Pediatrics

The effectiveness of the human papillomavirus (HPV) vaccine against HPV types 16 and 18 is highly dependent on the age at which it is given. Prevalence rates have been shown to be significantly lower among girls who are vaccinated at the recommended ages of 9-12 years, compared with those who are vaccinated after their sexual debut, data from the National Health and Nutrition Examination Survey (NHANES) indicate.

“HPV vaccination does not have any therapeutic effect on HPV infections already acquired, which is more likely to explain the difference in prevalence between predebut versus postdebut recipients than a lower immune response [among older recipients],” lead study author Didem Egemen, PhD, National Cancer Institute, Rockville, Md., told this news organization in an email.

“Still, among older females, the immune response of the vaccine is likely to still be quite strong, and we would encourage vaccination [of female patients] if unvaccinated, as our paper showed that vaccination post debut will still reduce HPV 16/18 prevalence by half,” she added.

The research letter was published online in JAMA Network Open.
 

National sample evaluated

Using data from NHANES, a biennial, cross-sectional sample (cycles 2011 through 2018), the researchers identified female persons who were aged 26 years or younger in 2006, when HPV vaccination was introduced, and who were eligible for routine vaccination or “catch-up” vaccination (given between the ages of 13 and 26 years), as per recommendations from the Advisory Committee on Immunization Practices. The investigators then compared the prevalence of HPV types 16 and 18 among unvaccinated female patients, female patients who had been vaccinated prior to their sexual debut (predebut group), and those who had been vaccinated after their sexual debut (postdebut group).

They also estimated vaccine uptake among those who were eligible for routine vaccination, as well as the proportion of vaccinated female patients with respect to racial and ethnic subgroups.

In the overall cohort, the prevalence of HPV types 16 and 18 decreased by 6% (95% confidence interval, 4%-7%) in the unvaccinated group to 3% (95% CI, 1%-6%) in the postdebut group and to less than 1% (95% CI, <1%-1%) in the predebut group, Dr. Egemen and colleagues report.

In real percentages, the prevalence of HPV 16 and 18 was 89% lower in the predebut group (P < .001) but only 41% lower in the postdebut group (P = .29) compared with unvaccinated female patients. And compared with female patients who were vaccinated after their sexual debut, the prevalence of HPV 16 and 18 was reduced by 82% among those who had received the vaccine at the recommended ages of 9-12 years (P = .08).

In the current study, Dr. Egeman acknowledged that only 38% of ever-eligible female patients received the vaccine, although the prevalence increased to 56% when only female patients who were eligible for routine vaccination were taken into account. On the other hand, only 21% (95% CI, 14%-28%) of female patients eligible for routine vaccination received their first dose by age 12 years.

Indeed, the mean age on receipt of the first vaccination dose was 14.5 years (95% CI, 14.1-14.8 years), the authors note, and only 59% of girls received their first dose prior to their sexual debut. Additionally, among routine vaccination–eligible girls aged 12 years or younger in 2006, 33% were vaccinated before and 23% after their sexual debut, and the rest were not vaccinated.

Interestingly, differences in the age at which the HPV vaccine was received by race and ethnicity were negligible, the investigators point out.
 

Vaccination rates increasing

Asked to comment on the findings, Rebecca Perkins, MD, professor of obstetrics and gynecology at Boston University, Boston Medical Center, pointed out that the investigators evaluated data from 2011 to 2018. “We know that HPV vaccination rates have increased over that period and continue to increase,” she emphasized in an email to this news organization.

Physicians also know that more persons are being vaccinated between the ages of 9 and 12 than was the case at the beginning of this study. “This is good news,” she said, “as it means that more adolescents now in 2022 are benefiting fully from vaccination than they were in 2011,” she added.

At the same time, Dr. Perkins acknowledged that many persons are still missing out on the chance to receive the vaccine on time – which means they are missing out on the chance to prevent cancer.

“Making sure that all adolescents receive vaccination between the ages of 9 to 12 has the potential to prevent up to 40,000 cancers every year in the U.S., [including] the most common HPV-related cancers, such as cervical cancer in women and tongue and tonsillar cancer in men,” Dr. Perkins noted.

“Thus, it’s critical that doctors and parents get the message that you can’t vaccinate too early, only too late,” she emphasized.

Dr. Edgman and Dr. Perkins report no relevant financial relationships.

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

The effectiveness of the human papillomavirus (HPV) vaccine against HPV types 16 and 18 is highly dependent on the age at which it is given. Prevalence rates have been shown to be significantly lower among girls who are vaccinated at the recommended ages of 9-12 years, compared with those who are vaccinated after their sexual debut, data from the National Health and Nutrition Examination Survey (NHANES) indicate.

“HPV vaccination does not have any therapeutic effect on HPV infections already acquired, which is more likely to explain the difference in prevalence between predebut versus postdebut recipients than a lower immune response [among older recipients],” lead study author Didem Egemen, PhD, National Cancer Institute, Rockville, Md., told this news organization in an email.

