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Infant anaphylaxis: Study characterizes symptoms, treatment
LOUISVILLE, KY. – , research findings indicate.
Given that early administration of epinephrine can be potentially lifesaving for infants with anaphylaxis, the study highlighted the real-world successes in increased uptake of treatment in this vulnerable patient population.
Most infants in the study who presented to the ED and received epinephrine were able to be discharged home after just a few hours, with only 1 out of 10 requiring hospitalization.
The study also reported that most symptoms were in the skin/mucosal, gastrointestinal, respiratory, and cardiovascular (CV) systems, providing improved characterization of anaphylaxis symptoms in the infant population.
Nearly “all episodes were triggered by food – especially egg, peanut, milk, and cashew,” commented Colleen Shannon, MD, a pediatrician at Children’s Hospital of Philadelphia, who presented the research findings at the annual meeting of the American College of Allergy, Asthma, and Immunology.
Dr. Shannon noted that despite previous research demonstrating age-based differences in the presentation of anaphylaxis, the symptomatology of anaphylaxis in infants has not been robustly characterized. Better characterization of anaphylaxis in infants with allergies may help ensure earlier and more accurate diagnosis and management, she said.
For the study, the researchers performed a retrospective chart review of 169 patients between 0 and 24 months of age (mean age, 1.0 years) who presented to the emergency department of a pediatric tertiary referral center between 2019 and 2022.
All patients in the study met diagnostic criteria for anaphylaxis. The investigators used the medical records of patients to evaluate for demographics, as well as presenting symptoms and treatment.
More than half (56.2%) of infants in the study were 12 months of age or younger, and 64.5% were male.
Nearly all (96.5%) anaphylaxis episodes presenting to the ED were triggered by food. The most common foods triggering these episodes were egg (26.6%), peanut (25.4%), milk (13.6%), and cashew (10.1%).
Most symptoms involved the skin/mucosal (97.6%) and GI (74.6%) systems, followed by respiratory (56.8%) and CV (34.3%) systems. Isolated tachycardia was recorded in 84.5% of patients with CV-related symptoms.
Epinephrine was administered to 86.4% of infants who presented to the ED with anaphylaxis. Nearly a third (30.1%) of these infants received epinephrine before arriving to the ED, and 9.5% required more than 1 dose.
The researchers also found that 10.1% of patients required hospital admission, but none had symptoms severe enough to require intensive care.
Jennifer Hoffmann, MD, an emergency medicine physician at the Lurie Children’s Hospital of Chicago, told this news organization that while characterizing anaphylaxis symptoms is relevant for clinicians, it also remains vitally important “to teach parents of infants how to recognize the signs of anaphylaxis, particularly as they begin to introduce new foods,” to ensure timely treatment.
She added that since most infants in the study improved after a single dose of epinephrine, most infants presenting to the ED with anaphylaxis can therefore be safely discharged home after only a brief period of observation. “That is, age alone should not be a reason for admission,” explained Dr. Hoffmann, who wasn’t involved in the research study.
The study was independently supported. Dr. Shannon and Dr. Hoffmann report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LOUISVILLE, KY. – , research findings indicate.
Given that early administration of epinephrine can be potentially lifesaving for infants with anaphylaxis, the study highlighted the real-world successes in increased uptake of treatment in this vulnerable patient population.
Most infants in the study who presented to the ED and received epinephrine were able to be discharged home after just a few hours, with only 1 out of 10 requiring hospitalization.
The study also reported that most symptoms were in the skin/mucosal, gastrointestinal, respiratory, and cardiovascular (CV) systems, providing improved characterization of anaphylaxis symptoms in the infant population.
Nearly “all episodes were triggered by food – especially egg, peanut, milk, and cashew,” commented Colleen Shannon, MD, a pediatrician at Children’s Hospital of Philadelphia, who presented the research findings at the annual meeting of the American College of Allergy, Asthma, and Immunology.
Dr. Shannon noted that despite previous research demonstrating age-based differences in the presentation of anaphylaxis, the symptomatology of anaphylaxis in infants has not been robustly characterized. Better characterization of anaphylaxis in infants with allergies may help ensure earlier and more accurate diagnosis and management, she said.
For the study, the researchers performed a retrospective chart review of 169 patients between 0 and 24 months of age (mean age, 1.0 years) who presented to the emergency department of a pediatric tertiary referral center between 2019 and 2022.
All patients in the study met diagnostic criteria for anaphylaxis. The investigators used the medical records of patients to evaluate for demographics, as well as presenting symptoms and treatment.
More than half (56.2%) of infants in the study were 12 months of age or younger, and 64.5% were male.
Nearly all (96.5%) anaphylaxis episodes presenting to the ED were triggered by food. The most common foods triggering these episodes were egg (26.6%), peanut (25.4%), milk (13.6%), and cashew (10.1%).
Most symptoms involved the skin/mucosal (97.6%) and GI (74.6%) systems, followed by respiratory (56.8%) and CV (34.3%) systems. Isolated tachycardia was recorded in 84.5% of patients with CV-related symptoms.
Epinephrine was administered to 86.4% of infants who presented to the ED with anaphylaxis. Nearly a third (30.1%) of these infants received epinephrine before arriving to the ED, and 9.5% required more than 1 dose.
The researchers also found that 10.1% of patients required hospital admission, but none had symptoms severe enough to require intensive care.
Jennifer Hoffmann, MD, an emergency medicine physician at the Lurie Children’s Hospital of Chicago, told this news organization that while characterizing anaphylaxis symptoms is relevant for clinicians, it also remains vitally important “to teach parents of infants how to recognize the signs of anaphylaxis, particularly as they begin to introduce new foods,” to ensure timely treatment.
She added that since most infants in the study improved after a single dose of epinephrine, most infants presenting to the ED with anaphylaxis can therefore be safely discharged home after only a brief period of observation. “That is, age alone should not be a reason for admission,” explained Dr. Hoffmann, who wasn’t involved in the research study.
The study was independently supported. Dr. Shannon and Dr. Hoffmann report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LOUISVILLE, KY. – , research findings indicate.
Given that early administration of epinephrine can be potentially lifesaving for infants with anaphylaxis, the study highlighted the real-world successes in increased uptake of treatment in this vulnerable patient population.
Most infants in the study who presented to the ED and received epinephrine were able to be discharged home after just a few hours, with only 1 out of 10 requiring hospitalization.
The study also reported that most symptoms were in the skin/mucosal, gastrointestinal, respiratory, and cardiovascular (CV) systems, providing improved characterization of anaphylaxis symptoms in the infant population.
Nearly “all episodes were triggered by food – especially egg, peanut, milk, and cashew,” commented Colleen Shannon, MD, a pediatrician at Children’s Hospital of Philadelphia, who presented the research findings at the annual meeting of the American College of Allergy, Asthma, and Immunology.
Dr. Shannon noted that despite previous research demonstrating age-based differences in the presentation of anaphylaxis, the symptomatology of anaphylaxis in infants has not been robustly characterized. Better characterization of anaphylaxis in infants with allergies may help ensure earlier and more accurate diagnosis and management, she said.
For the study, the researchers performed a retrospective chart review of 169 patients between 0 and 24 months of age (mean age, 1.0 years) who presented to the emergency department of a pediatric tertiary referral center between 2019 and 2022.
All patients in the study met diagnostic criteria for anaphylaxis. The investigators used the medical records of patients to evaluate for demographics, as well as presenting symptoms and treatment.
More than half (56.2%) of infants in the study were 12 months of age or younger, and 64.5% were male.
Nearly all (96.5%) anaphylaxis episodes presenting to the ED were triggered by food. The most common foods triggering these episodes were egg (26.6%), peanut (25.4%), milk (13.6%), and cashew (10.1%).
Most symptoms involved the skin/mucosal (97.6%) and GI (74.6%) systems, followed by respiratory (56.8%) and CV (34.3%) systems. Isolated tachycardia was recorded in 84.5% of patients with CV-related symptoms.
Epinephrine was administered to 86.4% of infants who presented to the ED with anaphylaxis. Nearly a third (30.1%) of these infants received epinephrine before arriving to the ED, and 9.5% required more than 1 dose.
The researchers also found that 10.1% of patients required hospital admission, but none had symptoms severe enough to require intensive care.
Jennifer Hoffmann, MD, an emergency medicine physician at the Lurie Children’s Hospital of Chicago, told this news organization that while characterizing anaphylaxis symptoms is relevant for clinicians, it also remains vitally important “to teach parents of infants how to recognize the signs of anaphylaxis, particularly as they begin to introduce new foods,” to ensure timely treatment.
She added that since most infants in the study improved after a single dose of epinephrine, most infants presenting to the ED with anaphylaxis can therefore be safely discharged home after only a brief period of observation. “That is, age alone should not be a reason for admission,” explained Dr. Hoffmann, who wasn’t involved in the research study.
The study was independently supported. Dr. Shannon and Dr. Hoffmann report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACAAI
ED visits for kids with suicidal thoughts increasing: Study
A new study sheds light on the escalating youth suicide crisis, revealing that emergency room visits for suicidal thoughts among kids and teens steeply increased even before the start of the COVID-19 pandemic.
Emergency room visits for “suicidal ideation” (or suicidal thoughts) among 5- to 19-year-olds increased 59% from 2016 to 2021, and hospitalizations rose 57% from fall 2019 to the fall of 2020, according to the study published in Pediatrics.
“A lot of people have talked about mental health problems in youth during the pandemic, but it was happening before the pandemic,” said author Audrey Brewer, MD, MPH, in a news release from the Ann and Robert H. Lurie Children’s Hospital of Chicago. “This has been an issue for so long, and it’s getting worse.”
Researchers looked at data for 81,105 emergency room visits across 205 Illinois hospitals from 2016 to 2021 for kids between the ages of 5 and 19.
The researchers found “there was a very sharp spike in fall 2019, followed by a similar spike during the pandemic fall of 2020, with the highest number of monthly visits during October 2020,” the authors said. “Youth aged 14-17 years had the highest frequency of [suicidal ideation emergency room] monthly visits, with visits in this group greater than the other age groups combined.”
Last year, the Centers for Disease Control and Prevention announced that suicide is the second leading cause of death among 10- to 19-year-olds.
The new research is being called a benchmark because it evaluates emergency room data for suicidal thoughts – a critical point of care for serving youths’ mental health needs. The data showed that providers were increasingly likely to list suicidal thoughts as the main diagnosis.
“Suicidal ideation can be thought about as two types: actively thinking about suicide or having thoughts, but not having a plan,” Dr. Brewer said in the news release. “That could be the difference in why someone might get admitted to the hospital.”
The researchers hypothesize that care in 2019 (when the initial spike occurred) was delayed in the early days of the pandemic, and that delay possibly contributed to the increase in providers identifying suicidal ideation as the main diagnosis.
“The early pandemic period coincided with constrained access to pediatric mental health services through schools, pediatric primary care homes, and mental health clinics for many children and their families,” the authors wrote. “The proportion of child mental health visits increased relative to other types as patients avoided ED visits during the early wave of the COVID-19 pandemic. Thus, the increase in hospitalizations during fall 2020 may reflect patients’ deferring care until symptoms became even more severe.”
Other health care scholars agreed the study spurred questions about whether the pandemic was truly the source of the crisis.
“Was it the pandemic that exacerbated the increase or is this a growing trend?” wrote Lisa M. Horowitz, PhD, MPH, and Jeffrey A. Bridge, PhD, in a commentary published along with the study. “These rising rates underscore the worsening mental health crisis for youth, as noted by the 2022 Surgeon General report and several youth mental health organizations.”
A version of this article first appeared on WebMD.com.
A new study sheds light on the escalating youth suicide crisis, revealing that emergency room visits for suicidal thoughts among kids and teens steeply increased even before the start of the COVID-19 pandemic.
