This was followed by a residency in child neurology and fellowship in MS and other demyelinating diseases at the University of Toronto and The Hospital for Sick Children (Toronto, Canada). Concurrent with fellowship training, Dr. Makhani obtained a Masters’ degree in public health from Harvard University. Dr. Makhani is the Director of the Pediatric MS Program at Yale and the lead investigator of a multi-center international study examining outcomes following the radiologically isolated syndrome in children.

Q1. Could you please provide an overview of Radiologically Isolated Syndrome ?

A1. Radiologically Isolated Syndrome (RIS) was first described in adults in 2009. Since then it has also been increasingly recognized and diagnosed in children. RIS is diagnosed after an MRI of the brain that the patient has sought for reasons other than suspected multiple sclerosis-- for instance, for evaluation of head trauma or headache. However, unexpectedly or incidentally, the patient’s MRI shows the typical findings that we see in multiple sclerosis, even in the absence of any typical clinical symptoms. RIS is generally considered a rare syndrome.

Q2. You created Yale Medicine’s Pediatric Multiple Sclerosis program which advocates for the eradication of MS. What  criteria defines a rare disease? Does RIS meet these criteria? And if so, how?

A2. The criteria for a rare disease vary, depending on the reference. In the US, a rare disease is defined as a condition that affects fewer than 200,000 people, in total, across the country.  By contrast, in Europe, a disease is considered rare if it affects fewer than one in every 2,000 people within the country’s population.

In the case of RIS, especially in children, we suspect that this is a rare condition, but we don't know for sure, as there have been very few population-based studies. There is one large study that was conducted in Europe that found one case of RIS among approximately 5,000 otherwise healthy children, who were between 7 and 14 years of age.  I think that's our best estimate of the overall prevalence of RIS in children. Using that finding, it likely would qualify as a rare condition, although, as I said, we really don't know for sure, as the prevalence may vary among different populations or age groups.

Q3. How do you investigate and manage RIS in children? What are some of the challenges?  

A3. For children with radiologically isolated syndrome, we usually undertake a comprehensive workup. This includes a detailed clinical neurological exam to ensure that there are no abnormalities that would, for instance, suggest a misdiagnosis of multiple sclerosis or an alternative diagnosis. In addition to the brain MRI, we usually obtain an MRI of the spinal cord to determine whether there is any spinal cord involvement. We also obtain blood tests. We often analyze spinal fluid as well, primarily to exclude other alternative processes that may explain the  MRI findings. A key challenge in this field is that there are currently no formal guidelines for the investigation and management of children with RIS. Collaborations within the pediatric MS community are needed to develop such consensus approaches to standardize care.

Q4. What are the most significant risk factors that indicate children with RIS could one day develop multiple sclerosis?

A4.This is an area of active research within our group. So far, we've found that approximately 42% of children with RIS develop multiple sclerosis in the future; on average, two years following their first abnormal MRI. Therefore, this is a high-risk group for developing  multiple sclerosis in the future. Thus far, we've determined that in children with RIS, it is the presence of abnormal spinal cord imaging and an abnormality in spinal fluid – namely, the presence of oligoclonal bands – that are likely the predictors of whether these children could develop MS in the future. a child’s possible development 

Q5. Based on your recent studies, are there data in children highlighting the potential for higher prevalence  in one population over another?

A5. Thus far, population-based studies assessing RIS, especially in children, have been rare and thus far have not identified particular subgroups with increased prevalence. We do know that the prevalence of multiple sclerosis varies across different age groups and across gender. Whether such associations are also present for RIS is an area of active research.

Naila Makhani, MD completed medical school training at the University of British Columbia (Vancouver, Canada). This was followed by a residency in child neurology and fellowship in MS and other demyelinating diseases at the University of Toronto and The Hospital for Sick Children (Toronto, Canada). Concurrent with fellowship training, Dr. Makhani obtained a Masters’ degree in public health from Harvard University. Dr. Makhani is the Director of the Pediatric MS Program at Yale and the lead investigator of a multi-center international study examining outcomes following the radiologically isolated syndrome in children.

Q1. Could you please provide an overview of Radiologically Isolated Syndrome ?

A1. Radiologically Isolated Syndrome (RIS) was first described in adults in 2009. Since then it has also been increasingly recognized and diagnosed in children. RIS is diagnosed after an MRI of the brain that the patient has sought for reasons other than suspected multiple sclerosis-- for instance, for evaluation of head trauma or headache. However, unexpectedly or incidentally, the patient’s MRI shows the typical findings that we see in multiple sclerosis, even in the absence of any typical clinical symptoms. RIS is generally considered a rare syndrome.

Q2. You created Yale Medicine’s Pediatric Multiple Sclerosis program which advocates for the eradication of MS. What  criteria defines a rare disease? Does RIS meet these criteria? And if so, how?

A2. The criteria for a rare disease vary, depending on the reference. In the US, a rare disease is defined as a condition that affects fewer than 200,000 people, in total, across the country.  By contrast, in Europe, a disease is considered rare if it affects fewer than one in every 2,000 people within the country’s population.

In the case of RIS, especially in children, we suspect that this is a rare condition, but we don't know for sure, as there have been very few population-based studies. There is one large study that was conducted in Europe that found one case of RIS among approximately 5,000 otherwise healthy children, who were between 7 and 14 years of age.  I think that's our best estimate of the overall prevalence of RIS in children. Using that finding, it likely would qualify as a rare condition, although, as I said, we really don't know for sure, as the prevalence may vary among different populations or age groups.

Q3. How do you investigate and manage RIS in children? What are some of the challenges?  

A3. For children with radiologically isolated syndrome, we usually undertake a comprehensive workup. This includes a detailed clinical neurological exam to ensure that there are no abnormalities that would, for instance, suggest a misdiagnosis of multiple sclerosis or an alternative diagnosis. In addition to the brain MRI, we usually obtain an MRI of the spinal cord to determine whether there is any spinal cord involvement. We also obtain blood tests. We often analyze spinal fluid as well, primarily to exclude other alternative processes that may explain the  MRI findings. A key challenge in this field is that there are currently no formal guidelines for the investigation and management of children with RIS. Collaborations within the pediatric MS community are needed to develop such consensus approaches to standardize care.

Q4. What are the most significant risk factors that indicate children with RIS could one day develop multiple sclerosis?

