Pediatrics

The homicide rate among children in the United States rose by more than 4% per year since 2013 but jumped nearly 28% from 2019 to 2020, new data show.

Although long-term trends varied by region and demographics, with some groups and areas seeing declines in killings, the increases were the highest among Black children and boys aged 11-17, according to the researchers, who attribute the surge in violent deaths to a recent rise in firearm-related killings in children. Gun violence is now the leading cause of death for children in the United States, claiming what the American Academy of Pediatrics has equated to a classroomful of lives each day.

“There are troubling recent rate increases among several groups, warranting immediate attention, with some racial and ethnic disparities persisting for more than 20 years,” said Rebecca F. Wilson, PhD, of the U.S. Centers for Disease Control and Prevention, who helped conduct the study.

Dr. Wilson and her colleagues, whose findings appear in JAMA Pediatrics, examined data on 38,362 homicide victims in the United States aged 0-17 years who were killed between 1999 and 2020.

The nation’s overall homicide rate for youth fell by 5.6% per year from 2007 to 2013 before reversing course. Between 2013 and 2020, the overall rate rose 4.3% annually.

The figures show that not all children are affected equally. The rate of child homicide has fallen significantly for girls, infants, and children ages 5 years and under – whose deaths often result from caregiver neglect or violence – as well as Asian or Pacific Islanders, Whites, and those living in the Northeast.

But the child homicide rate in the South increased 6.4% per year between 2013 and 2020, while that of children in both rural America and in cities is also rising after years of decline, according to the researchers.

The suspected perpetrator was known in about 64% of child killings. Nearly 80% of those perpetrators were male.

Dr. Wilson and her colleagues also note that the COVID-19 pandemic appears to have precipitated a wave of gun-related violence among children – a link borne out by another recent paper in JAMA Pediatrics. (Recent data suggest that intentional firearm injuries are often misclassified as accidental.)

The study found that gun-related injuries in youth remained elevated through 2021, with non-Hispanic Black children and those with public insurance making up greater proportions of victims during the pandemic. The researchers identified 1,815 firearm injuries per month before the pandemic and 2,759 per month during the outbreak, a 52% increase.

Although the two studies look at different data, both show that Black children are most affected by gun violence, experts said.

“This demonstrates a critical issue for the medical, public health, and legal communities: While homicide is often presented as a criminal justice problem, it is increasingly a racial justice problem,” said Katherine E. Hoops, MD, of the Center for Gun Violence Solutions at Johns Hopkins Bloomberg School of Public Health, Baltimore.

In an editorial about the homicide study, researchers at the University of Pennsylvania, Philadelphia, called the violent deaths “preventable and unacceptable.” Eliminating such deaths “must be among our first priorities,” they wrote.

The editorial authors also noted that researchers know relatively little about nonfatal violent injuries such as those involving firearms. “These injuries are important not only because they may have life-altering consequences for children and families but also because understanding only the most severe form of any health condition (death) will hamper our ability to design and evaluate prevention strategies,” they wrote.

Dr. Wilson’s group identified different causes of youth homicide for different age groups – and the potential interventions for each differ. Although the youngest children are more likely to die from abuse or neglect, those aged 6-10 years were most likely to die by firearm, often associated with abuse that ends in suicide. Meanwhile, adolescents aged 11-17 were more subject to peer violence.

For Dr. Hoops, “each of these differences has important policy implications, including the need for policies that address structural racism, poverty, and systematic disadvantage – but also firearm safe storage to prevent youth violence and suicide [and] reduction of access to lethal means, such as through extreme risk protective orders when someone is at risk of harming themselves or others.”

Dr. Wilson agreed. “We know child homicides are preventable,” she said. “The rate decrease for some groups is encouraging, yet more can be done to protect all children.”

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

The homicide rate among children in the United States rose by more than 4% per year since 2013 but jumped nearly 28% from 2019 to 2020, new data show.

Although long-term trends varied by region and demographics, with some groups and areas seeing declines in killings, the increases were the highest among Black children and boys aged 11-17, according to the researchers, who attribute the surge in violent deaths to a recent rise in firearm-related killings in children. Gun violence is now the leading cause of death for children in the United States, claiming what the American Academy of Pediatrics has equated to a classroomful of lives each day.

“There are troubling recent rate increases among several groups, warranting immediate attention, with some racial and ethnic disparities persisting for more than 20 years,” said Rebecca F. Wilson, PhD, of the U.S. Centers for Disease Control and Prevention, who helped conduct the study.

Dr. Wilson and her colleagues, whose findings appear in JAMA Pediatrics, examined data on 38,362 homicide victims in the United States aged 0-17 years who were killed between 1999 and 2020.

The nation’s overall homicide rate for youth fell by 5.6% per year from 2007 to 2013 before reversing course. Between 2013 and 2020, the overall rate rose 4.3% annually.

The figures show that not all children are affected equally. The rate of child homicide has fallen significantly for girls, infants, and children ages 5 years and under – whose deaths often result from caregiver neglect or violence – as well as Asian or Pacific Islanders, Whites, and those living in the Northeast.

But the child homicide rate in the South increased 6.4% per year between 2013 and 2020, while that of children in both rural America and in cities is also rising after years of decline, according to the researchers.

The suspected perpetrator was known in about 64% of child killings. Nearly 80% of those perpetrators were male.

Dr. Wilson and her colleagues also note that the COVID-19 pandemic appears to have precipitated a wave of gun-related violence among children – a link borne out by another recent paper in JAMA Pediatrics. (Recent data suggest that intentional firearm injuries are often misclassified as accidental.)

The study found that gun-related injuries in youth remained elevated through 2021, with non-Hispanic Black children and those with public insurance making up greater proportions of victims during the pandemic. The researchers identified 1,815 firearm injuries per month before the pandemic and 2,759 per month during the outbreak, a 52% increase.

Although the two studies look at different data, both show that Black children are most affected by gun violence, experts said.

“This demonstrates a critical issue for the medical, public health, and legal communities: While homicide is often presented as a criminal justice problem, it is increasingly a racial justice problem,” said Katherine E. Hoops, MD, of the Center for Gun Violence Solutions at Johns Hopkins Bloomberg School of Public Health, Baltimore.

In an editorial about the homicide study, researchers at the University of Pennsylvania, Philadelphia, called the violent deaths “preventable and unacceptable.” Eliminating such deaths “must be among our first priorities,” they wrote.

The editorial authors also noted that researchers know relatively little about nonfatal violent injuries such as those involving firearms. “These injuries are important not only because they may have life-altering consequences for children and families but also because understanding only the most severe form of any health condition (death) will hamper our ability to design and evaluate prevention strategies,” they wrote.

Dr. Wilson’s group identified different causes of youth homicide for different age groups – and the potential interventions for each differ. Although the youngest children are more likely to die from abuse or neglect, those aged 6-10 years were most likely to die by firearm, often associated with abuse that ends in suicide. Meanwhile, adolescents aged 11-17 were more subject to peer violence.

For Dr. Hoops, “each of these differences has important policy implications, including the need for policies that address structural racism, poverty, and systematic disadvantage – but also firearm safe storage to prevent youth violence and suicide [and] reduction of access to lethal means, such as through extreme risk protective orders when someone is at risk of harming themselves or others.”

Dr. Wilson agreed. “We know child homicides are preventable,” she said. “The rate decrease for some groups is encouraging, yet more can be done to protect all children.”

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

The homicide rate among children in the United States rose by more than 4% per year since 2013 but jumped nearly 28% from 2019 to 2020, new data show.

Although long-term trends varied by region and demographics, with some groups and areas seeing declines in killings, the increases were the highest among Black children and boys aged 11-17, according to the researchers, who attribute the surge in violent deaths to a recent rise in firearm-related killings in children. Gun violence is now the leading cause of death for children in the United States, claiming what the American Academy of Pediatrics has equated to a classroomful of lives each day.

“There are troubling recent rate increases among several groups, warranting immediate attention, with some racial and ethnic disparities persisting for more than 20 years,” said Rebecca F. Wilson, PhD, of the U.S. Centers for Disease Control and Prevention, who helped conduct the study.

Dr. Wilson and her colleagues, whose findings appear in JAMA Pediatrics, examined data on 38,362 homicide victims in the United States aged 0-17 years who were killed between 1999 and 2020.

The nation’s overall homicide rate for youth fell by 5.6% per year from 2007 to 2013 before reversing course. Between 2013 and 2020, the overall rate rose 4.3% annually.

The figures show that not all children are affected equally. The rate of child homicide has fallen significantly for girls, infants, and children ages 5 years and under – whose deaths often result from caregiver neglect or violence – as well as Asian or Pacific Islanders, Whites, and those living in the Northeast.

But the child homicide rate in the South increased 6.4% per year between 2013 and 2020, while that of children in both rural America and in cities is also rising after years of decline, according to the researchers.

The suspected perpetrator was known in about 64% of child killings. Nearly 80% of those perpetrators were male.

Dr. Wilson and her colleagues also note that the COVID-19 pandemic appears to have precipitated a wave of gun-related violence among children – a link borne out by another recent paper in JAMA Pediatrics. (Recent data suggest that intentional firearm injuries are often misclassified as accidental.)

The study found that gun-related injuries in youth remained elevated through 2021, with non-Hispanic Black children and those with public insurance making up greater proportions of victims during the pandemic. The researchers identified 1,815 firearm injuries per month before the pandemic and 2,759 per month during the outbreak, a 52% increase.

Although the two studies look at different data, both show that Black children are most affected by gun violence, experts said.

“This demonstrates a critical issue for the medical, public health, and legal communities: While homicide is often presented as a criminal justice problem, it is increasingly a racial justice problem,” said Katherine E. Hoops, MD, of the Center for Gun Violence Solutions at Johns Hopkins Bloomberg School of Public Health, Baltimore.

In an editorial about the homicide study, researchers at the University of Pennsylvania, Philadelphia, called the violent deaths “preventable and unacceptable.” Eliminating such deaths “must be among our first priorities,” they wrote.

The editorial authors also noted that researchers know relatively little about nonfatal violent injuries such as those involving firearms. “These injuries are important not only because they may have life-altering consequences for children and families but also because understanding only the most severe form of any health condition (death) will hamper our ability to design and evaluate prevention strategies,” they wrote.

Dr. Wilson’s group identified different causes of youth homicide for different age groups – and the potential interventions for each differ. Although the youngest children are more likely to die from abuse or neglect, those aged 6-10 years were most likely to die by firearm, often associated with abuse that ends in suicide. Meanwhile, adolescents aged 11-17 were more subject to peer violence.

For Dr. Hoops, “each of these differences has important policy implications, including the need for policies that address structural racism, poverty, and systematic disadvantage – but also firearm safe storage to prevent youth violence and suicide [and] reduction of access to lethal means, such as through extreme risk protective orders when someone is at risk of harming themselves or others.”

Dr. Wilson agreed. “We know child homicides are preventable,” she said. “The rate decrease for some groups is encouraging, yet more can be done to protect all children.”

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

In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.

“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”

The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.

As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.

Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”

Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”

Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?

Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.

• The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
• The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
• The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.

What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.

“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”

That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.

And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”

The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”

Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.

The study has no external funding. The authors report no disclosures.

In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.

“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”

The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.

As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.

Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”

Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”

Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?

Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.

• The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
• The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
• The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.

What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.

“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”

That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.

And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”

The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”

Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.

The study has no external funding. The authors report no disclosures.

In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.

“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”

The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.

As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.

Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”

Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”

Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?

Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.

• The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
• The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
• The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.

What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.

“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”

That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.

And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”

The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”

Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.

The study has no external funding. The authors report no disclosures.

The Ohio measles outbreak continues to expand, with cases now totaling 81 – a 37% increase in the course of just 2 weeks.

The lead health official where the outbreak is occurring said the driving force behind the spread is vaccine hesitancy. Most of the children infected were unvaccinated but were old enough to get the measles, mumps, and rubella (MMR) shot, which is 97% effective at preventing measles.

“I think these are individuals who are making a decision not to protect their children against vaccine-preventable diseases, and some of them are making a specific decision not to use the MMR vaccine,” Columbus Public Health Commissioner Mysheika W. Roberts, MD, told JAMA.

