Pediatrics

Children with severe atopic dermatitis (AD) are about twice as likely to develop depression and internalizing behavior as those without this condition, according to a newly published cohort study of more than 11,000 children between the ages of 3 and 18 years.

Along with previous studies that have also linked AD to depression and other mental health issues in children, these data highlight the need for “clinical awareness of the psychosocial needs of children and adolescents with AD,” reported a multicenter team of investigators from the University of California, San Francisco, the University of Pennsylvania, and the London School of Hygiene and Tropical Medicine.

Unlike some previous studies, in this study, published online in JAMA Dermatology on Sept. 1, children were evaluated longitudinally, rather than at a single point in time, with a mean follow-up of 10 years. For those with active AD, compared with children without AD, the odds ratio for depression overall in any child with AD relative to those without AD was not significant after adjustment for variables such socioeconomic factors.

However, among children with severe AD, the risk was more than twofold greater even after adjustment (adjusted OR, 2.38; 95% confidence interval, 1.21- 4.72), reported the investigators, led by senior author Katrina Abuabara, MD, associate professor of dermatology and epidemiology at UCSF.
 

Internalizing symptoms seen with mild to severe AD

Internalizing behavior, which is closely linked to depression and describes a spectrum of inward-focusing activities, such as social withdrawal, was significantly more common in children with any degree of AD relative to those without AD: After adjustment, the risk climbed from a 29% increased risk in those with mild AD (aOR, 1.29; 95% CI, 1.06-1.57) to a more than 80% increased risk in children with moderate AD (aOR, 1.84; 95% CI, 1.40-2.41) and in children with severe AD (aOR, 1.90; 95% CI, 1.14-3.16).

In the study, depression was measured with the Short Moods and Feelings Questionnaire (SMFQ). Parental response to the Emotional Symptoms subscale of the Strength and Difficulties Questionnaire (SDQ) was used to measure internalizing behaviors.

The data were drawn from the Avon Longitudinal Study for Parents and Children (ALSPAC), a cohort that enrolled pregnant women in a defined area in southwest England and then followed children born from these pregnancies. Of the 14,062 children enrolled in ALSPAC, data from 11,181 children were available for this study.

In a previous meta-analysis of studies that have documented a link between AD and adverse effects on mood and mental health, an impact was identified in both children and adults. In children, AD was associated with a 27% increase in risk of depression (OR, 1.27; 95% CI, 1.12 -1.45). In adults, the risk was more than doubled (OR, 2.19; 95% CI, 1.87-2.57). The same meta-analysis found that the risk of suicidal ideation among adolescents and adults with AD was increased more than fourfold (OR, 4.32; 95% CI, 1.93-9.66).

In the ALSPAC data, the investigators were unable to find compelling evidence that sleep disturbances or concomitant asthma contributed to the increased risk of depression, which is a mechanism proposed by past investigators.

In an interview, Dr. Abuabara said that these and other data provide the basis for encouraging clinical awareness of the psychological needs of children with AD, but she suggested there is a gap in understanding what this means clinically. “We need more data on how dermatologists can effectively screen and manage these patients before we try to set expectations for clinical practice,” she said.

In addition, these data along with previously published studies suggest that change in mental health outcomes should be included in the evaluation of new therapies, according to Dr. Abuabara. She noted that there are several tools for evaluating mental health in children that might be appropriate, each with their own advantages and disadvantages.

“Ideally, recommendations would be issued through a group consensus process with patients, clinicians, researchers, and industry representatives working together as has been done for other outcomes through the Harmonizing Measures for Eczema (HOME) group,” Dr. Abuabara said.

 

Mental health assessments recommended

Others who have looked at the relationship between AD and depression have also recommended adding mental health outcomes to an assessment of efficacy for AD therapies.

Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, is one such investigator. He is already monitoring depression systematically with the Hospital Anxiety and Depression Scale (HADS).

“HADS has been validated in AD and provides very important information about the emotional burden of AD,” explained Dr. Silverberg, whose most recent article on this topic appeared earlier this year. In that study, the relationship between AD and depression was found to be more pronounced in White children from families with lower incomes.

“Just a few hours ago, one of my patients thanked me for asking about their mental health and recognizing the holistic effects of AD,” Dr. Silverberg said.

The recent study based on ALSPAC data add to the evidence that AD, particularly severe AD, produces deleterious effects on mental health in children, and Dr. Silverberg believes clinicians should be acting on this evidence.

“I strongly encourage clinicians to routinely assess mental health. It will elevate the quality of care they provide, and their patients will appreciate them more for it,” he said.

Dr. Abuabara and another author report receiving research funding from Pfizer to their universities for unrelated work; there were no other disclosures. Dr. Silverberg reports financial relationships with more than 15 pharmaceutical companies.

Commentary by Lawrence F. Eichenfield, MD

More severe atopic dermatitis (AD) carries with it significant mental health concerns in children, as well as adults. Multiple studies have shown significantly higher rates of depression, anxiety, and “internalizing behaviors” (discussed as social withdrawal and other inward-focused activities) as well as attention-deficit/hyperactivity disorder. The study by Dr. Abuabara and colleagues is important as it followed children over time (an average of 10 years) and adjusted the data for socioeconomic factors, showing a rate of depression in children with severe AD twice that of those without. It appears that we are in the midst of a mental health crisis in children and teens, with markedly higher rates of pediatric and adolescent depression and anxiety, certainly influenced by COVID-19 societal changes. As the literature has developed on depression and AD, we have appreciated the importance of addressing this as part of our assessment of the disease effect on the individual and family, and it is one factor we consider in selections of systemic vs. topical therapies.  

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

Children with severe atopic dermatitis (AD) are about twice as likely to develop depression and internalizing behavior as those without this condition, according to a newly published cohort study of more than 11,000 children between the ages of 3 and 18 years.

Along with previous studies that have also linked AD to depression and other mental health issues in children, these data highlight the need for “clinical awareness of the psychosocial needs of children and adolescents with AD,” reported a multicenter team of investigators from the University of California, San Francisco, the University of Pennsylvania, and the London School of Hygiene and Tropical Medicine.

Unlike some previous studies, in this study, published online in JAMA Dermatology on Sept. 1, children were evaluated longitudinally, rather than at a single point in time, with a mean follow-up of 10 years. For those with active AD, compared with children without AD, the odds ratio for depression overall in any child with AD relative to those without AD was not significant after adjustment for variables such socioeconomic factors.

However, among children with severe AD, the risk was more than twofold greater even after adjustment (adjusted OR, 2.38; 95% confidence interval, 1.21- 4.72), reported the investigators, led by senior author Katrina Abuabara, MD, associate professor of dermatology and epidemiology at UCSF.
 

Internalizing symptoms seen with mild to severe AD

Internalizing behavior, which is closely linked to depression and describes a spectrum of inward-focusing activities, such as social withdrawal, was significantly more common in children with any degree of AD relative to those without AD: After adjustment, the risk climbed from a 29% increased risk in those with mild AD (aOR, 1.29; 95% CI, 1.06-1.57) to a more than 80% increased risk in children with moderate AD (aOR, 1.84; 95% CI, 1.40-2.41) and in children with severe AD (aOR, 1.90; 95% CI, 1.14-3.16).

In the study, depression was measured with the Short Moods and Feelings Questionnaire (SMFQ). Parental response to the Emotional Symptoms subscale of the Strength and Difficulties Questionnaire (SDQ) was used to measure internalizing behaviors.

The data were drawn from the Avon Longitudinal Study for Parents and Children (ALSPAC), a cohort that enrolled pregnant women in a defined area in southwest England and then followed children born from these pregnancies. Of the 14,062 children enrolled in ALSPAC, data from 11,181 children were available for this study.

In a previous meta-analysis of studies that have documented a link between AD and adverse effects on mood and mental health, an impact was identified in both children and adults. In children, AD was associated with a 27% increase in risk of depression (OR, 1.27; 95% CI, 1.12 -1.45). In adults, the risk was more than doubled (OR, 2.19; 95% CI, 1.87-2.57). The same meta-analysis found that the risk of suicidal ideation among adolescents and adults with AD was increased more than fourfold (OR, 4.32; 95% CI, 1.93-9.66).

In the ALSPAC data, the investigators were unable to find compelling evidence that sleep disturbances or concomitant asthma contributed to the increased risk of depression, which is a mechanism proposed by past investigators.

In an interview, Dr. Abuabara said that these and other data provide the basis for encouraging clinical awareness of the psychological needs of children with AD, but she suggested there is a gap in understanding what this means clinically. “We need more data on how dermatologists can effectively screen and manage these patients before we try to set expectations for clinical practice,” she said.

In addition, these data along with previously published studies suggest that change in mental health outcomes should be included in the evaluation of new therapies, according to Dr. Abuabara. She noted that there are several tools for evaluating mental health in children that might be appropriate, each with their own advantages and disadvantages.

“Ideally, recommendations would be issued through a group consensus process with patients, clinicians, researchers, and industry representatives working together as has been done for other outcomes through the Harmonizing Measures for Eczema (HOME) group,” Dr. Abuabara said.

 

Mental health assessments recommended

Others who have looked at the relationship between AD and depression have also recommended adding mental health outcomes to an assessment of efficacy for AD therapies.

Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, is one such investigator. He is already monitoring depression systematically with the Hospital Anxiety and Depression Scale (HADS).

“HADS has been validated in AD and provides very important information about the emotional burden of AD,” explained Dr. Silverberg, whose most recent article on this topic appeared earlier this year. In that study, the relationship between AD and depression was found to be more pronounced in White children from families with lower incomes.

“Just a few hours ago, one of my patients thanked me for asking about their mental health and recognizing the holistic effects of AD,” Dr. Silverberg said.

The recent study based on ALSPAC data add to the evidence that AD, particularly severe AD, produces deleterious effects on mental health in children, and Dr. Silverberg believes clinicians should be acting on this evidence.

“I strongly encourage clinicians to routinely assess mental health. It will elevate the quality of care they provide, and their patients will appreciate them more for it,” he said.

Dr. Abuabara and another author report receiving research funding from Pfizer to their universities for unrelated work; there were no other disclosures. Dr. Silverberg reports financial relationships with more than 15 pharmaceutical companies.

Commentary by Lawrence F. Eichenfield, MD

More severe atopic dermatitis (AD) carries with it significant mental health concerns in children, as well as adults. Multiple studies have shown significantly higher rates of depression, anxiety, and “internalizing behaviors” (discussed as social withdrawal and other inward-focused activities) as well as attention-deficit/hyperactivity disorder. The study by Dr. Abuabara and colleagues is important as it followed children over time (an average of 10 years) and adjusted the data for socioeconomic factors, showing a rate of depression in children with severe AD twice that of those without. It appears that we are in the midst of a mental health crisis in children and teens, with markedly higher rates of pediatric and adolescent depression and anxiety, certainly influenced by COVID-19 societal changes. As the literature has developed on depression and AD, we have appreciated the importance of addressing this as part of our assessment of the disease effect on the individual and family, and it is one factor we consider in selections of systemic vs. topical therapies.  

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

Children with severe atopic dermatitis (AD) are about twice as likely to develop depression and internalizing behavior as those without this condition, according to a newly published cohort study of more than 11,000 children between the ages of 3 and 18 years.

Along with previous studies that have also linked AD to depression and other mental health issues in children, these data highlight the need for “clinical awareness of the psychosocial needs of children and adolescents with AD,” reported a multicenter team of investigators from the University of California, San Francisco, the University of Pennsylvania, and the London School of Hygiene and Tropical Medicine.

Unlike some previous studies, in this study, published online in JAMA Dermatology on Sept. 1, children were evaluated longitudinally, rather than at a single point in time, with a mean follow-up of 10 years. For those with active AD, compared with children without AD, the odds ratio for depression overall in any child with AD relative to those without AD was not significant after adjustment for variables such socioeconomic factors.

However, among children with severe AD, the risk was more than twofold greater even after adjustment (adjusted OR, 2.38; 95% confidence interval, 1.21- 4.72), reported the investigators, led by senior author Katrina Abuabara, MD, associate professor of dermatology and epidemiology at UCSF.
 

Internalizing symptoms seen with mild to severe AD

Internalizing behavior, which is closely linked to depression and describes a spectrum of inward-focusing activities, such as social withdrawal, was significantly more common in children with any degree of AD relative to those without AD: After adjustment, the risk climbed from a 29% increased risk in those with mild AD (aOR, 1.29; 95% CI, 1.06-1.57) to a more than 80% increased risk in children with moderate AD (aOR, 1.84; 95% CI, 1.40-2.41) and in children with severe AD (aOR, 1.90; 95% CI, 1.14-3.16).

In the study, depression was measured with the Short Moods and Feelings Questionnaire (SMFQ). Parental response to the Emotional Symptoms subscale of the Strength and Difficulties Questionnaire (SDQ) was used to measure internalizing behaviors.

The data were drawn from the Avon Longitudinal Study for Parents and Children (ALSPAC), a cohort that enrolled pregnant women in a defined area in southwest England and then followed children born from these pregnancies. Of the 14,062 children enrolled in ALSPAC, data from 11,181 children were available for this study.

In a previous meta-analysis of studies that have documented a link between AD and adverse effects on mood and mental health, an impact was identified in both children and adults. In children, AD was associated with a 27% increase in risk of depression (OR, 1.27; 95% CI, 1.12 -1.45). In adults, the risk was more than doubled (OR, 2.19; 95% CI, 1.87-2.57). The same meta-analysis found that the risk of suicidal ideation among adolescents and adults with AD was increased more than fourfold (OR, 4.32; 95% CI, 1.93-9.66).

In the ALSPAC data, the investigators were unable to find compelling evidence that sleep disturbances or concomitant asthma contributed to the increased risk of depression, which is a mechanism proposed by past investigators.

In an interview, Dr. Abuabara said that these and other data provide the basis for encouraging clinical awareness of the psychological needs of children with AD, but she suggested there is a gap in understanding what this means clinically. “We need more data on how dermatologists can effectively screen and manage these patients before we try to set expectations for clinical practice,” she said.

In addition, these data along with previously published studies suggest that change in mental health outcomes should be included in the evaluation of new therapies, according to Dr. Abuabara. She noted that there are several tools for evaluating mental health in children that might be appropriate, each with their own advantages and disadvantages.

“Ideally, recommendations would be issued through a group consensus process with patients, clinicians, researchers, and industry representatives working together as has been done for other outcomes through the Harmonizing Measures for Eczema (HOME) group,” Dr. Abuabara said.

 

Mental health assessments recommended

Others who have looked at the relationship between AD and depression have also recommended adding mental health outcomes to an assessment of efficacy for AD therapies.

Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, is one such investigator. He is already monitoring depression systematically with the Hospital Anxiety and Depression Scale (HADS).

“HADS has been validated in AD and provides very important information about the emotional burden of AD,” explained Dr. Silverberg, whose most recent article on this topic appeared earlier this year. In that study, the relationship between AD and depression was found to be more pronounced in White children from families with lower incomes.

“Just a few hours ago, one of my patients thanked me for asking about their mental health and recognizing the holistic effects of AD,” Dr. Silverberg said.

The recent study based on ALSPAC data add to the evidence that AD, particularly severe AD, produces deleterious effects on mental health in children, and Dr. Silverberg believes clinicians should be acting on this evidence.