A4.This is an area of active research within our group. So far, we've found that approximately 42% of children with RIS develop multiple sclerosis in the future; on average, two years following their first abnormal MRI. Therefore, this is a high-risk group for developing  multiple sclerosis in the future. Thus far, we've determined that in children with RIS, it is the presence of abnormal spinal cord imaging and an abnormality in spinal fluid – namely, the presence of oligoclonal bands – that are likely the predictors of whether these children could develop MS in the future. a child’s possible development 

Q5. Based on your recent studies, are there data in children highlighting the potential for higher prevalence  in one population over another?

A5. Thus far, population-based studies assessing RIS, especially in children, have been rare and thus far have not identified particular subgroups with increased prevalence. We do know that the prevalence of multiple sclerosis varies across different age groups and across gender. Whether such associations are also present for RIS is an area of active research.

Universal screening for adolescent depression in schools, compared with the usual process of targeting students for referral after observing behaviors, resulted in significantly higher odds of identifying major depressive disorder (MDD) and of starting treatment for it, a study of more than 12,000 students suggests. Findings were published online in JAMA Network Open.

Deepa L. Sekhar, MD, MSc, with the department of pediatrics at Pennsylvania State College of Medicine in Hershey, Pa., and colleagues conducted a randomized clinical trial comparing the two screening methods from November 2018 to November 2020.

The trial included students in grades 9 through 12 enrolled at any of the 14 participating Pennsylvania public high schools. Researchers compared the two groups using mixed-effects logistic regression.

They found that adolescents in the universal screening intervention group had 5.92 times higher odds (95% confidence interval [CI], 5.07-6.93) of being identified with MDD symptoms, 3.30 times higher odds (95% CI, 2.49-4.38) of the Student Assistance Program (SAP) confirming follow-up needs, and 2.07 times higher odds (95% CI, 1.39-3.10) of starting MDD treatment.

The study comprised 12,909 students, with an average age of 16 years. Of those students, 2,687 (20.8%) were Hispanic; 2,891 (22.4%) were non-Hispanic Black, 5,842 (45.3%) were non-Hispanic White; and 1,489 (11.5%) were multiracial or of other race or ethnicity.

In the universal screening intervention (n = 6,473) all students completed the Patient Health Questionnaire–9 (PHQ-9). Students who screened positive proceeded to the Student Assistance Program. Students could receive a targeted referral to SAP if they had concerning behavior beyond the PHQ-9.

In the targeted screening group (n = 6,436), students with behaviors prompting concern for MDD were referred to the Student Assistance Program (SAP), mandated in all Pennsylvania schools. The SAP determined follow-up.

The U.S. Preventive Services Task Force (USPSTF) endorsed primary care screening in 2009 and again in 2016 for all adolescents 12-18 years old.

However, the study authors wrote, most U.S. adolescents (more than 60%) don’t have routine access to preventive health care, which limits primary care offices’ ability to properly address the growing numbers.

“[S]creening is inconsistent, with inequalities by race and ethnicity and region, and potential worsening with the COVID-19 pandemic,” they noted.

Depression rates see sharp increase

Meanwhile, the prevalence of adolescents reporting MDD symptoms has “nearly doubled in the last decade, increasing from 8.3% in 2008 to 14.4% in 2018.”

The American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association recently declared a national emergency in children’s mental health, citing COVID-19’s toll on top of existing challenges.

This study provides further evidence that universal screening is the better approach to identify and treat adolescent depression to save lives, Andres Pumariega, MD, a child and adolescent psychiatrist at University of Florida in Gainesville, told this news organization.

“If you catch these kids early, you can prevent suicide attempts and suicide. You can also prevent complicating costs of care,” he said.

He noted the universal screening removes the potential for bias.

“Relying purely on referral and clinical identification means a lot of kids in minority groups will not be identified and will not be treated accurately. Many clinicians have a problem identifying depression in diverse kids,” he said.

Pushback for universal screening likely

However, he said he has been part of such efforts to implement such programs in Mexico and the United States and said in the Unites States, the political climate will guarantee pushback from having schools more involved in health care and prevention. Recent controversy around COVID-19 vaccines for children illustrates the potential backlash, he said.

Parents often fight such programs as attempts to “label” their children, he said.

“If I have cancer, I sure want to be labeled. A label is used to get them help. We need to find ways to educate parents and support them in facing these issues,” he added.

One concern he has with this intervention is having the SAPs, composed largely of nonclinicians, be the triage point “instead of doing that objectively through objective criteria and by clinicians,” he said. “If we are to have a comprehensive health system where we can serve all kids and manage costs, schools need to be a major part of it.”

School settings offer the chance to see more children, collaborate with teachers and counselors, and integrate results with educational outcomes, he added.

In the study by Sekhar and colleagues, 7 of the 14 schools were classified as urban, with a median size of 370 students.

Researchers noted that the benefit of the universal screening is likely understated because of COVID-19–related school closures during the study period. The closures meant screening wasn’t completed for 7% of students.

The authors concluded that universal screening finds teens living with depression who otherwise would not be found. They said such a program likely works best in schools with strong SAP.

“Adolescents’ consistent contact with schools has been used to support physical health screenings that affect academic success,” the authors wrote. “Major depressive disorder similarly affects academic success, suggesting school-based screening may be especially beneficial.”

In the past 3 years, Dr. Sekhar reported receiving funding from Pfizer through the American Academy of Pediatrics, the Penn State Clinical and Translational Science Awards Program, and a Eugene Washington Patient-Centered Outcomes Research Institute Engagement Award. Full disclosures for coauthors are available in the journal article.

This work was supported in part by the Patient-Centered Outcomes Research Institute. The use of REDCap (Research Electronic Data Capture) in this project was supported by the National Institutes of Health.

Universal screening for adolescent depression in schools, compared with the usual process of targeting students for referral after observing behaviors, resulted in significantly higher odds of identifying major depressive disorder (MDD) and of starting treatment for it, a study of more than 12,000 students suggests. Findings were published online in JAMA Network Open.

Deepa L. Sekhar, MD, MSc, with the department of pediatrics at Pennsylvania State College of Medicine in Hershey, Pa., and colleagues conducted a randomized clinical trial comparing the two screening methods from November 2018 to November 2020.

The trial included students in grades 9 through 12 enrolled at any of the 14 participating Pennsylvania public high schools. Researchers compared the two groups using mixed-effects logistic regression.