Emergency room visits for “suicidal ideation” (or suicidal thoughts) among 5- to 19-year-olds increased 59% from 2016 to 2021, and hospitalizations rose 57% from fall 2019 to the fall of 2020, according to the study published in Pediatrics.
“A lot of people have talked about mental health problems in youth during the pandemic, but it was happening before the pandemic,” said author Audrey Brewer, MD, MPH, in a news release from the Ann and Robert H. Lurie Children’s Hospital of Chicago. “This has been an issue for so long, and it’s getting worse.”
Researchers looked at data for 81,105 emergency room visits across 205 Illinois hospitals from 2016 to 2021 for kids between the ages of 5 and 19.
The researchers found “there was a very sharp spike in fall 2019, followed by a similar spike during the pandemic fall of 2020, with the highest number of monthly visits during October 2020,” the authors said. “Youth aged 14-17 years had the highest frequency of [suicidal ideation emergency room] monthly visits, with visits in this group greater than the other age groups combined.”
Last year, the Centers for Disease Control and Prevention announced that suicide is the second leading cause of death among 10- to 19-year-olds.
The new research is being called a benchmark because it evaluates emergency room data for suicidal thoughts – a critical point of care for serving youths’ mental health needs. The data showed that providers were increasingly likely to list suicidal thoughts as the main diagnosis.
“Suicidal ideation can be thought about as two types: actively thinking about suicide or having thoughts, but not having a plan,” Dr. Brewer said in the news release. “That could be the difference in why someone might get admitted to the hospital.”
The researchers hypothesize that care in 2019 (when the initial spike occurred) was delayed in the early days of the pandemic, and that delay possibly contributed to the increase in providers identifying suicidal ideation as the main diagnosis.
“The early pandemic period coincided with constrained access to pediatric mental health services through schools, pediatric primary care homes, and mental health clinics for many children and their families,” the authors wrote. “The proportion of child mental health visits increased relative to other types as patients avoided ED visits during the early wave of the COVID-19 pandemic. Thus, the increase in hospitalizations during fall 2020 may reflect patients’ deferring care until symptoms became even more severe.”
Other health care scholars agreed the study spurred questions about whether the pandemic was truly the source of the crisis.
“Was it the pandemic that exacerbated the increase or is this a growing trend?” wrote Lisa M. Horowitz, PhD, MPH, and Jeffrey A. Bridge, PhD, in a commentary published along with the study. “These rising rates underscore the worsening mental health crisis for youth, as noted by the 2022 Surgeon General report and several youth mental health organizations.”
A version of this article first appeared on WebMD.com.
A new study sheds light on the escalating youth suicide crisis, revealing that emergency room visits for suicidal thoughts among kids and teens steeply increased even before the start of the COVID-19 pandemic.
Emergency room visits for “suicidal ideation” (or suicidal thoughts) among 5- to 19-year-olds increased 59% from 2016 to 2021, and hospitalizations rose 57% from fall 2019 to the fall of 2020, according to the study published in Pediatrics.
“A lot of people have talked about mental health problems in youth during the pandemic, but it was happening before the pandemic,” said author Audrey Brewer, MD, MPH, in a news release from the Ann and Robert H. Lurie Children’s Hospital of Chicago. “This has been an issue for so long, and it’s getting worse.”
Researchers looked at data for 81,105 emergency room visits across 205 Illinois hospitals from 2016 to 2021 for kids between the ages of 5 and 19.
The researchers found “there was a very sharp spike in fall 2019, followed by a similar spike during the pandemic fall of 2020, with the highest number of monthly visits during October 2020,” the authors said. “Youth aged 14-17 years had the highest frequency of [suicidal ideation emergency room] monthly visits, with visits in this group greater than the other age groups combined.”
Last year, the Centers for Disease Control and Prevention announced that suicide is the second leading cause of death among 10- to 19-year-olds.
The new research is being called a benchmark because it evaluates emergency room data for suicidal thoughts – a critical point of care for serving youths’ mental health needs. The data showed that providers were increasingly likely to list suicidal thoughts as the main diagnosis.
“Suicidal ideation can be thought about as two types: actively thinking about suicide or having thoughts, but not having a plan,” Dr. Brewer said in the news release. “That could be the difference in why someone might get admitted to the hospital.”
The researchers hypothesize that care in 2019 (when the initial spike occurred) was delayed in the early days of the pandemic, and that delay possibly contributed to the increase in providers identifying suicidal ideation as the main diagnosis.
“The early pandemic period coincided with constrained access to pediatric mental health services through schools, pediatric primary care homes, and mental health clinics for many children and their families,” the authors wrote. “The proportion of child mental health visits increased relative to other types as patients avoided ED visits during the early wave of the COVID-19 pandemic. Thus, the increase in hospitalizations during fall 2020 may reflect patients’ deferring care until symptoms became even more severe.”
Other health care scholars agreed the study spurred questions about whether the pandemic was truly the source of the crisis.
“Was it the pandemic that exacerbated the increase or is this a growing trend?” wrote Lisa M. Horowitz, PhD, MPH, and Jeffrey A. Bridge, PhD, in a commentary published along with the study. “These rising rates underscore the worsening mental health crisis for youth, as noted by the 2022 Surgeon General report and several youth mental health organizations.”
A version of this article first appeared on WebMD.com.
FROM PEDIATRICS
Watching violent TV in preschool linked with emotional, behavioral issues at age 12
Preschoolers who watch violent television are more likely to have emotional and behavioral issues at the age of 12, according to investigators.
These findings align with previous studies that have shown the negative effects of watching violent content, reinforcing the importance of restricting childhood screen time, lead author Linda S. Pagani, PhD, of Université de Montréal and colleagues reported.
Past research measured the immediate or short-term effects of seeing violent media. This study examined how TV violence could be leading to issues almost a decade later, the investigators wrote in the Journal of Developmental & Behavioral Pediatrics.
Their study looked at 1,976 children from the Quebec Longitudinal Study of Child Development, a random representative cohort of boys and girls followed since their births in 1997 and 1998.
At the cohort study follow-ups at ages 3.5 and 4.5 years, the parents of these children reported if their kids watched violent TV, showing that about half of them were exposed. At age 12, the same children were scored by their teachers on a range of psychosocial outcomes, including emotional distress, inattentive behavior, disorderly behavior, social withdrawal, classroom engagement, and overall academic achievement. At this second time point, the children also scored themselves on their own academic motivation and confidence in writing.
To adjust for other factors that could be playing a role, the investigators accounted for participant characteristics at various ages between 5 months and 12 years, as well as differences in parenting styles, home environment, and socioeconomic status.
Dr. Pagani noted that these were not “garden-variety” statistical techniques.
“We did them in such a way that we set ourselves up for not finding results,” Dr. Pagani said in an interview. “That’s why this is really interesting.”
She and her colleagues found that watching TV violence during preschool was significantly associated with multiple negative outcomes at age 12.
For girls, negative outcomes included greater emotional distress, less classroom engagement, lower academic achievement, and less academic motivation. Boys showed greater emotional distress, decreased attention, disorderly behavior, social withdrawal, less classroom engagement, lower academic achievement, and less academic motivation.
“As expected, early screen violence exposure seems to come at a cost,” the investigators wrote.
Seeing TV through a child’s eyes
According to Dr. Pagani, many parents think that TV shows watched by preschoolers – like cartoons – are harmless, but these parents need to understand that the brains of children are not yet fully developed.
“The kid has an interpretation that’s very concrete,” Dr. Pagani said. “They don’t have abstract thinking.”
Because of this, kids who see “good guys” beating up “bad guys” don’t understand that the violence is comical and justified; they just see violence being used to address social disagreement, Dr. Pagani said. This leads children to believe that violence is an acceptable way to solve problems in daily life. Children are also more likely to see hostility in others when it isn’t present, leading to conflict.
Although the natural response to these findings is to restrict childhood exposure to violent content, this may be easier said than done, the investigators noted, particularly because TV is no longer the only screen in the home, as it was when this study began. Nowadays, parents need to monitor multiple devices, including smartphones, tablets, and computers, all of which may negatively impact normal brain development.
“People think this technology is innocuous,” Dr. Pagani said. “We are asleep at the wheel.”
She advised parents to wake up and follow the World Health Organization guidelines for sedentary screen time. The guidelines call for no screen time at all until a child is at least 2 years old, and then less than 1 hour per day until age 5.
“It’s the parents who should be in charge,” she said. “They’re the ones who have the cognitive ability to make decisions for their children.”
Choosing quality time over screen time
Loredana Marchica, PhD, of Montreal Children’s Hospital and McGill University, also in Montreal, expressed confidence in the study findings, because the results line up with past research, and because the investigators accounted for other explanations.
There is a “very strong probability” that watching violent TV in preschool leads to psychological issues down the line, Dr. Marchica said.
If a child is exposed to violent content, then parents should help children understand the difference between what happens in TV shows and real life, she added, as this can reduce negative effects on behavior.
“Parents need to explain that it’s a TV show,” Dr. Marchica said. “It’s not real, and if [that violent act] happened in real life, it would actually hurt a person.”
In addition to limiting screen time and explaining any violent content, she encouraged parents to spend quality time with their children, especially during the preschool years.
“Those are the years to fortify the attachment you have with that child,” Dr. Marchica said. “Even 15 minutes a day of quality, interactive play time can make such a difference in their development, their imagination, and their social engagement and abilities.”
Parents should also try to have conversations with their young children, she said, noting that it’s okay to share personal feelings, as this teaches kids how to manage their own emotions.
“Not everything is wonderful in life, and we’re allowed to talk about that,” Dr. Marchica said. “[Parents can say,] ‘Mommy had a bad day today. This bad thing happened. But here’s what I did to make myself feel better.’ ”
Dr. Pagani and coauthors termed their findings “robust,” but also cautioned that, in their correlational study, TV violence cannot be interpreted as causal. In other limitations, they noted that the study relies on a single parent-reported item that yielded a low rate of reported exposure. Or the findings could result from other things, such as family chaos or parenting style or something else.
The longitudinal study was supported by Fondation Lucie et André Chagnon, the Institut de la Statistique du Québec, the Ministère de l’Éducation et de l’Enseignement supérieur, and others. The investigators and Dr. Marchica reported no relevant conflicts of interest.
Preschoolers who watch violent television are more likely to have emotional and behavioral issues at the age of 12, according to investigators.
These findings align with previous studies that have shown the negative effects of watching violent content, reinforcing the importance of restricting childhood screen time, lead author Linda S. Pagani, PhD, of Université de Montréal and colleagues reported.
Past research measured the immediate or short-term effects of seeing violent media. This study examined how TV violence could be leading to issues almost a decade later, the investigators wrote in the Journal of Developmental & Behavioral Pediatrics.
Their study looked at 1,976 children from the Quebec Longitudinal Study of Child Development, a random representative cohort of boys and girls followed since their births in 1997 and 1998.
At the cohort study follow-ups at ages 3.5 and 4.5 years, the parents of these children reported if their kids watched violent TV, showing that about half of them were exposed. At age 12, the same children were scored by their teachers on a range of psychosocial outcomes, including emotional distress, inattentive behavior, disorderly behavior, social withdrawal, classroom engagement, and overall academic achievement. At this second time point, the children also scored themselves on their own academic motivation and confidence in writing.
To adjust for other factors that could be playing a role, the investigators accounted for participant characteristics at various ages between 5 months and 12 years, as well as differences in parenting styles, home environment, and socioeconomic status.
Dr. Pagani noted that these were not “garden-variety” statistical techniques.
“We did them in such a way that we set ourselves up for not finding results,” Dr. Pagani said in an interview. “That’s why this is really interesting.”