“I strongly encourage clinicians to routinely assess mental health. It will elevate the quality of care they provide, and their patients will appreciate them more for it,” he said.

Dr. Abuabara and another author report receiving research funding from Pfizer to their universities for unrelated work; there were no other disclosures. Dr. Silverberg reports financial relationships with more than 15 pharmaceutical companies.

Commentary by Lawrence F. Eichenfield, MD

More severe atopic dermatitis (AD) carries with it significant mental health concerns in children, as well as adults. Multiple studies have shown significantly higher rates of depression, anxiety, and “internalizing behaviors” (discussed as social withdrawal and other inward-focused activities) as well as attention-deficit/hyperactivity disorder. The study by Dr. Abuabara and colleagues is important as it followed children over time (an average of 10 years) and adjusted the data for socioeconomic factors, showing a rate of depression in children with severe AD twice that of those without. It appears that we are in the midst of a mental health crisis in children and teens, with markedly higher rates of pediatric and adolescent depression and anxiety, certainly influenced by COVID-19 societal changes. As the literature has developed on depression and AD, we have appreciated the importance of addressing this as part of our assessment of the disease effect on the individual and family, and it is one factor we consider in selections of systemic vs. topical therapies.  

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

“Health care spending and health care waste is a huge problem in the U.S., including for children,” Vivian Lee, MD, of Children’s Hospital, Los Angeles, said in a presentation at the 2021 virtual Pediatric Hospital Medicine conference.

Data from a 2019 study suggested that approximately 25% of health care spending in the United States qualifies as “wasteful spending,” in categories such as overtesting, and unnecessary hospitalization, Dr. Lee said. “It is essential for physicians in hospitals to be stewards of high-value care,” she emphasized.

To combat wasteful spending and control health care costs, the Choosing Wisely campaign was created in 2012 as an initiative from the American Board of Internal Medicine Foundation. An ongoing goal of the campaign is to raise awareness among physicians and patients about potential areas of low-value services and overuse. The overall campaign includes clinician-driven recommendations from multiple medical organizations.

The PHM produced its first set of five recommendations in 2012, Dr. Lee said. These recommendations, titled “Five Things Physicians and Patients Should Question,” have been updated for 2021. The updated recommendations were created as a partnership among the Academic Pediatric Association, the American Academy of Pediatrics, and the Society of Hospital Medicine. A joint committee reviewed the latest evidence, and the updates were approved by the societies and published by the ABIM in January 2021.

“We think these recommendations truly reflect an exciting and evolving landscape for pediatric hospitalists,” Dr. Lee said. “There is a greater focus on opportunities to transition out of the hospital sooner, or avoid hospitalization altogether. There is an emphasis on antibiotic stewardship and a growing recognition of the impact that overuse may have on our vulnerable neonatal population,” she said. Several members of the Choosing Wisely panel presented the recommendations during the virtual presentation.
 

Revised recommendations

The new “Five Things Physicians and Patients Should Question” are as follows:

1. Do not prescribe IV antibiotics for predetermined durations for patients hospitalized with infections such as pyelonephritis, osteomyelitis, and complicated pneumonia. Consider early transition to oral antibiotics.

Many antibiotic doses used in clinical practice are preset durations that are not based on high-quality evidence, said Mike Tchou, MD, of Children’s Hospital of Colorado in Aurora. However, studies now show that earlier transition to enteral antibiotics can improve a range of outcomes including neonatal UTIs, osteomyelitis, and complicated pneumonia, he said. Considering early transition based on a patient’s response can decrease adverse events, pain, length of stay, and health care costs, he explained.

2. Do not continue hospitalization in well-appearing febrile infants once bacterial cultures (i.e., blood, cerebrospinal, and/or urine) have been confirmed negative for 24-36 hours, if adequate outpatient follow-up can be assured.

Recent data indicate that continuing hospitalization beyond 24-36 hours of confirmed negative bacterial cultures does not improve clinical outcomes for well-appearing infants admitted for concern of serious bacterial infection, said Paula Soung, MD, of Children’s Wisconsin in Milwaukee. In fact, “blood culture yield is highest in the first 12-36 hours after incubation with multiple studies demonstrating > 90% of pathogen cultures being positive by 24 hours,” Dr. Soung said. “If adequate outpatient follow-up can be assured, discharging well-appearing febrile infants at 24-36 hours after confirming cultures are negative has many positive outcomes,” she said.

3. Do not initiate phototherapy in term or late preterm well-appearing infants with neonatal hyperbilirubinemia if their bilirubin is below levels at which the AAP guidelines recommend treatment.

In making this recommendation, “we considered that the risk of kernicterus and cerebral palsy is extremely low in otherwise healthy term and late preterm newborns,” said Allison Holmes, MD, of Children’s Hospital at Dartmouth-Hitchcock, Manchester, N.H. “Subthreshold phototherapy leads to unnecessary hospitalization and its associated costs and harms,” and data show that kernicterus generally occurs close to 40 mg/dL and occurs most often in infants with hemolysis, she added.

The evidence for the recommendations included data showing that, among other factors, 8.6 of 100,000 babies have a bilirubin greater than 30 mg/dL, said Dr. Holmes. Risks of using subthreshold phototherapy include increased length of stay, increased readmissions, and increased costs, as well as decreased breastfeeding, bonding with parents, and increased parental anxiety. “Adding prolonged hospitalization for an intervention that might not be necessary can be stressful for parents,” she said.

4. Do not use broad-spectrum antibiotics such as ceftriaxone for children hospitalized with uncomplicated community-acquired pneumonia. Use narrow-spectrum antibiotics such as penicillin, ampicillin, or amoxicillin.

Michelle Lossius, MD, of the Shands Hospital for Children at the University of Florida, Gainesville, noted that the recommendations reflect IDSA guidelines from 2011 advising the use of ampicillin or penicillin for this population of children. More recent studies with large populations support the ability of narrow-spectrum antibiotics to limit the development of resistant organisms while achieving the same or better outcomes for children hospitalized with CAP, she said.

5. Do not start IV antibiotic therapy on well-appearing newborn infants with isolated risk factors for sepsis such as maternal chorioamnionitis, prolonged rupture of membranes, or untreated group-B streptococcal colonization. Use clinical tools such as an evidence-based sepsis risk calculator to guide management.

“This recommendation combines other recommendations,” said Prabi Rajbhandari, MD, of Akron (Ohio) Children’s Hospital. The evidence is ample, as the Centers for Disease Control and Prevention recommends the use of sepsis calculators to guide clinical management in sepsis patients, she said.

Data comparing periods before and after the adoption of a sepsis risk calculator showed a significant reduction in the use of blood cultures and antibiotics, she noted. Other risks of jumping to IV antibiotics include increased hospital stay, increased parental anxiety, and decreased parental bonding, Dr. Rajbhandari added.

Next steps include how to prioritize implementation, as well as deimplementation of outdated practices, said Francisco Alvarez, MD, of Lucile Packard Children’s Hospital, Palo Alto, Calif. “A lot of our practices were started without good evidence for why they should be done,” he said. Other steps include value improvement research; use of dashboards and benchmarking; involving other stakeholders including patients, families, and other health care providers; and addressing racial disparities, he concluded.

The presenters had no financial conflicts to disclose. The conference was sponsored by the Academic Pediatric Association, the American Academy of Pediatrics, and the Society of Hospital Medicine.

“Health care spending and health care waste is a huge problem in the U.S., including for children,” Vivian Lee, MD, of Children’s Hospital, Los Angeles, said in a presentation at the 2021 virtual Pediatric Hospital Medicine conference.

Data from a 2019 study suggested that approximately 25% of health care spending in the United States qualifies as “wasteful spending,” in categories such as overtesting, and unnecessary hospitalization, Dr. Lee said. “It is essential for physicians in hospitals to be stewards of high-value care,” she emphasized.

To combat wasteful spending and control health care costs, the Choosing Wisely campaign was created in 2012 as an initiative from the American Board of Internal Medicine Foundation. An ongoing goal of the campaign is to raise awareness among physicians and patients about potential areas of low-value services and overuse. The overall campaign includes clinician-driven recommendations from multiple medical organizations.

The PHM produced its first set of five recommendations in 2012, Dr. Lee said. These recommendations, titled “Five Things Physicians and Patients Should Question,” have been updated for 2021. The updated recommendations were created as a partnership among the Academic Pediatric Association, the American Academy of Pediatrics, and the Society of Hospital Medicine. A joint committee reviewed the latest evidence, and the updates were approved by the societies and published by the ABIM in January 2021.

“We think these recommendations truly reflect an exciting and evolving landscape for pediatric hospitalists,” Dr. Lee said. “There is a greater focus on opportunities to transition out of the hospital sooner, or avoid hospitalization altogether. There is an emphasis on antibiotic stewardship and a growing recognition of the impact that overuse may have on our vulnerable neonatal population,” she said. Several members of the Choosing Wisely panel presented the recommendations during the virtual presentation.
 

Revised recommendations

The new “Five Things Physicians and Patients Should Question” are as follows:

1. Do not prescribe IV antibiotics for predetermined durations for patients hospitalized with infections such as pyelonephritis, osteomyelitis, and complicated pneumonia. Consider early transition to oral antibiotics.

Many antibiotic doses used in clinical practice are preset durations that are not based on high-quality evidence, said Mike Tchou, MD, of Children’s Hospital of Colorado in Aurora. However, studies now show that earlier transition to enteral antibiotics can improve a range of outcomes including neonatal UTIs, osteomyelitis, and complicated pneumonia, he said. Considering early transition based on a patient’s response can decrease adverse events, pain, length of stay, and health care costs, he explained.

2. Do not continue hospitalization in well-appearing febrile infants once bacterial cultures (i.e., blood, cerebrospinal, and/or urine) have been confirmed negative for 24-36 hours, if adequate outpatient follow-up can be assured.

Recent data indicate that continuing hospitalization beyond 24-36 hours of confirmed negative bacterial cultures does not improve clinical outcomes for well-appearing infants admitted for concern of serious bacterial infection, said Paula Soung, MD, of Children’s Wisconsin in Milwaukee. In fact, “blood culture yield is highest in the first 12-36 hours after incubation with multiple studies demonstrating > 90% of pathogen cultures being positive by 24 hours,” Dr. Soung said. “If adequate outpatient follow-up can be assured, discharging well-appearing febrile infants at 24-36 hours after confirming cultures are negative has many positive outcomes,” she said.

3. Do not initiate phototherapy in term or late preterm well-appearing infants with neonatal hyperbilirubinemia if their bilirubin is below levels at which the AAP guidelines recommend treatment.

In making this recommendation, “we considered that the risk of kernicterus and cerebral palsy is extremely low in otherwise healthy term and late preterm newborns,” said Allison Holmes, MD, of Children’s Hospital at Dartmouth-Hitchcock, Manchester, N.H. “Subthreshold phototherapy leads to unnecessary hospitalization and its associated costs and harms,” and data show that kernicterus generally occurs close to 40 mg/dL and occurs most often in infants with hemolysis, she added.

The evidence for the recommendations included data showing that, among other factors, 8.6 of 100,000 babies have a bilirubin greater than 30 mg/dL, said Dr. Holmes. Risks of using subthreshold phototherapy include increased length of stay, increased readmissions, and increased costs, as well as decreased breastfeeding, bonding with parents, and increased parental anxiety. “Adding prolonged hospitalization for an intervention that might not be necessary can be stressful for parents,” she said.

4. Do not use broad-spectrum antibiotics such as ceftriaxone for children hospitalized with uncomplicated community-acquired pneumonia. Use narrow-spectrum antibiotics such as penicillin, ampicillin, or amoxicillin.

Michelle Lossius, MD, of the Shands Hospital for Children at the University of Florida, Gainesville, noted that the recommendations reflect IDSA guidelines from 2011 advising the use of ampicillin or penicillin for this population of children. More recent studies with large populations support the ability of narrow-spectrum antibiotics to limit the development of resistant organisms while achieving the same or better outcomes for children hospitalized with CAP, she said.

5. Do not start IV antibiotic therapy on well-appearing newborn infants with isolated risk factors for sepsis such as maternal chorioamnionitis, prolonged rupture of membranes, or untreated group-B streptococcal colonization. Use clinical tools such as an evidence-based sepsis risk calculator to guide management.

“This recommendation combines other recommendations,” said Prabi Rajbhandari, MD, of Akron (Ohio) Children’s Hospital. The evidence is ample, as the Centers for Disease Control and Prevention recommends the use of sepsis calculators to guide clinical management in sepsis patients, she said.

Data comparing periods before and after the adoption of a sepsis risk calculator showed a significant reduction in the use of blood cultures and antibiotics, she noted. Other risks of jumping to IV antibiotics include increased hospital stay, increased parental anxiety, and decreased parental bonding, Dr. Rajbhandari added.

Next steps include how to prioritize implementation, as well as deimplementation of outdated practices, said Francisco Alvarez, MD, of Lucile Packard Children’s Hospital, Palo Alto, Calif. “A lot of our practices were started without good evidence for why they should be done,” he said. Other steps include value improvement research; use of dashboards and benchmarking; involving other stakeholders including patients, families, and other health care providers; and addressing racial disparities, he concluded.

The presenters had no financial conflicts to disclose. The conference was sponsored by the Academic Pediatric Association, the American Academy of Pediatrics, and the Society of Hospital Medicine.

“Health care spending and health care waste is a huge problem in the U.S., including for children,” Vivian Lee, MD, of Children’s Hospital, Los Angeles, said in a presentation at the 2021 virtual Pediatric Hospital Medicine conference.

Data from a 2019 study suggested that approximately 25% of health care spending in the United States qualifies as “wasteful spending,” in categories such as overtesting, and unnecessary hospitalization, Dr. Lee said. “It is essential for physicians in hospitals to be stewards of high-value care,” she emphasized.

To combat wasteful spending and control health care costs, the Choosing Wisely campaign was created in 2012 as an initiative from the American Board of Internal Medicine Foundation. An ongoing goal of the campaign is to raise awareness among physicians and patients about potential areas of low-value services and overuse. The overall campaign includes clinician-driven recommendations from multiple medical organizations.

The PHM produced its first set of five recommendations in 2012, Dr. Lee said. These recommendations, titled “Five Things Physicians and Patients Should Question,” have been updated for 2021. The updated recommendations were created as a partnership among the Academic Pediatric Association, the American Academy of Pediatrics, and the Society of Hospital Medicine. A joint committee reviewed the latest evidence, and the updates were approved by the societies and published by the ABIM in January 2021.

“We think these recommendations truly reflect an exciting and evolving landscape for pediatric hospitalists,” Dr. Lee said. “There is a greater focus on opportunities to transition out of the hospital sooner, or avoid hospitalization altogether. There is an emphasis on antibiotic stewardship and a growing recognition of the impact that overuse may have on our vulnerable neonatal population,” she said. Several members of the Choosing Wisely panel presented the recommendations during the virtual presentation.
 

Revised recommendations

The new “Five Things Physicians and Patients Should Question” are as follows:

1. Do not prescribe IV antibiotics for predetermined durations for patients hospitalized with infections such as pyelonephritis, osteomyelitis, and complicated pneumonia. Consider early transition to oral antibiotics.