They found that adolescents in the universal screening intervention group had 5.92 times higher odds (95% confidence interval [CI], 5.07-6.93) of being identified with MDD symptoms, 3.30 times higher odds (95% CI, 2.49-4.38) of the Student Assistance Program (SAP) confirming follow-up needs, and 2.07 times higher odds (95% CI, 1.39-3.10) of starting MDD treatment.

The study comprised 12,909 students, with an average age of 16 years. Of those students, 2,687 (20.8%) were Hispanic; 2,891 (22.4%) were non-Hispanic Black, 5,842 (45.3%) were non-Hispanic White; and 1,489 (11.5%) were multiracial or of other race or ethnicity.

In the universal screening intervention (n = 6,473) all students completed the Patient Health Questionnaire–9 (PHQ-9). Students who screened positive proceeded to the Student Assistance Program. Students could receive a targeted referral to SAP if they had concerning behavior beyond the PHQ-9.

In the targeted screening group (n = 6,436), students with behaviors prompting concern for MDD were referred to the Student Assistance Program (SAP), mandated in all Pennsylvania schools. The SAP determined follow-up.

The U.S. Preventive Services Task Force (USPSTF) endorsed primary care screening in 2009 and again in 2016 for all adolescents 12-18 years old.

However, the study authors wrote, most U.S. adolescents (more than 60%) don’t have routine access to preventive health care, which limits primary care offices’ ability to properly address the growing numbers.

“[S]creening is inconsistent, with inequalities by race and ethnicity and region, and potential worsening with the COVID-19 pandemic,” they noted.

Depression rates see sharp increase

Meanwhile, the prevalence of adolescents reporting MDD symptoms has “nearly doubled in the last decade, increasing from 8.3% in 2008 to 14.4% in 2018.”

The American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association recently declared a national emergency in children’s mental health, citing COVID-19’s toll on top of existing challenges.

This study provides further evidence that universal screening is the better approach to identify and treat adolescent depression to save lives, Andres Pumariega, MD, a child and adolescent psychiatrist at University of Florida in Gainesville, told this news organization.

“If you catch these kids early, you can prevent suicide attempts and suicide. You can also prevent complicating costs of care,” he said.

He noted the universal screening removes the potential for bias.

“Relying purely on referral and clinical identification means a lot of kids in minority groups will not be identified and will not be treated accurately. Many clinicians have a problem identifying depression in diverse kids,” he said.

Pushback for universal screening likely

However, he said he has been part of such efforts to implement such programs in Mexico and the United States and said in the Unites States, the political climate will guarantee pushback from having schools more involved in health care and prevention. Recent controversy around COVID-19 vaccines for children illustrates the potential backlash, he said.

Parents often fight such programs as attempts to “label” their children, he said.

“If I have cancer, I sure want to be labeled. A label is used to get them help. We need to find ways to educate parents and support them in facing these issues,” he added.

One concern he has with this intervention is having the SAPs, composed largely of nonclinicians, be the triage point “instead of doing that objectively through objective criteria and by clinicians,” he said. “If we are to have a comprehensive health system where we can serve all kids and manage costs, schools need to be a major part of it.”

School settings offer the chance to see more children, collaborate with teachers and counselors, and integrate results with educational outcomes, he added.

In the study by Sekhar and colleagues, 7 of the 14 schools were classified as urban, with a median size of 370 students.

Researchers noted that the benefit of the universal screening is likely understated because of COVID-19–related school closures during the study period. The closures meant screening wasn’t completed for 7% of students.

The authors concluded that universal screening finds teens living with depression who otherwise would not be found. They said such a program likely works best in schools with strong SAP.

“Adolescents’ consistent contact with schools has been used to support physical health screenings that affect academic success,” the authors wrote. “Major depressive disorder similarly affects academic success, suggesting school-based screening may be especially beneficial.”

In the past 3 years, Dr. Sekhar reported receiving funding from Pfizer through the American Academy of Pediatrics, the Penn State Clinical and Translational Science Awards Program, and a Eugene Washington Patient-Centered Outcomes Research Institute Engagement Award. Full disclosures for coauthors are available in the journal article.

This work was supported in part by the Patient-Centered Outcomes Research Institute. The use of REDCap (Research Electronic Data Capture) in this project was supported by the National Institutes of Health.

Universal screening for adolescent depression in schools, compared with the usual process of targeting students for referral after observing behaviors, resulted in significantly higher odds of identifying major depressive disorder (MDD) and of starting treatment for it, a study of more than 12,000 students suggests. Findings were published online in JAMA Network Open.

Deepa L. Sekhar, MD, MSc, with the department of pediatrics at Pennsylvania State College of Medicine in Hershey, Pa., and colleagues conducted a randomized clinical trial comparing the two screening methods from November 2018 to November 2020.

The trial included students in grades 9 through 12 enrolled at any of the 14 participating Pennsylvania public high schools. Researchers compared the two groups using mixed-effects logistic regression.

They found that adolescents in the universal screening intervention group had 5.92 times higher odds (95% confidence interval [CI], 5.07-6.93) of being identified with MDD symptoms, 3.30 times higher odds (95% CI, 2.49-4.38) of the Student Assistance Program (SAP) confirming follow-up needs, and 2.07 times higher odds (95% CI, 1.39-3.10) of starting MDD treatment.

The study comprised 12,909 students, with an average age of 16 years. Of those students, 2,687 (20.8%) were Hispanic; 2,891 (22.4%) were non-Hispanic Black, 5,842 (45.3%) were non-Hispanic White; and 1,489 (11.5%) were multiracial or of other race or ethnicity.

In the universal screening intervention (n = 6,473) all students completed the Patient Health Questionnaire–9 (PHQ-9). Students who screened positive proceeded to the Student Assistance Program. Students could receive a targeted referral to SAP if they had concerning behavior beyond the PHQ-9.

In the targeted screening group (n = 6,436), students with behaviors prompting concern for MDD were referred to the Student Assistance Program (SAP), mandated in all Pennsylvania schools. The SAP determined follow-up.

The U.S. Preventive Services Task Force (USPSTF) endorsed primary care screening in 2009 and again in 2016 for all adolescents 12-18 years old.

However, the study authors wrote, most U.S. adolescents (more than 60%) don’t have routine access to preventive health care, which limits primary care offices’ ability to properly address the growing numbers.

“[S]creening is inconsistent, with inequalities by race and ethnicity and region, and potential worsening with the COVID-19 pandemic,” they noted.