She said that parents’ refusal to vaccinate their children was due to a misconception that the vaccine causes autism.

“We’re sounding the alarm that if your child is of age and not vaccinated, they should get vaccinated ASAP,” Dr. Roberts said, noting that she hasn’t seen that happening more.

Health officials have predicted the outbreak, which started in November, will last at least several months. Measles is so contagious that 9 out of 10 unvaccinated people in a room will become infected if exposed.

All of the infections have been in children. According to the Columbus Public Health measles dashboard, of the 81 confirmed cases:

• 29 children have been hospitalized.
• 22 cases are among children under 1 year old.
• No deaths have been reported.

Dr. Roberts said the hospitalized children have had symptoms including dehydration, diarrhea, and pneumonia. Some have had to go to the intensive care unit.

Measles infection causes a rash and a fever that can spike beyond 104° F. Sometimes, the illness can lead to brain swelling, brain damage, and even death, the CDC says.

One of the most recent cases was an infant too young to be vaccinated who lives 45 miles away from where the outbreak began, the Dayton Daily News reported. That’s the first case in Clark County in more than 20 years. At least 10% of kindergartners’ parents in the region’s elementary schools opted out of vaccines because of religious or moral objections.

“We knew this was coming. It was a matter of when, not if,” Yamini Teegala, MD, chief medical officer at Rocking Horse Community Health Center in Springfield, told the Dayton Daily News.

This is the second measles outbreak this year. Minnesota tallied 22 cases since June in an unrelated outbreak, JAMA reported.

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

The Ohio measles outbreak continues to expand, with cases now totaling 81 – a 37% increase in the course of just 2 weeks.

The lead health official where the outbreak is occurring said the driving force behind the spread is vaccine hesitancy. Most of the children infected were unvaccinated but were old enough to get the measles, mumps, and rubella (MMR) shot, which is 97% effective at preventing measles.

“I think these are individuals who are making a decision not to protect their children against vaccine-preventable diseases, and some of them are making a specific decision not to use the MMR vaccine,” Columbus Public Health Commissioner Mysheika W. Roberts, MD, told JAMA.

She said that parents’ refusal to vaccinate their children was due to a misconception that the vaccine causes autism.

“We’re sounding the alarm that if your child is of age and not vaccinated, they should get vaccinated ASAP,” Dr. Roberts said, noting that she hasn’t seen that happening more.

Health officials have predicted the outbreak, which started in November, will last at least several months. Measles is so contagious that 9 out of 10 unvaccinated people in a room will become infected if exposed.

All of the infections have been in children. According to the Columbus Public Health measles dashboard, of the 81 confirmed cases:

• 29 children have been hospitalized.
• 22 cases are among children under 1 year old.
• No deaths have been reported.

Dr. Roberts said the hospitalized children have had symptoms including dehydration, diarrhea, and pneumonia. Some have had to go to the intensive care unit.

Measles infection causes a rash and a fever that can spike beyond 104° F. Sometimes, the illness can lead to brain swelling, brain damage, and even death, the CDC says.

One of the most recent cases was an infant too young to be vaccinated who lives 45 miles away from where the outbreak began, the Dayton Daily News reported. That’s the first case in Clark County in more than 20 years. At least 10% of kindergartners’ parents in the region’s elementary schools opted out of vaccines because of religious or moral objections.

“We knew this was coming. It was a matter of when, not if,” Yamini Teegala, MD, chief medical officer at Rocking Horse Community Health Center in Springfield, told the Dayton Daily News.

This is the second measles outbreak this year. Minnesota tallied 22 cases since June in an unrelated outbreak, JAMA reported.

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

The Ohio measles outbreak continues to expand, with cases now totaling 81 – a 37% increase in the course of just 2 weeks.

The lead health official where the outbreak is occurring said the driving force behind the spread is vaccine hesitancy. Most of the children infected were unvaccinated but were old enough to get the measles, mumps, and rubella (MMR) shot, which is 97% effective at preventing measles.

“I think these are individuals who are making a decision not to protect their children against vaccine-preventable diseases, and some of them are making a specific decision not to use the MMR vaccine,” Columbus Public Health Commissioner Mysheika W. Roberts, MD, told JAMA.

She said that parents’ refusal to vaccinate their children was due to a misconception that the vaccine causes autism.

“We’re sounding the alarm that if your child is of age and not vaccinated, they should get vaccinated ASAP,” Dr. Roberts said, noting that she hasn’t seen that happening more.

Health officials have predicted the outbreak, which started in November, will last at least several months. Measles is so contagious that 9 out of 10 unvaccinated people in a room will become infected if exposed.

All of the infections have been in children. According to the Columbus Public Health measles dashboard, of the 81 confirmed cases:

• 29 children have been hospitalized.
• 22 cases are among children under 1 year old.
• No deaths have been reported.

Dr. Roberts said the hospitalized children have had symptoms including dehydration, diarrhea, and pneumonia. Some have had to go to the intensive care unit.

Measles infection causes a rash and a fever that can spike beyond 104° F. Sometimes, the illness can lead to brain swelling, brain damage, and even death, the CDC says.

One of the most recent cases was an infant too young to be vaccinated who lives 45 miles away from where the outbreak began, the Dayton Daily News reported. That’s the first case in Clark County in more than 20 years. At least 10% of kindergartners’ parents in the region’s elementary schools opted out of vaccines because of religious or moral objections.

“We knew this was coming. It was a matter of when, not if,” Yamini Teegala, MD, chief medical officer at Rocking Horse Community Health Center in Springfield, told the Dayton Daily News.

This is the second measles outbreak this year. Minnesota tallied 22 cases since June in an unrelated outbreak, JAMA reported.

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

I have assumed that being a parent has always been an anxiety-producing experience. Even back when the neonatal mortality rate was orders of magnitude greater than we are experiencing now, I suspect that each birth was still accompanied by a period of angst. However, as families no longer felt the need to produce more children to replace those lost to illness, each surviving child fell under the glare of an ever brightening spotlight.

Raising a child no longer became just something that came naturally, learned from one’s parents. Philosophers and eventually physicians felt obligated to advise parents on the best practices. My parents turned to Dr. Benjamin Spock’s classic work when they had a question, but I never got the feeling that they took his words as gospel.

By the time I started in practice the condition of being a parent was morphing into a verb. Books on “parenting” were beginning to fill the shelves of libraries and bookstores. Frustrated by what I saw as poorly conceived instruction manuals I succumbed to the temptation to spread my “better” advice for anxiety-tormented parents by writing books on how to feed picky eaters, or how to get erratic sleepers to sleep, or how to get a misbehaving child to understand the simple concept of “No!”

Back in the pre-Internet days I was competing for the attention of anxiety-driven parents not just with other self-described experts sitting at word processors, but with grandmothers, aunts, and the ladies next door. The book publishing market has cooled but the demand for advice on how to be the best parent has heated up. Into the void, enabled by the Internet, has erupted the phenomenon of social-media mom groups.

The lady next door and the mothers with strollers meeting informally at the playground are a tiny blip on the radar screen compared with the abundance of other mothers eager to listen and comment on social media–based mom groups unlimited by either geographic or temporal time restraints.

Unfortunately, as a recent article in the Wall Street Journal suggests, these support groups can often have a dark side. Researchers from Pepperdine University found in a small survey of a homogenous population of women that stress, as measured by saliva cortisol levels, increased with increasing use of “mom-centric social media” sites.

Citing anecdotal observations by mothers who did not participate in the study, the WSJ article describes episodes of shaming over topics such as steroid use in eczema and vaccine hesitancy. One mother described how she found group discussions about breastfeeding “particularly anxiety-producing.”

I have limited experience with online support groups but I have been surprised by how rude and condescending some of the contributors can be to what I could consider to be emotionally neutral subjects such as outboard motor oil pressure. I can imagine that when it comes to subjects in which there is no one best answer, the relative anonymity of the Internet provides cover for language that can be hurtful and stress inducing for someone already feeling isolated and anxious about being a parent.

Although this Pepperdine study is small, I suspect that a larger study would support the authors’ observations. For us as providers, it suggests that we need to find where parents are getting their information when we are trying to help those who seem particularly distressed. We should caution them that, while sharing information with peers can be reassuring and helpful at times, mom groups can be toxic as well. It also means that we should be careful in recommending social media sites – even those for which we have had good feedback.

And, most importantly, we must continue to work hard to make ourselves available to provide sensible and sensitive answers to those questions that are anxiety-producing for new parents.
 

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

I have assumed that being a parent has always been an anxiety-producing experience. Even back when the neonatal mortality rate was orders of magnitude greater than we are experiencing now, I suspect that each birth was still accompanied by a period of angst. However, as families no longer felt the need to produce more children to replace those lost to illness, each surviving child fell under the glare of an ever brightening spotlight.

Raising a child no longer became just something that came naturally, learned from one’s parents. Philosophers and eventually physicians felt obligated to advise parents on the best practices. My parents turned to Dr. Benjamin Spock’s classic work when they had a question, but I never got the feeling that they took his words as gospel.

By the time I started in practice the condition of being a parent was morphing into a verb. Books on “parenting” were beginning to fill the shelves of libraries and bookstores. Frustrated by what I saw as poorly conceived instruction manuals I succumbed to the temptation to spread my “better” advice for anxiety-tormented parents by writing books on how to feed picky eaters, or how to get erratic sleepers to sleep, or how to get a misbehaving child to understand the simple concept of “No!”

Back in the pre-Internet days I was competing for the attention of anxiety-driven parents not just with other self-described experts sitting at word processors, but with grandmothers, aunts, and the ladies next door. The book publishing market has cooled but the demand for advice on how to be the best parent has heated up. Into the void, enabled by the Internet, has erupted the phenomenon of social-media mom groups.

The lady next door and the mothers with strollers meeting informally at the playground are a tiny blip on the radar screen compared with the abundance of other mothers eager to listen and comment on social media–based mom groups unlimited by either geographic or temporal time restraints.

Unfortunately, as a recent article in the Wall Street Journal suggests, these support groups can often have a dark side. Researchers from Pepperdine University found in a small survey of a homogenous population of women that stress, as measured by saliva cortisol levels, increased with increasing use of “mom-centric social media” sites.

Citing anecdotal observations by mothers who did not participate in the study, the WSJ article describes episodes of shaming over topics such as steroid use in eczema and vaccine hesitancy. One mother described how she found group discussions about breastfeeding “particularly anxiety-producing.”

I have limited experience with online support groups but I have been surprised by how rude and condescending some of the contributors can be to what I could consider to be emotionally neutral subjects such as outboard motor oil pressure. I can imagine that when it comes to subjects in which there is no one best answer, the relative anonymity of the Internet provides cover for language that can be hurtful and stress inducing for someone already feeling isolated and anxious about being a parent.

Although this Pepperdine study is small, I suspect that a larger study would support the authors’ observations. For us as providers, it suggests that we need to find where parents are getting their information when we are trying to help those who seem particularly distressed. We should caution them that, while sharing information with peers can be reassuring and helpful at times, mom groups can be toxic as well. It also means that we should be careful in recommending social media sites – even those for which we have had good feedback.

And, most importantly, we must continue to work hard to make ourselves available to provide sensible and sensitive answers to those questions that are anxiety-producing for new parents.
 

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

I have assumed that being a parent has always been an anxiety-producing experience. Even back when the neonatal mortality rate was orders of magnitude greater than we are experiencing now, I suspect that each birth was still accompanied by a period of angst. However, as families no longer felt the need to produce more children to replace those lost to illness, each surviving child fell under the glare of an ever brightening spotlight.

Raising a child no longer became just something that came naturally, learned from one’s parents. Philosophers and eventually physicians felt obligated to advise parents on the best practices. My parents turned to Dr. Benjamin Spock’s classic work when they had a question, but I never got the feeling that they took his words as gospel.

By the time I started in practice the condition of being a parent was morphing into a verb. Books on “parenting” were beginning to fill the shelves of libraries and bookstores. Frustrated by what I saw as poorly conceived instruction manuals I succumbed to the temptation to spread my “better” advice for anxiety-tormented parents by writing books on how to feed picky eaters, or how to get erratic sleepers to sleep, or how to get a misbehaving child to understand the simple concept of “No!”