She and her colleagues found that watching TV violence during preschool was significantly associated with multiple negative outcomes at age 12.
For girls, negative outcomes included greater emotional distress, less classroom engagement, lower academic achievement, and less academic motivation. Boys showed greater emotional distress, decreased attention, disorderly behavior, social withdrawal, less classroom engagement, lower academic achievement, and less academic motivation.
“As expected, early screen violence exposure seems to come at a cost,” the investigators wrote.
Seeing TV through a child’s eyes
According to Dr. Pagani, many parents think that TV shows watched by preschoolers – like cartoons – are harmless, but these parents need to understand that the brains of children are not yet fully developed.
“The kid has an interpretation that’s very concrete,” Dr. Pagani said. “They don’t have abstract thinking.”
Because of this, kids who see “good guys” beating up “bad guys” don’t understand that the violence is comical and justified; they just see violence being used to address social disagreement, Dr. Pagani said. This leads children to believe that violence is an acceptable way to solve problems in daily life. Children are also more likely to see hostility in others when it isn’t present, leading to conflict.
Although the natural response to these findings is to restrict childhood exposure to violent content, this may be easier said than done, the investigators noted, particularly because TV is no longer the only screen in the home, as it was when this study began. Nowadays, parents need to monitor multiple devices, including smartphones, tablets, and computers, all of which may negatively impact normal brain development.
“People think this technology is innocuous,” Dr. Pagani said. “We are asleep at the wheel.”
She advised parents to wake up and follow the World Health Organization guidelines for sedentary screen time. The guidelines call for no screen time at all until a child is at least 2 years old, and then less than 1 hour per day until age 5.
“It’s the parents who should be in charge,” she said. “They’re the ones who have the cognitive ability to make decisions for their children.”
Choosing quality time over screen time
Loredana Marchica, PhD, of Montreal Children’s Hospital and McGill University, also in Montreal, expressed confidence in the study findings, because the results line up with past research, and because the investigators accounted for other explanations.
There is a “very strong probability” that watching violent TV in preschool leads to psychological issues down the line, Dr. Marchica said.
If a child is exposed to violent content, then parents should help children understand the difference between what happens in TV shows and real life, she added, as this can reduce negative effects on behavior.
“Parents need to explain that it’s a TV show,” Dr. Marchica said. “It’s not real, and if [that violent act] happened in real life, it would actually hurt a person.”
In addition to limiting screen time and explaining any violent content, she encouraged parents to spend quality time with their children, especially during the preschool years.
“Those are the years to fortify the attachment you have with that child,” Dr. Marchica said. “Even 15 minutes a day of quality, interactive play time can make such a difference in their development, their imagination, and their social engagement and abilities.”
Parents should also try to have conversations with their young children, she said, noting that it’s okay to share personal feelings, as this teaches kids how to manage their own emotions.
“Not everything is wonderful in life, and we’re allowed to talk about that,” Dr. Marchica said. “[Parents can say,] ‘Mommy had a bad day today. This bad thing happened. But here’s what I did to make myself feel better.’ ”
Dr. Pagani and coauthors termed their findings “robust,” but also cautioned that, in their correlational study, TV violence cannot be interpreted as causal. In other limitations, they noted that the study relies on a single parent-reported item that yielded a low rate of reported exposure. Or the findings could result from other things, such as family chaos or parenting style or something else.
The longitudinal study was supported by Fondation Lucie et André Chagnon, the Institut de la Statistique du Québec, the Ministère de l’Éducation et de l’Enseignement supérieur, and others. The investigators and Dr. Marchica reported no relevant conflicts of interest.
Preschoolers who watch violent television are more likely to have emotional and behavioral issues at the age of 12, according to investigators.
These findings align with previous studies that have shown the negative effects of watching violent content, reinforcing the importance of restricting childhood screen time, lead author Linda S. Pagani, PhD, of Université de Montréal and colleagues reported.
Past research measured the immediate or short-term effects of seeing violent media. This study examined how TV violence could be leading to issues almost a decade later, the investigators wrote in the Journal of Developmental & Behavioral Pediatrics.
Their study looked at 1,976 children from the Quebec Longitudinal Study of Child Development, a random representative cohort of boys and girls followed since their births in 1997 and 1998.
At the cohort study follow-ups at ages 3.5 and 4.5 years, the parents of these children reported if their kids watched violent TV, showing that about half of them were exposed. At age 12, the same children were scored by their teachers on a range of psychosocial outcomes, including emotional distress, inattentive behavior, disorderly behavior, social withdrawal, classroom engagement, and overall academic achievement. At this second time point, the children also scored themselves on their own academic motivation and confidence in writing.
To adjust for other factors that could be playing a role, the investigators accounted for participant characteristics at various ages between 5 months and 12 years, as well as differences in parenting styles, home environment, and socioeconomic status.
Dr. Pagani noted that these were not “garden-variety” statistical techniques.
“We did them in such a way that we set ourselves up for not finding results,” Dr. Pagani said in an interview. “That’s why this is really interesting.”
She and her colleagues found that watching TV violence during preschool was significantly associated with multiple negative outcomes at age 12.
For girls, negative outcomes included greater emotional distress, less classroom engagement, lower academic achievement, and less academic motivation. Boys showed greater emotional distress, decreased attention, disorderly behavior, social withdrawal, less classroom engagement, lower academic achievement, and less academic motivation.
“As expected, early screen violence exposure seems to come at a cost,” the investigators wrote.
Seeing TV through a child’s eyes
According to Dr. Pagani, many parents think that TV shows watched by preschoolers – like cartoons – are harmless, but these parents need to understand that the brains of children are not yet fully developed.
“The kid has an interpretation that’s very concrete,” Dr. Pagani said. “They don’t have abstract thinking.”
Because of this, kids who see “good guys” beating up “bad guys” don’t understand that the violence is comical and justified; they just see violence being used to address social disagreement, Dr. Pagani said. This leads children to believe that violence is an acceptable way to solve problems in daily life. Children are also more likely to see hostility in others when it isn’t present, leading to conflict.
Although the natural response to these findings is to restrict childhood exposure to violent content, this may be easier said than done, the investigators noted, particularly because TV is no longer the only screen in the home, as it was when this study began. Nowadays, parents need to monitor multiple devices, including smartphones, tablets, and computers, all of which may negatively impact normal brain development.
“People think this technology is innocuous,” Dr. Pagani said. “We are asleep at the wheel.”
She advised parents to wake up and follow the World Health Organization guidelines for sedentary screen time. The guidelines call for no screen time at all until a child is at least 2 years old, and then less than 1 hour per day until age 5.
“It’s the parents who should be in charge,” she said. “They’re the ones who have the cognitive ability to make decisions for their children.”
Choosing quality time over screen time
Loredana Marchica, PhD, of Montreal Children’s Hospital and McGill University, also in Montreal, expressed confidence in the study findings, because the results line up with past research, and because the investigators accounted for other explanations.
There is a “very strong probability” that watching violent TV in preschool leads to psychological issues down the line, Dr. Marchica said.
If a child is exposed to violent content, then parents should help children understand the difference between what happens in TV shows and real life, she added, as this can reduce negative effects on behavior.
“Parents need to explain that it’s a TV show,” Dr. Marchica said. “It’s not real, and if [that violent act] happened in real life, it would actually hurt a person.”
In addition to limiting screen time and explaining any violent content, she encouraged parents to spend quality time with their children, especially during the preschool years.
“Those are the years to fortify the attachment you have with that child,” Dr. Marchica said. “Even 15 minutes a day of quality, interactive play time can make such a difference in their development, their imagination, and their social engagement and abilities.”
Parents should also try to have conversations with their young children, she said, noting that it’s okay to share personal feelings, as this teaches kids how to manage their own emotions.
“Not everything is wonderful in life, and we’re allowed to talk about that,” Dr. Marchica said. “[Parents can say,] ‘Mommy had a bad day today. This bad thing happened. But here’s what I did to make myself feel better.’ ”
Dr. Pagani and coauthors termed their findings “robust,” but also cautioned that, in their correlational study, TV violence cannot be interpreted as causal. In other limitations, they noted that the study relies on a single parent-reported item that yielded a low rate of reported exposure. Or the findings could result from other things, such as family chaos or parenting style or something else.
The longitudinal study was supported by Fondation Lucie et André Chagnon, the Institut de la Statistique du Québec, the Ministère de l’Éducation et de l’Enseignement supérieur, and others. The investigators and Dr. Marchica reported no relevant conflicts of interest.
FROM THE JOURNAL OF DEVELOPMENTAL & BEHAVIORAL PEDIATRICS
Clinical signs differ between children and adults with vasculitis
Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).
The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.
AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).
The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
Data limited on child vs. adult characteristics
AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.
Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.
Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).
The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
More than 1,000 patients included
Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.
They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.
Differences between age groups included:
- Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
- About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood.
- More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
- Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.
Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.
“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
Bringing children into the clinical discussion
Dr. Bloom said in an interview that
For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.
“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”
Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”
However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”
Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).
The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.
AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).
The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
Data limited on child vs. adult characteristics
AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.
Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.
Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).
The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
More than 1,000 patients included
Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.
They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.
Differences between age groups included:
- Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
- About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood.
- More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
- Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.
Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.
“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
Bringing children into the clinical discussion
Dr. Bloom said in an interview that
For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.
“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”
Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”
However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”
Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).
The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.
AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).
The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
Data limited on child vs. adult characteristics
AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.
Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.
Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).
The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
More than 1,000 patients included
Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.
They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.
Differences between age groups included:
- Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
- About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood.
- More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
- Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.
Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.
“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
Bringing children into the clinical discussion
Dr. Bloom said in an interview that
For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.
“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”
Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”
However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”
Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACR 2022
Serum dupilumab levels do not predict clinical response
The finding that serum study published in JAMA Dermatology.
The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.
Addressing inadequate response
Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.
Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”
In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.
The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).
“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.
“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”
The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.
“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
Assessing AEs
As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.
A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.
For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.
Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”
It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.
The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.
Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)
The finding that serum study published in JAMA Dermatology.
The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.
Addressing inadequate response
Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.
Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”
In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.
The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).
“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.
“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”
The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.
“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
Assessing AEs
As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.
A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.
For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.
Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”
It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.
The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.
Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)
The finding that serum study published in JAMA Dermatology.
The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.
Addressing inadequate response
Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.
Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”
In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.
The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).
“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.
“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”
The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.
“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
Assessing AEs
As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.
A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.
For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.
Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”
It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.
The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.
Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)
FROM JAMA DERMATOLOGY
A new ultrabrief screening scale for pediatric OCD
Obsessive-compulsive disorder (OCD) affects 1-2% of the population. The disorder is characterized by recurrent intrusive unwanted thoughts (obsessions) that cause significant distress and anxiety, and behavioral or mental rituals (compulsions) that are performed to reduce distress stemming from obsessions. OCD may onset at any time in life, but most commonly begins in childhood or in early adulthood.
Cognitive behavioral therapy (CBT) with exposure and response prevention is an empirically based and highly effective treatment for OCD. However, most youth with OCD do not receive any treatment, which is related to a shortage of mental health care providers with expertise in assessment and treatment of the disorder, and misdiagnosis of the disorder is all too prevalent.
Aside from the subjective emotional toll associated with OCD, individuals living with this disorder frequently experience interpersonal, academic, and vocational impairments. Nevertheless, OCD is often overlooked or misdiagnosed. This may be more pronounced in youth with OCD, particularly in primary health care settings and large nonspecialized medical institutions. In fact, research indicates that pediatric OCD is often underrecognized even among mental health professionals. This situation is not new, and in fact the National Institute for Health and Care Excellence (NICE) in the United Kingdom stated that there is an urgent need to develop brief reliable screeners for OCD nearly 20 years ago.