“Still, among older females, the immune response of the vaccine is likely to still be quite strong, and we would encourage vaccination [of female patients] if unvaccinated, as our paper showed that vaccination post debut will still reduce HPV 16/18 prevalence by half,” she added.

The research letter was published online in JAMA Network Open.
 

National sample evaluated

Using data from NHANES, a biennial, cross-sectional sample (cycles 2011 through 2018), the researchers identified female persons who were aged 26 years or younger in 2006, when HPV vaccination was introduced, and who were eligible for routine vaccination or “catch-up” vaccination (given between the ages of 13 and 26 years), as per recommendations from the Advisory Committee on Immunization Practices. The investigators then compared the prevalence of HPV types 16 and 18 among unvaccinated female patients, female patients who had been vaccinated prior to their sexual debut (predebut group), and those who had been vaccinated after their sexual debut (postdebut group).

They also estimated vaccine uptake among those who were eligible for routine vaccination, as well as the proportion of vaccinated female patients with respect to racial and ethnic subgroups.

In the overall cohort, the prevalence of HPV types 16 and 18 decreased by 6% (95% confidence interval, 4%-7%) in the unvaccinated group to 3% (95% CI, 1%-6%) in the postdebut group and to less than 1% (95% CI, <1%-1%) in the predebut group, Dr. Egemen and colleagues report.

In real percentages, the prevalence of HPV 16 and 18 was 89% lower in the predebut group (P < .001) but only 41% lower in the postdebut group (P = .29) compared with unvaccinated female patients. And compared with female patients who were vaccinated after their sexual debut, the prevalence of HPV 16 and 18 was reduced by 82% among those who had received the vaccine at the recommended ages of 9-12 years (P = .08).

In the current study, Dr. Egeman acknowledged that only 38% of ever-eligible female patients received the vaccine, although the prevalence increased to 56% when only female patients who were eligible for routine vaccination were taken into account. On the other hand, only 21% (95% CI, 14%-28%) of female patients eligible for routine vaccination received their first dose by age 12 years.

Indeed, the mean age on receipt of the first vaccination dose was 14.5 years (95% CI, 14.1-14.8 years), the authors note, and only 59% of girls received their first dose prior to their sexual debut. Additionally, among routine vaccination–eligible girls aged 12 years or younger in 2006, 33% were vaccinated before and 23% after their sexual debut, and the rest were not vaccinated.

Interestingly, differences in the age at which the HPV vaccine was received by race and ethnicity were negligible, the investigators point out.
 

Vaccination rates increasing

Asked to comment on the findings, Rebecca Perkins, MD, professor of obstetrics and gynecology at Boston University, Boston Medical Center, pointed out that the investigators evaluated data from 2011 to 2018. “We know that HPV vaccination rates have increased over that period and continue to increase,” she emphasized in an email to this news organization.

Physicians also know that more persons are being vaccinated between the ages of 9 and 12 than was the case at the beginning of this study. “This is good news,” she said, “as it means that more adolescents now in 2022 are benefiting fully from vaccination than they were in 2011,” she added.

At the same time, Dr. Perkins acknowledged that many persons are still missing out on the chance to receive the vaccine on time – which means they are missing out on the chance to prevent cancer.

“Making sure that all adolescents receive vaccination between the ages of 9 to 12 has the potential to prevent up to 40,000 cancers every year in the U.S., [including] the most common HPV-related cancers, such as cervical cancer in women and tongue and tonsillar cancer in men,” Dr. Perkins noted.

“Thus, it’s critical that doctors and parents get the message that you can’t vaccinate too early, only too late,” she emphasized.

Dr. Edgman and Dr. Perkins report no relevant financial relationships.

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

The effectiveness of the human papillomavirus (HPV) vaccine against HPV types 16 and 18 is highly dependent on the age at which it is given. Prevalence rates have been shown to be significantly lower among girls who are vaccinated at the recommended ages of 9-12 years, compared with those who are vaccinated after their sexual debut, data from the National Health and Nutrition Examination Survey (NHANES) indicate.

“HPV vaccination does not have any therapeutic effect on HPV infections already acquired, which is more likely to explain the difference in prevalence between predebut versus postdebut recipients than a lower immune response [among older recipients],” lead study author Didem Egemen, PhD, National Cancer Institute, Rockville, Md., told this news organization in an email.

“Still, among older females, the immune response of the vaccine is likely to still be quite strong, and we would encourage vaccination [of female patients] if unvaccinated, as our paper showed that vaccination post debut will still reduce HPV 16/18 prevalence by half,” she added.

The research letter was published online in JAMA Network Open.
 

National sample evaluated

Using data from NHANES, a biennial, cross-sectional sample (cycles 2011 through 2018), the researchers identified female persons who were aged 26 years or younger in 2006, when HPV vaccination was introduced, and who were eligible for routine vaccination or “catch-up” vaccination (given between the ages of 13 and 26 years), as per recommendations from the Advisory Committee on Immunization Practices. The investigators then compared the prevalence of HPV types 16 and 18 among unvaccinated female patients, female patients who had been vaccinated prior to their sexual debut (predebut group), and those who had been vaccinated after their sexual debut (postdebut group).