Depression rates see sharp increase

Meanwhile, the prevalence of adolescents reporting MDD symptoms has “nearly doubled in the last decade, increasing from 8.3% in 2008 to 14.4% in 2018.”

The American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association recently declared a national emergency in children’s mental health, citing COVID-19’s toll on top of existing challenges.

This study provides further evidence that universal screening is the better approach to identify and treat adolescent depression to save lives, Andres Pumariega, MD, a child and adolescent psychiatrist at University of Florida in Gainesville, told this news organization.

“If you catch these kids early, you can prevent suicide attempts and suicide. You can also prevent complicating costs of care,” he said.

He noted the universal screening removes the potential for bias.

“Relying purely on referral and clinical identification means a lot of kids in minority groups will not be identified and will not be treated accurately. Many clinicians have a problem identifying depression in diverse kids,” he said.

Pushback for universal screening likely

However, he said he has been part of such efforts to implement such programs in Mexico and the United States and said in the Unites States, the political climate will guarantee pushback from having schools more involved in health care and prevention. Recent controversy around COVID-19 vaccines for children illustrates the potential backlash, he said.

Parents often fight such programs as attempts to “label” their children, he said.

“If I have cancer, I sure want to be labeled. A label is used to get them help. We need to find ways to educate parents and support them in facing these issues,” he added.

One concern he has with this intervention is having the SAPs, composed largely of nonclinicians, be the triage point “instead of doing that objectively through objective criteria and by clinicians,” he said. “If we are to have a comprehensive health system where we can serve all kids and manage costs, schools need to be a major part of it.”

School settings offer the chance to see more children, collaborate with teachers and counselors, and integrate results with educational outcomes, he added.

In the study by Sekhar and colleagues, 7 of the 14 schools were classified as urban, with a median size of 370 students.

Researchers noted that the benefit of the universal screening is likely understated because of COVID-19–related school closures during the study period. The closures meant screening wasn’t completed for 7% of students.

The authors concluded that universal screening finds teens living with depression who otherwise would not be found. They said such a program likely works best in schools with strong SAP.

“Adolescents’ consistent contact with schools has been used to support physical health screenings that affect academic success,” the authors wrote. “Major depressive disorder similarly affects academic success, suggesting school-based screening may be especially beneficial.”

In the past 3 years, Dr. Sekhar reported receiving funding from Pfizer through the American Academy of Pediatrics, the Penn State Clinical and Translational Science Awards Program, and a Eugene Washington Patient-Centered Outcomes Research Institute Engagement Award. Full disclosures for coauthors are available in the journal article.

This work was supported in part by the Patient-Centered Outcomes Research Institute. The use of REDCap (Research Electronic Data Capture) in this project was supported by the National Institutes of Health.

The Diagnosis: Linear Lichen Planus

The patient was clinically diagnosed with linear lichen planus and was started on betamethasone dipropionate ointment 0.05% applied once daily with improvement in both the pruritus and appearance at 4-month follow-up. A biopsy was deferred based on the parents’ wishes.

Lichen planus is an inflammatory disorder involving the skin and oral mucosa. Cutaneous lichen planus classically presents as flat-topped, violaceous, pruritic, polygonal papules with overlying fine white or grey lines known as Wickham striae.¹ Postinflammatory hyperpigmentation is common, especially in patients with darker skin tones. Expected histologic findings include orthokeratosis, apoptotic keratinocytes, and bandlike lymphocytic infiltration at the dermoepidermal junction.¹

An estimated 5% of cases of cutaneous lichen planus occur in children.² A study of 316 children with lichen planus demonstrated that the classic morphology remained the most common presentation, while the linear variant was present in only 6.9% of pediatric cases.³ Linear lichen planus appears to be more common among children than adults. A study of 36 pediatric cases showed a greater representation of lichen planus in Black children (67% affected vs 21% cohort).²

Cutaneous lichen planus often clears spontaneously in approximately 1 year.⁴ Treatment in children primarily is focused on shortening the time to resolution and relieving pruritus, with topical corticosteroids as firstline therapy.^3,4 Oral corticosteroids have a faster clinical response; greater efficacy; and more effectively prevent residual hyperpigmentation, which is especially relevant in individuals with darker skin.³ Nonetheless, oral corticosteroids are considered a second-line treatment due to their unfavorable side-effect profile. Additional treatment options include oral aromatic retinoids (acitretin) and phototherapy.³

Incontinentia pigmenti is characterized by a defect in the inhibitor of nuclear factor–κB kinase regulatory subunit gamma, IKBKG, gene on the X chromosome. Incontinentia pigmenti usually is lethal in males; in females, it leads to ectodermal dysplasia associated with skin findings in a blaschkoid distribution occurring in 4 stages.⁵ The verrucous stage is preceded by the vesicular stage and expected to occur within the first few months of life, making it unlikely in our 5-year-old patient. Inflammatory linear verrucous epidermal nevus usually occurs in children younger than 5 years and is characterized by psoriasiform papules coalescing into a plaque with substantial scale instead of Wickham striae, as seen in our patient.⁶ Lichen striatus consists of smaller, pink to flesh-colored papules that rarely are pruritic.⁷ It is more common among atopic individuals and is associated with postinflammatory hypopigmentation.⁸ Linear psoriasis presents similarly to inflammatory linear verrucous epidermal nevus, with greater erythema and scale compared to the fine lacy Wickham striae that were seen in our patient.⁸

The Diagnosis: Linear Lichen Planus

The patient was clinically diagnosed with linear lichen planus and was started on betamethasone dipropionate ointment 0.05% applied once daily with improvement in both the pruritus and appearance at 4-month follow-up. A biopsy was deferred based on the parents’ wishes.