Back in the pre-Internet days I was competing for the attention of anxiety-driven parents not just with other self-described experts sitting at word processors, but with grandmothers, aunts, and the ladies next door. The book publishing market has cooled but the demand for advice on how to be the best parent has heated up. Into the void, enabled by the Internet, has erupted the phenomenon of social-media mom groups.

The lady next door and the mothers with strollers meeting informally at the playground are a tiny blip on the radar screen compared with the abundance of other mothers eager to listen and comment on social media–based mom groups unlimited by either geographic or temporal time restraints.

Unfortunately, as a recent article in the Wall Street Journal suggests, these support groups can often have a dark side. Researchers from Pepperdine University found in a small survey of a homogenous population of women that stress, as measured by saliva cortisol levels, increased with increasing use of “mom-centric social media” sites.

Citing anecdotal observations by mothers who did not participate in the study, the WSJ article describes episodes of shaming over topics such as steroid use in eczema and vaccine hesitancy. One mother described how she found group discussions about breastfeeding “particularly anxiety-producing.”

I have limited experience with online support groups but I have been surprised by how rude and condescending some of the contributors can be to what I could consider to be emotionally neutral subjects such as outboard motor oil pressure. I can imagine that when it comes to subjects in which there is no one best answer, the relative anonymity of the Internet provides cover for language that can be hurtful and stress inducing for someone already feeling isolated and anxious about being a parent.

Although this Pepperdine study is small, I suspect that a larger study would support the authors’ observations. For us as providers, it suggests that we need to find where parents are getting their information when we are trying to help those who seem particularly distressed. We should caution them that, while sharing information with peers can be reassuring and helpful at times, mom groups can be toxic as well. It also means that we should be careful in recommending social media sites – even those for which we have had good feedback.

And, most importantly, we must continue to work hard to make ourselves available to provide sensible and sensitive answers to those questions that are anxiety-producing for new parents.
 

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

To the Editor:

Juvenile dermatomyositis (JDM) is an autoimmune disorder with childhood onset that predominantly affects the muscles and skin, among other organs. Since the recognition of dermatomyositis (DM) more than 100 years ago, a variety of clinical diagnostic criteria have been utilized. Classically, DM presents with muscle weakness and a pathognomonic cutaneous macular, violaceous, erythematous eruption. The juvenile variant is defined by onset prior to 16 years of age. Histologically, these entities are indistinguishable and demonstrate an interface dermatitis with epidermal atrophy. Clinically, JDM has a higher incidence of calcinosis cutis and is not associated with an increased risk for malignancy in contrast to the adult-onset variant.¹ Panniculitis is a rare but serious complication in a subset of patients with DM and may represent a precursor to calcinosis cutis.² We describe a case of JDM-associated panniculitis that was difficult to control with prednisone and rituximab.

A 21-year-old woman with fever, fatigue, muscle pain, and new-onset swelling of 2 weeks’ duration was admitted to the hospital. She had a 5-year history of intermittent muscle weakness and concomitant rash. Prior to presentation, she had been hospitalized twice for fever of unknown origin, and the source remained undetermined. Physical examination revealed prominent facial and periorbital edema. There was tender nonpitting edema present on all 4 extremities and hyperpigmented indurated nodules on the shins (Figure 1). A full laboratory and imaging workup was performed for autoantibodies and infectious etiologies. The complete blood cell count was notable for pancytopenia, and a thorough infectious workup was negative. Creatine kinase level was within reference range. A biopsy of the right shin was performed, and histopathology revealed a lobular panniculitis with fat necrosis and mixed inflammation with neutrophils with perieccrine involvement as well as an interface dermatitis (Figure 2). Periodic acid–Schiff, Grocott methenamine-silver, and Gram stains were negative. Myositis-specific antibody testing revealed anti-p155/140 autoantibodies, and magnetic resonance imaging did not reveal active myositis within the visualized muscles, consistent with stable nonprogressing DM. A diagnosis of JDM with panniculitis was made. The patient was started on oral prednisone. Subsequently, a trial of rituximab was initiated. Although the patient’s symptoms initially improved, the response was not sustained on rituximab, and the patient was continued on systemic steroids with initiation of cyclosporine.

Juvenile dermatomyositis is an autoimmune disorder with childhood onset that involves systemic inflammation of the muscles, skin, and internal organs. It often can present diagnostic and therapeutic challenges.^2,3 Bohan and Peter^4,5 clinical criteria may help identify potential patients with JDM, but magnetic resonance imaging, electromyography, and muscle biopsy often are required to confirm the diagnosis.⁶ Skin manifestations include heliotrope rash; V sign; shawl sign; Gottron papules; periorbital edema; and infrequently panniculitis, the subcutaneous inflammation of adipose tissue.^3,7

Although panniculitis is found in approximately 10% of skin biopsies in patients with DM, our patient presented with anti-p155/140 antibodies.^8-10 Fat involvement in these patients traditionally manifests as lipodystrophy. Panniculitis also may precede calcinosis cutis, a debilitating skin change that may occur in approximately 46% of patients with JDM and can cause severe morbidity.^2,6,9

Subcutaneous edema rarely is described in DM-panniculitis, present in only 6% of 86 DM patients in one study.⁷ The pathophysiology of DM may be due to antibodies that target endothelial cells and activate complement, resulting in the membranolytic attack complex. This leads to microischemia, and microinfarction of the muscle fibers has been suggested to result in edema of the subcutaneous tissue in severe cases.^7,11 Microinfarction has been found to be present 2.3 times more often in edematous DM compared with nonedematous DM.⁷ Subcutaneous edema may be an isolated presentation of DM that arises more quickly with severe disease activity. As such, recommendations have been made to consider edema in future classification schemes.⁷

Because of the severity of edematous and/or subcutaneous DM, aggressive therapy may be required. First-line therapy consists of corticosteroids with additional immunosuppressants and immunomodulatory agents if adequate response is not achieved.^3,12 The effectiveness of rituximab in DM has been suggested.^2,12,13 The Rituximab in Myositis (RIM) trial (N=200) was the first double-blind, placebo-controlled, phase 3 clinical trial to assess rituximab’s efficacy in refractory compared with early-onset inflammatory myopathies. Although outcomes were similar in both groups, 83% of patients overall, including the JDM subset, met the definition of improvement.¹² In re-examining the RIM trial data and other cases using rituximab to treat inflammatory myopathies, an overall response rate of 78.3% was observed, with 52.1% of patients with DM reporting improvement in skin lesions (N=458, pooled from 48 studies).¹³ Further analysis of the RIM data revealed that panniculitis affected 10.4% of patients with JDM at baseline, which decreased to 6.8% at 36 weeks of rituximab therapy (N=48).¹²

As exhibited in our patient, subcutaneous tissue involvement, including calcinosis cutis and panniculitis, is seen more often in JDM than adult DM.^2,6 However, panniculitis in anti-p155/140 patients is rare. Our patient also had antibody positivity, which likely predisposed her to a more severe course. Despite not having sustained improvement on rituximab, initiating aggressive therapy earlier in the disease course may be beneficial, and our patient continues with alternative therapies.

To the Editor:

Juvenile dermatomyositis (JDM) is an autoimmune disorder with childhood onset that predominantly affects the muscles and skin, among other organs. Since the recognition of dermatomyositis (DM) more than 100 years ago, a variety of clinical diagnostic criteria have been utilized. Classically, DM presents with muscle weakness and a pathognomonic cutaneous macular, violaceous, erythematous eruption. The juvenile variant is defined by onset prior to 16 years of age. Histologically, these entities are indistinguishable and demonstrate an interface dermatitis with epidermal atrophy. Clinically, JDM has a higher incidence of calcinosis cutis and is not associated with an increased risk for malignancy in contrast to the adult-onset variant.¹ Panniculitis is a rare but serious complication in a subset of patients with DM and may represent a precursor to calcinosis cutis.² We describe a case of JDM-associated panniculitis that was difficult to control with prednisone and rituximab.

A 21-year-old woman with fever, fatigue, muscle pain, and new-onset swelling of 2 weeks’ duration was admitted to the hospital. She had a 5-year history of intermittent muscle weakness and concomitant rash. Prior to presentation, she had been hospitalized twice for fever of unknown origin, and the source remained undetermined. Physical examination revealed prominent facial and periorbital edema. There was tender nonpitting edema present on all 4 extremities and hyperpigmented indurated nodules on the shins (Figure 1). A full laboratory and imaging workup was performed for autoantibodies and infectious etiologies. The complete blood cell count was notable for pancytopenia, and a thorough infectious workup was negative. Creatine kinase level was within reference range. A biopsy of the right shin was performed, and histopathology revealed a lobular panniculitis with fat necrosis and mixed inflammation with neutrophils with perieccrine involvement as well as an interface dermatitis (Figure 2). Periodic acid–Schiff, Grocott methenamine-silver, and Gram stains were negative. Myositis-specific antibody testing revealed anti-p155/140 autoantibodies, and magnetic resonance imaging did not reveal active myositis within the visualized muscles, consistent with stable nonprogressing DM. A diagnosis of JDM with panniculitis was made. The patient was started on oral prednisone. Subsequently, a trial of rituximab was initiated. Although the patient’s symptoms initially improved, the response was not sustained on rituximab, and the patient was continued on systemic steroids with initiation of cyclosporine.

Juvenile dermatomyositis is an autoimmune disorder with childhood onset that involves systemic inflammation of the muscles, skin, and internal organs. It often can present diagnostic and therapeutic challenges.^2,3 Bohan and Peter^4,5 clinical criteria may help identify potential patients with JDM, but magnetic resonance imaging, electromyography, and muscle biopsy often are required to confirm the diagnosis.⁶ Skin manifestations include heliotrope rash; V sign; shawl sign; Gottron papules; periorbital edema; and infrequently panniculitis, the subcutaneous inflammation of adipose tissue.^3,7

Although panniculitis is found in approximately 10% of skin biopsies in patients with DM, our patient presented with anti-p155/140 antibodies.^8-10 Fat involvement in these patients traditionally manifests as lipodystrophy. Panniculitis also may precede calcinosis cutis, a debilitating skin change that may occur in approximately 46% of patients with JDM and can cause severe morbidity.^2,6,9

Subcutaneous edema rarely is described in DM-panniculitis, present in only 6% of 86 DM patients in one study.⁷ The pathophysiology of DM may be due to antibodies that target endothelial cells and activate complement, resulting in the membranolytic attack complex. This leads to microischemia, and microinfarction of the muscle fibers has been suggested to result in edema of the subcutaneous tissue in severe cases.^7,11 Microinfarction has been found to be present 2.3 times more often in edematous DM compared with nonedematous DM.⁷ Subcutaneous edema may be an isolated presentation of DM that arises more quickly with severe disease activity. As such, recommendations have been made to consider edema in future classification schemes.⁷

Because of the severity of edematous and/or subcutaneous DM, aggressive therapy may be required. First-line therapy consists of corticosteroids with additional immunosuppressants and immunomodulatory agents if adequate response is not achieved.^3,12 The effectiveness of rituximab in DM has been suggested.^2,12,13 The Rituximab in Myositis (RIM) trial (N=200) was the first double-blind, placebo-controlled, phase 3 clinical trial to assess rituximab’s efficacy in refractory compared with early-onset inflammatory myopathies. Although outcomes were similar in both groups, 83% of patients overall, including the JDM subset, met the definition of improvement.¹² In re-examining the RIM trial data and other cases using rituximab to treat inflammatory myopathies, an overall response rate of 78.3% was observed, with 52.1% of patients with DM reporting improvement in skin lesions (N=458, pooled from 48 studies).¹³ Further analysis of the RIM data revealed that panniculitis affected 10.4% of patients with JDM at baseline, which decreased to 6.8% at 36 weeks of rituximab therapy (N=48).¹²

As exhibited in our patient, subcutaneous tissue involvement, including calcinosis cutis and panniculitis, is seen more often in JDM than adult DM.^2,6 However, panniculitis in anti-p155/140 patients is rare. Our patient also had antibody positivity, which likely predisposed her to a more severe course. Despite not having sustained improvement on rituximab, initiating aggressive therapy earlier in the disease course may be beneficial, and our patient continues with alternative therapies.