Many antibiotic doses used in clinical practice are preset durations that are not based on high-quality evidence, said Mike Tchou, MD, of Children’s Hospital of Colorado in Aurora. However, studies now show that earlier transition to enteral antibiotics can improve a range of outcomes including neonatal UTIs, osteomyelitis, and complicated pneumonia, he said. Considering early transition based on a patient’s response can decrease adverse events, pain, length of stay, and health care costs, he explained.

2. Do not continue hospitalization in well-appearing febrile infants once bacterial cultures (i.e., blood, cerebrospinal, and/or urine) have been confirmed negative for 24-36 hours, if adequate outpatient follow-up can be assured.

Recent data indicate that continuing hospitalization beyond 24-36 hours of confirmed negative bacterial cultures does not improve clinical outcomes for well-appearing infants admitted for concern of serious bacterial infection, said Paula Soung, MD, of Children’s Wisconsin in Milwaukee. In fact, “blood culture yield is highest in the first 12-36 hours after incubation with multiple studies demonstrating > 90% of pathogen cultures being positive by 24 hours,” Dr. Soung said. “If adequate outpatient follow-up can be assured, discharging well-appearing febrile infants at 24-36 hours after confirming cultures are negative has many positive outcomes,” she said.

3. Do not initiate phototherapy in term or late preterm well-appearing infants with neonatal hyperbilirubinemia if their bilirubin is below levels at which the AAP guidelines recommend treatment.

In making this recommendation, “we considered that the risk of kernicterus and cerebral palsy is extremely low in otherwise healthy term and late preterm newborns,” said Allison Holmes, MD, of Children’s Hospital at Dartmouth-Hitchcock, Manchester, N.H. “Subthreshold phototherapy leads to unnecessary hospitalization and its associated costs and harms,” and data show that kernicterus generally occurs close to 40 mg/dL and occurs most often in infants with hemolysis, she added.

The evidence for the recommendations included data showing that, among other factors, 8.6 of 100,000 babies have a bilirubin greater than 30 mg/dL, said Dr. Holmes. Risks of using subthreshold phototherapy include increased length of stay, increased readmissions, and increased costs, as well as decreased breastfeeding, bonding with parents, and increased parental anxiety. “Adding prolonged hospitalization for an intervention that might not be necessary can be stressful for parents,” she said.

4. Do not use broad-spectrum antibiotics such as ceftriaxone for children hospitalized with uncomplicated community-acquired pneumonia. Use narrow-spectrum antibiotics such as penicillin, ampicillin, or amoxicillin.

Michelle Lossius, MD, of the Shands Hospital for Children at the University of Florida, Gainesville, noted that the recommendations reflect IDSA guidelines from 2011 advising the use of ampicillin or penicillin for this population of children. More recent studies with large populations support the ability of narrow-spectrum antibiotics to limit the development of resistant organisms while achieving the same or better outcomes for children hospitalized with CAP, she said.

5. Do not start IV antibiotic therapy on well-appearing newborn infants with isolated risk factors for sepsis such as maternal chorioamnionitis, prolonged rupture of membranes, or untreated group-B streptococcal colonization. Use clinical tools such as an evidence-based sepsis risk calculator to guide management.

“This recommendation combines other recommendations,” said Prabi Rajbhandari, MD, of Akron (Ohio) Children’s Hospital. The evidence is ample, as the Centers for Disease Control and Prevention recommends the use of sepsis calculators to guide clinical management in sepsis patients, she said.

Data comparing periods before and after the adoption of a sepsis risk calculator showed a significant reduction in the use of blood cultures and antibiotics, she noted. Other risks of jumping to IV antibiotics include increased hospital stay, increased parental anxiety, and decreased parental bonding, Dr. Rajbhandari added.

Next steps include how to prioritize implementation, as well as deimplementation of outdated practices, said Francisco Alvarez, MD, of Lucile Packard Children’s Hospital, Palo Alto, Calif. “A lot of our practices were started without good evidence for why they should be done,” he said. Other steps include value improvement research; use of dashboards and benchmarking; involving other stakeholders including patients, families, and other health care providers; and addressing racial disparities, he concluded.

The presenters had no financial conflicts to disclose. The conference was sponsored by the Academic Pediatric Association, the American Academy of Pediatrics, and the Society of Hospital Medicine.

Cases of child COVID-19 set a new 1-week record and the total number of children infected during the pandemic passed 5 million, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The nearly 282,000 new cases reported in the United States during the week ending Sept. 2 broke the record of 211,000 set in mid-January and brought the cumulative count to 5,049,465 children with COVID-19 since the pandemic began, the AAP and the CHA said in their weekly COVID report.

Hospitalizations in children aged 0-17 years have also reached record levels in recent days. The highest daily admission rate since the pandemic began, 0.51 per 100,000 population, was recorded on Sept. 2, less than 2 months after the nation saw its lowest child COVID admission rate for 1 day: 0.07 per 100,000 on July 4. That’s an increase of 629%, according to data from the Centers for Disease Control and Prevention.

Vaccinations in children, however, did not follow suit. New vaccinations in children aged 12-17 years dropped by 4.5% for the week ending Sept. 6, compared with the week before. Initiations were actually up almost 12% for children aged 16-17, but that was not enough to overcome the continued decline among 12- to 15-year-olds, the CDC said on its COVID Data Tracker.

Despite the decline in new vaccinations, those younger children passed a noteworthy group milestone: 50.9% of all 12- to 15-year-olds now have received at least one dose, with 38.6% having completed the regimen. The 16- to 17-year-olds got an earlier start and have reached 58.9% coverage for one dose and 47.6% for two, the CDC said.

A total of 12.2 million children aged 12-17 years had received at least one dose of COVID vaccine as of Sept. 6, of whom almost 9.5 million are fully vaccinated, based on the CDC data.

At the state level, Vermont has the highest rates for vaccine initiation (75%) and full vaccination (65%), with Massachusetts (75%/62%) and Connecticut (73%/59%) just behind. The other end of the scale is occupied by Wyoming (28% initiation/19% full vaccination), Alabama (32%/19%), and North Dakota (32%/23%), the AAP said in a separate report.

In a recent letter to the Food and Drug Administration, AAP President Lee Savio Beers, MD, said that the “Delta variant is surging at extremely alarming rates in every region of America. This surge is seriously impacting all populations, including children.” Dr. Beers urged the FDA to work “aggressively toward authorizing safe and effective COVID-19 vaccines for children under age 12 as soon as possible.”

[email protected]

Cases of child COVID-19 set a new 1-week record and the total number of children infected during the pandemic passed 5 million, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The nearly 282,000 new cases reported in the United States during the week ending Sept. 2 broke the record of 211,000 set in mid-January and brought the cumulative count to 5,049,465 children with COVID-19 since the pandemic began, the AAP and the CHA said in their weekly COVID report.

Hospitalizations in children aged 0-17 years have also reached record levels in recent days. The highest daily admission rate since the pandemic began, 0.51 per 100,000 population, was recorded on Sept. 2, less than 2 months after the nation saw its lowest child COVID admission rate for 1 day: 0.07 per 100,000 on July 4. That’s an increase of 629%, according to data from the Centers for Disease Control and Prevention.

Vaccinations in children, however, did not follow suit. New vaccinations in children aged 12-17 years dropped by 4.5% for the week ending Sept. 6, compared with the week before. Initiations were actually up almost 12% for children aged 16-17, but that was not enough to overcome the continued decline among 12- to 15-year-olds, the CDC said on its COVID Data Tracker.

Despite the decline in new vaccinations, those younger children passed a noteworthy group milestone: 50.9% of all 12- to 15-year-olds now have received at least one dose, with 38.6% having completed the regimen. The 16- to 17-year-olds got an earlier start and have reached 58.9% coverage for one dose and 47.6% for two, the CDC said.

A total of 12.2 million children aged 12-17 years had received at least one dose of COVID vaccine as of Sept. 6, of whom almost 9.5 million are fully vaccinated, based on the CDC data.

At the state level, Vermont has the highest rates for vaccine initiation (75%) and full vaccination (65%), with Massachusetts (75%/62%) and Connecticut (73%/59%) just behind. The other end of the scale is occupied by Wyoming (28% initiation/19% full vaccination), Alabama (32%/19%), and North Dakota (32%/23%), the AAP said in a separate report.

In a recent letter to the Food and Drug Administration, AAP President Lee Savio Beers, MD, said that the “Delta variant is surging at extremely alarming rates in every region of America. This surge is seriously impacting all populations, including children.” Dr. Beers urged the FDA to work “aggressively toward authorizing safe and effective COVID-19 vaccines for children under age 12 as soon as possible.”

[email protected]

Cases of child COVID-19 set a new 1-week record and the total number of children infected during the pandemic passed 5 million, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The nearly 282,000 new cases reported in the United States during the week ending Sept. 2 broke the record of 211,000 set in mid-January and brought the cumulative count to 5,049,465 children with COVID-19 since the pandemic began, the AAP and the CHA said in their weekly COVID report.

Hospitalizations in children aged 0-17 years have also reached record levels in recent days. The highest daily admission rate since the pandemic began, 0.51 per 100,000 population, was recorded on Sept. 2, less than 2 months after the nation saw its lowest child COVID admission rate for 1 day: 0.07 per 100,000 on July 4. That’s an increase of 629%, according to data from the Centers for Disease Control and Prevention.

Vaccinations in children, however, did not follow suit. New vaccinations in children aged 12-17 years dropped by 4.5% for the week ending Sept. 6, compared with the week before. Initiations were actually up almost 12% for children aged 16-17, but that was not enough to overcome the continued decline among 12- to 15-year-olds, the CDC said on its COVID Data Tracker.

Despite the decline in new vaccinations, those younger children passed a noteworthy group milestone: 50.9% of all 12- to 15-year-olds now have received at least one dose, with 38.6% having completed the regimen. The 16- to 17-year-olds got an earlier start and have reached 58.9% coverage for one dose and 47.6% for two, the CDC said.

A total of 12.2 million children aged 12-17 years had received at least one dose of COVID vaccine as of Sept. 6, of whom almost 9.5 million are fully vaccinated, based on the CDC data.

At the state level, Vermont has the highest rates for vaccine initiation (75%) and full vaccination (65%), with Massachusetts (75%/62%) and Connecticut (73%/59%) just behind. The other end of the scale is occupied by Wyoming (28% initiation/19% full vaccination), Alabama (32%/19%), and North Dakota (32%/23%), the AAP said in a separate report.

In a recent letter to the Food and Drug Administration, AAP President Lee Savio Beers, MD, said that the “Delta variant is surging at extremely alarming rates in every region of America. This surge is seriously impacting all populations, including children.” Dr. Beers urged the FDA to work “aggressively toward authorizing safe and effective COVID-19 vaccines for children under age 12 as soon as possible.”

[email protected]

The COVID-19 pandemic continues to impact child and adolescent mental health, and clinicians are learning as they go to develop strategies that address the challenges of providing both medical and mental health care to young patients, including those who test positive for COVID-19, according to Hani Talebi, PhD, director of pediatric psychology, and Jorge Ganem, MD, FAAP, director of pediatric hospital medicine, both of the University of Texas at Austin and Dell Children’s Medical Center.

In a presentation at the 2021 virtual Pediatric Hospital Medicine conference, Dr. Talebi and Dr. Ganem shared their experiences in identifying the impact of the pandemic on mental health services in a freestanding hospital, and synthesizing inpatient mental health care and medical care outside of a dedicated mental health unit.

Mental health is a significant pediatric issue; approximately one in five children have a diagnosable mental or behavioral health problem, but nearly two-thirds get little or no help, Dr. Talebi said. “COVID-19 has only exacerbated these mental health challenges,” he said.

He noted that beginning in April 2020, the proportion of children’s mental health-related emergency department visits increased and remained elevated through the spring, summer, and fall of 2020, as families fearful of COVID-19 avoided regular hospital visits.

Data suggest that up to 50% of all adolescent psychiatric crises that led to inpatient admissions were related in some way to COVID-19, Dr. Talebi said. In addition, “individuals with a recent diagnosis of a mental health disorder are at increased risk for COVID-19 infection,” and the risk is even higher among women and African Americans, he said.

The past year significantly impacted the mental wellbeing of parents and children, Dr. Talebi said. He cited a June 2020 study in Pediatrics in which 27% of parents reported worsening mental health for themselves, and 14% reported worsening behavioral health for their children. Ongoing issues including food insecurity, loss of regular child care, and an overall “very disorienting experience in the day-to-day” compromised the mental health of families, Dr. Talebi emphasized. Children isolated at home were not meeting developmental milestones that organically occur when socializing with peers, parents didn’t know how to handle some of their children’s issues without support from schools, and many people were struggling with other preexisting health conditions, he said.

This confluence of factors helped drive a surge in emergency department visits, meaning longer wait times and concerns about meeting urgent medical and mental health needs while maintaining safety, he added.

Parents and children waited longer to seek care, and community hospitals such as Dell Children’s Medical Center were faced with children in the emergency department with crisis-level mental health issues, along with children already waiting in the ED to address medical emergencies. All these patients had to be tested for COVID-19 and managed accordingly, Dr. Talebi noted.

Dr. Talebi emphasized the need for clinically robust care of the children who were in isolation for 10 days on the medical unit, waiting to test negative. New protocols were created for social workers to conduct daily safety checks, and to develop regular schedules for screening, “so they are having an experience on the medical floors similar to what they would have in a mental health unit,” he said.

Dr. Ganem reflected on the logistical challenges of managing mental health care while observing COVID-19 safety protocols. “COVID-19 added a new wrinkle of isolation,” he said. As institutional guidelines on testing and isolation evolved, negative COVID-19 tests were required for admission to the mental health units both in the hospital and throughout the region. Patients who tested positive had to be quarantined for 10 days, at which time they could be admitted to a mental health unit if necessary, he said.

Dr. Ganem shared details of some strategies adopted by Dell Children’s. He explained that the COVID-19 psychiatry patient workflow started with an ED evaluation, followed by medical clearance and consideration for admission.

“There was significant coordination between the social worker in the emergency department and the psychiatry social worker,” he said.

Key elements of the treatment plan for children with positive COVID-19 tests included an “interprofessional huddle” to coordinate the plan of care, goals for admission, and goals for safety, Dr. Ganem said.

Patients who required admission were expected to have an initial length of stay of 72 hours, and those who tested positive for COVID-19 were admitted to a medical unit with COVID-19 isolation, he said.

Once a patient is admitted, an RN activates a suicide prevention pathway, and an interprofessional team meets to determine what patients need for safe and effective discharge, said Dr. Ganem. He cited the SAFE-T protocol (Suicide Assessment Five-step Evaluation and Triage) as one of the tools used to determine safe discharge criteria. Considerations on the SAFE-T list include family support, an established outpatient therapist and psychiatrist, no suicide attempts prior to the current admission, or a low lethality attempt, and access to partial hospitalization or intensive outpatient programs.

Patients who could not be discharged because of suicidality or inadequate support or concerns about safety at home were considered for inpatient admission. Patients with COVID-19–positive tests who had continued need for inpatient mental health services could be transferred to an inpatient mental health unit after a 10-day quarantine.