Lichen planus is an inflammatory disorder involving the skin and oral mucosa. Cutaneous lichen planus classically presents as flat-topped, violaceous, pruritic, polygonal papules with overlying fine white or grey lines known as Wickham striae.¹ Postinflammatory hyperpigmentation is common, especially in patients with darker skin tones. Expected histologic findings include orthokeratosis, apoptotic keratinocytes, and bandlike lymphocytic infiltration at the dermoepidermal junction.¹

An estimated 5% of cases of cutaneous lichen planus occur in children.² A study of 316 children with lichen planus demonstrated that the classic morphology remained the most common presentation, while the linear variant was present in only 6.9% of pediatric cases.³ Linear lichen planus appears to be more common among children than adults. A study of 36 pediatric cases showed a greater representation of lichen planus in Black children (67% affected vs 21% cohort).²

Cutaneous lichen planus often clears spontaneously in approximately 1 year.⁴ Treatment in children primarily is focused on shortening the time to resolution and relieving pruritus, with topical corticosteroids as firstline therapy.^3,4 Oral corticosteroids have a faster clinical response; greater efficacy; and more effectively prevent residual hyperpigmentation, which is especially relevant in individuals with darker skin.³ Nonetheless, oral corticosteroids are considered a second-line treatment due to their unfavorable side-effect profile. Additional treatment options include oral aromatic retinoids (acitretin) and phototherapy.³

Incontinentia pigmenti is characterized by a defect in the inhibitor of nuclear factor–κB kinase regulatory subunit gamma, IKBKG, gene on the X chromosome. Incontinentia pigmenti usually is lethal in males; in females, it leads to ectodermal dysplasia associated with skin findings in a blaschkoid distribution occurring in 4 stages.⁵ The verrucous stage is preceded by the vesicular stage and expected to occur within the first few months of life, making it unlikely in our 5-year-old patient. Inflammatory linear verrucous epidermal nevus usually occurs in children younger than 5 years and is characterized by psoriasiform papules coalescing into a plaque with substantial scale instead of Wickham striae, as seen in our patient.⁶ Lichen striatus consists of smaller, pink to flesh-colored papules that rarely are pruritic.⁷ It is more common among atopic individuals and is associated with postinflammatory hypopigmentation.⁸ Linear psoriasis presents similarly to inflammatory linear verrucous epidermal nevus, with greater erythema and scale compared to the fine lacy Wickham striae that were seen in our patient.⁸

The Diagnosis: Linear Lichen Planus

The patient was clinically diagnosed with linear lichen planus and was started on betamethasone dipropionate ointment 0.05% applied once daily with improvement in both the pruritus and appearance at 4-month follow-up. A biopsy was deferred based on the parents’ wishes.

Lichen planus is an inflammatory disorder involving the skin and oral mucosa. Cutaneous lichen planus classically presents as flat-topped, violaceous, pruritic, polygonal papules with overlying fine white or grey lines known as Wickham striae.¹ Postinflammatory hyperpigmentation is common, especially in patients with darker skin tones. Expected histologic findings include orthokeratosis, apoptotic keratinocytes, and bandlike lymphocytic infiltration at the dermoepidermal junction.¹

An estimated 5% of cases of cutaneous lichen planus occur in children.² A study of 316 children with lichen planus demonstrated that the classic morphology remained the most common presentation, while the linear variant was present in only 6.9% of pediatric cases.³ Linear lichen planus appears to be more common among children than adults. A study of 36 pediatric cases showed a greater representation of lichen planus in Black children (67% affected vs 21% cohort).²

Cutaneous lichen planus often clears spontaneously in approximately 1 year.⁴ Treatment in children primarily is focused on shortening the time to resolution and relieving pruritus, with topical corticosteroids as firstline therapy.^3,4 Oral corticosteroids have a faster clinical response; greater efficacy; and more effectively prevent residual hyperpigmentation, which is especially relevant in individuals with darker skin.³ Nonetheless, oral corticosteroids are considered a second-line treatment due to their unfavorable side-effect profile. Additional treatment options include oral aromatic retinoids (acitretin) and phototherapy.³

Incontinentia pigmenti is characterized by a defect in the inhibitor of nuclear factor–κB kinase regulatory subunit gamma, IKBKG, gene on the X chromosome. Incontinentia pigmenti usually is lethal in males; in females, it leads to ectodermal dysplasia associated with skin findings in a blaschkoid distribution occurring in 4 stages.⁵ The verrucous stage is preceded by the vesicular stage and expected to occur within the first few months of life, making it unlikely in our 5-year-old patient. Inflammatory linear verrucous epidermal nevus usually occurs in children younger than 5 years and is characterized by psoriasiform papules coalescing into a plaque with substantial scale instead of Wickham striae, as seen in our patient.⁶ Lichen striatus consists of smaller, pink to flesh-colored papules that rarely are pruritic.⁷ It is more common among atopic individuals and is associated with postinflammatory hypopigmentation.⁸ Linear psoriasis presents similarly to inflammatory linear verrucous epidermal nevus, with greater erythema and scale compared to the fine lacy Wickham striae that were seen in our patient.⁸

New data from England show the success of the national program for vaccinating girls against human papillomavirus (HPV) to prevent cervical cancer.

Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.

“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.

Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.

“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.

The study was published online Nov. 3, 2021, in The Lancet.

Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.

“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.

“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
 

National vaccination program

The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.

In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.

The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
 

Population-based registry

The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.

The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.

The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.

In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.

The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.

The team analyzed the data for each of these cohorts.

Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.

For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.

For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.

The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
 

Editorial commentary

“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.

“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.

“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”

The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

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

New data from England show the success of the national program for vaccinating girls against human papillomavirus (HPV) to prevent cervical cancer.

Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.

“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.

Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.

“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.

The study was published online Nov. 3, 2021, in The Lancet.

Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.

“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.

“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
 

National vaccination program

The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.

In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.

The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
 

Population-based registry

The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.

The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.

The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.

In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.

The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.

The team analyzed the data for each of these cohorts.

Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.

For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.

For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.

The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
 

Editorial commentary

“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.

“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.

“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”

The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

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

New data from England show the success of the national program for vaccinating girls against human papillomavirus (HPV) to prevent cervical cancer.

Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.

“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.

Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.

“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.

The study was published online Nov. 3, 2021, in The Lancet.

Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.

“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.

“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
 

National vaccination program

The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.

In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.

The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
 

Population-based registry

The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.

The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.

The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.

In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.

The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.

The team analyzed the data for each of these cohorts.

Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.

For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.

For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.

The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
 

Editorial commentary

“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.

“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.

“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”

The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

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

Pediatric dermatology is a relatively young subspecialty. The Society for Pediatric Dermatology (SPD) was established in 1975, followed by the creation of the journal Pediatric Dermatology in 1982 and the American Academy of Pediatrics Section on Dermatology in 1986.¹ In 2000, the Accreditation Council for Graduate Medical Education (ACGME) officially recognized pediatric dermatology as a unique subspecialty of the American Board of Dermatology (ABD). During that time, informal fellowship experiences emerged, and formal 1-year training programs approved by the ABD evolved by 2006. A subspecialty certification examination was created and has been administered every other year since 2004.¹ Data provided by the SPD indicate that approximately 431 US dermatologists have passed the ABD’s pediatric dermatology board certification examination thus far (unpublished data, September 2021).