To the Editor:

Juvenile dermatomyositis (JDM) is an autoimmune disorder with childhood onset that predominantly affects the muscles and skin, among other organs. Since the recognition of dermatomyositis (DM) more than 100 years ago, a variety of clinical diagnostic criteria have been utilized. Classically, DM presents with muscle weakness and a pathognomonic cutaneous macular, violaceous, erythematous eruption. The juvenile variant is defined by onset prior to 16 years of age. Histologically, these entities are indistinguishable and demonstrate an interface dermatitis with epidermal atrophy. Clinically, JDM has a higher incidence of calcinosis cutis and is not associated with an increased risk for malignancy in contrast to the adult-onset variant.¹ Panniculitis is a rare but serious complication in a subset of patients with DM and may represent a precursor to calcinosis cutis.² We describe a case of JDM-associated panniculitis that was difficult to control with prednisone and rituximab.

A 21-year-old woman with fever, fatigue, muscle pain, and new-onset swelling of 2 weeks’ duration was admitted to the hospital. She had a 5-year history of intermittent muscle weakness and concomitant rash. Prior to presentation, she had been hospitalized twice for fever of unknown origin, and the source remained undetermined. Physical examination revealed prominent facial and periorbital edema. There was tender nonpitting edema present on all 4 extremities and hyperpigmented indurated nodules on the shins (Figure 1). A full laboratory and imaging workup was performed for autoantibodies and infectious etiologies. The complete blood cell count was notable for pancytopenia, and a thorough infectious workup was negative. Creatine kinase level was within reference range. A biopsy of the right shin was performed, and histopathology revealed a lobular panniculitis with fat necrosis and mixed inflammation with neutrophils with perieccrine involvement as well as an interface dermatitis (Figure 2). Periodic acid–Schiff, Grocott methenamine-silver, and Gram stains were negative. Myositis-specific antibody testing revealed anti-p155/140 autoantibodies, and magnetic resonance imaging did not reveal active myositis within the visualized muscles, consistent with stable nonprogressing DM. A diagnosis of JDM with panniculitis was made. The patient was started on oral prednisone. Subsequently, a trial of rituximab was initiated. Although the patient’s symptoms initially improved, the response was not sustained on rituximab, and the patient was continued on systemic steroids with initiation of cyclosporine.

Juvenile dermatomyositis is an autoimmune disorder with childhood onset that involves systemic inflammation of the muscles, skin, and internal organs. It often can present diagnostic and therapeutic challenges.^2,3 Bohan and Peter^4,5 clinical criteria may help identify potential patients with JDM, but magnetic resonance imaging, electromyography, and muscle biopsy often are required to confirm the diagnosis.⁶ Skin manifestations include heliotrope rash; V sign; shawl sign; Gottron papules; periorbital edema; and infrequently panniculitis, the subcutaneous inflammation of adipose tissue.^3,7

Although panniculitis is found in approximately 10% of skin biopsies in patients with DM, our patient presented with anti-p155/140 antibodies.^8-10 Fat involvement in these patients traditionally manifests as lipodystrophy. Panniculitis also may precede calcinosis cutis, a debilitating skin change that may occur in approximately 46% of patients with JDM and can cause severe morbidity.^2,6,9

Subcutaneous edema rarely is described in DM-panniculitis, present in only 6% of 86 DM patients in one study.⁷ The pathophysiology of DM may be due to antibodies that target endothelial cells and activate complement, resulting in the membranolytic attack complex. This leads to microischemia, and microinfarction of the muscle fibers has been suggested to result in edema of the subcutaneous tissue in severe cases.^7,11 Microinfarction has been found to be present 2.3 times more often in edematous DM compared with nonedematous DM.⁷ Subcutaneous edema may be an isolated presentation of DM that arises more quickly with severe disease activity. As such, recommendations have been made to consider edema in future classification schemes.⁷

Because of the severity of edematous and/or subcutaneous DM, aggressive therapy may be required. First-line therapy consists of corticosteroids with additional immunosuppressants and immunomodulatory agents if adequate response is not achieved.^3,12 The effectiveness of rituximab in DM has been suggested.^2,12,13 The Rituximab in Myositis (RIM) trial (N=200) was the first double-blind, placebo-controlled, phase 3 clinical trial to assess rituximab’s efficacy in refractory compared with early-onset inflammatory myopathies. Although outcomes were similar in both groups, 83% of patients overall, including the JDM subset, met the definition of improvement.¹² In re-examining the RIM trial data and other cases using rituximab to treat inflammatory myopathies, an overall response rate of 78.3% was observed, with 52.1% of patients with DM reporting improvement in skin lesions (N=458, pooled from 48 studies).¹³ Further analysis of the RIM data revealed that panniculitis affected 10.4% of patients with JDM at baseline, which decreased to 6.8% at 36 weeks of rituximab therapy (N=48).¹²

As exhibited in our patient, subcutaneous tissue involvement, including calcinosis cutis and panniculitis, is seen more often in JDM than adult DM.^2,6 However, panniculitis in anti-p155/140 patients is rare. Our patient also had antibody positivity, which likely predisposed her to a more severe course. Despite not having sustained improvement on rituximab, initiating aggressive therapy earlier in the disease course may be beneficial, and our patient continues with alternative therapies.

Case Report

A 7-year-old girl who was otherwise healthy was referred by pediatric gastroenterology for evaluation of cutaneous Crohn disease (CD). The patient had a 4-year history of persistent lip swelling and a 3-year history of asymmetric erythematous labial swelling and perianal erythema with skin tags. She had been applying the calcineurin inhibitor tacrolimus ointment 0.03% 1 or 2 times daily to her lesions with minimal improvement. She did not have a medical history of recurrent or unusual infectious diseases. There was no family history of autoimmune disease.

The patient and her guardian reported intermittent perianal pain but denied constipation, diarrhea, abdominal pain, and blood in the stool. She denied throat and tongue swelling, dysphagia, dyspnea, drooling, facial paralysis, and eyelid edema. She was a well-nourished child whose height and weight percentiles tracked at 30% and 25%, respectively. Physical examination revealed confluent symmetric lip swelling with mild angular cheilitis. Multiple 1- to 2-mm white pustules with pinpoint erosions covered the upper and lower labial mucosa and extended onto the buccal mucosa (Figure 1). She had symmetric erythema and swelling of the left labia majora extending to and involving the left perianal mucosa. Three perianal erythematous skin tags and a perianal fissure were identified.

The patient had been assessed 2 years earlier by pediatric dermatology and gastroenterology with an extensive evaluation that favored a diagnosis of cutaneous CD because the combination of orofacial granulomatosis (OFG), vulvar edema, and perianal skin tags is strongly associated.^1-3 Contact dermatitis affecting the mouth was considered; however, allergen testing did not demonstrate a trigger.

A trial of a benzoate- and cinnamon-free diet, which has been reported to improve OFG,⁴ did not provide symptomatic improvement. Topical corticosteroids and tacrolimus reduced the perioral erythema, but the swelling persisted. An infectious cause was considered; however, topical mupirocin had no effect, and amoxicillin resulted in oral candidiasis.

A perianal biopsy revealed a granulomatous dermatitis. Fungal and bacterial cultures were negative. Upper and lower gastrointestinal (GI) endoscopy and a fecal calprotectin assay were not suggestive of inflammatory bowel disease (IBD). A complete blood cell count and QuantiFERON-TB Gold test measuring the immune response to tuberculosis antigens were normal. Chronic granulomatous disease, RAG1/RAG2 deficiency, common variable immunodeficiency, and NOD2 defects were ruled out with normal tests of dihydrorhodamine, quantitative immunoglobulins, and toll-like receptors.

Because of the discomfort associated with the patient’s lesions, she was offered treatment with tumor necrosis factor α inhibitors, including infliximab and adalimumab. These agents had been offered since the onset of symptoms; however, her parents declined systemic medication unless she developed GI involvement. Instead, the tacrolimus concentration was increased to 0.1% applied to the lips, labia, and perianal area, and fluocinonide gel 0.05% applied nightly to the oral pustules was added.

Two months later the patient had notably fewer oral pustules and diminished erythema but only slightly reduced oral, vulvar, and perianal swelling. A trial of oral metronidazole, which has been reported to clear a patient with cutaneous CD,⁵ was discontinued by her parents after 6 weeks because of a lack of interval improvement.

One year later, a pre-existing perianal skin tag doubled in size and became exquisitely tender. The calprotectin level—previously within reference range at less than 16 μg/g—was now elevated at 149 μg/g (reference range, 1–120 μg/g) and increased to 336 μg/g 3 weeks later. Testing for C-reactive protein, zinc, and stool occult blood; a comprehensive metabolic panel; and a complete blood cell count were unremarkable.

Repeat upper and lower GI endoscopy did not suggest CD. A biopsy using direct immunofluorescence (DIF) was obtained to evaluate for pyostomatitis vegetans (PSV) and rule out pemphigus vegetans of Hallopeau (PVH). Biopsy of a pustule was attempted but was challenging because of the patient’s age and difficulty cooperating.

The captured biopsy did not demonstrate the intended pustule; instead, it included less-affected mucosa and was obtained during topical treatment when few pustules and erosions persisted. Pathologic analysis revealed noncaseating granulomas without an increase in microabscesses, neutrophils, or eosinophils (Figure 2). Direct immunofluorescence staining for IgG, IgA, and C3 and indirect immunofluorescence staining for desmoglein-1 and desmoglein-3 antibodies were negative. Although the biopsy did not capture the intended pustule, diagnosis of PV was made based on clinical features and the constellation of cutaneous findings associated with IBD.

Intralesional triamcinolone, which has been of benefit for pediatric patients with orofacial granulomatosis,^1,6,7 was instituted and normalized the vulva and perianal mucosa; however, lip swelling improved only minimally.

Comment

Pyostomatitis vegetans is characterized by multiple white or yellow, friable, miliary pustules that rupture, leaving behind ulcerations and erosions that cause a varying degree of oral pain.⁸ The disorder can involve any area of the oral mucosa—most often the labia-attached gingiva, soft and hard palates, buccal mucosa, vestibule, and tonsillar areas—but often spares the floor of the mouth and tongue.^8-11 The term pyostomatitis vegetans was proposed in 1949 by McCarthy¹² when he noted in a patient who presented with the characteristic appearance of the oral mucosa, though cases of vaginal, nasal, and periocular involvement have been reported.^8,13,14

Histopathology—Pyostomatitis vegetans displays pseudoepithelial hyperplasia with acanthosis, hyperkeratosis, and intraepithelial or subepithelial microabscesses (or both) with neutrophils and eosinophils.^8,9,15 There are a few possible explanations for this patient’s lack of tissue eosinophilia. It has been theorized that the presence of granulomas could mask concurrent PSV¹⁶ or that tissue in PSV contains fewer eosinophils as the disorder progresses.¹¹ The oral biopsy obtained from our patient did not capture a pustule, and the condition had noticeably improved with topical tacrolimus at the time of biopsy; therefore, neither neutrophils nor eosinophils were identified. Peripheral eosinophilia, which is present in 42% to 90% of cases of PSV,^9,17 can be a diagnostic clue.¹⁸ However, PE is associated with IBD,²⁴ which usually occurs with PSV, so the absence of peripheral eosinophilia in our patient may be explained by her lack of bowel disease.

Pathogenesis—The pathogenesis of PSV is unknown. A proposed etiology includes cross-reacting antigens in the bowel and skin secondary to IBD as well as an aberrant immune response to an unidentified factor.⁸ Pyostomatitis vegetans is considered by many to be the mucosal variant of pyodermatitis vegetans,^9,15,19 a neutrophilic dermatosis characterized by asymmetric, crusted, erythematous papulopustules that extend peripherally and coalesce to form large vegetating plaques. These lesions commonly manifest in the axillary folds, groin, and scalp and can involve the face, trunk, and distal extremities.^9,18 Infection has been suggested as a cause of PSV, though cultures for pathogenic bacteria, viruses, and fungi consistently show only normal flora.²⁰ Zinc deficiency attributed to malabsorption from CD was reported in an adult with PSV.²¹ The PSV resolved after 6 weeks of zinc supplementation.