Overall, “this has been a continuum of lessons learned, with some things we know now that we didn’t know in April or May of 2020,” Dr. Ganem said. Early in the pandemic, the focus was on minimizing risk, securing personal protective equipment, and determining who provided services in a patient’s room. “We developed new paradigms on the fly,” he said, including the use of virtual visits, which included securing and cleaning devices, as well as learning how to use them in this setting,” he said.

More recently, the emphasis has been on providing services to patients before they need to visit the hospital, rather than automatically admitting any patients with suicidal ideation and a positive COVID-19 test, Dr. Ganem said.

Dr. Talebi and Dr. Ganem had no financial conflicts to disclose. The conference was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The COVID-19 pandemic continues to impact child and adolescent mental health, and clinicians are learning as they go to develop strategies that address the challenges of providing both medical and mental health care to young patients, including those who test positive for COVID-19, according to Hani Talebi, PhD, director of pediatric psychology, and Jorge Ganem, MD, FAAP, director of pediatric hospital medicine, both of the University of Texas at Austin and Dell Children’s Medical Center.

In a presentation at the 2021 virtual Pediatric Hospital Medicine conference, Dr. Talebi and Dr. Ganem shared their experiences in identifying the impact of the pandemic on mental health services in a freestanding hospital, and synthesizing inpatient mental health care and medical care outside of a dedicated mental health unit.

Mental health is a significant pediatric issue; approximately one in five children have a diagnosable mental or behavioral health problem, but nearly two-thirds get little or no help, Dr. Talebi said. “COVID-19 has only exacerbated these mental health challenges,” he said.

He noted that beginning in April 2020, the proportion of children’s mental health-related emergency department visits increased and remained elevated through the spring, summer, and fall of 2020, as families fearful of COVID-19 avoided regular hospital visits.

Data suggest that up to 50% of all adolescent psychiatric crises that led to inpatient admissions were related in some way to COVID-19, Dr. Talebi said. In addition, “individuals with a recent diagnosis of a mental health disorder are at increased risk for COVID-19 infection,” and the risk is even higher among women and African Americans, he said.

The past year significantly impacted the mental wellbeing of parents and children, Dr. Talebi said. He cited a June 2020 study in Pediatrics in which 27% of parents reported worsening mental health for themselves, and 14% reported worsening behavioral health for their children. Ongoing issues including food insecurity, loss of regular child care, and an overall “very disorienting experience in the day-to-day” compromised the mental health of families, Dr. Talebi emphasized. Children isolated at home were not meeting developmental milestones that organically occur when socializing with peers, parents didn’t know how to handle some of their children’s issues without support from schools, and many people were struggling with other preexisting health conditions, he said.

This confluence of factors helped drive a surge in emergency department visits, meaning longer wait times and concerns about meeting urgent medical and mental health needs while maintaining safety, he added.

Parents and children waited longer to seek care, and community hospitals such as Dell Children’s Medical Center were faced with children in the emergency department with crisis-level mental health issues, along with children already waiting in the ED to address medical emergencies. All these patients had to be tested for COVID-19 and managed accordingly, Dr. Talebi noted.

Dr. Talebi emphasized the need for clinically robust care of the children who were in isolation for 10 days on the medical unit, waiting to test negative. New protocols were created for social workers to conduct daily safety checks, and to develop regular schedules for screening, “so they are having an experience on the medical floors similar to what they would have in a mental health unit,” he said.

Dr. Ganem reflected on the logistical challenges of managing mental health care while observing COVID-19 safety protocols. “COVID-19 added a new wrinkle of isolation,” he said. As institutional guidelines on testing and isolation evolved, negative COVID-19 tests were required for admission to the mental health units both in the hospital and throughout the region. Patients who tested positive had to be quarantined for 10 days, at which time they could be admitted to a mental health unit if necessary, he said.

Dr. Ganem shared details of some strategies adopted by Dell Children’s. He explained that the COVID-19 psychiatry patient workflow started with an ED evaluation, followed by medical clearance and consideration for admission.

“There was significant coordination between the social worker in the emergency department and the psychiatry social worker,” he said.

Key elements of the treatment plan for children with positive COVID-19 tests included an “interprofessional huddle” to coordinate the plan of care, goals for admission, and goals for safety, Dr. Ganem said.

Patients who required admission were expected to have an initial length of stay of 72 hours, and those who tested positive for COVID-19 were admitted to a medical unit with COVID-19 isolation, he said.

Once a patient is admitted, an RN activates a suicide prevention pathway, and an interprofessional team meets to determine what patients need for safe and effective discharge, said Dr. Ganem. He cited the SAFE-T protocol (Suicide Assessment Five-step Evaluation and Triage) as one of the tools used to determine safe discharge criteria. Considerations on the SAFE-T list include family support, an established outpatient therapist and psychiatrist, no suicide attempts prior to the current admission, or a low lethality attempt, and access to partial hospitalization or intensive outpatient programs.

Patients who could not be discharged because of suicidality or inadequate support or concerns about safety at home were considered for inpatient admission. Patients with COVID-19–positive tests who had continued need for inpatient mental health services could be transferred to an inpatient mental health unit after a 10-day quarantine.

Overall, “this has been a continuum of lessons learned, with some things we know now that we didn’t know in April or May of 2020,” Dr. Ganem said. Early in the pandemic, the focus was on minimizing risk, securing personal protective equipment, and determining who provided services in a patient’s room. “We developed new paradigms on the fly,” he said, including the use of virtual visits, which included securing and cleaning devices, as well as learning how to use them in this setting,” he said.

More recently, the emphasis has been on providing services to patients before they need to visit the hospital, rather than automatically admitting any patients with suicidal ideation and a positive COVID-19 test, Dr. Ganem said.

Dr. Talebi and Dr. Ganem had no financial conflicts to disclose. The conference was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The COVID-19 pandemic continues to impact child and adolescent mental health, and clinicians are learning as they go to develop strategies that address the challenges of providing both medical and mental health care to young patients, including those who test positive for COVID-19, according to Hani Talebi, PhD, director of pediatric psychology, and Jorge Ganem, MD, FAAP, director of pediatric hospital medicine, both of the University of Texas at Austin and Dell Children’s Medical Center.

In a presentation at the 2021 virtual Pediatric Hospital Medicine conference, Dr. Talebi and Dr. Ganem shared their experiences in identifying the impact of the pandemic on mental health services in a freestanding hospital, and synthesizing inpatient mental health care and medical care outside of a dedicated mental health unit.

Mental health is a significant pediatric issue; approximately one in five children have a diagnosable mental or behavioral health problem, but nearly two-thirds get little or no help, Dr. Talebi said. “COVID-19 has only exacerbated these mental health challenges,” he said.

He noted that beginning in April 2020, the proportion of children’s mental health-related emergency department visits increased and remained elevated through the spring, summer, and fall of 2020, as families fearful of COVID-19 avoided regular hospital visits.

Data suggest that up to 50% of all adolescent psychiatric crises that led to inpatient admissions were related in some way to COVID-19, Dr. Talebi said. In addition, “individuals with a recent diagnosis of a mental health disorder are at increased risk for COVID-19 infection,” and the risk is even higher among women and African Americans, he said.

The past year significantly impacted the mental wellbeing of parents and children, Dr. Talebi said. He cited a June 2020 study in Pediatrics in which 27% of parents reported worsening mental health for themselves, and 14% reported worsening behavioral health for their children. Ongoing issues including food insecurity, loss of regular child care, and an overall “very disorienting experience in the day-to-day” compromised the mental health of families, Dr. Talebi emphasized. Children isolated at home were not meeting developmental milestones that organically occur when socializing with peers, parents didn’t know how to handle some of their children’s issues without support from schools, and many people were struggling with other preexisting health conditions, he said.

This confluence of factors helped drive a surge in emergency department visits, meaning longer wait times and concerns about meeting urgent medical and mental health needs while maintaining safety, he added.

Parents and children waited longer to seek care, and community hospitals such as Dell Children’s Medical Center were faced with children in the emergency department with crisis-level mental health issues, along with children already waiting in the ED to address medical emergencies. All these patients had to be tested for COVID-19 and managed accordingly, Dr. Talebi noted.

Dr. Talebi emphasized the need for clinically robust care of the children who were in isolation for 10 days on the medical unit, waiting to test negative. New protocols were created for social workers to conduct daily safety checks, and to develop regular schedules for screening, “so they are having an experience on the medical floors similar to what they would have in a mental health unit,” he said.

Dr. Ganem reflected on the logistical challenges of managing mental health care while observing COVID-19 safety protocols. “COVID-19 added a new wrinkle of isolation,” he said. As institutional guidelines on testing and isolation evolved, negative COVID-19 tests were required for admission to the mental health units both in the hospital and throughout the region. Patients who tested positive had to be quarantined for 10 days, at which time they could be admitted to a mental health unit if necessary, he said.

Dr. Ganem shared details of some strategies adopted by Dell Children’s. He explained that the COVID-19 psychiatry patient workflow started with an ED evaluation, followed by medical clearance and consideration for admission.

“There was significant coordination between the social worker in the emergency department and the psychiatry social worker,” he said.

Key elements of the treatment plan for children with positive COVID-19 tests included an “interprofessional huddle” to coordinate the plan of care, goals for admission, and goals for safety, Dr. Ganem said.

Patients who required admission were expected to have an initial length of stay of 72 hours, and those who tested positive for COVID-19 were admitted to a medical unit with COVID-19 isolation, he said.

Once a patient is admitted, an RN activates a suicide prevention pathway, and an interprofessional team meets to determine what patients need for safe and effective discharge, said Dr. Ganem. He cited the SAFE-T protocol (Suicide Assessment Five-step Evaluation and Triage) as one of the tools used to determine safe discharge criteria. Considerations on the SAFE-T list include family support, an established outpatient therapist and psychiatrist, no suicide attempts prior to the current admission, or a low lethality attempt, and access to partial hospitalization or intensive outpatient programs.

Patients who could not be discharged because of suicidality or inadequate support or concerns about safety at home were considered for inpatient admission. Patients with COVID-19–positive tests who had continued need for inpatient mental health services could be transferred to an inpatient mental health unit after a 10-day quarantine.

Overall, “this has been a continuum of lessons learned, with some things we know now that we didn’t know in April or May of 2020,” Dr. Ganem said. Early in the pandemic, the focus was on minimizing risk, securing personal protective equipment, and determining who provided services in a patient’s room. “We developed new paradigms on the fly,” he said, including the use of virtual visits, which included securing and cleaning devices, as well as learning how to use them in this setting,” he said.

More recently, the emphasis has been on providing services to patients before they need to visit the hospital, rather than automatically admitting any patients with suicidal ideation and a positive COVID-19 test, Dr. Ganem said.

Dr. Talebi and Dr. Ganem had no financial conflicts to disclose. The conference was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

With more than 300 genetic skin disorders involving more than 1,000 genes and hundreds of genetic tests available on the market, it can be daunting for health care providers and families of pediatric patients to navigate the landscape.

“Testing options range from targeted variant testing and single-gene testing to exome and genome sequencing,” Gabriele Richard, MD, said at the annual meeting of the Society for Pediatric Dermatology. “It is not always easy to determine which testing is right.”

Increasingly, clinical genomic tests, including exome and genome sequencing, are used for patients with complex phenotypes, and possibly multiple disorders, who might have no diagnosis despite extensive prior testing, said Dr. Richard, medical director at Gaithersburg, Md.–based GeneDx., a molecular diagnostic laboratory that performs comprehensive testing for rare genetic disorders. These tests are also being used more for first-line testing in critically ill patients in the neonatal and pediatric intensive care units, and “have heralded a whole new era of gene and disease discovery,” she added.

Targeted variant testing is used for known familial variants, to test family members for carrier status and segregation, and to make a prenatal diagnosis, she said. Single-gene testing is available for most genes and has its place for conditions that can be clinically well-recognized, such as ichthyosis vulgaris, Darier disease, or Papillon-Lefèvre syndrome.

Specific tests for identifying gene deletions or duplications are exon-level microarrays, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray analysis. “The latter has been successful in identifying diseases causing chromosomal abnormalities in over 10% of cases overall,” Dr. Richard said. An example of a skin disorder is X-linked ichthyosis caused by a deletion of the steroid sulfatase locus in more than 95% of affected males, she said.

“However, the current staple of molecular diagnostic testing is multigene next-generation sequencing (NGS) panels, which allow you to interrogate two to hundreds of genes concurrently, including sequencing and deletion duplication testing.” These tests are the most cost effective, she said, and are available for almost any genodermatosis or group of disorders with overlapping phenotypes, such as albinism or ichthyosis, epidermolysis bullosa and skin fragility, ectodermal dysplasia, or porphyria. According to Dr. Richard, the diagnostic outcomes of NGS panels mainly depend on test indication, panel size and gene curation, age of onset, and prevailing inheritance pattern of disorders.

Her recommended criteria for distinguishing the myriad of available NGS panels include checking gene content, technical sensitivity of sequencing and deletion/duplication analysis, quality of variant interpretation and reporting, turn-around time, and available familial follow-up testing. “If a family might consider future prenatal diagnosis, choose the lab that performs prenatal and diagnostic testing,” Dr. Richard said. “Equally important are client services such as ease of ordering, insurance coverage, and the ability to determine out-of-pocket cost to patients.”

Resources that enable consumers to compare panel content, methodology, turnaround time, and other parameters include the Genetic Testing Registry (GTR) operated by the National Center for Biotechnology Information, and Concert Genetics, a genetic testing company. The National Society of Genetic Counselors also offers a searchable database for finding a genetic counselor.

Exome sequencing includes the coding sequences of about 20,000 genes and has an average depth of 50 to about 150 reads. “It is a phenotype-driven test where only select variants are being reported fitting the phenotype,” Dr. Richard said. “The outcome of exome and genome sequencing much depends on optimization of bioinformatic pipelines and tools.” Besides small sequence variants, exome sequencing is able to identify a variety of different types of disease-causing variants, such as gene copy number variants seen in about 6% of positive cases, mosaicism, regions of homozygosity, uniparental disomy, and other unusual events and is cost effective.

Whole-genome sequencing, meanwhile, includes the entire genome, particularly noncoding regions, and has an average depth of more than 30 reads. “It’s based on single-molecule sequencing, has longer reads and more uniform coverage, compared to exome sequencing,” she said. “Higher cost, variant interpretation, and lack of coverage by payers are still presenting challenges for genome sequencing.” Genome sequencing can be done in a day or less.

According to diagnostic outcomes based on 280,000 individuals including 125,000 probands from GeneDx data, a definitive diagnosis was made in 26% of probands, of which 2.8% had more than one diagnostic finding and 1.8% had actionable secondary findings. In addition, 7% of the variants were found in candidate genes; 31% of probands had variants of uncertain significance, while 36% tested negative. “Nevertheless, the diagnostic yield of exome sequencing depends on the phenotype and cohort studied,” Dr. Richard continued.

At her company, she said, the highest positive rate is for multiple congenital anomalies (34%), skeletal system abnormalities (30%), and nervous system abnormalities (29%). Trio testing – the concurrent analysis of both biological parents and proband for all genes – “is a critical factor for success,” she added. “It not only improves the variant calling because we have three times the data and increases test sensitivity, it also provides more certain results, determines inheritance and allows for detection of parental mosaicism.”