Although there were several attempts to develop brief screening scales for adults and youth with OCD, none of them were found to be suitable for use as rapid screening tools in nonspecialized settings. One of the primary reasons is that OCD is associated with different “themes” or dimensions. For example, a child with OCD may engage in cleaning rituals because the context (or dimension) of their obsessions is contamination concerns. Another child with OCD, who may suffer from similar overall symptom severity, may primarily engage in checking rituals which are related with obsessions associated with fear of being responsible for harm. Therefore, one child with OCD may score very high on items assessing one dimension (e.g., contamination concerns), but very low on another dimension (e.g., harm obsessions).
This results in a known challenge in the assessment and psychometrics of self-report (as opposed to clinician administered) measures of OCD. Secondly, development of such measures requires very large carefully screened samples of individuals with OCD, with other disorders, and those without a known psychological disorder – which may be more challenging than requiring adult participants.
To accomplish this, we harmonized data from several sites that included three samples of carefully screened youths with OCD, with other disorders, and without known disorders who completed multiple self-report questionnaires, including the 21-item Obsessive-Compulsive Inventory – Child Version (OCI-CV).
Utilizing psychometric analyses including factor analyses, invariance analyses, and item response theory methodologies, we were able to develop an ultrabrief measure extracted from the OCI-CV: the 5-item Obsessive-Compulsive Inventory – Child Version (OCI-CV-5). This very brief self-report measure was found to have very good psychometric properties including a sensitive and specific clinical cutoff score. Youth who score at or above the cutoff score are nearly 21 times more likely to meet criteria for OCD.
This measure corresponds to a need to rapidly screen for OCD in children in nonspecialized settings, including community mental health clinics, primary care settings, and pediatric treatment facilities. However, it is important to note it is not a diagnostic measure. The measure is intended to identify youth who should be referred to a mental health care professional to conduct a diagnostic interview.
Dr. Abramovitch is a clinical psychologist and neuropsychologist based in Austin, Tex., and an associate professor at Texas State University. Dr. Abramowitz is professor and director of clinical training in the Anxiety and Stress Lab at University of North Carolina at Chapel Hill. Dr. McKay is professor of psychology at Fordham University, Bronx, N.Y.
Obsessive-compulsive disorder (OCD) affects 1-2% of the population. The disorder is characterized by recurrent intrusive unwanted thoughts (obsessions) that cause significant distress and anxiety, and behavioral or mental rituals (compulsions) that are performed to reduce distress stemming from obsessions. OCD may onset at any time in life, but most commonly begins in childhood or in early adulthood.
Cognitive behavioral therapy (CBT) with exposure and response prevention is an empirically based and highly effective treatment for OCD. However, most youth with OCD do not receive any treatment, which is related to a shortage of mental health care providers with expertise in assessment and treatment of the disorder, and misdiagnosis of the disorder is all too prevalent.
Aside from the subjective emotional toll associated with OCD, individuals living with this disorder frequently experience interpersonal, academic, and vocational impairments. Nevertheless, OCD is often overlooked or misdiagnosed. This may be more pronounced in youth with OCD, particularly in primary health care settings and large nonspecialized medical institutions. In fact, research indicates that pediatric OCD is often underrecognized even among mental health professionals. This situation is not new, and in fact the National Institute for Health and Care Excellence (NICE) in the United Kingdom stated that there is an urgent need to develop brief reliable screeners for OCD nearly 20 years ago.
Although there were several attempts to develop brief screening scales for adults and youth with OCD, none of them were found to be suitable for use as rapid screening tools in nonspecialized settings. One of the primary reasons is that OCD is associated with different “themes” or dimensions. For example, a child with OCD may engage in cleaning rituals because the context (or dimension) of their obsessions is contamination concerns. Another child with OCD, who may suffer from similar overall symptom severity, may primarily engage in checking rituals which are related with obsessions associated with fear of being responsible for harm. Therefore, one child with OCD may score very high on items assessing one dimension (e.g., contamination concerns), but very low on another dimension (e.g., harm obsessions).
This results in a known challenge in the assessment and psychometrics of self-report (as opposed to clinician administered) measures of OCD. Secondly, development of such measures requires very large carefully screened samples of individuals with OCD, with other disorders, and those without a known psychological disorder – which may be more challenging than requiring adult participants.
To accomplish this, we harmonized data from several sites that included three samples of carefully screened youths with OCD, with other disorders, and without known disorders who completed multiple self-report questionnaires, including the 21-item Obsessive-Compulsive Inventory – Child Version (OCI-CV).
Utilizing psychometric analyses including factor analyses, invariance analyses, and item response theory methodologies, we were able to develop an ultrabrief measure extracted from the OCI-CV: the 5-item Obsessive-Compulsive Inventory – Child Version (OCI-CV-5). This very brief self-report measure was found to have very good psychometric properties including a sensitive and specific clinical cutoff score. Youth who score at or above the cutoff score are nearly 21 times more likely to meet criteria for OCD.
This measure corresponds to a need to rapidly screen for OCD in children in nonspecialized settings, including community mental health clinics, primary care settings, and pediatric treatment facilities. However, it is important to note it is not a diagnostic measure. The measure is intended to identify youth who should be referred to a mental health care professional to conduct a diagnostic interview.
Dr. Abramovitch is a clinical psychologist and neuropsychologist based in Austin, Tex., and an associate professor at Texas State University. Dr. Abramowitz is professor and director of clinical training in the Anxiety and Stress Lab at University of North Carolina at Chapel Hill. Dr. McKay is professor of psychology at Fordham University, Bronx, N.Y.
Obsessive-compulsive disorder (OCD) affects 1-2% of the population. The disorder is characterized by recurrent intrusive unwanted thoughts (obsessions) that cause significant distress and anxiety, and behavioral or mental rituals (compulsions) that are performed to reduce distress stemming from obsessions. OCD may onset at any time in life, but most commonly begins in childhood or in early adulthood.
Cognitive behavioral therapy (CBT) with exposure and response prevention is an empirically based and highly effective treatment for OCD. However, most youth with OCD do not receive any treatment, which is related to a shortage of mental health care providers with expertise in assessment and treatment of the disorder, and misdiagnosis of the disorder is all too prevalent.
Aside from the subjective emotional toll associated with OCD, individuals living with this disorder frequently experience interpersonal, academic, and vocational impairments. Nevertheless, OCD is often overlooked or misdiagnosed. This may be more pronounced in youth with OCD, particularly in primary health care settings and large nonspecialized medical institutions. In fact, research indicates that pediatric OCD is often underrecognized even among mental health professionals. This situation is not new, and in fact the National Institute for Health and Care Excellence (NICE) in the United Kingdom stated that there is an urgent need to develop brief reliable screeners for OCD nearly 20 years ago.
Although there were several attempts to develop brief screening scales for adults and youth with OCD, none of them were found to be suitable for use as rapid screening tools in nonspecialized settings. One of the primary reasons is that OCD is associated with different “themes” or dimensions. For example, a child with OCD may engage in cleaning rituals because the context (or dimension) of their obsessions is contamination concerns. Another child with OCD, who may suffer from similar overall symptom severity, may primarily engage in checking rituals which are related with obsessions associated with fear of being responsible for harm. Therefore, one child with OCD may score very high on items assessing one dimension (e.g., contamination concerns), but very low on another dimension (e.g., harm obsessions).
This results in a known challenge in the assessment and psychometrics of self-report (as opposed to clinician administered) measures of OCD. Secondly, development of such measures requires very large carefully screened samples of individuals with OCD, with other disorders, and those without a known psychological disorder – which may be more challenging than requiring adult participants.
To accomplish this, we harmonized data from several sites that included three samples of carefully screened youths with OCD, with other disorders, and without known disorders who completed multiple self-report questionnaires, including the 21-item Obsessive-Compulsive Inventory – Child Version (OCI-CV).
Utilizing psychometric analyses including factor analyses, invariance analyses, and item response theory methodologies, we were able to develop an ultrabrief measure extracted from the OCI-CV: the 5-item Obsessive-Compulsive Inventory – Child Version (OCI-CV-5). This very brief self-report measure was found to have very good psychometric properties including a sensitive and specific clinical cutoff score. Youth who score at or above the cutoff score are nearly 21 times more likely to meet criteria for OCD.
This measure corresponds to a need to rapidly screen for OCD in children in nonspecialized settings, including community mental health clinics, primary care settings, and pediatric treatment facilities. However, it is important to note it is not a diagnostic measure. The measure is intended to identify youth who should be referred to a mental health care professional to conduct a diagnostic interview.
Dr. Abramovitch is a clinical psychologist and neuropsychologist based in Austin, Tex., and an associate professor at Texas State University. Dr. Abramowitz is professor and director of clinical training in the Anxiety and Stress Lab at University of North Carolina at Chapel Hill. Dr. McKay is professor of psychology at Fordham University, Bronx, N.Y.
Children from poorer ZIP codes often untreated for ear infections
Children from socially disadvantaged backgrounds are less likely to be treated for middle ear infections and are likely to experience serious complications from the condition – potentially with lifelong economic consequences – researchers have found.
Problems such as hearing loss and chronic ear infections were more common for children who lived in areas marked by difficult socioeconomic circumstances, according to the researchers, who linked the complications to a lack of adequate treatment in this population.
“We are treating socially disadvantaged kids differently than we are treating more advantaged kids,” said Jason Qian, MD, a resident in otolaryngology and head and neck surgery at Stanford (Calif.) University, who helped conduct the new study. “We have to think about social inequalities so we can ensure all kids are receiving the same level and type of care.”
In the United States, 80% of children will experience otitis media during their lifetime. Untreated ear infections can lead to symptoms ranging from mild discharge from the ear to life-threatening conditions like mastoiditis and intracranial abscesses.
For the new study, published online in JAMA Otolaryngology–Head & Neck Surgery, Dr. Qian and colleagues looked at 4.8 million children with private health insurance across the United States using a database with information on inpatient and outpatient visits and medication use. The researchers identified patients between January 2003 and March 2021 who received treatment for recurrent and suppurative otitis media, those who received tympanostomy tubes, and children who experienced severe complications from undertreated ear infections.
Social disadvantage was assessed using the Social Deprivation Index (SDI), a tool used to measure indicators of poverty throughout the United States based on seven demographic factors including level of educational attainment, the number of single-parent households, the share of people living in overcrowded homes, and other factors.
Every point increase in the SDI score was associated with a 14% lower likelihood of being treated for recurrent ear infections despite having them and a 28% greater chance of being hospitalized for severe ear infections, according to the researchers.
Previous research established that children with government health insurance or no coverage have more difficulty receiving proper treatment for ear infections. Although people with commercial insurance are generally wealthier than those without private coverage, Dr. Qian said, the new data indicate that significant social disparities in care exist even within this group.
Although some studies have found that wealthier children are more likely to develop otitis media, Dr. Qian’s group said that association likely reflects the better access to health care money affords.
“We found that socially disadvantaged children not only have a higher burden of otitis media but are also undertreated both medically and surgically for [ear infections]. Because chronic and complicated forms of otitis media can cause childhood hearing loss, which in turn limits academic and economic potential, undertreatment of [otitis media] in socially disadvantaged populations can contribute to generational cycles of poverty, unemployment, and low pay,” they write.
“The biggest take home is that we are not treating children equitably when it comes to ear infections,” Dr. Qian added. “In order to give children equal access to care, we as health care providers need to find strategies to do better.”
The study was supported by the Stanford Center for Population Health Science Data Core, which is supported by a grant from the National Institutes of Health and internal funding. Dr. Qian has reported receiving grant funding from Merck.
A version of this article first appeared on Medscape.com.
Children from socially disadvantaged backgrounds are less likely to be treated for middle ear infections and are likely to experience serious complications from the condition – potentially with lifelong economic consequences – researchers have found.