Differential Diagnosis—The main entity in the clinical differential diagnosis for PSV is PVH, which is considered a variant of pemphigus vulgaris. Pemphigus vegetans of Hallopeau presents with pustules and progresses to hyperpigmented vegetative plaques with peripheral hypertrophic granulation tissue.²² The clinical and histological presentation of PVH can be similar to PSV; in PVH, however, DIF demonstrates intercellular IgG and C3 due to circulating IgG autoantibodies specific for desmoglein 3, a cell adhesion molecule.^22-24 In PSV, DIF typically is negative for IgG, IgA, and C3.⁸ Immunohistochemical findings of PSV may overlap with IgA pemphigus, IgG/IgA pemphigus, and IgG pemphigus, which has sparked debate if PSV is an autoimmune blistering disorder or a secondary finding of epithelial injury.^9,18,24

Pyostomatitis vegetans is most prevalent in patients aged 20 to 59 years²⁵ but can occur at any age.^8,19 Overall, extraintestinal symptoms, including mucocutaneous findings, are common in pediatric patients—in 30% to 71% of children with CD and 21% to 22% of children with ulcerative colitis²⁶—and can predate onset of GI symptoms in 6% of pediatric patients.²⁷

Oral disease is common in CD; manifestations are listed in the Table.^28,29 In a prospective study of 48 children with CD, 42% (20/48) had oral manifestations identified at diagnosis²⁸; in a similar study of 25 children, researchers noted that 48% (12/25) had disease-specific oral lesions.²⁹ None of these children recognized the oral findings prior to the onset of systemic symptoms.²⁸ Pyostomatitis vegetans was the least common oral manifestation, reported in 1 of 73 patients in the 2 studies combined.^28,29

Two recent articles that looked at PSV in pediatric and adolescent populations identified only 9 patients with PSV.^24,30 Only 2 patients (siblings) had documented onset of PSV before 12 years of age,³¹ which suggests an underlying genetic predisposition in young children.

It has been reported that active or subclinical (ie, asymptomatic with positive endoscopic findings) IBD in adults precedes onset of PSV, which may be considered a sign of relapse.^9,30 However, PSV is incredibly rare in children and adolescents and can be an early finding of IBD in children.^16,31,32

Our patient has not developed GI involvement since her initial presentation 5 years prior, though another pediatric patient developed symptomatic CD 9 years after onset of OFG.⁵ A retrospective review of pediatric OFG without CD met criteria for CD at a median of 3.1 years (range, 0.4–6.9 years).³³ Regrettably, the early presence of PSV has been associated with future progression to CD and a complicated disease course.^12,34

Management—Pyoderma stomatitis vegetans is treated with management of underlying IBD,⁸ with scarce literature available regarding pediatric patients. Oral lesions have been treated with antiseptics and topical corticosteroids, though these have limited benefit.⁸ In an adult with IBD, topical tacrolimus initially cleared PSV; however, lesions recurred until mesalamine was initiated.³⁵ Systemic steroids were effective in a 16-year-old patient with CD and PSV,¹² but recurrence is common after corticosteroids are stopped.³⁴

Some patients benefit from steroid-sparing medications, such as dapsone, azathioprine, sulfamethoxypyridazine, methotrexate, mycophenolate mofetil, and tumor necrosis factor α inhibitors such as infliximab and adalimumab.^{8,9,15,23,34,36} A 12-year-old patient with pyodermatitis–PSV without intestinal disease was treated with prednisone, dapsone, and azathioprine with improvement but not complete resolution of oral erosions after 18 weeks of treatment.³² A 15-year-old patient with CD and pyodermatitis–PSV did not show improvement on prednisone, dapsone, and azathioprine but rapidly responded to infliximab.²³ Infliximab led to complete clearance of oral lesions in an adult with severe fistulizing CD who developed PSV.¹¹ However, 2 adolescent patients with CD developed PSV while on adalimumab,^6,34 though 1 did improve after increasing adalimumab from once to twice weekly.⁶

Conclusion

The case described here—PSV in a prepubertal 7-year-old with multiple cutaneous findings suggestive of CD, including OFG, perianal and vulvar edema with biopsy-proven noncaseating granulomas, anal skin tags, and an elevated calprotectin level, noted during a cutaneous flare without clinical or endoscopically identified underlying bowel involvement—is an extremely rare presentation. Literature regarding management of PSV primarily is found in the form of case reports and focuses on treating underlying IBD. In patients with intestinal disease, treatment with biologic therapy appears most effective.^6,23

ADDENDUM

Interestingly, 3 years after the patient’s original presentation to our clinic, chromosomal sequencing analysis to assess for copy number variants and whole exome gene sequencing identified a variant of unknown significance in the heat shock protein family A member 1-like gene, HSPA1L, which has an unknown mode of inheritance, but the literature suggests that both truncating and missense variants could be associated with individuals with ulcerative colitis, CD, and IBD.^37,38 Although we cannot use this information to render a molecular diagnosis, it is highly suspicious that this is the cause of her clinical findings. Additionally, the patient currently is aged 10 years with unchanged cutaneous findings and has not developed gastrointestinal findings of IBD.

Case Report

A 7-year-old girl who was otherwise healthy was referred by pediatric gastroenterology for evaluation of cutaneous Crohn disease (CD). The patient had a 4-year history of persistent lip swelling and a 3-year history of asymmetric erythematous labial swelling and perianal erythema with skin tags. She had been applying the calcineurin inhibitor tacrolimus ointment 0.03% 1 or 2 times daily to her lesions with minimal improvement. She did not have a medical history of recurrent or unusual infectious diseases. There was no family history of autoimmune disease.

The patient and her guardian reported intermittent perianal pain but denied constipation, diarrhea, abdominal pain, and blood in the stool. She denied throat and tongue swelling, dysphagia, dyspnea, drooling, facial paralysis, and eyelid edema. She was a well-nourished child whose height and weight percentiles tracked at 30% and 25%, respectively. Physical examination revealed confluent symmetric lip swelling with mild angular cheilitis. Multiple 1- to 2-mm white pustules with pinpoint erosions covered the upper and lower labial mucosa and extended onto the buccal mucosa (Figure 1). She had symmetric erythema and swelling of the left labia majora extending to and involving the left perianal mucosa. Three perianal erythematous skin tags and a perianal fissure were identified.

The patient had been assessed 2 years earlier by pediatric dermatology and gastroenterology with an extensive evaluation that favored a diagnosis of cutaneous CD because the combination of orofacial granulomatosis (OFG), vulvar edema, and perianal skin tags is strongly associated.^1-3 Contact dermatitis affecting the mouth was considered; however, allergen testing did not demonstrate a trigger.

A trial of a benzoate- and cinnamon-free diet, which has been reported to improve OFG,⁴ did not provide symptomatic improvement. Topical corticosteroids and tacrolimus reduced the perioral erythema, but the swelling persisted. An infectious cause was considered; however, topical mupirocin had no effect, and amoxicillin resulted in oral candidiasis.

A perianal biopsy revealed a granulomatous dermatitis. Fungal and bacterial cultures were negative. Upper and lower gastrointestinal (GI) endoscopy and a fecal calprotectin assay were not suggestive of inflammatory bowel disease (IBD). A complete blood cell count and QuantiFERON-TB Gold test measuring the immune response to tuberculosis antigens were normal. Chronic granulomatous disease, RAG1/RAG2 deficiency, common variable immunodeficiency, and NOD2 defects were ruled out with normal tests of dihydrorhodamine, quantitative immunoglobulins, and toll-like receptors.

Because of the discomfort associated with the patient’s lesions, she was offered treatment with tumor necrosis factor α inhibitors, including infliximab and adalimumab. These agents had been offered since the onset of symptoms; however, her parents declined systemic medication unless she developed GI involvement. Instead, the tacrolimus concentration was increased to 0.1% applied to the lips, labia, and perianal area, and fluocinonide gel 0.05% applied nightly to the oral pustules was added.

Two months later the patient had notably fewer oral pustules and diminished erythema but only slightly reduced oral, vulvar, and perianal swelling. A trial of oral metronidazole, which has been reported to clear a patient with cutaneous CD,⁵ was discontinued by her parents after 6 weeks because of a lack of interval improvement.

One year later, a pre-existing perianal skin tag doubled in size and became exquisitely tender. The calprotectin level—previously within reference range at less than 16 μg/g—was now elevated at 149 μg/g (reference range, 1–120 μg/g) and increased to 336 μg/g 3 weeks later. Testing for C-reactive protein, zinc, and stool occult blood; a comprehensive metabolic panel; and a complete blood cell count were unremarkable.

Repeat upper and lower GI endoscopy did not suggest CD. A biopsy using direct immunofluorescence (DIF) was obtained to evaluate for pyostomatitis vegetans (PSV) and rule out pemphigus vegetans of Hallopeau (PVH). Biopsy of a pustule was attempted but was challenging because of the patient’s age and difficulty cooperating.

The captured biopsy did not demonstrate the intended pustule; instead, it included less-affected mucosa and was obtained during topical treatment when few pustules and erosions persisted. Pathologic analysis revealed noncaseating granulomas without an increase in microabscesses, neutrophils, or eosinophils (Figure 2). Direct immunofluorescence staining for IgG, IgA, and C3 and indirect immunofluorescence staining for desmoglein-1 and desmoglein-3 antibodies were negative. Although the biopsy did not capture the intended pustule, diagnosis of PV was made based on clinical features and the constellation of cutaneous findings associated with IBD.

Intralesional triamcinolone, which has been of benefit for pediatric patients with orofacial granulomatosis,^1,6,7 was instituted and normalized the vulva and perianal mucosa; however, lip swelling improved only minimally.

Comment

Pyostomatitis vegetans is characterized by multiple white or yellow, friable, miliary pustules that rupture, leaving behind ulcerations and erosions that cause a varying degree of oral pain.⁸ The disorder can involve any area of the oral mucosa—most often the labia-attached gingiva, soft and hard palates, buccal mucosa, vestibule, and tonsillar areas—but often spares the floor of the mouth and tongue.^8-11 The term pyostomatitis vegetans was proposed in 1949 by McCarthy¹² when he noted in a patient who presented with the characteristic appearance of the oral mucosa, though cases of vaginal, nasal, and periocular involvement have been reported.^8,13,14

Histopathology—Pyostomatitis vegetans displays pseudoepithelial hyperplasia with acanthosis, hyperkeratosis, and intraepithelial or subepithelial microabscesses (or both) with neutrophils and eosinophils.^8,9,15 There are a few possible explanations for this patient’s lack of tissue eosinophilia. It has been theorized that the presence of granulomas could mask concurrent PSV¹⁶ or that tissue in PSV contains fewer eosinophils as the disorder progresses.¹¹ The oral biopsy obtained from our patient did not capture a pustule, and the condition had noticeably improved with topical tacrolimus at the time of biopsy; therefore, neither neutrophils nor eosinophils were identified. Peripheral eosinophilia, which is present in 42% to 90% of cases of PSV,^9,17 can be a diagnostic clue.¹⁸ However, PE is associated with IBD,²⁴ which usually occurs with PSV, so the absence of peripheral eosinophilia in our patient may be explained by her lack of bowel disease.

Pathogenesis—The pathogenesis of PSV is unknown. A proposed etiology includes cross-reacting antigens in the bowel and skin secondary to IBD as well as an aberrant immune response to an unidentified factor.⁸ Pyostomatitis vegetans is considered by many to be the mucosal variant of pyodermatitis vegetans,^9,15,19 a neutrophilic dermatosis characterized by asymmetric, crusted, erythematous papulopustules that extend peripherally and coalesce to form large vegetating plaques. These lesions commonly manifest in the axillary folds, groin, and scalp and can involve the face, trunk, and distal extremities.^9,18 Infection has been suggested as a cause of PSV, though cultures for pathogenic bacteria, viruses, and fungi consistently show only normal flora.²⁰ Zinc deficiency attributed to malabsorption from CD was reported in an adult with PSV.²¹ The PSV resolved after 6 weeks of zinc supplementation.