According to Dr. Richard, trio testing has a one-third higher diagnostic rate than sequencing of the proband alone. Citing a published prospective study that compiled data from eight different exome- and genome-sequencing studies in critically ill neonates and children, trio testing made it possible to make a genetic diagnosis in up to 58% of children.

Whole-genome sequencing is estimated to have a 5%-10% higher diagnostic rate than exome sequencing. “However, we are still a ways away from using it as a routine diagnostic test for all test indications,” Dr. Richard said. “Automation, special bioinformatics algorithms and databases, and combination of genome sequencing with mRNA sequencing are being explored and built to further improve the diagnostic yield.”

Dr. Richard had no disclosures other than being an employee of GeneDx.

[email protected]

With more than 300 genetic skin disorders involving more than 1,000 genes and hundreds of genetic tests available on the market, it can be daunting for health care providers and families of pediatric patients to navigate the landscape.

“Testing options range from targeted variant testing and single-gene testing to exome and genome sequencing,” Gabriele Richard, MD, said at the annual meeting of the Society for Pediatric Dermatology. “It is not always easy to determine which testing is right.”

Increasingly, clinical genomic tests, including exome and genome sequencing, are used for patients with complex phenotypes, and possibly multiple disorders, who might have no diagnosis despite extensive prior testing, said Dr. Richard, medical director at Gaithersburg, Md.–based GeneDx., a molecular diagnostic laboratory that performs comprehensive testing for rare genetic disorders. These tests are also being used more for first-line testing in critically ill patients in the neonatal and pediatric intensive care units, and “have heralded a whole new era of gene and disease discovery,” she added.

Targeted variant testing is used for known familial variants, to test family members for carrier status and segregation, and to make a prenatal diagnosis, she said. Single-gene testing is available for most genes and has its place for conditions that can be clinically well-recognized, such as ichthyosis vulgaris, Darier disease, or Papillon-Lefèvre syndrome.

Specific tests for identifying gene deletions or duplications are exon-level microarrays, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray analysis. “The latter has been successful in identifying diseases causing chromosomal abnormalities in over 10% of cases overall,” Dr. Richard said. An example of a skin disorder is X-linked ichthyosis caused by a deletion of the steroid sulfatase locus in more than 95% of affected males, she said.

“However, the current staple of molecular diagnostic testing is multigene next-generation sequencing (NGS) panels, which allow you to interrogate two to hundreds of genes concurrently, including sequencing and deletion duplication testing.” These tests are the most cost effective, she said, and are available for almost any genodermatosis or group of disorders with overlapping phenotypes, such as albinism or ichthyosis, epidermolysis bullosa and skin fragility, ectodermal dysplasia, or porphyria. According to Dr. Richard, the diagnostic outcomes of NGS panels mainly depend on test indication, panel size and gene curation, age of onset, and prevailing inheritance pattern of disorders.

Her recommended criteria for distinguishing the myriad of available NGS panels include checking gene content, technical sensitivity of sequencing and deletion/duplication analysis, quality of variant interpretation and reporting, turn-around time, and available familial follow-up testing. “If a family might consider future prenatal diagnosis, choose the lab that performs prenatal and diagnostic testing,” Dr. Richard said. “Equally important are client services such as ease of ordering, insurance coverage, and the ability to determine out-of-pocket cost to patients.”

Resources that enable consumers to compare panel content, methodology, turnaround time, and other parameters include the Genetic Testing Registry (GTR) operated by the National Center for Biotechnology Information, and Concert Genetics, a genetic testing company. The National Society of Genetic Counselors also offers a searchable database for finding a genetic counselor.

Exome sequencing includes the coding sequences of about 20,000 genes and has an average depth of 50 to about 150 reads. “It is a phenotype-driven test where only select variants are being reported fitting the phenotype,” Dr. Richard said. “The outcome of exome and genome sequencing much depends on optimization of bioinformatic pipelines and tools.” Besides small sequence variants, exome sequencing is able to identify a variety of different types of disease-causing variants, such as gene copy number variants seen in about 6% of positive cases, mosaicism, regions of homozygosity, uniparental disomy, and other unusual events and is cost effective.

Whole-genome sequencing, meanwhile, includes the entire genome, particularly noncoding regions, and has an average depth of more than 30 reads. “It’s based on single-molecule sequencing, has longer reads and more uniform coverage, compared to exome sequencing,” she said. “Higher cost, variant interpretation, and lack of coverage by payers are still presenting challenges for genome sequencing.” Genome sequencing can be done in a day or less.

According to diagnostic outcomes based on 280,000 individuals including 125,000 probands from GeneDx data, a definitive diagnosis was made in 26% of probands, of which 2.8% had more than one diagnostic finding and 1.8% had actionable secondary findings. In addition, 7% of the variants were found in candidate genes; 31% of probands had variants of uncertain significance, while 36% tested negative. “Nevertheless, the diagnostic yield of exome sequencing depends on the phenotype and cohort studied,” Dr. Richard continued.

At her company, she said, the highest positive rate is for multiple congenital anomalies (34%), skeletal system abnormalities (30%), and nervous system abnormalities (29%). Trio testing – the concurrent analysis of both biological parents and proband for all genes – “is a critical factor for success,” she added. “It not only improves the variant calling because we have three times the data and increases test sensitivity, it also provides more certain results, determines inheritance and allows for detection of parental mosaicism.”

According to Dr. Richard, trio testing has a one-third higher diagnostic rate than sequencing of the proband alone. Citing a published prospective study that compiled data from eight different exome- and genome-sequencing studies in critically ill neonates and children, trio testing made it possible to make a genetic diagnosis in up to 58% of children.

Whole-genome sequencing is estimated to have a 5%-10% higher diagnostic rate than exome sequencing. “However, we are still a ways away from using it as a routine diagnostic test for all test indications,” Dr. Richard said. “Automation, special bioinformatics algorithms and databases, and combination of genome sequencing with mRNA sequencing are being explored and built to further improve the diagnostic yield.”

Dr. Richard had no disclosures other than being an employee of GeneDx.

[email protected]

With more than 300 genetic skin disorders involving more than 1,000 genes and hundreds of genetic tests available on the market, it can be daunting for health care providers and families of pediatric patients to navigate the landscape.

“Testing options range from targeted variant testing and single-gene testing to exome and genome sequencing,” Gabriele Richard, MD, said at the annual meeting of the Society for Pediatric Dermatology. “It is not always easy to determine which testing is right.”

Increasingly, clinical genomic tests, including exome and genome sequencing, are used for patients with complex phenotypes, and possibly multiple disorders, who might have no diagnosis despite extensive prior testing, said Dr. Richard, medical director at Gaithersburg, Md.–based GeneDx., a molecular diagnostic laboratory that performs comprehensive testing for rare genetic disorders. These tests are also being used more for first-line testing in critically ill patients in the neonatal and pediatric intensive care units, and “have heralded a whole new era of gene and disease discovery,” she added.

Targeted variant testing is used for known familial variants, to test family members for carrier status and segregation, and to make a prenatal diagnosis, she said. Single-gene testing is available for most genes and has its place for conditions that can be clinically well-recognized, such as ichthyosis vulgaris, Darier disease, or Papillon-Lefèvre syndrome.

Specific tests for identifying gene deletions or duplications are exon-level microarrays, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray analysis. “The latter has been successful in identifying diseases causing chromosomal abnormalities in over 10% of cases overall,” Dr. Richard said. An example of a skin disorder is X-linked ichthyosis caused by a deletion of the steroid sulfatase locus in more than 95% of affected males, she said.

“However, the current staple of molecular diagnostic testing is multigene next-generation sequencing (NGS) panels, which allow you to interrogate two to hundreds of genes concurrently, including sequencing and deletion duplication testing.” These tests are the most cost effective, she said, and are available for almost any genodermatosis or group of disorders with overlapping phenotypes, such as albinism or ichthyosis, epidermolysis bullosa and skin fragility, ectodermal dysplasia, or porphyria. According to Dr. Richard, the diagnostic outcomes of NGS panels mainly depend on test indication, panel size and gene curation, age of onset, and prevailing inheritance pattern of disorders.

Her recommended criteria for distinguishing the myriad of available NGS panels include checking gene content, technical sensitivity of sequencing and deletion/duplication analysis, quality of variant interpretation and reporting, turn-around time, and available familial follow-up testing. “If a family might consider future prenatal diagnosis, choose the lab that performs prenatal and diagnostic testing,” Dr. Richard said. “Equally important are client services such as ease of ordering, insurance coverage, and the ability to determine out-of-pocket cost to patients.”

Resources that enable consumers to compare panel content, methodology, turnaround time, and other parameters include the Genetic Testing Registry (GTR) operated by the National Center for Biotechnology Information, and Concert Genetics, a genetic testing company. The National Society of Genetic Counselors also offers a searchable database for finding a genetic counselor.

Exome sequencing includes the coding sequences of about 20,000 genes and has an average depth of 50 to about 150 reads. “It is a phenotype-driven test where only select variants are being reported fitting the phenotype,” Dr. Richard said. “The outcome of exome and genome sequencing much depends on optimization of bioinformatic pipelines and tools.” Besides small sequence variants, exome sequencing is able to identify a variety of different types of disease-causing variants, such as gene copy number variants seen in about 6% of positive cases, mosaicism, regions of homozygosity, uniparental disomy, and other unusual events and is cost effective.

Whole-genome sequencing, meanwhile, includes the entire genome, particularly noncoding regions, and has an average depth of more than 30 reads. “It’s based on single-molecule sequencing, has longer reads and more uniform coverage, compared to exome sequencing,” she said. “Higher cost, variant interpretation, and lack of coverage by payers are still presenting challenges for genome sequencing.” Genome sequencing can be done in a day or less.

According to diagnostic outcomes based on 280,000 individuals including 125,000 probands from GeneDx data, a definitive diagnosis was made in 26% of probands, of which 2.8% had more than one diagnostic finding and 1.8% had actionable secondary findings. In addition, 7% of the variants were found in candidate genes; 31% of probands had variants of uncertain significance, while 36% tested negative. “Nevertheless, the diagnostic yield of exome sequencing depends on the phenotype and cohort studied,” Dr. Richard continued.

At her company, she said, the highest positive rate is for multiple congenital anomalies (34%), skeletal system abnormalities (30%), and nervous system abnormalities (29%). Trio testing – the concurrent analysis of both biological parents and proband for all genes – “is a critical factor for success,” she added. “It not only improves the variant calling because we have three times the data and increases test sensitivity, it also provides more certain results, determines inheritance and allows for detection of parental mosaicism.”

According to Dr. Richard, trio testing has a one-third higher diagnostic rate than sequencing of the proband alone. Citing a published prospective study that compiled data from eight different exome- and genome-sequencing studies in critically ill neonates and children, trio testing made it possible to make a genetic diagnosis in up to 58% of children.

Whole-genome sequencing is estimated to have a 5%-10% higher diagnostic rate than exome sequencing. “However, we are still a ways away from using it as a routine diagnostic test for all test indications,” Dr. Richard said. “Automation, special bioinformatics algorithms and databases, and combination of genome sequencing with mRNA sequencing are being explored and built to further improve the diagnostic yield.”

Dr. Richard had no disclosures other than being an employee of GeneDx.

[email protected]

The Diagnosis: Microcystic Lymphatic Malformation 

The shave biopsy demonstrated numerous thin-walled vascular spaces filled with lymphatic fluid within the dermis (Figure), consistent with a diagnosis of microcystic lymphatic malformation (LM). Lymphatic malformations represent a class of benign vascular lesions consisting of anomalous or dilated lymphatic vessels, which can be broadly categorized as macrocystic (formerly cavernous lymphangioma or cystic hygroma), microcystic (formerly lymphangioma circumscriptum), or mixed.¹ Patients often will present with pruritus, crusting, secondary infection, edema, or oozing.² The superficial blebs of microcystic LMs resemble frog spawn and range in color from clear to pink, brawny, or deep maroon.³ Although the lymphatic vessels involved in microcystic LMs appear disconnected from the major lymphatic circulation,³ systemic fluid overload could plausibly promote lesional swelling and tenderness; we attributed our patient's worsening symptoms to the cumulative ^7.8 L of intravenous fluid he received intraoperatively during his cardiac transplant. The excess fluid allowed communication between lymphatic cisterns and thin-walled vesicles on the skin surface through dilated channels. Overall, LMs represent roughly 26% of pediatric benign vascular tumors and approximately 4% of all vascular tumors.⁴  

Although microcystic LMs may appear especially vascular or verrucous, the differential diagnosis for our patient's LM included condyloma acuminatum,^5,6 condyloma lata,⁷ epidermal nevus, and lymphangiosarcoma. Epidermal nevi are congenital lesions, varying in appearance from velvety to verrucous patches and plaques that often evolve during puberty and become thicker, more verrucous, and hyperpigmented. Keratinocytic epidermal nevus syndromes and other entities such as nevus sebaceous have been associated with somatic mutations affecting proteins in the fibroblast growth factor receptor signaling pathway (eg, FGFR3, HRAS).⁸ Although the clinical appearance alone may be similar, lymphangiosarcoma can be distinguished from LM via biopsy.  

There are several methods to diagnose LM. Duplex sonography is possibly the best noninvasive method to identify the flow between venous valves. Magnetic resonance imaging can detect larger occurrences of LM, and lymphangiography can be utilized to confirm a normal or abnormal lymphatic network.⁴ Treatment options are broad, including surgical excision, laser ablation, and topical sirolimus. Hypertonic saline sclerotherapy can be injected into the afflicted lymphatic channels to decrease inflammation, erythema, and hyperpigmentation without further treatment or major side effects.⁴

However, the benefits of sclerotherapy alone in the treatment of LM often come gradually, and radiofrequency ablation may need to be utilized to achieve more immediate results.² Overall, outcomes are highly variable, but favorable outcomes often can be difficult to obtain due to a high recurrence rate.^2,8 Our patient's symptoms improved during his postoperative recovery, and he declined further intervention.  

The Diagnosis: Microcystic Lymphatic Malformation 

The shave biopsy demonstrated numerous thin-walled vascular spaces filled with lymphatic fluid within the dermis (Figure), consistent with a diagnosis of microcystic lymphatic malformation (LM). Lymphatic malformations represent a class of benign vascular lesions consisting of anomalous or dilated lymphatic vessels, which can be broadly categorized as macrocystic (formerly cavernous lymphangioma or cystic hygroma), microcystic (formerly lymphangioma circumscriptum), or mixed.¹ Patients often will present with pruritus, crusting, secondary infection, edema, or oozing.² The superficial blebs of microcystic LMs resemble frog spawn and range in color from clear to pink, brawny, or deep maroon.³ Although the lymphatic vessels involved in microcystic LMs appear disconnected from the major lymphatic circulation,³ systemic fluid overload could plausibly promote lesional swelling and tenderness; we attributed our patient's worsening symptoms to the cumulative ^7.8 L of intravenous fluid he received intraoperatively during his cardiac transplant. The excess fluid allowed communication between lymphatic cisterns and thin-walled vesicles on the skin surface through dilated channels. Overall, LMs represent roughly 26% of pediatric benign vascular tumors and approximately 4% of all vascular tumors.⁴  

Although microcystic LMs may appear especially vascular or verrucous, the differential diagnosis for our patient's LM included condyloma acuminatum,^5,6 condyloma lata,⁷ epidermal nevus, and lymphangiosarcoma. Epidermal nevi are congenital lesions, varying in appearance from velvety to verrucous patches and plaques that often evolve during puberty and become thicker, more verrucous, and hyperpigmented. Keratinocytic epidermal nevus syndromes and other entities such as nevus sebaceous have been associated with somatic mutations affecting proteins in the fibroblast growth factor receptor signaling pathway (eg, FGFR3, HRAS).⁸ Although the clinical appearance alone may be similar, lymphangiosarcoma can be distinguished from LM via biopsy.  