In 1986, the first systematic evaluation of the US pediatric dermatology workforce revealed a total of 57 practicing pediatric dermatologists and concluded that job opportunities appeared to be limited at that time.² Since then, the demand for pediatric dermatology services has continued to grow steadily, and the number of board-certified pediatric dermatologists practicing in the United States has increased to at least 317 per data from a 2020 survey.³ However, given that there are more than 11,000 board-certified dermatologists in the United States, there continues to be a severe shortage of pediatric dermatologists.¹

Increased Demand for Pediatric Dermatologists

Approximately 10% to 30% of almost 200 million annual outpatient pediatric primary care visits involve a skin concern. Although many of these problems can be handled by primary care physicians, more than 80% of pediatricians report having difficulty accessing dermatology services for their patients.⁴ In surveys of pediatricians, pediatric dermatology has the third highest referral rate but has consistently ranked third among the specialties deemed most difficult to access.^5-7 In addition, it is not uncommon for the wait time to see a pediatric dermatologist to be 6 weeks or longer.^5,8

Recent population data estimate that there are 73 million children living in the United States.⁹ If there are roughly 317 practicing board-certified pediatric dermatologists, that translates into approximately 4.3 pediatric dermatologists per million children. This number is far smaller than the 4 general dermatologists per 100,000 individuals recommended by Glazer et al¹⁰ in 2017. To meet this suggested ratio goal, the workforce of pediatric dermatologists would have to increase to 2920. In addition to this severe workforce shortage, there is an additional problem with geographic maldistribution of pediatric dermatologists. More than 98% of pediatric dermatologists practice in metropolitan areas. At least 8 states and 95% of counties have no pediatric dermatologist, and there are no pediatric dermatologists practicing in rural counties.⁹ This disparity has considerable implications for barriers to care and lack of access for children living in underserved areas. Suggestions for attracting pediatric dermatologists to practice in these areas have included loan forgiveness programs as well as remote mentorship programs to provide professional support.^8,9

Training in Pediatrics

There currently are 38 ABD-approved pediatric dermatology fellowship training programs in the United States. Beginning in 2009, pediatric dermatology fellowship programs have participated in the SF Match program. Data provided by the SPD show that, since 2012, up to 27 programs have participated in the annual Match, offering a total number of positions ranging from 27 to 38; however, only 11 to 21 positions have been filled each year, leaving a large number of post-Match vacancies (unpublished data, September 2021).

Surveys have explored the reasons behind this lack of interest in pediatric dermatology training among dermatology residents. Factors that have been mentioned include lack of exposure and mentorship in medical school and residency, the financial hardship of an additional year of fellowship training, and historically lower salaries for pediatric dermatologists compared to general dermatologists.^3,6

A 2004 survey revealed that more than 75% of dermatology department chairs believed it was important to have a pediatric dermatologist on the faculty; however, at that time only 48% of dermatology programs reported having at least 1 full-time pediatric dermatology faculty member.¹¹ By 2008, a follow-up survey showed an increase to 70% of dermatology training programs reporting at least 1 full-time pediatric dermatologist; however, 43% of departments still had at least 1 open position, and 76% of those programs shared that they had been searching for more than 1 year.² Currently, the Accreditation Data System of the ACGME shows a total of 144 accredited US dermatology training programs. Of those, 117 programs have 1 or more board-certified pediatric dermatology faculty member, and 27 programs still have none (unpublished data, September 2021).

A shortage of pediatric dermatologists in training programs contributes to the lack of exposure and mentorship for medical students and residents during a critical time in professional development. Studies show that up to 91% of pediatric dermatologists decided to pursue training in pediatric dermatology during medical school, pediatrics residency, or dermatology residency. In one survey, 84% of respondents (N=109) cited early mentorship as the most important factor in their decision to pursue pediatric dermatology.⁶

A lack of pediatric dermatologists also results in suboptimal dermatology training for residents who care for children in primary care specialties, including pediatrics, combined internal medicine and pediatrics, and family practice. Multiple surveys have shown that many pediatricians feel they received inadequate training in dermatology during residency. Up to 38% have cited a need for more pediatric dermatology education (N=755).^5,6 In addition, studies show a wide disparity in diagnostic accuracy between dermatologists and pediatricians, with one concluding that more than one-third of referrals to pediatric dermatologists were initially misdiagnosed and/or incorrectly treated.^5,7

Recruitment Efforts for Pediatric Dermatologists

There are multiple strategies for recruiting trainees into the pediatric dermatology workforce. First, given the importance of early exposure to the field and role models/mentors, pediatric dermatologists must take advantage of every opportunity to interact with medical students and residents. They can share their genuine enthusiasm and love for the specialty while encouraging and supporting those who show interest. They also should seek opportunities for teaching, lecturing, and advising at every level of training. In addition, they can enhance visibility of the specialty by participating in career forums and/or assuming leadership roles within their departments or institutions.¹² Another suggestion is for dermatology training programs to consider giving priority to qualified applicants who express sincere interest in pursuing pediatric dermatology training (including those who have already completed pediatrics residency). Although a 2008 survey revealed that 39% of dermatology residency programs (N=80) favored giving priority to applicants demonstrating interest in pediatric dermatology, others were against it, citing issues such as lack of funding for additional residency training, lack of pediatric dermatology mentors within the program, and an overall mistrust of applicants’ sincerity.²

Final Thoughts

The subspecialty of pediatric dermatology has experienced remarkable growth over the last 40 years; however, demand for pediatric dermatology services has continued to outpace supply, resulting in a persistent and notable workforce shortage. Overall, the current supply of pediatric dermatologists can neither meet the clinical demands of the pediatric population nor fulfill academic needs of existing training programs. We must continue to develop novel strategies for increasing the pool of students and residents who are interested in pursuing careers in pediatric dermatology. Ultimately, we also must create incentives and develop tactics to address the geographic maldistribution that exists within the specialty.

Pediatric dermatology is a relatively young subspecialty. The Society for Pediatric Dermatology (SPD) was established in 1975, followed by the creation of the journal Pediatric Dermatology in 1982 and the American Academy of Pediatrics Section on Dermatology in 1986.¹ In 2000, the Accreditation Council for Graduate Medical Education (ACGME) officially recognized pediatric dermatology as a unique subspecialty of the American Board of Dermatology (ABD). During that time, informal fellowship experiences emerged, and formal 1-year training programs approved by the ABD evolved by 2006. A subspecialty certification examination was created and has been administered every other year since 2004.¹ Data provided by the SPD indicate that approximately 431 US dermatologists have passed the ABD’s pediatric dermatology board certification examination thus far (unpublished data, September 2021).