Differential Diagnosis—The main entity in the clinical differential diagnosis for PSV is PVH, which is considered a variant of pemphigus vulgaris. Pemphigus vegetans of Hallopeau presents with pustules and progresses to hyperpigmented vegetative plaques with peripheral hypertrophic granulation tissue.²² The clinical and histological presentation of PVH can be similar to PSV; in PVH, however, DIF demonstrates intercellular IgG and C3 due to circulating IgG autoantibodies specific for desmoglein 3, a cell adhesion molecule.^22-24 In PSV, DIF typically is negative for IgG, IgA, and C3.⁸ Immunohistochemical findings of PSV may overlap with IgA pemphigus, IgG/IgA pemphigus, and IgG pemphigus, which has sparked debate if PSV is an autoimmune blistering disorder or a secondary finding of epithelial injury.^9,18,24

Pyostomatitis vegetans is most prevalent in patients aged 20 to 59 years²⁵ but can occur at any age.^8,19 Overall, extraintestinal symptoms, including mucocutaneous findings, are common in pediatric patients—in 30% to 71% of children with CD and 21% to 22% of children with ulcerative colitis²⁶—and can predate onset of GI symptoms in 6% of pediatric patients.²⁷

Oral disease is common in CD; manifestations are listed in the Table.^28,29 In a prospective study of 48 children with CD, 42% (20/48) had oral manifestations identified at diagnosis²⁸; in a similar study of 25 children, researchers noted that 48% (12/25) had disease-specific oral lesions.²⁹ None of these children recognized the oral findings prior to the onset of systemic symptoms.²⁸ Pyostomatitis vegetans was the least common oral manifestation, reported in 1 of 73 patients in the 2 studies combined.^28,29

Two recent articles that looked at PSV in pediatric and adolescent populations identified only 9 patients with PSV.^24,30 Only 2 patients (siblings) had documented onset of PSV before 12 years of age,³¹ which suggests an underlying genetic predisposition in young children.

It has been reported that active or subclinical (ie, asymptomatic with positive endoscopic findings) IBD in adults precedes onset of PSV, which may be considered a sign of relapse.^9,30 However, PSV is incredibly rare in children and adolescents and can be an early finding of IBD in children.^16,31,32

Our patient has not developed GI involvement since her initial presentation 5 years prior, though another pediatric patient developed symptomatic CD 9 years after onset of OFG.⁵ A retrospective review of pediatric OFG without CD met criteria for CD at a median of 3.1 years (range, 0.4–6.9 years).³³ Regrettably, the early presence of PSV has been associated with future progression to CD and a complicated disease course.^12,34

Management—Pyoderma stomatitis vegetans is treated with management of underlying IBD,⁸ with scarce literature available regarding pediatric patients. Oral lesions have been treated with antiseptics and topical corticosteroids, though these have limited benefit.⁸ In an adult with IBD, topical tacrolimus initially cleared PSV; however, lesions recurred until mesalamine was initiated.³⁵ Systemic steroids were effective in a 16-year-old patient with CD and PSV,¹² but recurrence is common after corticosteroids are stopped.³⁴

Some patients benefit from steroid-sparing medications, such as dapsone, azathioprine, sulfamethoxypyridazine, methotrexate, mycophenolate mofetil, and tumor necrosis factor α inhibitors such as infliximab and adalimumab.^{8,9,15,23,34,36} A 12-year-old patient with pyodermatitis–PSV without intestinal disease was treated with prednisone, dapsone, and azathioprine with improvement but not complete resolution of oral erosions after 18 weeks of treatment.³² A 15-year-old patient with CD and pyodermatitis–PSV did not show improvement on prednisone, dapsone, and azathioprine but rapidly responded to infliximab.²³ Infliximab led to complete clearance of oral lesions in an adult with severe fistulizing CD who developed PSV.¹¹ However, 2 adolescent patients with CD developed PSV while on adalimumab,^6,34 though 1 did improve after increasing adalimumab from once to twice weekly.⁶

Conclusion

The case described here—PSV in a prepubertal 7-year-old with multiple cutaneous findings suggestive of CD, including OFG, perianal and vulvar edema with biopsy-proven noncaseating granulomas, anal skin tags, and an elevated calprotectin level, noted during a cutaneous flare without clinical or endoscopically identified underlying bowel involvement—is an extremely rare presentation. Literature regarding management of PSV primarily is found in the form of case reports and focuses on treating underlying IBD. In patients with intestinal disease, treatment with biologic therapy appears most effective.^6,23

ADDENDUM

Interestingly, 3 years after the patient’s original presentation to our clinic, chromosomal sequencing analysis to assess for copy number variants and whole exome gene sequencing identified a variant of unknown significance in the heat shock protein family A member 1-like gene, HSPA1L, which has an unknown mode of inheritance, but the literature suggests that both truncating and missense variants could be associated with individuals with ulcerative colitis, CD, and IBD.^37,38 Although we cannot use this information to render a molecular diagnosis, it is highly suspicious that this is the cause of her clinical findings. Additionally, the patient currently is aged 10 years with unchanged cutaneous findings and has not developed gastrointestinal findings of IBD.

Case Report

A 7-year-old girl who was otherwise healthy was referred by pediatric gastroenterology for evaluation of cutaneous Crohn disease (CD). The patient had a 4-year history of persistent lip swelling and a 3-year history of asymmetric erythematous labial swelling and perianal erythema with skin tags. She had been applying the calcineurin inhibitor tacrolimus ointment 0.03% 1 or 2 times daily to her lesions with minimal improvement. She did not have a medical history of recurrent or unusual infectious diseases. There was no family history of autoimmune disease.

The patient and her guardian reported intermittent perianal pain but denied constipation, diarrhea, abdominal pain, and blood in the stool. She denied throat and tongue swelling, dysphagia, dyspnea, drooling, facial paralysis, and eyelid edema. She was a well-nourished child whose height and weight percentiles tracked at 30% and 25%, respectively. Physical examination revealed confluent symmetric lip swelling with mild angular cheilitis. Multiple 1- to 2-mm white pustules with pinpoint erosions covered the upper and lower labial mucosa and extended onto the buccal mucosa (Figure 1). She had symmetric erythema and swelling of the left labia majora extending to and involving the left perianal mucosa. Three perianal erythematous skin tags and a perianal fissure were identified.

The patient had been assessed 2 years earlier by pediatric dermatology and gastroenterology with an extensive evaluation that favored a diagnosis of cutaneous CD because the combination of orofacial granulomatosis (OFG), vulvar edema, and perianal skin tags is strongly associated.^1-3 Contact dermatitis affecting the mouth was considered; however, allergen testing did not demonstrate a trigger.

A trial of a benzoate- and cinnamon-free diet, which has been reported to improve OFG,⁴ did not provide symptomatic improvement. Topical corticosteroids and tacrolimus reduced the perioral erythema, but the swelling persisted. An infectious cause was considered; however, topical mupirocin had no effect, and amoxicillin resulted in oral candidiasis.

A perianal biopsy revealed a granulomatous dermatitis. Fungal and bacterial cultures were negative. Upper and lower gastrointestinal (GI) endoscopy and a fecal calprotectin assay were not suggestive of inflammatory bowel disease (IBD). A complete blood cell count and QuantiFERON-TB Gold test measuring the immune response to tuberculosis antigens were normal. Chronic granulomatous disease, RAG1/RAG2 deficiency, common variable immunodeficiency, and NOD2 defects were ruled out with normal tests of dihydrorhodamine, quantitative immunoglobulins, and toll-like receptors.

Because of the discomfort associated with the patient’s lesions, she was offered treatment with tumor necrosis factor α inhibitors, including infliximab and adalimumab. These agents had been offered since the onset of symptoms; however, her parents declined systemic medication unless she developed GI involvement. Instead, the tacrolimus concentration was increased to 0.1% applied to the lips, labia, and perianal area, and fluocinonide gel 0.05% applied nightly to the oral pustules was added.

Two months later the patient had notably fewer oral pustules and diminished erythema but only slightly reduced oral, vulvar, and perianal swelling. A trial of oral metronidazole, which has been reported to clear a patient with cutaneous CD,⁵ was discontinued by her parents after 6 weeks because of a lack of interval improvement.

One year later, a pre-existing perianal skin tag doubled in size and became exquisitely tender. The calprotectin level—previously within reference range at less than 16 μg/g—was now elevated at 149 μg/g (reference range, 1–120 μg/g) and increased to 336 μg/g 3 weeks later. Testing for C-reactive protein, zinc, and stool occult blood; a comprehensive metabolic panel; and a complete blood cell count were unremarkable.

Repeat upper and lower GI endoscopy did not suggest CD. A biopsy using direct immunofluorescence (DIF) was obtained to evaluate for pyostomatitis vegetans (PSV) and rule out pemphigus vegetans of Hallopeau (PVH). Biopsy of a pustule was attempted but was challenging because of the patient’s age and difficulty cooperating.

The captured biopsy did not demonstrate the intended pustule; instead, it included less-affected mucosa and was obtained during topical treatment when few pustules and erosions persisted. Pathologic analysis revealed noncaseating granulomas without an increase in microabscesses, neutrophils, or eosinophils (Figure 2). Direct immunofluorescence staining for IgG, IgA, and C3 and indirect immunofluorescence staining for desmoglein-1 and desmoglein-3 antibodies were negative. Although the biopsy did not capture the intended pustule, diagnosis of PV was made based on clinical features and the constellation of cutaneous findings associated with IBD.

Intralesional triamcinolone, which has been of benefit for pediatric patients with orofacial granulomatosis,^1,6,7 was instituted and normalized the vulva and perianal mucosa; however, lip swelling improved only minimally.

Comment

Pyostomatitis vegetans is characterized by multiple white or yellow, friable, miliary pustules that rupture, leaving behind ulcerations and erosions that cause a varying degree of oral pain.⁸ The disorder can involve any area of the oral mucosa—most often the labia-attached gingiva, soft and hard palates, buccal mucosa, vestibule, and tonsillar areas—but often spares the floor of the mouth and tongue.^8-11 The term pyostomatitis vegetans was proposed in 1949 by McCarthy¹² when he noted in a patient who presented with the characteristic appearance of the oral mucosa, though cases of vaginal, nasal, and periocular involvement have been reported.^8,13,14

Histopathology—Pyostomatitis vegetans displays pseudoepithelial hyperplasia with acanthosis, hyperkeratosis, and intraepithelial or subepithelial microabscesses (or both) with neutrophils and eosinophils.^8,9,15 There are a few possible explanations for this patient’s lack of tissue eosinophilia. It has been theorized that the presence of granulomas could mask concurrent PSV¹⁶ or that tissue in PSV contains fewer eosinophils as the disorder progresses.¹¹ The oral biopsy obtained from our patient did not capture a pustule, and the condition had noticeably improved with topical tacrolimus at the time of biopsy; therefore, neither neutrophils nor eosinophils were identified. Peripheral eosinophilia, which is present in 42% to 90% of cases of PSV,^9,17 can be a diagnostic clue.¹⁸ However, PE is associated with IBD,²⁴ which usually occurs with PSV, so the absence of peripheral eosinophilia in our patient may be explained by her lack of bowel disease.

Pathogenesis—The pathogenesis of PSV is unknown. A proposed etiology includes cross-reacting antigens in the bowel and skin secondary to IBD as well as an aberrant immune response to an unidentified factor.⁸ Pyostomatitis vegetans is considered by many to be the mucosal variant of pyodermatitis vegetans,^9,15,19 a neutrophilic dermatosis characterized by asymmetric, crusted, erythematous papulopustules that extend peripherally and coalesce to form large vegetating plaques. These lesions commonly manifest in the axillary folds, groin, and scalp and can involve the face, trunk, and distal extremities.^9,18 Infection has been suggested as a cause of PSV, though cultures for pathogenic bacteria, viruses, and fungi consistently show only normal flora.²⁰ Zinc deficiency attributed to malabsorption from CD was reported in an adult with PSV.²¹ The PSV resolved after 6 weeks of zinc supplementation.