Problems such as hearing loss and chronic ear infections were more common for children who lived in areas marked by difficult socioeconomic circumstances, according to the researchers, who linked the complications to a lack of adequate treatment in this population.
“We are treating socially disadvantaged kids differently than we are treating more advantaged kids,” said Jason Qian, MD, a resident in otolaryngology and head and neck surgery at Stanford (Calif.) University, who helped conduct the new study. “We have to think about social inequalities so we can ensure all kids are receiving the same level and type of care.”
In the United States, 80% of children will experience otitis media during their lifetime. Untreated ear infections can lead to symptoms ranging from mild discharge from the ear to life-threatening conditions like mastoiditis and intracranial abscesses.
For the new study, published online in JAMA Otolaryngology–Head & Neck Surgery, Dr. Qian and colleagues looked at 4.8 million children with private health insurance across the United States using a database with information on inpatient and outpatient visits and medication use. The researchers identified patients between January 2003 and March 2021 who received treatment for recurrent and suppurative otitis media, those who received tympanostomy tubes, and children who experienced severe complications from undertreated ear infections.
Social disadvantage was assessed using the Social Deprivation Index (SDI), a tool used to measure indicators of poverty throughout the United States based on seven demographic factors including level of educational attainment, the number of single-parent households, the share of people living in overcrowded homes, and other factors.
Every point increase in the SDI score was associated with a 14% lower likelihood of being treated for recurrent ear infections despite having them and a 28% greater chance of being hospitalized for severe ear infections, according to the researchers.
Previous research established that children with government health insurance or no coverage have more difficulty receiving proper treatment for ear infections. Although people with commercial insurance are generally wealthier than those without private coverage, Dr. Qian said, the new data indicate that significant social disparities in care exist even within this group.
Although some studies have found that wealthier children are more likely to develop otitis media, Dr. Qian’s group said that association likely reflects the better access to health care money affords.
“We found that socially disadvantaged children not only have a higher burden of otitis media but are also undertreated both medically and surgically for [ear infections]. Because chronic and complicated forms of otitis media can cause childhood hearing loss, which in turn limits academic and economic potential, undertreatment of [otitis media] in socially disadvantaged populations can contribute to generational cycles of poverty, unemployment, and low pay,” they write.
“The biggest take home is that we are not treating children equitably when it comes to ear infections,” Dr. Qian added. “In order to give children equal access to care, we as health care providers need to find strategies to do better.”
The study was supported by the Stanford Center for Population Health Science Data Core, which is supported by a grant from the National Institutes of Health and internal funding. Dr. Qian has reported receiving grant funding from Merck.
A version of this article first appeared on Medscape.com.
Children from socially disadvantaged backgrounds are less likely to be treated for middle ear infections and are likely to experience serious complications from the condition – potentially with lifelong economic consequences – researchers have found.
Problems such as hearing loss and chronic ear infections were more common for children who lived in areas marked by difficult socioeconomic circumstances, according to the researchers, who linked the complications to a lack of adequate treatment in this population.
“We are treating socially disadvantaged kids differently than we are treating more advantaged kids,” said Jason Qian, MD, a resident in otolaryngology and head and neck surgery at Stanford (Calif.) University, who helped conduct the new study. “We have to think about social inequalities so we can ensure all kids are receiving the same level and type of care.”
In the United States, 80% of children will experience otitis media during their lifetime. Untreated ear infections can lead to symptoms ranging from mild discharge from the ear to life-threatening conditions like mastoiditis and intracranial abscesses.
For the new study, published online in JAMA Otolaryngology–Head & Neck Surgery, Dr. Qian and colleagues looked at 4.8 million children with private health insurance across the United States using a database with information on inpatient and outpatient visits and medication use. The researchers identified patients between January 2003 and March 2021 who received treatment for recurrent and suppurative otitis media, those who received tympanostomy tubes, and children who experienced severe complications from undertreated ear infections.
Social disadvantage was assessed using the Social Deprivation Index (SDI), a tool used to measure indicators of poverty throughout the United States based on seven demographic factors including level of educational attainment, the number of single-parent households, the share of people living in overcrowded homes, and other factors.
Every point increase in the SDI score was associated with a 14% lower likelihood of being treated for recurrent ear infections despite having them and a 28% greater chance of being hospitalized for severe ear infections, according to the researchers.
Previous research established that children with government health insurance or no coverage have more difficulty receiving proper treatment for ear infections. Although people with commercial insurance are generally wealthier than those without private coverage, Dr. Qian said, the new data indicate that significant social disparities in care exist even within this group.
Although some studies have found that wealthier children are more likely to develop otitis media, Dr. Qian’s group said that association likely reflects the better access to health care money affords.
“We found that socially disadvantaged children not only have a higher burden of otitis media but are also undertreated both medically and surgically for [ear infections]. Because chronic and complicated forms of otitis media can cause childhood hearing loss, which in turn limits academic and economic potential, undertreatment of [otitis media] in socially disadvantaged populations can contribute to generational cycles of poverty, unemployment, and low pay,” they write.
“The biggest take home is that we are not treating children equitably when it comes to ear infections,” Dr. Qian added. “In order to give children equal access to care, we as health care providers need to find strategies to do better.”
The study was supported by the Stanford Center for Population Health Science Data Core, which is supported by a grant from the National Institutes of Health and internal funding. Dr. Qian has reported receiving grant funding from Merck.
A version of this article first appeared on Medscape.com.
Monkeypox in children appears rare and relatively mild
Monkeypox virus infections in children and adolescents in the United States are rare, and young patients with known infections have all recovered, according to a study from the Centers for Disease Control and Prevention.
In addition, evidence suggests that secondary transmission in schools or childcare facilities may be unlikely.
The study was the first comprehensive study on the impact of monkeypox on children during the 2022 outbreak, according to a statement emailed to this news organization from the California Department of Public Health, one of the state health departments that partnered with the CDC to share information.
News of low infection rates and relatively mild disease was welcome to clinicians, who had braced for severe findings on the basis of sparse prior data, according to Peter Chin-Hong, MD, a professor of medicine and an infectious diseases physician at the University of California, San Francisco.
“We were on heightened alert that kids may do poorly,” said Dr. Chin-Hong, who was not involved in the study but who cared for monkeypox patients during the outbreak. “I think this study is reassuring.
“The other silver lining about it is that most of the kids got infected in the household setting from ways that you would expect them to get [infected],” Dr. Chin-Hong said in an interview.
However, Black and Hispanic children were more likely to contract the disease, underscoring troubling inequities.
“Early on, individuals of color were much less likely to be able to successfully access vaccination,” said first author Ian Hennessee, PhD, MPH, an epidemic intelligence service officer with the CDC and a member of the Special Case Investigation Unit of the Multinational Monkeypox Response Team at the CDC. “We think those kinds of structural inequities really trickled down towards the children and adolescents that have been affected by this outbreak.”
The study was published in Morbidity and Mortality Weekly Report.
A nationwide look at the data
The researchers discussed 83 children and adolescents with monkeypox who came to the CDC’s attention between May 17 and Sept. 24, 2022.
The 83 cases represent 0.3% of the 25,038 reported monkeypox cases in the United States over that period. Of the 28 children aged 12 years or younger, 18 (64%) were boys. Sixteen children were younger than 4 years.
Exposure data were available for 20 (71%) of those aged 0-12. In that group, 19 were exposed at home; 17 cases were due to routine skin-to-skin contact with a household caregiver; and one case was suspected to be caused by fomites (such as a shared towel). Exposure information was unavailable for the remaining case.
Most of the children experienced lesions on the trunk. No lesions were anogenital. Two patients in the youngest age group were hospitalized because of widespread rash that involved the eyelids, and a patient in the 5- to 12-year-old group was hospitalized because of periorbital cellulitis and conjunctivitis.
Among those aged 13-17, there were 55 cases. Of these patients, 89% were boys. Exposure data were available for 35 (64%). In 32 of these patients, the infection occurred from presumed sexual contact. Twenty-three of those adolescents reported male-to-male sexual contact. No case was found to be connected with sexual abuse.
Lesions in the adolescents were mostly truncal or anogenital. Six in this group were hospitalized, and all of them recovered. One adolescent was found to be HIV positive.
Black and Hispanic children accounted for 47% and 35% of all cases, respectively.
Eleven percent of all the children and adolescents were hospitalized, and none received intensive care.
Treatments, when given, included the antiviral drug tecovirimat, intravenous vaccinia immune globulin, and topical trifluridine. There were no deaths.
Ten symptomatic patients attended school or daycare. Among these patients, no secondary transmissions were found to have occurred. Some contacts were offered the JYNNEOS monkeypox vaccine as postexposure prophylaxis.
Limitations of the study included potentially overlooked cases. Data were collected through routine surveillance, children frequently experience rashes, and access to testing has been a challenge, Dr. Hennessee explained.
In addition, data on exposure characteristics were missing for some children.
Inequities and the risks of being judged
The outbreak in the United States has eased in recent months. However, though uncommon in children, monkeypox has affected some racial groups disproportionately.
“Especially in the later course of the outbreak, the majority of cases were among Black and Hispanic individuals,” said co-author Rachel E. Harold, MD, an infectious diseases specialist and supervisory medical officer with the District of Columbia Department of Health’s HIV/AIDS, Hepatitis, STDs, and TB Administration.
“Unfortunately, the pediatric cases do reflect the outbreak overall,” she told this news organization.
Dr. Harold noted there have been efforts in D.C. and other jurisdictions, as well as by the White House monkeypox response team, to reach populations at greatest risk and that they were “really trying to make vaccine available to people of color.”
Vaccination clinics often popped up in unexpected locations at short notice, and that made it hard for some people to get to them, Dr. Chin-Hong pointed out.
Another factor was “the public aspect of accessing diagnostics and vaccines and the way that that’s linked to potential judgment or sexual risk,” he added.
“Not everybody’s out,” Dr. Chin-Hong said, referring to members of the LGBTQ community. “In many communities of color, going to get a test or going to get a vaccine essentially means that you’re out.”
For clinicians who suspect monkeypox in a child, Dr. Harold suggests keeping a broad differential diagnosis, looking for an epidemiologic link, and contacting the CDC for assistance. Infected children should be encouraged to avoid touching their own eyes or mucous membranes, she added.
In addition, she said, tecovirimat is a reasonable treatment and is well tolerated by pediatric monkeypox patients with eczema, an underlying condition that could lead to severe disease.
For infected caregivers, Dr. Hennessee said, measures to prevent infecting children at home include isolation, contact precautions, and in some cases, postexposure prophylaxis via vaccination.
For sexually active adolescents, he advised that clinicians offer vaccination, education on sexual health, and testing for HIV and other sexually transmitted infections.
“It’s important to remember that adolescents may be sexually active, and clinicians should do a thorough and nonjudgmental sexual history,” Dr. Harold added. “That is always true, but especially if there is concern for [monkeypox].”
Dr. Hennessee, Dr. Chin-Hong, and Dr. Harold have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Monkeypox virus infections in children and adolescents in the United States are rare, and young patients with known infections have all recovered, according to a study from the Centers for Disease Control and Prevention.
In addition, evidence suggests that secondary transmission in schools or childcare facilities may be unlikely.
The study was the first comprehensive study on the impact of monkeypox on children during the 2022 outbreak, according to a statement emailed to this news organization from the California Department of Public Health, one of the state health departments that partnered with the CDC to share information.
News of low infection rates and relatively mild disease was welcome to clinicians, who had braced for severe findings on the basis of sparse prior data, according to Peter Chin-Hong, MD, a professor of medicine and an infectious diseases physician at the University of California, San Francisco.