In 1986, the first systematic evaluation of the US pediatric dermatology workforce revealed a total of 57 practicing pediatric dermatologists and concluded that job opportunities appeared to be limited at that time.² Since then, the demand for pediatric dermatology services has continued to grow steadily, and the number of board-certified pediatric dermatologists practicing in the United States has increased to at least 317 per data from a 2020 survey.³ However, given that there are more than 11,000 board-certified dermatologists in the United States, there continues to be a severe shortage of pediatric dermatologists.¹

Increased Demand for Pediatric Dermatologists

Approximately 10% to 30% of almost 200 million annual outpatient pediatric primary care visits involve a skin concern. Although many of these problems can be handled by primary care physicians, more than 80% of pediatricians report having difficulty accessing dermatology services for their patients.⁴ In surveys of pediatricians, pediatric dermatology has the third highest referral rate but has consistently ranked third among the specialties deemed most difficult to access.^5-7 In addition, it is not uncommon for the wait time to see a pediatric dermatologist to be 6 weeks or longer.^5,8

Recent population data estimate that there are 73 million children living in the United States.⁹ If there are roughly 317 practicing board-certified pediatric dermatologists, that translates into approximately 4.3 pediatric dermatologists per million children. This number is far smaller than the 4 general dermatologists per 100,000 individuals recommended by Glazer et al¹⁰ in 2017. To meet this suggested ratio goal, the workforce of pediatric dermatologists would have to increase to 2920. In addition to this severe workforce shortage, there is an additional problem with geographic maldistribution of pediatric dermatologists. More than 98% of pediatric dermatologists practice in metropolitan areas. At least 8 states and 95% of counties have no pediatric dermatologist, and there are no pediatric dermatologists practicing in rural counties.⁹ This disparity has considerable implications for barriers to care and lack of access for children living in underserved areas. Suggestions for attracting pediatric dermatologists to practice in these areas have included loan forgiveness programs as well as remote mentorship programs to provide professional support.^8,9

Training in Pediatrics

There currently are 38 ABD-approved pediatric dermatology fellowship training programs in the United States. Beginning in 2009, pediatric dermatology fellowship programs have participated in the SF Match program. Data provided by the SPD show that, since 2012, up to 27 programs have participated in the annual Match, offering a total number of positions ranging from 27 to 38; however, only 11 to 21 positions have been filled each year, leaving a large number of post-Match vacancies (unpublished data, September 2021).

Surveys have explored the reasons behind this lack of interest in pediatric dermatology training among dermatology residents. Factors that have been mentioned include lack of exposure and mentorship in medical school and residency, the financial hardship of an additional year of fellowship training, and historically lower salaries for pediatric dermatologists compared to general dermatologists.^3,6

A 2004 survey revealed that more than 75% of dermatology department chairs believed it was important to have a pediatric dermatologist on the faculty; however, at that time only 48% of dermatology programs reported having at least 1 full-time pediatric dermatology faculty member.¹¹ By 2008, a follow-up survey showed an increase to 70% of dermatology training programs reporting at least 1 full-time pediatric dermatologist; however, 43% of departments still had at least 1 open position, and 76% of those programs shared that they had been searching for more than 1 year.² Currently, the Accreditation Data System of the ACGME shows a total of 144 accredited US dermatology training programs. Of those, 117 programs have 1 or more board-certified pediatric dermatology faculty member, and 27 programs still have none (unpublished data, September 2021).

A shortage of pediatric dermatologists in training programs contributes to the lack of exposure and mentorship for medical students and residents during a critical time in professional development. Studies show that up to 91% of pediatric dermatologists decided to pursue training in pediatric dermatology during medical school, pediatrics residency, or dermatology residency. In one survey, 84% of respondents (N=109) cited early mentorship as the most important factor in their decision to pursue pediatric dermatology.⁶

A lack of pediatric dermatologists also results in suboptimal dermatology training for residents who care for children in primary care specialties, including pediatrics, combined internal medicine and pediatrics, and family practice. Multiple surveys have shown that many pediatricians feel they received inadequate training in dermatology during residency. Up to 38% have cited a need for more pediatric dermatology education (N=755).^5,6 In addition, studies show a wide disparity in diagnostic accuracy between dermatologists and pediatricians, with one concluding that more than one-third of referrals to pediatric dermatologists were initially misdiagnosed and/or incorrectly treated.^5,7

Recruitment Efforts for Pediatric Dermatologists

There are multiple strategies for recruiting trainees into the pediatric dermatology workforce. First, given the importance of early exposure to the field and role models/mentors, pediatric dermatologists must take advantage of every opportunity to interact with medical students and residents. They can share their genuine enthusiasm and love for the specialty while encouraging and supporting those who show interest. They also should seek opportunities for teaching, lecturing, and advising at every level of training. In addition, they can enhance visibility of the specialty by participating in career forums and/or assuming leadership roles within their departments or institutions.¹² Another suggestion is for dermatology training programs to consider giving priority to qualified applicants who express sincere interest in pursuing pediatric dermatology training (including those who have already completed pediatrics residency). Although a 2008 survey revealed that 39% of dermatology residency programs (N=80) favored giving priority to applicants demonstrating interest in pediatric dermatology, others were against it, citing issues such as lack of funding for additional residency training, lack of pediatric dermatology mentors within the program, and an overall mistrust of applicants’ sincerity.²

Final Thoughts

The subspecialty of pediatric dermatology has experienced remarkable growth over the last 40 years; however, demand for pediatric dermatology services has continued to outpace supply, resulting in a persistent and notable workforce shortage. Overall, the current supply of pediatric dermatologists can neither meet the clinical demands of the pediatric population nor fulfill academic needs of existing training programs. We must continue to develop novel strategies for increasing the pool of students and residents who are interested in pursuing careers in pediatric dermatology. Ultimately, we also must create incentives and develop tactics to address the geographic maldistribution that exists within the specialty.