Differential Diagnosis—The main entity in the clinical differential diagnosis for PSV is PVH, which is considered a variant of pemphigus vulgaris. Pemphigus vegetans of Hallopeau presents with pustules and progresses to hyperpigmented vegetative plaques with peripheral hypertrophic granulation tissue.²² The clinical and histological presentation of PVH can be similar to PSV; in PVH, however, DIF demonstrates intercellular IgG and C3 due to circulating IgG autoantibodies specific for desmoglein 3, a cell adhesion molecule.^22-24 In PSV, DIF typically is negative for IgG, IgA, and C3.⁸ Immunohistochemical findings of PSV may overlap with IgA pemphigus, IgG/IgA pemphigus, and IgG pemphigus, which has sparked debate if PSV is an autoimmune blistering disorder or a secondary finding of epithelial injury.^9,18,24

Pyostomatitis vegetans is most prevalent in patients aged 20 to 59 years²⁵ but can occur at any age.^8,19 Overall, extraintestinal symptoms, including mucocutaneous findings, are common in pediatric patients—in 30% to 71% of children with CD and 21% to 22% of children with ulcerative colitis²⁶—and can predate onset of GI symptoms in 6% of pediatric patients.²⁷

Oral disease is common in CD; manifestations are listed in the Table.^28,29 In a prospective study of 48 children with CD, 42% (20/48) had oral manifestations identified at diagnosis²⁸; in a similar study of 25 children, researchers noted that 48% (12/25) had disease-specific oral lesions.²⁹ None of these children recognized the oral findings prior to the onset of systemic symptoms.²⁸ Pyostomatitis vegetans was the least common oral manifestation, reported in 1 of 73 patients in the 2 studies combined.^28,29

Two recent articles that looked at PSV in pediatric and adolescent populations identified only 9 patients with PSV.^24,30 Only 2 patients (siblings) had documented onset of PSV before 12 years of age,³¹ which suggests an underlying genetic predisposition in young children.

It has been reported that active or subclinical (ie, asymptomatic with positive endoscopic findings) IBD in adults precedes onset of PSV, which may be considered a sign of relapse.^9,30 However, PSV is incredibly rare in children and adolescents and can be an early finding of IBD in children.^16,31,32

Our patient has not developed GI involvement since her initial presentation 5 years prior, though another pediatric patient developed symptomatic CD 9 years after onset of OFG.⁵ A retrospective review of pediatric OFG without CD met criteria for CD at a median of 3.1 years (range, 0.4–6.9 years).³³ Regrettably, the early presence of PSV has been associated with future progression to CD and a complicated disease course.^12,34

Management—Pyoderma stomatitis vegetans is treated with management of underlying IBD,⁸ with scarce literature available regarding pediatric patients. Oral lesions have been treated with antiseptics and topical corticosteroids, though these have limited benefit.⁸ In an adult with IBD, topical tacrolimus initially cleared PSV; however, lesions recurred until mesalamine was initiated.³⁵ Systemic steroids were effective in a 16-year-old patient with CD and PSV,¹² but recurrence is common after corticosteroids are stopped.³⁴

Some patients benefit from steroid-sparing medications, such as dapsone, azathioprine, sulfamethoxypyridazine, methotrexate, mycophenolate mofetil, and tumor necrosis factor α inhibitors such as infliximab and adalimumab.^{8,9,15,23,34,36} A 12-year-old patient with pyodermatitis–PSV without intestinal disease was treated with prednisone, dapsone, and azathioprine with improvement but not complete resolution of oral erosions after 18 weeks of treatment.³² A 15-year-old patient with CD and pyodermatitis–PSV did not show improvement on prednisone, dapsone, and azathioprine but rapidly responded to infliximab.²³ Infliximab led to complete clearance of oral lesions in an adult with severe fistulizing CD who developed PSV.¹¹ However, 2 adolescent patients with CD developed PSV while on adalimumab,^6,34 though 1 did improve after increasing adalimumab from once to twice weekly.⁶

Conclusion

The case described here—PSV in a prepubertal 7-year-old with multiple cutaneous findings suggestive of CD, including OFG, perianal and vulvar edema with biopsy-proven noncaseating granulomas, anal skin tags, and an elevated calprotectin level, noted during a cutaneous flare without clinical or endoscopically identified underlying bowel involvement—is an extremely rare presentation. Literature regarding management of PSV primarily is found in the form of case reports and focuses on treating underlying IBD. In patients with intestinal disease, treatment with biologic therapy appears most effective.^6,23

ADDENDUM

Interestingly, 3 years after the patient’s original presentation to our clinic, chromosomal sequencing analysis to assess for copy number variants and whole exome gene sequencing identified a variant of unknown significance in the heat shock protein family A member 1-like gene, HSPA1L, which has an unknown mode of inheritance, but the literature suggests that both truncating and missense variants could be associated with individuals with ulcerative colitis, CD, and IBD.^37,38 Although we cannot use this information to render a molecular diagnosis, it is highly suspicious that this is the cause of her clinical findings. Additionally, the patient currently is aged 10 years with unchanged cutaneous findings and has not developed gastrointestinal findings of IBD.

New COVID-19 cases in children jumped by 66% during the first 2 weeks of December after an 8-week steady period lasting through October and November, according to the American Academy of Pediatrics and the Children’s Hospital Association.

New cases reached close to 48,000 for the most recent reporting week, Dec. 9-15, after rising to just over 41,000 the previous week and totaling less than 29,000 for the week of Nov. 25 to Dec. 1. That increase of almost 19,000 cases is the largest over a 2-week period since late July, the AAP and CHA said in their weekly COVID report based on data collected from state and territorial health department websites.

[This publication has been following the AAP/CHA report since the summer of 2020 and continues to share the data for the sake of consistency, but it must be noted that a number of states are no longer updating their public COVID dashboards. As a result, there is now a considerable discrepancy between the AAP/CHA weekly figures and those reported by the Centers for Disease Control and Prevention, which has no such limitations on state data.]

The situation involving new cases over the last 2 weeks is quite different from the CDC’s perspective. The agency does not publish a weekly count, instead offering cumulative cases, which stood at almost 16.1 million as of Dec. 14. Calculating a 2-week total puts the new-case count for Dec. 1-14 at 113,572 among children aged 0-17 years. That is higher than the AAP/CHA count (88,629) for roughly the same period, but it is actually lower than the CDC’s figure (161,832) for the last 2 weeks of November.

The CDC data, in other words, suggest that new cases have gone down in the last 2 weeks, while the AAP and CHA, with their somewhat limited perspective, announced that new cases have gone up.

One COVID-related measure from the CDC that is not contradicted by other sources is hospitalization rates, which had climbed from 0.16 new admissions in children aged 0-17 years with confirmed COVID per 100,000 population on Oct. 22 to 0.29 per 100,000 on Dec. 9. Visits to the emergency department with diagnosed COVID, meanwhile, have been fairly steady so far through December in children, according to the CDC.

New COVID-19 cases in children jumped by 66% during the first 2 weeks of December after an 8-week steady period lasting through October and November, according to the American Academy of Pediatrics and the Children’s Hospital Association.

New cases reached close to 48,000 for the most recent reporting week, Dec. 9-15, after rising to just over 41,000 the previous week and totaling less than 29,000 for the week of Nov. 25 to Dec. 1. That increase of almost 19,000 cases is the largest over a 2-week period since late July, the AAP and CHA said in their weekly COVID report based on data collected from state and territorial health department websites.

[This publication has been following the AAP/CHA report since the summer of 2020 and continues to share the data for the sake of consistency, but it must be noted that a number of states are no longer updating their public COVID dashboards. As a result, there is now a considerable discrepancy between the AAP/CHA weekly figures and those reported by the Centers for Disease Control and Prevention, which has no such limitations on state data.]

The situation involving new cases over the last 2 weeks is quite different from the CDC’s perspective. The agency does not publish a weekly count, instead offering cumulative cases, which stood at almost 16.1 million as of Dec. 14. Calculating a 2-week total puts the new-case count for Dec. 1-14 at 113,572 among children aged 0-17 years. That is higher than the AAP/CHA count (88,629) for roughly the same period, but it is actually lower than the CDC’s figure (161,832) for the last 2 weeks of November.

The CDC data, in other words, suggest that new cases have gone down in the last 2 weeks, while the AAP and CHA, with their somewhat limited perspective, announced that new cases have gone up.

One COVID-related measure from the CDC that is not contradicted by other sources is hospitalization rates, which had climbed from 0.16 new admissions in children aged 0-17 years with confirmed COVID per 100,000 population on Oct. 22 to 0.29 per 100,000 on Dec. 9. Visits to the emergency department with diagnosed COVID, meanwhile, have been fairly steady so far through December in children, according to the CDC.

New COVID-19 cases in children jumped by 66% during the first 2 weeks of December after an 8-week steady period lasting through October and November, according to the American Academy of Pediatrics and the Children’s Hospital Association.

New cases reached close to 48,000 for the most recent reporting week, Dec. 9-15, after rising to just over 41,000 the previous week and totaling less than 29,000 for the week of Nov. 25 to Dec. 1. That increase of almost 19,000 cases is the largest over a 2-week period since late July, the AAP and CHA said in their weekly COVID report based on data collected from state and territorial health department websites.

[This publication has been following the AAP/CHA report since the summer of 2020 and continues to share the data for the sake of consistency, but it must be noted that a number of states are no longer updating their public COVID dashboards. As a result, there is now a considerable discrepancy between the AAP/CHA weekly figures and those reported by the Centers for Disease Control and Prevention, which has no such limitations on state data.]

The situation involving new cases over the last 2 weeks is quite different from the CDC’s perspective. The agency does not publish a weekly count, instead offering cumulative cases, which stood at almost 16.1 million as of Dec. 14. Calculating a 2-week total puts the new-case count for Dec. 1-14 at 113,572 among children aged 0-17 years. That is higher than the AAP/CHA count (88,629) for roughly the same period, but it is actually lower than the CDC’s figure (161,832) for the last 2 weeks of November.

The CDC data, in other words, suggest that new cases have gone down in the last 2 weeks, while the AAP and CHA, with their somewhat limited perspective, announced that new cases have gone up.

One COVID-related measure from the CDC that is not contradicted by other sources is hospitalization rates, which had climbed from 0.16 new admissions in children aged 0-17 years with confirmed COVID per 100,000 population on Oct. 22 to 0.29 per 100,000 on Dec. 9. Visits to the emergency department with diagnosed COVID, meanwhile, have been fairly steady so far through December in children, according to the CDC.

An investigational vaccine against respiratory syncytial virus (RSV) in pregnant women has been shown to help protect infants against severe disease, according to the vaccine’s manufacturer.

Pfizer recently announced that in the course of a randomized, double-blind, placebo-controlled phase 3 study, the vaccine RSVpreF had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life, according to a company press release.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. A total of 7,400 women had received a single dose of 120 mcg RSVpreF in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Due to the good results, the enrollment in the study was halted on the recommendation of the study’s Data Monitoring Committee after achieving a primary endpoint. The company plans to apply for marketing authorization to the U.S. Food and Drug Administration by the end of 2022 and to other regulatory agencies in 2023.

“The directness of the strategy, to vaccinate expectant mothers during pregnancy so that their newborn is then later protected, is new and a very interesting approach,” commented Prof. Ortwin Adams, MD, head of virologic diagnostics at the Institute for Virology of the University Hospital of Düsseldorf (Germany) to the Science Media Centre (SMC).

In terms of the RSV vaccination strategy presented, “the unborn child has taken center stage from the outset.” Because the vaccination route is the placental transfer of antibodies from mother to child (“passive immunity”), “... the medical points of contact for this vaccination will be the gynecologists, not the pediatricians,” Dr. Adams said.

“This concept imitates the natural process, since the mother normally passes immune defenses she acquired through infections to the child via the umbilical cord and her breast milk before and after birth. This procedure is long-proven and practiced worldwide, especially in nonindustrialized countries, for a variety of diseases, including tetanus, whooping cough (pertussis), and viral flu (influenza),” explained Markus Rose, MD, PhD, head of Pediatric Pulmonology at the Olgahospital, Stuttgart, Germany.

The development of an RSV vaccine had ground to a halt for many decades: A tragedy in the 1960s set the whole field of research back. Using the model of the first polio vaccine, scientists had manufactured an experimental vaccine with inactivated viruses. However, tests showed that the vaccine did not protect the children vaccinated, but it actually infected them with RSV, they then fell ill, and two children died. Today, potential RSV vaccines are first tested on adults and not on children.
 