There are several methods to diagnose LM. Duplex sonography is possibly the best noninvasive method to identify the flow between venous valves. Magnetic resonance imaging can detect larger occurrences of LM, and lymphangiography can be utilized to confirm a normal or abnormal lymphatic network.⁴ Treatment options are broad, including surgical excision, laser ablation, and topical sirolimus. Hypertonic saline sclerotherapy can be injected into the afflicted lymphatic channels to decrease inflammation, erythema, and hyperpigmentation without further treatment or major side effects.⁴

However, the benefits of sclerotherapy alone in the treatment of LM often come gradually, and radiofrequency ablation may need to be utilized to achieve more immediate results.² Overall, outcomes are highly variable, but favorable outcomes often can be difficult to obtain due to a high recurrence rate.^2,8 Our patient's symptoms improved during his postoperative recovery, and he declined further intervention.  

The Diagnosis: Microcystic Lymphatic Malformation 

The shave biopsy demonstrated numerous thin-walled vascular spaces filled with lymphatic fluid within the dermis (Figure), consistent with a diagnosis of microcystic lymphatic malformation (LM). Lymphatic malformations represent a class of benign vascular lesions consisting of anomalous or dilated lymphatic vessels, which can be broadly categorized as macrocystic (formerly cavernous lymphangioma or cystic hygroma), microcystic (formerly lymphangioma circumscriptum), or mixed.¹ Patients often will present with pruritus, crusting, secondary infection, edema, or oozing.² The superficial blebs of microcystic LMs resemble frog spawn and range in color from clear to pink, brawny, or deep maroon.³ Although the lymphatic vessels involved in microcystic LMs appear disconnected from the major lymphatic circulation,³ systemic fluid overload could plausibly promote lesional swelling and tenderness; we attributed our patient's worsening symptoms to the cumulative ^7.8 L of intravenous fluid he received intraoperatively during his cardiac transplant. The excess fluid allowed communication between lymphatic cisterns and thin-walled vesicles on the skin surface through dilated channels. Overall, LMs represent roughly 26% of pediatric benign vascular tumors and approximately 4% of all vascular tumors.⁴  

Although microcystic LMs may appear especially vascular or verrucous, the differential diagnosis for our patient's LM included condyloma acuminatum,^5,6 condyloma lata,⁷ epidermal nevus, and lymphangiosarcoma. Epidermal nevi are congenital lesions, varying in appearance from velvety to verrucous patches and plaques that often evolve during puberty and become thicker, more verrucous, and hyperpigmented. Keratinocytic epidermal nevus syndromes and other entities such as nevus sebaceous have been associated with somatic mutations affecting proteins in the fibroblast growth factor receptor signaling pathway (eg, FGFR3, HRAS).⁸ Although the clinical appearance alone may be similar, lymphangiosarcoma can be distinguished from LM via biopsy.  

There are several methods to diagnose LM. Duplex sonography is possibly the best noninvasive method to identify the flow between venous valves. Magnetic resonance imaging can detect larger occurrences of LM, and lymphangiography can be utilized to confirm a normal or abnormal lymphatic network.⁴ Treatment options are broad, including surgical excision, laser ablation, and topical sirolimus. Hypertonic saline sclerotherapy can be injected into the afflicted lymphatic channels to decrease inflammation, erythema, and hyperpigmentation without further treatment or major side effects.⁴

However, the benefits of sclerotherapy alone in the treatment of LM often come gradually, and radiofrequency ablation may need to be utilized to achieve more immediate results.² Overall, outcomes are highly variable, but favorable outcomes often can be difficult to obtain due to a high recurrence rate.^2,8 Our patient's symptoms improved during his postoperative recovery, and he declined further intervention.  

When Denise M. Adams, MD, began her career as a pediatric oncologist 25 years ago, there were many interventions for vascular anomalies, but most were surgery based and medical options were limited.

“The medicines we had were believed to be antiangiogenic and they were used not only for tumors but for all sorts of malformations,” Dr. Adams, a pediatric hematologist-oncologist at Children’s Hospital of Philadelphia, recalled during the annual meeting of the Society for Pediatric Dermatology. “I didn’t understand how so many different phenotypes could respond to the same medicine. Not all of them did, but some did have some response.”

She also grew frustrated by the lack of clinical trials and collaborative research groups involving patients with vascular anomalies. “I called this the chicken soup of medical management,” she said. “As we got more involved in vascular anomalies, the power of one patient or that power of a few patients led us in a direction for improved medical management. Or knowledge was gained by one patient who failed all noted medical management and led us into a direction repurposing a drug that actually wound up working.”

Propranolol, for example, became a key medicine for the treatment of vascular anomalies when it was found to improve hemangiomas in children who were given the drug for other reasons. “From this observation a key prospective study was performed and this beta-blocker became FDA approved for the treatment of complicated hemangiomas,” said Dr. Adams, who directs the hospital’s Comprehensive Vascular Anomalies Program. “That was how a bedside observation let to bench intervention, and how presently we are investigating bench interventions related to the mechanism of propranolol therapy.”

Then there is the story of the mammalian target of rapamycin (mTOR) inhibitor sirolimus. In her previous role as medical director of the Hemangioma and Vascular Malformation Center at Cincinnati Children’s Hospital, Dr. Adams and colleagues cared for an infant who presented with a Kaposiform hemangioendothelioma (KHE). “At that time, she was given our standard of practice for the treatment, but our standard of practice was not good enough,” she said.

While other options were being discussed for this patient, “we had been doing some collaborative work with pathology and nephrology on the PIKC3A pathway, because we knew that germline mutations of TEK were involved in this pathway, and we knew that 50% of patients with PTEN mutations had vascular anomalies. So, we hypothesized that this pathway was involved in vascular anomalies.”

They also had earlier success using mTOR inhibition for tuberous sclerosis patients with angiomyolipomas and patients with neurofibromatosis. “We needed a medicine that could be given orally because we did not think this patient was going to do well, so we started her on sirolimus,” Dr. Adams said. “She had a great response. This was followed by a phase 2 study, which proved efficacy and led to discovery of biomarkers.” This is where the angiopoietin-2 story started, she said, noting that this biomarker is now used “to differentiate KLA [Kaposiform lymphangiomatosis] from KHE and KLAs and KHE from other disorders.”

This bedside work helped researchers to better understand the mechanism of action in other disorders, such as observing somatic mutations in PIK3CA in patients with CLOVES syndrome. “This meant that we could now correlate the phenotype to the genotype, and it opened up targeted therapy with developmental therapeutics that were already in use for oncology,” Dr. Adams said. “We know we had mTOR inhibition with sirolimus and everolimus. We now have an AKT inhibitor, a PIK3CA inhibitor, and we now have another side of the pathway which deals with RASopathies, and some other medicines that we can use.”

Miransertib, a potent PAN-AKT inhibitor initially used for breast cancer, is currently being evaluated in open-label, phase 1 and 2 trials in patients with PIK3CA-related overgrowth spectrum (PROS) and Proteus syndrome. The dose used in a pilot study is about one-sixth of the dose used for oncology patients, Dr. Adams said.

She and her colleagues used miransertib to treat a 3-year-old with CLOVES syndrome who had lipomatous infiltration of the abdomen and retroperitoneum with failure to thrive. “He was not eating and was G-tube dependent,” she recalled. “After a month of therapy, he started eating and had improvement in his quality of life,” although despite this improvement volumetric MRI remained unchanged.

Advances in bench to bedside approaches are also under way. Hakon Hakonarson, MD, PhD, the founding director of the Center for Applied Genomics at CHOP, has discovered several genes with in vitro testing and zebra fish modeling, which has been followed by testing medicines on patients.

One such patient, according to Dr. Adams, had a severe central conducting lymphatic anomaly, with a pericardial effusion and significant dysfunction of the central conducting system. The patient was found to have an ARAF mutation, which induces ERK activation. “ERK is downstream of MEK, so the question was whether a MEK inhibitor, trametinib, could be used to treat this patient,” she said. “Trametinib was first used in tissue culture, then used in a zebra fish model and it showed some positive results. Then it was taken to the patient, who had improvement of pulmonary function, remodeling of the lymphatic system, and decrease in the size of his legs.”

Other antiangiogenic agents being used for the treatment of vascular anomalies include bevacizumab, which is being used in hereditary hemorrhagic telangiectasia, and thalidomide for HHT and arteriovenous malformations. For more information, Dr. Adams recommended a comprehensive review of vascular anomalies, related genes, and treatments that was published in Circulation Research.

The goal of future drug therapies is to support normal growth, “so we don’t need a maximum tolerated dose,” Dr. Adams said. “We need to be very careful of short-term and long-term side effects.”

Going forward, she said that she would like to see more natural history studies of vascular anomalies, improved outcome measures for clinical trials, adaptive study design, preclinical testing, animal model studies, universal availability of genomic testing, improvement of NIH funding, research collaboration nationally and internationally, and industry support.

Dr. Adams disclosed that she is a consultant to Venthera and Novartis.

[email protected]

When Denise M. Adams, MD, began her career as a pediatric oncologist 25 years ago, there were many interventions for vascular anomalies, but most were surgery based and medical options were limited.

“The medicines we had were believed to be antiangiogenic and they were used not only for tumors but for all sorts of malformations,” Dr. Adams, a pediatric hematologist-oncologist at Children’s Hospital of Philadelphia, recalled during the annual meeting of the Society for Pediatric Dermatology. “I didn’t understand how so many different phenotypes could respond to the same medicine. Not all of them did, but some did have some response.”

She also grew frustrated by the lack of clinical trials and collaborative research groups involving patients with vascular anomalies. “I called this the chicken soup of medical management,” she said. “As we got more involved in vascular anomalies, the power of one patient or that power of a few patients led us in a direction for improved medical management. Or knowledge was gained by one patient who failed all noted medical management and led us into a direction repurposing a drug that actually wound up working.”

Propranolol, for example, became a key medicine for the treatment of vascular anomalies when it was found to improve hemangiomas in children who were given the drug for other reasons. “From this observation a key prospective study was performed and this beta-blocker became FDA approved for the treatment of complicated hemangiomas,” said Dr. Adams, who directs the hospital’s Comprehensive Vascular Anomalies Program. “That was how a bedside observation let to bench intervention, and how presently we are investigating bench interventions related to the mechanism of propranolol therapy.”

Then there is the story of the mammalian target of rapamycin (mTOR) inhibitor sirolimus. In her previous role as medical director of the Hemangioma and Vascular Malformation Center at Cincinnati Children’s Hospital, Dr. Adams and colleagues cared for an infant who presented with a Kaposiform hemangioendothelioma (KHE). “At that time, she was given our standard of practice for the treatment, but our standard of practice was not good enough,” she said.

While other options were being discussed for this patient, “we had been doing some collaborative work with pathology and nephrology on the PIKC3A pathway, because we knew that germline mutations of TEK were involved in this pathway, and we knew that 50% of patients with PTEN mutations had vascular anomalies. So, we hypothesized that this pathway was involved in vascular anomalies.”

They also had earlier success using mTOR inhibition for tuberous sclerosis patients with angiomyolipomas and patients with neurofibromatosis. “We needed a medicine that could be given orally because we did not think this patient was going to do well, so we started her on sirolimus,” Dr. Adams said. “She had a great response. This was followed by a phase 2 study, which proved efficacy and led to discovery of biomarkers.” This is where the angiopoietin-2 story started, she said, noting that this biomarker is now used “to differentiate KLA [Kaposiform lymphangiomatosis] from KHE and KLAs and KHE from other disorders.”

This bedside work helped researchers to better understand the mechanism of action in other disorders, such as observing somatic mutations in PIK3CA in patients with CLOVES syndrome. “This meant that we could now correlate the phenotype to the genotype, and it opened up targeted therapy with developmental therapeutics that were already in use for oncology,” Dr. Adams said. “We know we had mTOR inhibition with sirolimus and everolimus. We now have an AKT inhibitor, a PIK3CA inhibitor, and we now have another side of the pathway which deals with RASopathies, and some other medicines that we can use.”

Miransertib, a potent PAN-AKT inhibitor initially used for breast cancer, is currently being evaluated in open-label, phase 1 and 2 trials in patients with PIK3CA-related overgrowth spectrum (PROS) and Proteus syndrome. The dose used in a pilot study is about one-sixth of the dose used for oncology patients, Dr. Adams said.

She and her colleagues used miransertib to treat a 3-year-old with CLOVES syndrome who had lipomatous infiltration of the abdomen and retroperitoneum with failure to thrive. “He was not eating and was G-tube dependent,” she recalled. “After a month of therapy, he started eating and had improvement in his quality of life,” although despite this improvement volumetric MRI remained unchanged.

Advances in bench to bedside approaches are also under way. Hakon Hakonarson, MD, PhD, the founding director of the Center for Applied Genomics at CHOP, has discovered several genes with in vitro testing and zebra fish modeling, which has been followed by testing medicines on patients.

One such patient, according to Dr. Adams, had a severe central conducting lymphatic anomaly, with a pericardial effusion and significant dysfunction of the central conducting system. The patient was found to have an ARAF mutation, which induces ERK activation. “ERK is downstream of MEK, so the question was whether a MEK inhibitor, trametinib, could be used to treat this patient,” she said. “Trametinib was first used in tissue culture, then used in a zebra fish model and it showed some positive results. Then it was taken to the patient, who had improvement of pulmonary function, remodeling of the lymphatic system, and decrease in the size of his legs.”

Other antiangiogenic agents being used for the treatment of vascular anomalies include bevacizumab, which is being used in hereditary hemorrhagic telangiectasia, and thalidomide for HHT and arteriovenous malformations. For more information, Dr. Adams recommended a comprehensive review of vascular anomalies, related genes, and treatments that was published in Circulation Research.

The goal of future drug therapies is to support normal growth, “so we don’t need a maximum tolerated dose,” Dr. Adams said. “We need to be very careful of short-term and long-term side effects.”

Going forward, she said that she would like to see more natural history studies of vascular anomalies, improved outcome measures for clinical trials, adaptive study design, preclinical testing, animal model studies, universal availability of genomic testing, improvement of NIH funding, research collaboration nationally and internationally, and industry support.

Dr. Adams disclosed that she is a consultant to Venthera and Novartis.

[email protected]

When Denise M. Adams, MD, began her career as a pediatric oncologist 25 years ago, there were many interventions for vascular anomalies, but most were surgery based and medical options were limited.

“The medicines we had were believed to be antiangiogenic and they were used not only for tumors but for all sorts of malformations,” Dr. Adams, a pediatric hematologist-oncologist at Children’s Hospital of Philadelphia, recalled during the annual meeting of the Society for Pediatric Dermatology. “I didn’t understand how so many different phenotypes could respond to the same medicine. Not all of them did, but some did have some response.”