Pediatric dermatology is a relatively young subspecialty. The Society for Pediatric Dermatology (SPD) was established in 1975, followed by the creation of the journal Pediatric Dermatology in 1982 and the American Academy of Pediatrics Section on Dermatology in 1986.¹ In 2000, the Accreditation Council for Graduate Medical Education (ACGME) officially recognized pediatric dermatology as a unique subspecialty of the American Board of Dermatology (ABD). During that time, informal fellowship experiences emerged, and formal 1-year training programs approved by the ABD evolved by 2006. A subspecialty certification examination was created and has been administered every other year since 2004.¹ Data provided by the SPD indicate that approximately 431 US dermatologists have passed the ABD’s pediatric dermatology board certification examination thus far (unpublished data, September 2021).

In 1986, the first systematic evaluation of the US pediatric dermatology workforce revealed a total of 57 practicing pediatric dermatologists and concluded that job opportunities appeared to be limited at that time.² Since then, the demand for pediatric dermatology services has continued to grow steadily, and the number of board-certified pediatric dermatologists practicing in the United States has increased to at least 317 per data from a 2020 survey.³ However, given that there are more than 11,000 board-certified dermatologists in the United States, there continues to be a severe shortage of pediatric dermatologists.¹

Increased Demand for Pediatric Dermatologists

Approximately 10% to 30% of almost 200 million annual outpatient pediatric primary care visits involve a skin concern. Although many of these problems can be handled by primary care physicians, more than 80% of pediatricians report having difficulty accessing dermatology services for their patients.⁴ In surveys of pediatricians, pediatric dermatology has the third highest referral rate but has consistently ranked third among the specialties deemed most difficult to access.^5-7 In addition, it is not uncommon for the wait time to see a pediatric dermatologist to be 6 weeks or longer.^5,8

Recent population data estimate that there are 73 million children living in the United States.⁹ If there are roughly 317 practicing board-certified pediatric dermatologists, that translates into approximately 4.3 pediatric dermatologists per million children. This number is far smaller than the 4 general dermatologists per 100,000 individuals recommended by Glazer et al¹⁰ in 2017. To meet this suggested ratio goal, the workforce of pediatric dermatologists would have to increase to 2920. In addition to this severe workforce shortage, there is an additional problem with geographic maldistribution of pediatric dermatologists. More than 98% of pediatric dermatologists practice in metropolitan areas. At least 8 states and 95% of counties have no pediatric dermatologist, and there are no pediatric dermatologists practicing in rural counties.⁹ This disparity has considerable implications for barriers to care and lack of access for children living in underserved areas. Suggestions for attracting pediatric dermatologists to practice in these areas have included loan forgiveness programs as well as remote mentorship programs to provide professional support.^8,9

Training in Pediatrics

There currently are 38 ABD-approved pediatric dermatology fellowship training programs in the United States. Beginning in 2009, pediatric dermatology fellowship programs have participated in the SF Match program. Data provided by the SPD show that, since 2012, up to 27 programs have participated in the annual Match, offering a total number of positions ranging from 27 to 38; however, only 11 to 21 positions have been filled each year, leaving a large number of post-Match vacancies (unpublished data, September 2021).

Surveys have explored the reasons behind this lack of interest in pediatric dermatology training among dermatology residents. Factors that have been mentioned include lack of exposure and mentorship in medical school and residency, the financial hardship of an additional year of fellowship training, and historically lower salaries for pediatric dermatologists compared to general dermatologists.^3,6

A 2004 survey revealed that more than 75% of dermatology department chairs believed it was important to have a pediatric dermatologist on the faculty; however, at that time only 48% of dermatology programs reported having at least 1 full-time pediatric dermatology faculty member.¹¹ By 2008, a follow-up survey showed an increase to 70% of dermatology training programs reporting at least 1 full-time pediatric dermatologist; however, 43% of departments still had at least 1 open position, and 76% of those programs shared that they had been searching for more than 1 year.² Currently, the Accreditation Data System of the ACGME shows a total of 144 accredited US dermatology training programs. Of those, 117 programs have 1 or more board-certified pediatric dermatology faculty member, and 27 programs still have none (unpublished data, September 2021).

A shortage of pediatric dermatologists in training programs contributes to the lack of exposure and mentorship for medical students and residents during a critical time in professional development. Studies show that up to 91% of pediatric dermatologists decided to pursue training in pediatric dermatology during medical school, pediatrics residency, or dermatology residency. In one survey, 84% of respondents (N=109) cited early mentorship as the most important factor in their decision to pursue pediatric dermatology.⁶

A lack of pediatric dermatologists also results in suboptimal dermatology training for residents who care for children in primary care specialties, including pediatrics, combined internal medicine and pediatrics, and family practice. Multiple surveys have shown that many pediatricians feel they received inadequate training in dermatology during residency. Up to 38% have cited a need for more pediatric dermatology education (N=755).^5,6 In addition, studies show a wide disparity in diagnostic accuracy between dermatologists and pediatricians, with one concluding that more than one-third of referrals to pediatric dermatologists were initially misdiagnosed and/or incorrectly treated.^5,7

Recruitment Efforts for Pediatric Dermatologists

There are multiple strategies for recruiting trainees into the pediatric dermatology workforce. First, given the importance of early exposure to the field and role models/mentors, pediatric dermatologists must take advantage of every opportunity to interact with medical students and residents. They can share their genuine enthusiasm and love for the specialty while encouraging and supporting those who show interest. They also should seek opportunities for teaching, lecturing, and advising at every level of training. In addition, they can enhance visibility of the specialty by participating in career forums and/or assuming leadership roles within their departments or institutions.¹² Another suggestion is for dermatology training programs to consider giving priority to qualified applicants who express sincere interest in pursuing pediatric dermatology training (including those who have already completed pediatrics residency). Although a 2008 survey revealed that 39% of dermatology residency programs (N=80) favored giving priority to applicants demonstrating interest in pediatric dermatology, others were against it, citing issues such as lack of funding for additional residency training, lack of pediatric dermatology mentors within the program, and an overall mistrust of applicants’ sincerity.²

Final Thoughts

The subspecialty of pediatric dermatology has experienced remarkable growth over the last 40 years; however, demand for pediatric dermatology services has continued to outpace supply, resulting in a persistent and notable workforce shortage. Overall, the current supply of pediatric dermatologists can neither meet the clinical demands of the pediatric population nor fulfill academic needs of existing training programs. We must continue to develop novel strategies for increasing the pool of students and residents who are interested in pursuing careers in pediatric dermatology. Ultimately, we also must create incentives and develop tactics to address the geographic maldistribution that exists within the specialty.