“We were on heightened alert that kids may do poorly,” said Dr. Chin-Hong, who was not involved in the study but who cared for monkeypox patients during the outbreak. “I think this study is reassuring.
“The other silver lining about it is that most of the kids got infected in the household setting from ways that you would expect them to get [infected],” Dr. Chin-Hong said in an interview.
However, Black and Hispanic children were more likely to contract the disease, underscoring troubling inequities.
“Early on, individuals of color were much less likely to be able to successfully access vaccination,” said first author Ian Hennessee, PhD, MPH, an epidemic intelligence service officer with the CDC and a member of the Special Case Investigation Unit of the Multinational Monkeypox Response Team at the CDC. “We think those kinds of structural inequities really trickled down towards the children and adolescents that have been affected by this outbreak.”
The study was published in Morbidity and Mortality Weekly Report.
A nationwide look at the data
The researchers discussed 83 children and adolescents with monkeypox who came to the CDC’s attention between May 17 and Sept. 24, 2022.
The 83 cases represent 0.3% of the 25,038 reported monkeypox cases in the United States over that period. Of the 28 children aged 12 years or younger, 18 (64%) were boys. Sixteen children were younger than 4 years.
Exposure data were available for 20 (71%) of those aged 0-12. In that group, 19 were exposed at home; 17 cases were due to routine skin-to-skin contact with a household caregiver; and one case was suspected to be caused by fomites (such as a shared towel). Exposure information was unavailable for the remaining case.
Most of the children experienced lesions on the trunk. No lesions were anogenital. Two patients in the youngest age group were hospitalized because of widespread rash that involved the eyelids, and a patient in the 5- to 12-year-old group was hospitalized because of periorbital cellulitis and conjunctivitis.
Among those aged 13-17, there were 55 cases. Of these patients, 89% were boys. Exposure data were available for 35 (64%). In 32 of these patients, the infection occurred from presumed sexual contact. Twenty-three of those adolescents reported male-to-male sexual contact. No case was found to be connected with sexual abuse.
Lesions in the adolescents were mostly truncal or anogenital. Six in this group were hospitalized, and all of them recovered. One adolescent was found to be HIV positive.
Black and Hispanic children accounted for 47% and 35% of all cases, respectively.
Eleven percent of all the children and adolescents were hospitalized, and none received intensive care.
Treatments, when given, included the antiviral drug tecovirimat, intravenous vaccinia immune globulin, and topical trifluridine. There were no deaths.
Ten symptomatic patients attended school or daycare. Among these patients, no secondary transmissions were found to have occurred. Some contacts were offered the JYNNEOS monkeypox vaccine as postexposure prophylaxis.
Limitations of the study included potentially overlooked cases. Data were collected through routine surveillance, children frequently experience rashes, and access to testing has been a challenge, Dr. Hennessee explained.
In addition, data on exposure characteristics were missing for some children.
Inequities and the risks of being judged
The outbreak in the United States has eased in recent months. However, though uncommon in children, monkeypox has affected some racial groups disproportionately.
“Especially in the later course of the outbreak, the majority of cases were among Black and Hispanic individuals,” said co-author Rachel E. Harold, MD, an infectious diseases specialist and supervisory medical officer with the District of Columbia Department of Health’s HIV/AIDS, Hepatitis, STDs, and TB Administration.
“Unfortunately, the pediatric cases do reflect the outbreak overall,” she told this news organization.
Dr. Harold noted there have been efforts in D.C. and other jurisdictions, as well as by the White House monkeypox response team, to reach populations at greatest risk and that they were “really trying to make vaccine available to people of color.”
Vaccination clinics often popped up in unexpected locations at short notice, and that made it hard for some people to get to them, Dr. Chin-Hong pointed out.
Another factor was “the public aspect of accessing diagnostics and vaccines and the way that that’s linked to potential judgment or sexual risk,” he added.
“Not everybody’s out,” Dr. Chin-Hong said, referring to members of the LGBTQ community. “In many communities of color, going to get a test or going to get a vaccine essentially means that you’re out.”
For clinicians who suspect monkeypox in a child, Dr. Harold suggests keeping a broad differential diagnosis, looking for an epidemiologic link, and contacting the CDC for assistance. Infected children should be encouraged to avoid touching their own eyes or mucous membranes, she added.
In addition, she said, tecovirimat is a reasonable treatment and is well tolerated by pediatric monkeypox patients with eczema, an underlying condition that could lead to severe disease.
For infected caregivers, Dr. Hennessee said, measures to prevent infecting children at home include isolation, contact precautions, and in some cases, postexposure prophylaxis via vaccination.
For sexually active adolescents, he advised that clinicians offer vaccination, education on sexual health, and testing for HIV and other sexually transmitted infections.
“It’s important to remember that adolescents may be sexually active, and clinicians should do a thorough and nonjudgmental sexual history,” Dr. Harold added. “That is always true, but especially if there is concern for [monkeypox].”
Dr. Hennessee, Dr. Chin-Hong, and Dr. Harold have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Monkeypox virus infections in children and adolescents in the United States are rare, and young patients with known infections have all recovered, according to a study from the Centers for Disease Control and Prevention.
In addition, evidence suggests that secondary transmission in schools or childcare facilities may be unlikely.
The study was the first comprehensive study on the impact of monkeypox on children during the 2022 outbreak, according to a statement emailed to this news organization from the California Department of Public Health, one of the state health departments that partnered with the CDC to share information.
News of low infection rates and relatively mild disease was welcome to clinicians, who had braced for severe findings on the basis of sparse prior data, according to Peter Chin-Hong, MD, a professor of medicine and an infectious diseases physician at the University of California, San Francisco.
“We were on heightened alert that kids may do poorly,” said Dr. Chin-Hong, who was not involved in the study but who cared for monkeypox patients during the outbreak. “I think this study is reassuring.
“The other silver lining about it is that most of the kids got infected in the household setting from ways that you would expect them to get [infected],” Dr. Chin-Hong said in an interview.
However, Black and Hispanic children were more likely to contract the disease, underscoring troubling inequities.
“Early on, individuals of color were much less likely to be able to successfully access vaccination,” said first author Ian Hennessee, PhD, MPH, an epidemic intelligence service officer with the CDC and a member of the Special Case Investigation Unit of the Multinational Monkeypox Response Team at the CDC. “We think those kinds of structural inequities really trickled down towards the children and adolescents that have been affected by this outbreak.”
The study was published in Morbidity and Mortality Weekly Report.
A nationwide look at the data
The researchers discussed 83 children and adolescents with monkeypox who came to the CDC’s attention between May 17 and Sept. 24, 2022.
The 83 cases represent 0.3% of the 25,038 reported monkeypox cases in the United States over that period. Of the 28 children aged 12 years or younger, 18 (64%) were boys. Sixteen children were younger than 4 years.
Exposure data were available for 20 (71%) of those aged 0-12. In that group, 19 were exposed at home; 17 cases were due to routine skin-to-skin contact with a household caregiver; and one case was suspected to be caused by fomites (such as a shared towel). Exposure information was unavailable for the remaining case.
Most of the children experienced lesions on the trunk. No lesions were anogenital. Two patients in the youngest age group were hospitalized because of widespread rash that involved the eyelids, and a patient in the 5- to 12-year-old group was hospitalized because of periorbital cellulitis and conjunctivitis.
Among those aged 13-17, there were 55 cases. Of these patients, 89% were boys. Exposure data were available for 35 (64%). In 32 of these patients, the infection occurred from presumed sexual contact. Twenty-three of those adolescents reported male-to-male sexual contact. No case was found to be connected with sexual abuse.
Lesions in the adolescents were mostly truncal or anogenital. Six in this group were hospitalized, and all of them recovered. One adolescent was found to be HIV positive.
Black and Hispanic children accounted for 47% and 35% of all cases, respectively.
Eleven percent of all the children and adolescents were hospitalized, and none received intensive care.
Treatments, when given, included the antiviral drug tecovirimat, intravenous vaccinia immune globulin, and topical trifluridine. There were no deaths.
Ten symptomatic patients attended school or daycare. Among these patients, no secondary transmissions were found to have occurred. Some contacts were offered the JYNNEOS monkeypox vaccine as postexposure prophylaxis.
Limitations of the study included potentially overlooked cases. Data were collected through routine surveillance, children frequently experience rashes, and access to testing has been a challenge, Dr. Hennessee explained.
In addition, data on exposure characteristics were missing for some children.
Inequities and the risks of being judged
The outbreak in the United States has eased in recent months. However, though uncommon in children, monkeypox has affected some racial groups disproportionately.
“Especially in the later course of the outbreak, the majority of cases were among Black and Hispanic individuals,” said co-author Rachel E. Harold, MD, an infectious diseases specialist and supervisory medical officer with the District of Columbia Department of Health’s HIV/AIDS, Hepatitis, STDs, and TB Administration.
“Unfortunately, the pediatric cases do reflect the outbreak overall,” she told this news organization.
Dr. Harold noted there have been efforts in D.C. and other jurisdictions, as well as by the White House monkeypox response team, to reach populations at greatest risk and that they were “really trying to make vaccine available to people of color.”
Vaccination clinics often popped up in unexpected locations at short notice, and that made it hard for some people to get to them, Dr. Chin-Hong pointed out.
Another factor was “the public aspect of accessing diagnostics and vaccines and the way that that’s linked to potential judgment or sexual risk,” he added.
“Not everybody’s out,” Dr. Chin-Hong said, referring to members of the LGBTQ community. “In many communities of color, going to get a test or going to get a vaccine essentially means that you’re out.”
For clinicians who suspect monkeypox in a child, Dr. Harold suggests keeping a broad differential diagnosis, looking for an epidemiologic link, and contacting the CDC for assistance. Infected children should be encouraged to avoid touching their own eyes or mucous membranes, she added.
In addition, she said, tecovirimat is a reasonable treatment and is well tolerated by pediatric monkeypox patients with eczema, an underlying condition that could lead to severe disease.
For infected caregivers, Dr. Hennessee said, measures to prevent infecting children at home include isolation, contact precautions, and in some cases, postexposure prophylaxis via vaccination.
For sexually active adolescents, he advised that clinicians offer vaccination, education on sexual health, and testing for HIV and other sexually transmitted infections.
“It’s important to remember that adolescents may be sexually active, and clinicians should do a thorough and nonjudgmental sexual history,” Dr. Harold added. “That is always true, but especially if there is concern for [monkeypox].”
Dr. Hennessee, Dr. Chin-Hong, and Dr. Harold have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Yellow Papules and Plaques on a Child
The Diagnosis: Tuberous Xanthoma
The skin biopsy revealed a nodular collection of foam cells (quiz image [bottom]). Tuberous xanthoma was the most likely diagnosis based on the patient’s history as well as the clinical and histologic findings. Tuberous xanthomas are flat or elevated nodules in the dermis and subcutaneous tissue, commonly occurring on the skin over the joints.1 Smaller nodules and papules often are referred to as tuberoeruptive xanthomas and exist on a continuum with the larger tuberous xanthomas. All xanthomas appear histologically similar, with collections of foam cells present within the dermis.2 Foam cells form when serum lipoproteins diffuse through capillary walls, deposit in the skin or tendons, and are scavenged by monocytes.3 Tuberous xanthomas, along with tendinous, eruptive, and planar xanthomas, are the most likely to be associated with hyperlipidemia.4 They may indicate an underlying disorder of lipid metabolism, such as familial hypercholesterolemia.1,3 This is the most common cause of inheritable cardiovascular disease, with a prevalence of approximately 1:250.2 Premature cardiovascular disease risk increases 2 to 4 times in patients with familial hypercholesterolemia and tendinous xanthomas,1 illustrating that recognition of cutaneous lesions can lead to earlier diagnosis and prevention of patient morbidity and mortality.