She also grew frustrated by the lack of clinical trials and collaborative research groups involving patients with vascular anomalies. “I called this the chicken soup of medical management,” she said. “As we got more involved in vascular anomalies, the power of one patient or that power of a few patients led us in a direction for improved medical management. Or knowledge was gained by one patient who failed all noted medical management and led us into a direction repurposing a drug that actually wound up working.”

Propranolol, for example, became a key medicine for the treatment of vascular anomalies when it was found to improve hemangiomas in children who were given the drug for other reasons. “From this observation a key prospective study was performed and this beta-blocker became FDA approved for the treatment of complicated hemangiomas,” said Dr. Adams, who directs the hospital’s Comprehensive Vascular Anomalies Program. “That was how a bedside observation let to bench intervention, and how presently we are investigating bench interventions related to the mechanism of propranolol therapy.”

Then there is the story of the mammalian target of rapamycin (mTOR) inhibitor sirolimus. In her previous role as medical director of the Hemangioma and Vascular Malformation Center at Cincinnati Children’s Hospital, Dr. Adams and colleagues cared for an infant who presented with a Kaposiform hemangioendothelioma (KHE). “At that time, she was given our standard of practice for the treatment, but our standard of practice was not good enough,” she said.

While other options were being discussed for this patient, “we had been doing some collaborative work with pathology and nephrology on the PIKC3A pathway, because we knew that germline mutations of TEK were involved in this pathway, and we knew that 50% of patients with PTEN mutations had vascular anomalies. So, we hypothesized that this pathway was involved in vascular anomalies.”

They also had earlier success using mTOR inhibition for tuberous sclerosis patients with angiomyolipomas and patients with neurofibromatosis. “We needed a medicine that could be given orally because we did not think this patient was going to do well, so we started her on sirolimus,” Dr. Adams said. “She had a great response. This was followed by a phase 2 study, which proved efficacy and led to discovery of biomarkers.” This is where the angiopoietin-2 story started, she said, noting that this biomarker is now used “to differentiate KLA [Kaposiform lymphangiomatosis] from KHE and KLAs and KHE from other disorders.”

This bedside work helped researchers to better understand the mechanism of action in other disorders, such as observing somatic mutations in PIK3CA in patients with CLOVES syndrome. “This meant that we could now correlate the phenotype to the genotype, and it opened up targeted therapy with developmental therapeutics that were already in use for oncology,” Dr. Adams said. “We know we had mTOR inhibition with sirolimus and everolimus. We now have an AKT inhibitor, a PIK3CA inhibitor, and we now have another side of the pathway which deals with RASopathies, and some other medicines that we can use.”

Miransertib, a potent PAN-AKT inhibitor initially used for breast cancer, is currently being evaluated in open-label, phase 1 and 2 trials in patients with PIK3CA-related overgrowth spectrum (PROS) and Proteus syndrome. The dose used in a pilot study is about one-sixth of the dose used for oncology patients, Dr. Adams said.

She and her colleagues used miransertib to treat a 3-year-old with CLOVES syndrome who had lipomatous infiltration of the abdomen and retroperitoneum with failure to thrive. “He was not eating and was G-tube dependent,” she recalled. “After a month of therapy, he started eating and had improvement in his quality of life,” although despite this improvement volumetric MRI remained unchanged.

Advances in bench to bedside approaches are also under way. Hakon Hakonarson, MD, PhD, the founding director of the Center for Applied Genomics at CHOP, has discovered several genes with in vitro testing and zebra fish modeling, which has been followed by testing medicines on patients.

One such patient, according to Dr. Adams, had a severe central conducting lymphatic anomaly, with a pericardial effusion and significant dysfunction of the central conducting system. The patient was found to have an ARAF mutation, which induces ERK activation. “ERK is downstream of MEK, so the question was whether a MEK inhibitor, trametinib, could be used to treat this patient,” she said. “Trametinib was first used in tissue culture, then used in a zebra fish model and it showed some positive results. Then it was taken to the patient, who had improvement of pulmonary function, remodeling of the lymphatic system, and decrease in the size of his legs.”

Other antiangiogenic agents being used for the treatment of vascular anomalies include bevacizumab, which is being used in hereditary hemorrhagic telangiectasia, and thalidomide for HHT and arteriovenous malformations. For more information, Dr. Adams recommended a comprehensive review of vascular anomalies, related genes, and treatments that was published in Circulation Research.

The goal of future drug therapies is to support normal growth, “so we don’t need a maximum tolerated dose,” Dr. Adams said. “We need to be very careful of short-term and long-term side effects.”

Going forward, she said that she would like to see more natural history studies of vascular anomalies, improved outcome measures for clinical trials, adaptive study design, preclinical testing, animal model studies, universal availability of genomic testing, improvement of NIH funding, research collaboration nationally and internationally, and industry support.

Dr. Adams disclosed that she is a consultant to Venthera and Novartis.

[email protected]

The U.S. Food and Drug Administration has approved lonapegsomatropin (Skytrofa, Ascendis Pharma), the first weekly subcutaneous injectable growth hormone for children with growth hormone deficiency (GHD).

The approval was based on the findings of the 52-week, phase 3 heiGHt trial in 161 treatment-naive pediatric patients with GHD, which was recently published in the Journal of Clinical Endocrinology & Metabolism.

Since 1987, the standard treatment for pediatric GHD, in which the pituitary gland does not produce enough growth hormone, has been a daily injection of somatropin (recombinant DNA human growth hormone).

“I am excited to be able to reduce the number of shots for some children requiring growth hormone therapy” with this new dosing option, Bradley S. Miller, MD, PhD, who was not involved with the research, said in an email.

“I am hopeful that a once-weekly growth hormone option will improve adherence to growth hormone therapy, leading to improved growth and metabolic outcomes,” added Dr. Miller, professor and division director, pediatric endocrinology, at the University of Minnesota Masonic Children’s Hospital, Minneapolis.

Lonapegsomatropin is approved for the treatment of pediatric patients age 1 year and older who weigh at least 11.5 kg (25.4 pounds) and have short stature due to inadequate secretion of endogenous growth hormone, according to the prescribing information.

The drug molecule consists of a prodrug of somatropin that is inactive when it is bound to a proprietary TransCon (transient conjugation) inert carrier using a TransCon linker. The three-part molecule breaks apart after injection, exposing the active somatropin that is slowly released.

The heiGHt trial demonstrated noninferiority of lonapegsomatropin to somatropin daily injections. Children who received weekly lonapegsomatropin grew 11.2 cm (4.4 inches) per year, whereas those who received an equivalent total dose of somatropin daily injections grew 10.3 cm (4.1 inches) per year.

Safety outcomes – the ratio of bone age to chronologic age, adverse events, tolerability, and immunogenicity – were similar in both groups.
 

Anticipated uptake, other drugs on horizon

Lonapegsomatropin is expected to be available shortly in the United States along with a suite of patient support programs, according to a company press release.

“The impact of the approval of lonapegsomatropin on clinical practice will depend upon its availability, coverage by insurance providers, and patient/provider comfort with using a new product,” Dr. Miller said.

For most pediatric endocrinologists, daily growth hormone has been available their entire careers, so he expects it will take some time for the pediatric endocrinology community to be comfortable prescribing long-acting growth hormone (LAGH), the name given to the once-weekly products.

In the meantime, an FDA decision on another once-weekly growth hormone, somatrogon (OPKO Health/Pfizer) for children with GHD is expected very soon, in October 2021.

And a weekly injectable somapacitan (Sogroya, Novo Nordisk), approved by the FDA in September last year for adults with GHD, is also being studied in children, with estimated study completion in 2024.

“Approval of more LAGH molecules, approval of LAGH for more indications, real-world evidence of safety, efficacy, and improved adherence, and personal experience with LAGH will all likely lead to increased LAGH use over time,” Dr. Miller speculated.

“Over the long-term, I expect insurance providers will cover LAGH products,” he surmised, “but that the price will be similar to or slightly higher than daily growth hormone.”

However, if improved adherence with LAGH is demonstrated and associated with better treatment outcomes, the price of LAGH will likely increase and use of daily growth hormone will decrease, he predicts.

Paul Saenger, MD, who was not involved with the research, believes “all three long-acting growth hormone drugs will eventually be approved for GHD in children.”

“The price will be the same or may be at most 10% more than daily growth hormone replacement,” Dr. Saenger, a pediatric endocrinologist and clinical assistant professor at NYU Long Island School of Medicine, New York, said in an email.

However, daily subcutaneous injections will still be warranted for certain children with GHD, Dr. Miller noted.

“Daily growth hormone may be better than LAGH for a small number of children who have severe GHD associated with hypoglycemia,” he said. “The low levels of growth hormone at the end of the weekly interval of LAGH may allow hypoglycemia to occur in this population.”
 

Phase 3 trial in 161 treatment-naive children with GHD

The heiGHt trial randomized treatment-naive prepubertal children with GHD 2:1 to weekly lonapegsomatropin or daily somatropin (Genotropin, Pfizer) at 73 sites in 15 countries.

The children were a mean age of 8.5 years (range, 3.2-13.1 years), 82% were boys, and 94% were White.

There were no reported serious adverse events or discontinuations related to lonapegsomatropin.

The most common adverse reactions in ≥5% of these pediatric patients were viral infection (15%), pyrexia (15%), cough (11%), nausea and vomiting (11%), hemorrhage (7%), diarrhea (6%), abdominal pain (6%), and arthralgia and arthritis (6%).

Both study groups reported low incidences of transient, non-neutralizing anti-hGH binding antibodies and no cases of persistent antibodies.

Trial limitations include the fact the study was not blinded (as patients received a weekly or daily injection) and drug doses were fixed at 0.24 mg human growth hormone/kg/week, although in real-world clinical practice, doses may be titrated.

Lonapegsomatropin has been studied in more than 300 children with GHD in the phase 3 program in the heiGHt trial (treatment-naive patients), fliGHt trial (treatment-experienced patients), and enliGHten trial (an ongoing long-term extension trial that includes some patients who have been taking lonapegsomatropin for more than 4 years).

The study was sponsored by Ascendis Pharma. Some of the phase 3 study authors are company employees.

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

The U.S. Food and Drug Administration has approved lonapegsomatropin (Skytrofa, Ascendis Pharma), the first weekly subcutaneous injectable growth hormone for children with growth hormone deficiency (GHD).

The approval was based on the findings of the 52-week, phase 3 heiGHt trial in 161 treatment-naive pediatric patients with GHD, which was recently published in the Journal of Clinical Endocrinology & Metabolism.

Since 1987, the standard treatment for pediatric GHD, in which the pituitary gland does not produce enough growth hormone, has been a daily injection of somatropin (recombinant DNA human growth hormone).

“I am excited to be able to reduce the number of shots for some children requiring growth hormone therapy” with this new dosing option, Bradley S. Miller, MD, PhD, who was not involved with the research, said in an email.

“I am hopeful that a once-weekly growth hormone option will improve adherence to growth hormone therapy, leading to improved growth and metabolic outcomes,” added Dr. Miller, professor and division director, pediatric endocrinology, at the University of Minnesota Masonic Children’s Hospital, Minneapolis.

Lonapegsomatropin is approved for the treatment of pediatric patients age 1 year and older who weigh at least 11.5 kg (25.4 pounds) and have short stature due to inadequate secretion of endogenous growth hormone, according to the prescribing information.

The drug molecule consists of a prodrug of somatropin that is inactive when it is bound to a proprietary TransCon (transient conjugation) inert carrier using a TransCon linker. The three-part molecule breaks apart after injection, exposing the active somatropin that is slowly released.

The heiGHt trial demonstrated noninferiority of lonapegsomatropin to somatropin daily injections. Children who received weekly lonapegsomatropin grew 11.2 cm (4.4 inches) per year, whereas those who received an equivalent total dose of somatropin daily injections grew 10.3 cm (4.1 inches) per year.

Safety outcomes – the ratio of bone age to chronologic age, adverse events, tolerability, and immunogenicity – were similar in both groups.
 

Anticipated uptake, other drugs on horizon

Lonapegsomatropin is expected to be available shortly in the United States along with a suite of patient support programs, according to a company press release.

“The impact of the approval of lonapegsomatropin on clinical practice will depend upon its availability, coverage by insurance providers, and patient/provider comfort with using a new product,” Dr. Miller said.

For most pediatric endocrinologists, daily growth hormone has been available their entire careers, so he expects it will take some time for the pediatric endocrinology community to be comfortable prescribing long-acting growth hormone (LAGH), the name given to the once-weekly products.

In the meantime, an FDA decision on another once-weekly growth hormone, somatrogon (OPKO Health/Pfizer) for children with GHD is expected very soon, in October 2021.

And a weekly injectable somapacitan (Sogroya, Novo Nordisk), approved by the FDA in September last year for adults with GHD, is also being studied in children, with estimated study completion in 2024.

“Approval of more LAGH molecules, approval of LAGH for more indications, real-world evidence of safety, efficacy, and improved adherence, and personal experience with LAGH will all likely lead to increased LAGH use over time,” Dr. Miller speculated.

“Over the long-term, I expect insurance providers will cover LAGH products,” he surmised, “but that the price will be similar to or slightly higher than daily growth hormone.”

However, if improved adherence with LAGH is demonstrated and associated with better treatment outcomes, the price of LAGH will likely increase and use of daily growth hormone will decrease, he predicts.

Paul Saenger, MD, who was not involved with the research, believes “all three long-acting growth hormone drugs will eventually be approved for GHD in children.”

“The price will be the same or may be at most 10% more than daily growth hormone replacement,” Dr. Saenger, a pediatric endocrinologist and clinical assistant professor at NYU Long Island School of Medicine, New York, said in an email.

However, daily subcutaneous injections will still be warranted for certain children with GHD, Dr. Miller noted.

“Daily growth hormone may be better than LAGH for a small number of children who have severe GHD associated with hypoglycemia,” he said. “The low levels of growth hormone at the end of the weekly interval of LAGH may allow hypoglycemia to occur in this population.”
 

Phase 3 trial in 161 treatment-naive children with GHD

The heiGHt trial randomized treatment-naive prepubertal children with GHD 2:1 to weekly lonapegsomatropin or daily somatropin (Genotropin, Pfizer) at 73 sites in 15 countries.

The children were a mean age of 8.5 years (range, 3.2-13.1 years), 82% were boys, and 94% were White.

There were no reported serious adverse events or discontinuations related to lonapegsomatropin.

The most common adverse reactions in ≥5% of these pediatric patients were viral infection (15%), pyrexia (15%), cough (11%), nausea and vomiting (11%), hemorrhage (7%), diarrhea (6%), abdominal pain (6%), and arthralgia and arthritis (6%).

Both study groups reported low incidences of transient, non-neutralizing anti-hGH binding antibodies and no cases of persistent antibodies.

Trial limitations include the fact the study was not blinded (as patients received a weekly or daily injection) and drug doses were fixed at 0.24 mg human growth hormone/kg/week, although in real-world clinical practice, doses may be titrated.

Lonapegsomatropin has been studied in more than 300 children with GHD in the phase 3 program in the heiGHt trial (treatment-naive patients), fliGHt trial (treatment-experienced patients), and enliGHten trial (an ongoing long-term extension trial that includes some patients who have been taking lonapegsomatropin for more than 4 years).