Few treatment options

RSV causes seasonal epidemics, can lead to bronchiolitis and pneumonia in infants, and is one of the main causes of hospital stays in young children. Monoclonal antibodies are currently the only preventive option, since there is still no vaccine. Usually, 60%-70% of infants and nearly all children younger than 2 years are infected with RSV, but the virus can also trigger pneumonia in adults.

“RSV infections constitute a major public health challenge: It is the most dangerous respiratory virus for young infants, it is also a threat to the chronically ill and immunocompromised of all ages, and [it] is the second most common cause of death worldwide (after malaria) in young children,” stated Dr. Rose.

Recently, pandemic-related measures (face masks, more intense disinfection) meant that the “normal” RSV infections in healthy adults, which usually progress like a mild cold, were prevented, and mothers were unable to pass on as much RSV immune defense to their children. “This was presumably responsible in part for the massive wave of RSV infections in fall and winter of 2021/22,” explained Dr. Rose.

Thomas Mertens, MD, PhD, chair of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) and former director of the Institute for Virology at Ulm University Hospital, Germany, also noted: “It would be an important and potentially achievable goal to significantly reduce the incidence rate of hospitalizations. In this respect, RSV poses a significant problem for young children, their parents, and the burden on pediatric clinics.”
 

Final evaluation pending

“I am definitely finding the data interesting, but the original data are needed,” Dr. Mertens said. Once the data are published at a conference or published in a peer-reviewed journal, physicians will be able to better judge the data for themselves, he said.

Dr. Rose characterized the new vaccine as “novel,” including in terms of its composition. Earlier RSV vaccines used the so-called postfusion F protein as their starting point. But it has become known in the meantime that the key to immunogenicity is the continued prefusion state of the apical epitope: Prefusion F-specific memory B cells in adults naturally infected with RSV produce potent neutralizing antibodies.

The new vaccine is bivalent and protects against both RSV A and RSV B.

To date, RSV vaccination directly in young infants have had only had a weak efficacy and were sometimes poorly tolerated. The vaccine presented here is expected to be tested in young adults first, then in school children, then young children.

Through successful vaccination of the entire population, the transfer of RS viruses to young children could be prevented. “To what extent this, or any other RSV vaccine still to be developed on the same basis, will also be effective and well tolerated in young infants is still difficult to assess,” said Dr. Rose.

Dr. Mertens emphasized that all of the study data now needs to be seen as quickly as possible: “This is also a general requirement for transparency from the pharmaceutical companies, which is also rightly criticized.”

This article was originally published in Medscape’s German edition and a version appeared on Medscape.com.

An investigational vaccine against respiratory syncytial virus (RSV) in pregnant women has been shown to help protect infants against severe disease, according to the vaccine’s manufacturer.

Pfizer recently announced that in the course of a randomized, double-blind, placebo-controlled phase 3 study, the vaccine RSVpreF had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life, according to a company press release.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. A total of 7,400 women had received a single dose of 120 mcg RSVpreF in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Due to the good results, the enrollment in the study was halted on the recommendation of the study’s Data Monitoring Committee after achieving a primary endpoint. The company plans to apply for marketing authorization to the U.S. Food and Drug Administration by the end of 2022 and to other regulatory agencies in 2023.

“The directness of the strategy, to vaccinate expectant mothers during pregnancy so that their newborn is then later protected, is new and a very interesting approach,” commented Prof. Ortwin Adams, MD, head of virologic diagnostics at the Institute for Virology of the University Hospital of Düsseldorf (Germany) to the Science Media Centre (SMC).

In terms of the RSV vaccination strategy presented, “the unborn child has taken center stage from the outset.” Because the vaccination route is the placental transfer of antibodies from mother to child (“passive immunity”), “... the medical points of contact for this vaccination will be the gynecologists, not the pediatricians,” Dr. Adams said.

“This concept imitates the natural process, since the mother normally passes immune defenses she acquired through infections to the child via the umbilical cord and her breast milk before and after birth. This procedure is long-proven and practiced worldwide, especially in nonindustrialized countries, for a variety of diseases, including tetanus, whooping cough (pertussis), and viral flu (influenza),” explained Markus Rose, MD, PhD, head of Pediatric Pulmonology at the Olgahospital, Stuttgart, Germany.

The development of an RSV vaccine had ground to a halt for many decades: A tragedy in the 1960s set the whole field of research back. Using the model of the first polio vaccine, scientists had manufactured an experimental vaccine with inactivated viruses. However, tests showed that the vaccine did not protect the children vaccinated, but it actually infected them with RSV, they then fell ill, and two children died. Today, potential RSV vaccines are first tested on adults and not on children.
 

Few treatment options

RSV causes seasonal epidemics, can lead to bronchiolitis and pneumonia in infants, and is one of the main causes of hospital stays in young children. Monoclonal antibodies are currently the only preventive option, since there is still no vaccine. Usually, 60%-70% of infants and nearly all children younger than 2 years are infected with RSV, but the virus can also trigger pneumonia in adults.

“RSV infections constitute a major public health challenge: It is the most dangerous respiratory virus for young infants, it is also a threat to the chronically ill and immunocompromised of all ages, and [it] is the second most common cause of death worldwide (after malaria) in young children,” stated Dr. Rose.

Recently, pandemic-related measures (face masks, more intense disinfection) meant that the “normal” RSV infections in healthy adults, which usually progress like a mild cold, were prevented, and mothers were unable to pass on as much RSV immune defense to their children. “This was presumably responsible in part for the massive wave of RSV infections in fall and winter of 2021/22,” explained Dr. Rose.

Thomas Mertens, MD, PhD, chair of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) and former director of the Institute for Virology at Ulm University Hospital, Germany, also noted: “It would be an important and potentially achievable goal to significantly reduce the incidence rate of hospitalizations. In this respect, RSV poses a significant problem for young children, their parents, and the burden on pediatric clinics.”
 

Final evaluation pending

“I am definitely finding the data interesting, but the original data are needed,” Dr. Mertens said. Once the data are published at a conference or published in a peer-reviewed journal, physicians will be able to better judge the data for themselves, he said.

Dr. Rose characterized the new vaccine as “novel,” including in terms of its composition. Earlier RSV vaccines used the so-called postfusion F protein as their starting point. But it has become known in the meantime that the key to immunogenicity is the continued prefusion state of the apical epitope: Prefusion F-specific memory B cells in adults naturally infected with RSV produce potent neutralizing antibodies.

The new vaccine is bivalent and protects against both RSV A and RSV B.

To date, RSV vaccination directly in young infants have had only had a weak efficacy and were sometimes poorly tolerated. The vaccine presented here is expected to be tested in young adults first, then in school children, then young children.

Through successful vaccination of the entire population, the transfer of RS viruses to young children could be prevented. “To what extent this, or any other RSV vaccine still to be developed on the same basis, will also be effective and well tolerated in young infants is still difficult to assess,” said Dr. Rose.

Dr. Mertens emphasized that all of the study data now needs to be seen as quickly as possible: “This is also a general requirement for transparency from the pharmaceutical companies, which is also rightly criticized.”

This article was originally published in Medscape’s German edition and a version appeared on Medscape.com.

An investigational vaccine against respiratory syncytial virus (RSV) in pregnant women has been shown to help protect infants against severe disease, according to the vaccine’s manufacturer.

Pfizer recently announced that in the course of a randomized, double-blind, placebo-controlled phase 3 study, the vaccine RSVpreF had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life, according to a company press release.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. A total of 7,400 women had received a single dose of 120 mcg RSVpreF in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Due to the good results, the enrollment in the study was halted on the recommendation of the study’s Data Monitoring Committee after achieving a primary endpoint. The company plans to apply for marketing authorization to the U.S. Food and Drug Administration by the end of 2022 and to other regulatory agencies in 2023.

“The directness of the strategy, to vaccinate expectant mothers during pregnancy so that their newborn is then later protected, is new and a very interesting approach,” commented Prof. Ortwin Adams, MD, head of virologic diagnostics at the Institute for Virology of the University Hospital of Düsseldorf (Germany) to the Science Media Centre (SMC).

In terms of the RSV vaccination strategy presented, “the unborn child has taken center stage from the outset.” Because the vaccination route is the placental transfer of antibodies from mother to child (“passive immunity”), “... the medical points of contact for this vaccination will be the gynecologists, not the pediatricians,” Dr. Adams said.

“This concept imitates the natural process, since the mother normally passes immune defenses she acquired through infections to the child via the umbilical cord and her breast milk before and after birth. This procedure is long-proven and practiced worldwide, especially in nonindustrialized countries, for a variety of diseases, including tetanus, whooping cough (pertussis), and viral flu (influenza),” explained Markus Rose, MD, PhD, head of Pediatric Pulmonology at the Olgahospital, Stuttgart, Germany.

The development of an RSV vaccine had ground to a halt for many decades: A tragedy in the 1960s set the whole field of research back. Using the model of the first polio vaccine, scientists had manufactured an experimental vaccine with inactivated viruses. However, tests showed that the vaccine did not protect the children vaccinated, but it actually infected them with RSV, they then fell ill, and two children died. Today, potential RSV vaccines are first tested on adults and not on children.
 

Few treatment options

RSV causes seasonal epidemics, can lead to bronchiolitis and pneumonia in infants, and is one of the main causes of hospital stays in young children. Monoclonal antibodies are currently the only preventive option, since there is still no vaccine. Usually, 60%-70% of infants and nearly all children younger than 2 years are infected with RSV, but the virus can also trigger pneumonia in adults.

“RSV infections constitute a major public health challenge: It is the most dangerous respiratory virus for young infants, it is also a threat to the chronically ill and immunocompromised of all ages, and [it] is the second most common cause of death worldwide (after malaria) in young children,” stated Dr. Rose.

Recently, pandemic-related measures (face masks, more intense disinfection) meant that the “normal” RSV infections in healthy adults, which usually progress like a mild cold, were prevented, and mothers were unable to pass on as much RSV immune defense to their children. “This was presumably responsible in part for the massive wave of RSV infections in fall and winter of 2021/22,” explained Dr. Rose.

Thomas Mertens, MD, PhD, chair of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) and former director of the Institute for Virology at Ulm University Hospital, Germany, also noted: “It would be an important and potentially achievable goal to significantly reduce the incidence rate of hospitalizations. In this respect, RSV poses a significant problem for young children, their parents, and the burden on pediatric clinics.”
 

Final evaluation pending

“I am definitely finding the data interesting, but the original data are needed,” Dr. Mertens said. Once the data are published at a conference or published in a peer-reviewed journal, physicians will be able to better judge the data for themselves, he said.

Dr. Rose characterized the new vaccine as “novel,” including in terms of its composition. Earlier RSV vaccines used the so-called postfusion F protein as their starting point. But it has become known in the meantime that the key to immunogenicity is the continued prefusion state of the apical epitope: Prefusion F-specific memory B cells in adults naturally infected with RSV produce potent neutralizing antibodies.

The new vaccine is bivalent and protects against both RSV A and RSV B.

To date, RSV vaccination directly in young infants have had only had a weak efficacy and were sometimes poorly tolerated. The vaccine presented here is expected to be tested in young adults first, then in school children, then young children.

Through successful vaccination of the entire population, the transfer of RS viruses to young children could be prevented. “To what extent this, or any other RSV vaccine still to be developed on the same basis, will also be effective and well tolerated in young infants is still difficult to assess,” said Dr. Rose.

Dr. Mertens emphasized that all of the study data now needs to be seen as quickly as possible: “This is also a general requirement for transparency from the pharmaceutical companies, which is also rightly criticized.”

This article was originally published in Medscape’s German edition and a version appeared on Medscape.com.

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

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

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

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

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

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

Roflumilast cream 0.3% is under review by the Food and Drug Administration for the treatment of plaque psoriasis in children as young as 2 years, according to a press release from the manufacturer.

The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.

The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.

Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.

Roflumilast cream 0.3% is under review by the Food and Drug Administration for the treatment of plaque psoriasis in children as young as 2 years, according to a press release from the manufacturer.

The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.

The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.

Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.

Roflumilast cream 0.3% is under review by the Food and Drug Administration for the treatment of plaque psoriasis in children as young as 2 years, according to a press release from the manufacturer.

The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.

The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.

Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.