Juvenile xanthogranuloma typically presents as smooth yellow papules or nodules on the head and neck, with a characteristic “setting-sun” appearance (ie, yellow center with an erythematous halo) on dermoscopy.5 Histologically, juvenile xanthogranulomas are composed of foam cells and a mixed lymphohistiocytic infiltrate with eosinophils within the dermis. Giant cells with a ring of nuclei surrounded by cytoplasm containing lipid vacuoles (called Touton giant cells) are characteristic (Figure 1). In contrast to tuberous xanthomas, juvenile xanthogranulomas often present within the first year of life.6
Keloid scars are more prevalent in patients with skin of color. They are characterized by eosinophilic keloidal collagen with a whorled proliferation of fibroblasts on histology (Figure 2).7 They occur spontaneously or at sites of injury and present as bluish-red or flesh-colored firm papules or nodules.8 In our patient, keloid scars were an unlikely diagnosis due to the lack of trauma and the absence of keloidal collagen on histology.
Necrobiosis lipoidica diabeticorum typically presents as an erythematous, yellow-brown, circular plaque on the anterior lower leg in patients with diabetes mellitus; it rarely occurs in children.9 Microscopy shows palisaded granulomas surrounding necrobiotic collagen arranged horizontally in a layer cake–like fashion (Figure 3).9,10 The etiology of necrobiosis lipoidica diabeticorum currently is unknown, though immune complex deposition may contribute to its pathology. It has been associated with type 1 diabetes mellitus, though severity of the lesions is not associated with extent of glycemic control.10
Rosai-Dorfman disease is an uncommon disorder characterized by a proliferation of histiocytes that most often presents as bilateral cervical lymphadenopathy in children and young adults but rarely can present with cutaneous lesions when extranodal involvement is present.11,12 The cutaneous form most commonly presents as red papules or nodules. On histology, the lesions exhibit a nodular dermal proliferation of histiocytes and smaller lymphocytoid cells with a marbled or starry sky–like appearance on low power (Figure 4). On higher magnification, the characteristic finding of emperipolesis can be seen.11 On immunohistochemistry, the histiocytes stain positively for CD68 and S-100. Although the pathogenesis currently is unknown, evidence of clonality indicates the disease may be related to a neoplastic process.12
- Zak A, Zeman M, Slaby A, et al. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014;158:181-188. doi:10.5507/bp.2014.016
- Ison HE, Clarke SL, Knowles JW. Familial hypercholesterolemia. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews. University of Washington, Seattle; 1993-2022. https://www.ncbi.nlm.nih.gov/books/NBK174884/
- Sathiyakumar V, Jones SR, Martin SS. Xanthomas and lipoprotein disorders. In: Kang S, Amagai M, Bruckner AL, et al, eds. Fitzpatrick’s Dermatology. 9th ed. McGraw Hill; 2019.
- Massangale WT. Xanthomas. In: Bolognia JL, Schaffer JV, Cerroni L, et al, eds. Dermatology. Elsevier; 2018:1634-1643.
- Collie JS, Harper CD, Fillman EP. Juvenile xanthogranuloma. StatPearls. StatPearls Publishing; 2021. https://www.ncbi.nlm.nih.gov/books/NBK526103/
- Hernández-San Martín MJ, Vargas-Mora P, Aranibar L. Juvenile xanthogranuloma: an entity with a wide clinical spectrum. Actas Dermosifiliogr (Engl Ed). 2020;111:725-733. doi:10.1016/j.ad.2020.07.004
- Lee JY, Yang C, Chao S, et al. Histopathological differential diagnosis of keloid and hypertrophic scar. Am J Dermatopathology. 2004;26:379-384.
- Wolff K, Johnson R, Saavedra AP, et al. Benign neoplasms and hyperplasias. In: Wolff K, Johnson R, Saavedra AP, et al, eds. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 8th ed. McGraw Hill; 2017:141-188.
- Bonura C, Frontino G, Rigamonti A, et al. Necrobiosis lipoidica diabeticorum: a pediatric case report. Dermatoendocrinol. 2014;6:E27790. doi:10.4161/derm.27790
- Lepe K, Riley CA, Salazar FJ. Necrobiosis lipoidica. StatPearls. StatPearls Publishing; 2021. https://www-ncbi-nlm-nih-gov.proxy.kumc.edu/books/NBK459318/
- Parrent T, Clark T, Hall D. Cutaneous Rosai-Dorfman disease. Cutis. 2012;90:237-238.
- Bruce-Brand C, Schneider JW, Schubert P. Rosai-Dorfman disease: an overview. J Clin Pathol. 2020;73:697-705. doi:10.1136/jclinpath-2020-206733
The Diagnosis: Tuberous Xanthoma
The skin biopsy revealed a nodular collection of foam cells (quiz image [bottom]). Tuberous xanthoma was the most likely diagnosis based on the patient’s history as well as the clinical and histologic findings. Tuberous xanthomas are flat or elevated nodules in the dermis and subcutaneous tissue, commonly occurring on the skin over the joints.1 Smaller nodules and papules often are referred to as tuberoeruptive xanthomas and exist on a continuum with the larger tuberous xanthomas. All xanthomas appear histologically similar, with collections of foam cells present within the dermis.2 Foam cells form when serum lipoproteins diffuse through capillary walls, deposit in the skin or tendons, and are scavenged by monocytes.3 Tuberous xanthomas, along with tendinous, eruptive, and planar xanthomas, are the most likely to be associated with hyperlipidemia.4 They may indicate an underlying disorder of lipid metabolism, such as familial hypercholesterolemia.1,3 This is the most common cause of inheritable cardiovascular disease, with a prevalence of approximately 1:250.2 Premature cardiovascular disease risk increases 2 to 4 times in patients with familial hypercholesterolemia and tendinous xanthomas,1 illustrating that recognition of cutaneous lesions can lead to earlier diagnosis and prevention of patient morbidity and mortality.
Juvenile xanthogranuloma typically presents as smooth yellow papules or nodules on the head and neck, with a characteristic “setting-sun” appearance (ie, yellow center with an erythematous halo) on dermoscopy.5 Histologically, juvenile xanthogranulomas are composed of foam cells and a mixed lymphohistiocytic infiltrate with eosinophils within the dermis. Giant cells with a ring of nuclei surrounded by cytoplasm containing lipid vacuoles (called Touton giant cells) are characteristic (Figure 1). In contrast to tuberous xanthomas, juvenile xanthogranulomas often present within the first year of life.6
Keloid scars are more prevalent in patients with skin of color. They are characterized by eosinophilic keloidal collagen with a whorled proliferation of fibroblasts on histology (Figure 2).7 They occur spontaneously or at sites of injury and present as bluish-red or flesh-colored firm papules or nodules.8 In our patient, keloid scars were an unlikely diagnosis due to the lack of trauma and the absence of keloidal collagen on histology.
Necrobiosis lipoidica diabeticorum typically presents as an erythematous, yellow-brown, circular plaque on the anterior lower leg in patients with diabetes mellitus; it rarely occurs in children.9 Microscopy shows palisaded granulomas surrounding necrobiotic collagen arranged horizontally in a layer cake–like fashion (Figure 3).9,10 The etiology of necrobiosis lipoidica diabeticorum currently is unknown, though immune complex deposition may contribute to its pathology. It has been associated with type 1 diabetes mellitus, though severity of the lesions is not associated with extent of glycemic control.10
Rosai-Dorfman disease is an uncommon disorder characterized by a proliferation of histiocytes that most often presents as bilateral cervical lymphadenopathy in children and young adults but rarely can present with cutaneous lesions when extranodal involvement is present.11,12 The cutaneous form most commonly presents as red papules or nodules. On histology, the lesions exhibit a nodular dermal proliferation of histiocytes and smaller lymphocytoid cells with a marbled or starry sky–like appearance on low power (Figure 4). On higher magnification, the characteristic finding of emperipolesis can be seen.11 On immunohistochemistry, the histiocytes stain positively for CD68 and S-100. Although the pathogenesis currently is unknown, evidence of clonality indicates the disease may be related to a neoplastic process.12
The Diagnosis: Tuberous Xanthoma
The skin biopsy revealed a nodular collection of foam cells (quiz image [bottom]). Tuberous xanthoma was the most likely diagnosis based on the patient’s history as well as the clinical and histologic findings. Tuberous xanthomas are flat or elevated nodules in the dermis and subcutaneous tissue, commonly occurring on the skin over the joints.1 Smaller nodules and papules often are referred to as tuberoeruptive xanthomas and exist on a continuum with the larger tuberous xanthomas. All xanthomas appear histologically similar, with collections of foam cells present within the dermis.2 Foam cells form when serum lipoproteins diffuse through capillary walls, deposit in the skin or tendons, and are scavenged by monocytes.3 Tuberous xanthomas, along with tendinous, eruptive, and planar xanthomas, are the most likely to be associated with hyperlipidemia.4 They may indicate an underlying disorder of lipid metabolism, such as familial hypercholesterolemia.1,3 This is the most common cause of inheritable cardiovascular disease, with a prevalence of approximately 1:250.2 Premature cardiovascular disease risk increases 2 to 4 times in patients with familial hypercholesterolemia and tendinous xanthomas,1 illustrating that recognition of cutaneous lesions can lead to earlier diagnosis and prevention of patient morbidity and mortality.
Juvenile xanthogranuloma typically presents as smooth yellow papules or nodules on the head and neck, with a characteristic “setting-sun” appearance (ie, yellow center with an erythematous halo) on dermoscopy.5 Histologically, juvenile xanthogranulomas are composed of foam cells and a mixed lymphohistiocytic infiltrate with eosinophils within the dermis. Giant cells with a ring of nuclei surrounded by cytoplasm containing lipid vacuoles (called Touton giant cells) are characteristic (Figure 1). In contrast to tuberous xanthomas, juvenile xanthogranulomas often present within the first year of life.6
Keloid scars are more prevalent in patients with skin of color. They are characterized by eosinophilic keloidal collagen with a whorled proliferation of fibroblasts on histology (Figure 2).7 They occur spontaneously or at sites of injury and present as bluish-red or flesh-colored firm papules or nodules.8 In our patient, keloid scars were an unlikely diagnosis due to the lack of trauma and the absence of keloidal collagen on histology.
Necrobiosis lipoidica diabeticorum typically presents as an erythematous, yellow-brown, circular plaque on the anterior lower leg in patients with diabetes mellitus; it rarely occurs in children.9 Microscopy shows palisaded granulomas surrounding necrobiotic collagen arranged horizontally in a layer cake–like fashion (Figure 3).9,10 The etiology of necrobiosis lipoidica diabeticorum currently is unknown, though immune complex deposition may contribute to its pathology. It has been associated with type 1 diabetes mellitus, though severity of the lesions is not associated with extent of glycemic control.10
Rosai-Dorfman disease is an uncommon disorder characterized by a proliferation of histiocytes that most often presents as bilateral cervical lymphadenopathy in children and young adults but rarely can present with cutaneous lesions when extranodal involvement is present.11,12 The cutaneous form most commonly presents as red papules or nodules. On histology, the lesions exhibit a nodular dermal proliferation of histiocytes and smaller lymphocytoid cells with a marbled or starry sky–like appearance on low power (Figure 4). On higher magnification, the characteristic finding of emperipolesis can be seen.11 On immunohistochemistry, the histiocytes stain positively for CD68 and S-100. Although the pathogenesis currently is unknown, evidence of clonality indicates the disease may be related to a neoplastic process.12
- Zak A, Zeman M, Slaby A, et al. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014;158:181-188. doi:10.5507/bp.2014.016
- Ison HE, Clarke SL, Knowles JW. Familial hypercholesterolemia. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews. University of Washington, Seattle; 1993-2022. https://www.ncbi.nlm.nih.gov/books/NBK174884/
- Sathiyakumar V, Jones SR, Martin SS. Xanthomas and lipoprotein disorders. In: Kang S, Amagai M, Bruckner AL, et al, eds. Fitzpatrick’s Dermatology. 9th ed. McGraw Hill; 2019.