The study was sponsored by Ascendis Pharma. Some of the phase 3 study authors are company employees.

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

The U.S. Food and Drug Administration has approved lonapegsomatropin (Skytrofa, Ascendis Pharma), the first weekly subcutaneous injectable growth hormone for children with growth hormone deficiency (GHD).

The approval was based on the findings of the 52-week, phase 3 heiGHt trial in 161 treatment-naive pediatric patients with GHD, which was recently published in the Journal of Clinical Endocrinology & Metabolism.

Since 1987, the standard treatment for pediatric GHD, in which the pituitary gland does not produce enough growth hormone, has been a daily injection of somatropin (recombinant DNA human growth hormone).

“I am excited to be able to reduce the number of shots for some children requiring growth hormone therapy” with this new dosing option, Bradley S. Miller, MD, PhD, who was not involved with the research, said in an email.

“I am hopeful that a once-weekly growth hormone option will improve adherence to growth hormone therapy, leading to improved growth and metabolic outcomes,” added Dr. Miller, professor and division director, pediatric endocrinology, at the University of Minnesota Masonic Children’s Hospital, Minneapolis.

Lonapegsomatropin is approved for the treatment of pediatric patients age 1 year and older who weigh at least 11.5 kg (25.4 pounds) and have short stature due to inadequate secretion of endogenous growth hormone, according to the prescribing information.

The drug molecule consists of a prodrug of somatropin that is inactive when it is bound to a proprietary TransCon (transient conjugation) inert carrier using a TransCon linker. The three-part molecule breaks apart after injection, exposing the active somatropin that is slowly released.

The heiGHt trial demonstrated noninferiority of lonapegsomatropin to somatropin daily injections. Children who received weekly lonapegsomatropin grew 11.2 cm (4.4 inches) per year, whereas those who received an equivalent total dose of somatropin daily injections grew 10.3 cm (4.1 inches) per year.

Safety outcomes – the ratio of bone age to chronologic age, adverse events, tolerability, and immunogenicity – were similar in both groups.
 

Anticipated uptake, other drugs on horizon

Lonapegsomatropin is expected to be available shortly in the United States along with a suite of patient support programs, according to a company press release.

“The impact of the approval of lonapegsomatropin on clinical practice will depend upon its availability, coverage by insurance providers, and patient/provider comfort with using a new product,” Dr. Miller said.

For most pediatric endocrinologists, daily growth hormone has been available their entire careers, so he expects it will take some time for the pediatric endocrinology community to be comfortable prescribing long-acting growth hormone (LAGH), the name given to the once-weekly products.

In the meantime, an FDA decision on another once-weekly growth hormone, somatrogon (OPKO Health/Pfizer) for children with GHD is expected very soon, in October 2021.

And a weekly injectable somapacitan (Sogroya, Novo Nordisk), approved by the FDA in September last year for adults with GHD, is also being studied in children, with estimated study completion in 2024.

“Approval of more LAGH molecules, approval of LAGH for more indications, real-world evidence of safety, efficacy, and improved adherence, and personal experience with LAGH will all likely lead to increased LAGH use over time,” Dr. Miller speculated.

“Over the long-term, I expect insurance providers will cover LAGH products,” he surmised, “but that the price will be similar to or slightly higher than daily growth hormone.”

However, if improved adherence with LAGH is demonstrated and associated with better treatment outcomes, the price of LAGH will likely increase and use of daily growth hormone will decrease, he predicts.

Paul Saenger, MD, who was not involved with the research, believes “all three long-acting growth hormone drugs will eventually be approved for GHD in children.”

“The price will be the same or may be at most 10% more than daily growth hormone replacement,” Dr. Saenger, a pediatric endocrinologist and clinical assistant professor at NYU Long Island School of Medicine, New York, said in an email.

However, daily subcutaneous injections will still be warranted for certain children with GHD, Dr. Miller noted.

“Daily growth hormone may be better than LAGH for a small number of children who have severe GHD associated with hypoglycemia,” he said. “The low levels of growth hormone at the end of the weekly interval of LAGH may allow hypoglycemia to occur in this population.”
 

Phase 3 trial in 161 treatment-naive children with GHD

The heiGHt trial randomized treatment-naive prepubertal children with GHD 2:1 to weekly lonapegsomatropin or daily somatropin (Genotropin, Pfizer) at 73 sites in 15 countries.

The children were a mean age of 8.5 years (range, 3.2-13.1 years), 82% were boys, and 94% were White.

There were no reported serious adverse events or discontinuations related to lonapegsomatropin.

The most common adverse reactions in ≥5% of these pediatric patients were viral infection (15%), pyrexia (15%), cough (11%), nausea and vomiting (11%), hemorrhage (7%), diarrhea (6%), abdominal pain (6%), and arthralgia and arthritis (6%).

Both study groups reported low incidences of transient, non-neutralizing anti-hGH binding antibodies and no cases of persistent antibodies.

Trial limitations include the fact the study was not blinded (as patients received a weekly or daily injection) and drug doses were fixed at 0.24 mg human growth hormone/kg/week, although in real-world clinical practice, doses may be titrated.

Lonapegsomatropin has been studied in more than 300 children with GHD in the phase 3 program in the heiGHt trial (treatment-naive patients), fliGHt trial (treatment-experienced patients), and enliGHten trial (an ongoing long-term extension trial that includes some patients who have been taking lonapegsomatropin for more than 4 years).

The study was sponsored by Ascendis Pharma. Some of the phase 3 study authors are company employees.

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

With the number of pediatric infections with SARS-CoV-2 rising it is not surprising that children with persistent symptoms are beginning to accumulate. Who are these pediatric “long haulers” and do they differ from their adult counterparts? The answer is far from clear because the terms “long COVID” and “long hauler” are not well defined. But, I suspect we will find that they will be similar in most respects.

In a recent Guest Essay in the New York Times, two medical school professors attempt to inject some common sense into the long hauler phenomenon. (“The Truth About Long Covid is Complicated. Better Treatment Isn’t,” Adam Gaffney and Zackary Berger, The New York Times, Aug. 18, 2021).

The authors divide the patients with long COVID into three categories. The first includes those who are complaining of persistent cough and fatigue for up to 3 months, a not unexpected course for patients recovering from a significant respiratory illness like pneumonia.

The second group comprises patients who developed acute respiratory distress syndrome during the course of their SARS-CoV-2 infection. These unfortunate individuals likely incurred lung damage that may have triggered renal damage and delirium and may never regain full function.

The third group of patients reports a wide variety of less specific symptoms including, but not limited to, severe fatigue, brain fog, shortness of breath, gastrointestinal symptoms, chronic pain, and palpitations.

The authors of the essay refer to several studies in which there was little if any correlation between these patients’ complaints and their antibody levels. In fact, one study of adolescents found that in a group with similar symptoms many of the individuals had no serologic evidence of SARS-CoV-2 infection.

Unfortunately, the lay public, the media, and some physicians make no distinction between these three groups and lump them all under the same long COVID umbrella. The resulting confusion seeds unwarranted anxiety among the first and third groups and may prevent some individuals from receiving the appropriate attention they deserve.

I suspect that like me, many of you see some similarities between this third group of long COVID patients and adolescents whose persistent symptoms don’t quite fit with their primary illness. Patients labeled as having post-concussion syndrome or “chronic Lyme disease” come immediately to mind. In both conditions, many of the patients had little if any evidence of severe insult from the initial event but continue to complain about a variety of symptoms including severe fatigue and brain fog.

We have done a very poor job of properly managing these patients. And there are a lot of them. A large part of the problem is labeling. In the old days one might have said these patients were having “psychosomatic” symptoms. But, while it may be an accurate description, like the term “retardation” it has been permanently tarnished. Fortunately, most of us are smart enough to avoid telling these patients that it is all in their heads.

However, convincing an individual that many of his symptoms may be the result of the psychological insult from the original disease compounded by other stresses and lifestyle factors can be a difficult sell. The task is made particularly difficult when there continue to be physicians who will miss or ignore the obvious and embark on therapeutic endeavors that are not only ineffective but can serve as a distraction from the real work of listening to and engaging these patients whose suffering may be just as real as that of those long haulers with structural damage.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

With the number of pediatric infections with SARS-CoV-2 rising it is not surprising that children with persistent symptoms are beginning to accumulate. Who are these pediatric “long haulers” and do they differ from their adult counterparts? The answer is far from clear because the terms “long COVID” and “long hauler” are not well defined. But, I suspect we will find that they will be similar in most respects.

In a recent Guest Essay in the New York Times, two medical school professors attempt to inject some common sense into the long hauler phenomenon. (“The Truth About Long Covid is Complicated. Better Treatment Isn’t,” Adam Gaffney and Zackary Berger, The New York Times, Aug. 18, 2021).

The authors divide the patients with long COVID into three categories. The first includes those who are complaining of persistent cough and fatigue for up to 3 months, a not unexpected course for patients recovering from a significant respiratory illness like pneumonia.

The second group comprises patients who developed acute respiratory distress syndrome during the course of their SARS-CoV-2 infection. These unfortunate individuals likely incurred lung damage that may have triggered renal damage and delirium and may never regain full function.

The third group of patients reports a wide variety of less specific symptoms including, but not limited to, severe fatigue, brain fog, shortness of breath, gastrointestinal symptoms, chronic pain, and palpitations.

The authors of the essay refer to several studies in which there was little if any correlation between these patients’ complaints and their antibody levels. In fact, one study of adolescents found that in a group with similar symptoms many of the individuals had no serologic evidence of SARS-CoV-2 infection.

Unfortunately, the lay public, the media, and some physicians make no distinction between these three groups and lump them all under the same long COVID umbrella. The resulting confusion seeds unwarranted anxiety among the first and third groups and may prevent some individuals from receiving the appropriate attention they deserve.

I suspect that like me, many of you see some similarities between this third group of long COVID patients and adolescents whose persistent symptoms don’t quite fit with their primary illness. Patients labeled as having post-concussion syndrome or “chronic Lyme disease” come immediately to mind. In both conditions, many of the patients had little if any evidence of severe insult from the initial event but continue to complain about a variety of symptoms including severe fatigue and brain fog.

We have done a very poor job of properly managing these patients. And there are a lot of them. A large part of the problem is labeling. In the old days one might have said these patients were having “psychosomatic” symptoms. But, while it may be an accurate description, like the term “retardation” it has been permanently tarnished. Fortunately, most of us are smart enough to avoid telling these patients that it is all in their heads.

However, convincing an individual that many of his symptoms may be the result of the psychological insult from the original disease compounded by other stresses and lifestyle factors can be a difficult sell. The task is made particularly difficult when there continue to be physicians who will miss or ignore the obvious and embark on therapeutic endeavors that are not only ineffective but can serve as a distraction from the real work of listening to and engaging these patients whose suffering may be just as real as that of those long haulers with structural damage.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

With the number of pediatric infections with SARS-CoV-2 rising it is not surprising that children with persistent symptoms are beginning to accumulate. Who are these pediatric “long haulers” and do they differ from their adult counterparts? The answer is far from clear because the terms “long COVID” and “long hauler” are not well defined. But, I suspect we will find that they will be similar in most respects.

In a recent Guest Essay in the New York Times, two medical school professors attempt to inject some common sense into the long hauler phenomenon. (“The Truth About Long Covid is Complicated. Better Treatment Isn’t,” Adam Gaffney and Zackary Berger, The New York Times, Aug. 18, 2021).

The authors divide the patients with long COVID into three categories. The first includes those who are complaining of persistent cough and fatigue for up to 3 months, a not unexpected course for patients recovering from a significant respiratory illness like pneumonia.

The second group comprises patients who developed acute respiratory distress syndrome during the course of their SARS-CoV-2 infection. These unfortunate individuals likely incurred lung damage that may have triggered renal damage and delirium and may never regain full function.

The third group of patients reports a wide variety of less specific symptoms including, but not limited to, severe fatigue, brain fog, shortness of breath, gastrointestinal symptoms, chronic pain, and palpitations.

The authors of the essay refer to several studies in which there was little if any correlation between these patients’ complaints and their antibody levels. In fact, one study of adolescents found that in a group with similar symptoms many of the individuals had no serologic evidence of SARS-CoV-2 infection.

Unfortunately, the lay public, the media, and some physicians make no distinction between these three groups and lump them all under the same long COVID umbrella. The resulting confusion seeds unwarranted anxiety among the first and third groups and may prevent some individuals from receiving the appropriate attention they deserve.

I suspect that like me, many of you see some similarities between this third group of long COVID patients and adolescents whose persistent symptoms don’t quite fit with their primary illness. Patients labeled as having post-concussion syndrome or “chronic Lyme disease” come immediately to mind. In both conditions, many of the patients had little if any evidence of severe insult from the initial event but continue to complain about a variety of symptoms including severe fatigue and brain fog.

We have done a very poor job of properly managing these patients. And there are a lot of them. A large part of the problem is labeling. In the old days one might have said these patients were having “psychosomatic” symptoms. But, while it may be an accurate description, like the term “retardation” it has been permanently tarnished. Fortunately, most of us are smart enough to avoid telling these patients that it is all in their heads.

However, convincing an individual that many of his symptoms may be the result of the psychological insult from the original disease compounded by other stresses and lifestyle factors can be a difficult sell. The task is made particularly difficult when there continue to be physicians who will miss or ignore the obvious and embark on therapeutic endeavors that are not only ineffective but can serve as a distraction from the real work of listening to and engaging these patients whose suffering may be just as real as that of those long haulers with structural damage.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.

“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”

Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”

Treating pediatric psoriasis

Dr. Paller discussed her approach to managing patients with pediatric psoriasis, an inflammatory disorder with IL-23/Th17 skewing. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”

Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.

Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.

“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”

Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.

In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments (JAMA Dermatol. 2020;156[1]:72-8).

Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.

Commentary by Robert Sidbury, MD, MPH

Dr. Paller reminds us of some essential features of pediatric psoriasis:
•    It can hurt. Ask your patients if it does.
•    It can itch. Look for excoriations, especially in the scalp.
•    It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
•    Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above. 
•    With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream. 

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.

“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”

Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”

Treating pediatric psoriasis

Dr. Paller discussed her approach to managing patients with pediatric psoriasis, an inflammatory disorder with IL-23/Th17 skewing. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”

Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.

Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.

“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”

Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.

In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments (JAMA Dermatol. 2020;156[1]:72-8).

Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.

Commentary by Robert Sidbury, MD, MPH

Dr. Paller reminds us of some essential features of pediatric psoriasis:
•    It can hurt. Ask your patients if it does.
•    It can itch. Look for excoriations, especially in the scalp.
•    It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
•    Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above. 
•    With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream. 

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.

“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”

Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”

Treating pediatric psoriasis

Dr. Paller discussed her approach to managing patients with pediatric psoriasis, an inflammatory disorder with IL-23/Th17 skewing. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”

Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.

Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.

“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”

Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.

In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments (JAMA Dermatol. 2020;156[1]:72-8).

Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.

Commentary by Robert Sidbury, MD, MPH

Dr. Paller reminds us of some essential features of pediatric psoriasis:
•    It can hurt. Ask your patients if it does.
•    It can itch. Look for excoriations, especially in the scalp.
•    It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
•    Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above. 
•    With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream. 

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.