- Massangale WT. Xanthomas. In: Bolognia JL, Schaffer JV, Cerroni L, et al, eds. Dermatology. Elsevier; 2018:1634-1643.
- Collie JS, Harper CD, Fillman EP. Juvenile xanthogranuloma. StatPearls. StatPearls Publishing; 2021. https://www.ncbi.nlm.nih.gov/books/NBK526103/
- Hernández-San Martín MJ, Vargas-Mora P, Aranibar L. Juvenile xanthogranuloma: an entity with a wide clinical spectrum. Actas Dermosifiliogr (Engl Ed). 2020;111:725-733. doi:10.1016/j.ad.2020.07.004
- Lee JY, Yang C, Chao S, et al. Histopathological differential diagnosis of keloid and hypertrophic scar. Am J Dermatopathology. 2004;26:379-384.
- Wolff K, Johnson R, Saavedra AP, et al. Benign neoplasms and hyperplasias. In: Wolff K, Johnson R, Saavedra AP, et al, eds. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 8th ed. McGraw Hill; 2017:141-188.
- Bonura C, Frontino G, Rigamonti A, et al. Necrobiosis lipoidica diabeticorum: a pediatric case report. Dermatoendocrinol. 2014;6:E27790. doi:10.4161/derm.27790
- Lepe K, Riley CA, Salazar FJ. Necrobiosis lipoidica. StatPearls. StatPearls Publishing; 2021. https://www-ncbi-nlm-nih-gov.proxy.kumc.edu/books/NBK459318/
- Parrent T, Clark T, Hall D. Cutaneous Rosai-Dorfman disease. Cutis. 2012;90:237-238.
- Bruce-Brand C, Schneider JW, Schubert P. Rosai-Dorfman disease: an overview. J Clin Pathol. 2020;73:697-705. doi:10.1136/jclinpath-2020-206733
- Zak A, Zeman M, Slaby A, et al. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014;158:181-188. doi:10.5507/bp.2014.016
- Ison HE, Clarke SL, Knowles JW. Familial hypercholesterolemia. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews. University of Washington, Seattle; 1993-2022. https://www.ncbi.nlm.nih.gov/books/NBK174884/
- Sathiyakumar V, Jones SR, Martin SS. Xanthomas and lipoprotein disorders. In: Kang S, Amagai M, Bruckner AL, et al, eds. Fitzpatrick’s Dermatology. 9th ed. McGraw Hill; 2019.
- Massangale WT. Xanthomas. In: Bolognia JL, Schaffer JV, Cerroni L, et al, eds. Dermatology. Elsevier; 2018:1634-1643.
- Collie JS, Harper CD, Fillman EP. Juvenile xanthogranuloma. StatPearls. StatPearls Publishing; 2021. https://www.ncbi.nlm.nih.gov/books/NBK526103/
- Hernández-San Martín MJ, Vargas-Mora P, Aranibar L. Juvenile xanthogranuloma: an entity with a wide clinical spectrum. Actas Dermosifiliogr (Engl Ed). 2020;111:725-733. doi:10.1016/j.ad.2020.07.004
- Lee JY, Yang C, Chao S, et al. Histopathological differential diagnosis of keloid and hypertrophic scar. Am J Dermatopathology. 2004;26:379-384.
- Wolff K, Johnson R, Saavedra AP, et al. Benign neoplasms and hyperplasias. In: Wolff K, Johnson R, Saavedra AP, et al, eds. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 8th ed. McGraw Hill; 2017:141-188.
- Bonura C, Frontino G, Rigamonti A, et al. Necrobiosis lipoidica diabeticorum: a pediatric case report. Dermatoendocrinol. 2014;6:E27790. doi:10.4161/derm.27790
- Lepe K, Riley CA, Salazar FJ. Necrobiosis lipoidica. StatPearls. StatPearls Publishing; 2021. https://www-ncbi-nlm-nih-gov.proxy.kumc.edu/books/NBK459318/
- Parrent T, Clark T, Hall D. Cutaneous Rosai-Dorfman disease. Cutis. 2012;90:237-238.
- Bruce-Brand C, Schneider JW, Schubert P. Rosai-Dorfman disease: an overview. J Clin Pathol. 2020;73:697-705. doi:10.1136/jclinpath-2020-206733
A 3-year-old girl presented with raised, firm, enlarging, asymptomatic, well-defined, subcutaneous papules, plaques, and nodules on the hands, knees, and posterior ankles of 1 year’s duration. The patient’s mother stated that the lesions began on the ankles (top), and she initially believed them to be due to friction from the child’s shoes until the more recent involvement of the knees and hands. The patient’s father, paternal grandfather, and paternal great-grandfather had a history of elevated cholesterol levels. A shave biopsy was performed (bottom).
An adolescent male presents with an eroded bump on the temple
The correct answer is (D), molluscum contagiosum. Upon surgical excision, the pathology indicated the lesion was consistent with molluscum contagiosum.
Molluscum contagiosum is a benign skin disorder caused by a pox virus and is frequently seen in children. This disease is transmitted primarily through direct skin contact with an infected individual.1 Contaminated fomites have been suggested as another source of infection.2 The typical lesion appears dome-shaped, round, and pinkish-purple in color.1 The incubation period ranges from 2 weeks to 6 months and is typically self-limited in immunocompetent hosts; however, in immunocompromised persons, molluscum contagiosum lesions may present atypically such that they are larger in size and/or resemble malignancies, such as basal cell carcinoma or keratoacanthoma (for single lesions), or other infectious diseases, such as cryptococcosis and histoplasmosis (for more numerous lesions).3,4 A giant atypical molluscum contagiosum is rarely seen in healthy individuals.
What’s on the differential?
The recent episode of bleeding raises concern for other neoplastic processes of the skin including squamous cell carcinoma or basal cell carcinoma as well as cutaneous metastatic rhabdoid tumor, given the patient’s history.
Eruptive keratoacanthomas are also reported in patients taking nivolumab, an anti-PD-1 immunotherapy, which the patient has received for treatment of his recurrent metastatic rhabdoid tumor.5 More common entities such as a pyogenic granuloma or verruca are also included on the differential. The initial presentation of the lesion, however, is more consistent with the pearly umbilicated papules associated with molluscum contagiosum.
Comments from Dr. Eichenfield
This is a very hard diagnosis to make with the clinical findings and history.
Molluscum contagiosum infections are common, but with this patient’s medical history, biopsy and excision with pathologic examination was an appropriate approach to make a certain diagnosis.
Ms. Moyal is a research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego.
References
1. Brown J et al. Int J Dermatol. 2006 Feb;45(2):93-9.
2. Hanson D and Diven DG. Dermatol Online J. 2003 Mar;9(2).
3. Badri T and Gandhi GR. Molluscum contagiosum. 2022. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing.
4. Schwartz JJ and Myskowski PL. J Am Acad Dermatol. 1992 Oct 1;27(4):583-8.
5. Antonov NK et al. JAAD Case Rep. 2019 Apr 5;5(4):342-5.
The correct answer is (D), molluscum contagiosum. Upon surgical excision, the pathology indicated the lesion was consistent with molluscum contagiosum.
Molluscum contagiosum is a benign skin disorder caused by a pox virus and is frequently seen in children. This disease is transmitted primarily through direct skin contact with an infected individual.1 Contaminated fomites have been suggested as another source of infection.2 The typical lesion appears dome-shaped, round, and pinkish-purple in color.1 The incubation period ranges from 2 weeks to 6 months and is typically self-limited in immunocompetent hosts; however, in immunocompromised persons, molluscum contagiosum lesions may present atypically such that they are larger in size and/or resemble malignancies, such as basal cell carcinoma or keratoacanthoma (for single lesions), or other infectious diseases, such as cryptococcosis and histoplasmosis (for more numerous lesions).3,4 A giant atypical molluscum contagiosum is rarely seen in healthy individuals.
What’s on the differential?
The recent episode of bleeding raises concern for other neoplastic processes of the skin including squamous cell carcinoma or basal cell carcinoma as well as cutaneous metastatic rhabdoid tumor, given the patient’s history.
Eruptive keratoacanthomas are also reported in patients taking nivolumab, an anti-PD-1 immunotherapy, which the patient has received for treatment of his recurrent metastatic rhabdoid tumor.5 More common entities such as a pyogenic granuloma or verruca are also included on the differential. The initial presentation of the lesion, however, is more consistent with the pearly umbilicated papules associated with molluscum contagiosum.
Comments from Dr. Eichenfield
This is a very hard diagnosis to make with the clinical findings and history.
Molluscum contagiosum infections are common, but with this patient’s medical history, biopsy and excision with pathologic examination was an appropriate approach to make a certain diagnosis.
Ms. Moyal is a research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego.
References
1. Brown J et al. Int J Dermatol. 2006 Feb;45(2):93-9.
2. Hanson D and Diven DG. Dermatol Online J. 2003 Mar;9(2).
3. Badri T and Gandhi GR. Molluscum contagiosum. 2022. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing.
4. Schwartz JJ and Myskowski PL. J Am Acad Dermatol. 1992 Oct 1;27(4):583-8.
5. Antonov NK et al. JAAD Case Rep. 2019 Apr 5;5(4):342-5.
The correct answer is (D), molluscum contagiosum. Upon surgical excision, the pathology indicated the lesion was consistent with molluscum contagiosum.
Molluscum contagiosum is a benign skin disorder caused by a pox virus and is frequently seen in children. This disease is transmitted primarily through direct skin contact with an infected individual.1 Contaminated fomites have been suggested as another source of infection.2 The typical lesion appears dome-shaped, round, and pinkish-purple in color.1 The incubation period ranges from 2 weeks to 6 months and is typically self-limited in immunocompetent hosts; however, in immunocompromised persons, molluscum contagiosum lesions may present atypically such that they are larger in size and/or resemble malignancies, such as basal cell carcinoma or keratoacanthoma (for single lesions), or other infectious diseases, such as cryptococcosis and histoplasmosis (for more numerous lesions).3,4 A giant atypical molluscum contagiosum is rarely seen in healthy individuals.
What’s on the differential?
The recent episode of bleeding raises concern for other neoplastic processes of the skin including squamous cell carcinoma or basal cell carcinoma as well as cutaneous metastatic rhabdoid tumor, given the patient’s history.
Eruptive keratoacanthomas are also reported in patients taking nivolumab, an anti-PD-1 immunotherapy, which the patient has received for treatment of his recurrent metastatic rhabdoid tumor.5 More common entities such as a pyogenic granuloma or verruca are also included on the differential. The initial presentation of the lesion, however, is more consistent with the pearly umbilicated papules associated with molluscum contagiosum.
Comments from Dr. Eichenfield
This is a very hard diagnosis to make with the clinical findings and history.
Molluscum contagiosum infections are common, but with this patient’s medical history, biopsy and excision with pathologic examination was an appropriate approach to make a certain diagnosis.
Ms. Moyal is a research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego.
References
1. Brown J et al. Int J Dermatol. 2006 Feb;45(2):93-9.
2. Hanson D and Diven DG. Dermatol Online J. 2003 Mar;9(2).
3. Badri T and Gandhi GR. Molluscum contagiosum. 2022. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing.
4. Schwartz JJ and Myskowski PL. J Am Acad Dermatol. 1992 Oct 1;27(4):583-8.
5. Antonov NK et al. JAAD Case Rep. 2019 Apr 5;5(4):342-5.