They also estimated vaccine uptake among those who were eligible for routine vaccination, as well as the proportion of vaccinated female patients with respect to racial and ethnic subgroups.

In the overall cohort, the prevalence of HPV types 16 and 18 decreased by 6% (95% confidence interval, 4%-7%) in the unvaccinated group to 3% (95% CI, 1%-6%) in the postdebut group and to less than 1% (95% CI, <1%-1%) in the predebut group, Dr. Egemen and colleagues report.

In real percentages, the prevalence of HPV 16 and 18 was 89% lower in the predebut group (P < .001) but only 41% lower in the postdebut group (P = .29) compared with unvaccinated female patients. And compared with female patients who were vaccinated after their sexual debut, the prevalence of HPV 16 and 18 was reduced by 82% among those who had received the vaccine at the recommended ages of 9-12 years (P = .08).

In the current study, Dr. Egeman acknowledged that only 38% of ever-eligible female patients received the vaccine, although the prevalence increased to 56% when only female patients who were eligible for routine vaccination were taken into account. On the other hand, only 21% (95% CI, 14%-28%) of female patients eligible for routine vaccination received their first dose by age 12 years.

Indeed, the mean age on receipt of the first vaccination dose was 14.5 years (95% CI, 14.1-14.8 years), the authors note, and only 59% of girls received their first dose prior to their sexual debut. Additionally, among routine vaccination–eligible girls aged 12 years or younger in 2006, 33% were vaccinated before and 23% after their sexual debut, and the rest were not vaccinated.

Interestingly, differences in the age at which the HPV vaccine was received by race and ethnicity were negligible, the investigators point out.
 

Vaccination rates increasing

Asked to comment on the findings, Rebecca Perkins, MD, professor of obstetrics and gynecology at Boston University, Boston Medical Center, pointed out that the investigators evaluated data from 2011 to 2018. “We know that HPV vaccination rates have increased over that period and continue to increase,” she emphasized in an email to this news organization.

Physicians also know that more persons are being vaccinated between the ages of 9 and 12 than was the case at the beginning of this study. “This is good news,” she said, “as it means that more adolescents now in 2022 are benefiting fully from vaccination than they were in 2011,” she added.

At the same time, Dr. Perkins acknowledged that many persons are still missing out on the chance to receive the vaccine on time – which means they are missing out on the chance to prevent cancer.

“Making sure that all adolescents receive vaccination between the ages of 9 to 12 has the potential to prevent up to 40,000 cancers every year in the U.S., [including] the most common HPV-related cancers, such as cervical cancer in women and tongue and tonsillar cancer in men,” Dr. Perkins noted.

“Thus, it’s critical that doctors and parents get the message that you can’t vaccinate too early, only too late,” she emphasized.

Dr. Edgman and Dr. Perkins report no relevant financial relationships.

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

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

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

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

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

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

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

The Food and Drug Administration has expanded the indication for tenofovir alafenamide (Vemlidy) to children aged 12 years and older with chronic hepatitis B virus (HBV) infection with compensated liver disease, the drug’s manufacturer has announced.

The approval in the pediatric patient population was supported by 24-week data from a phase 2 clinical trial comparing treatment with tenofovir alafenamide (25 mg once daily) with placebo in 70 treatment-naive and treatment-experienced patients aged 12-18 years weighing at least 35 kg.

The study met its primary endpoint of percentage of patients with HBV DNA levels less than 20 IU/mL at 24 weeks of therapy, Gilead Sciences said in a press release.

Overall, 10 of 47 (21%) patients treated with tenofovir alafenamide achieved HBV DNA less than 20 IU/mL at 24 weeks, compared with 0 of 23 (0%) treated with placebo.

The rates of serum ALT normalization were higher with tenofovir alafenamide than with placebo (44% vs 0%).

The mean percent changes in bone mineral density (BMD) from baseline to 24 weeks were numerically similar for tenofovir alafenamide– and placebo-treated patients (2.4% and 1.9% for lumbar spine, and 1.5% and 1.9% for whole body, respectively).

The mean changes from baseline BMD z scores were –0.03 and –0.09 for lumbar spine, and –0.05 and –0.01 for whole body, for tenofovir alafenamide and placebo groups, respectively.

The FDA initially approved the nucleoside analog reverse transcriptase inhibitor in 2016 for adults with chronic HBV.

The drug was approved in Europe in 2017 for chronic HBV infection in adults and adolescents aged 12 years and older weighing at least 35 kg.

Tenofovir alafenamide carries a boxed warning citing risks for lactic acidosis/severe hepatomegaly with steatosis and posttreatment severe acute exacerbation of HBV.

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

The Food and Drug Administration has expanded the indication for tenofovir alafenamide (Vemlidy) to children aged 12 years and older with chronic hepatitis B virus (HBV) infection with compensated liver disease, the drug’s manufacturer has announced.

The approval in the pediatric patient population was supported by 24-week data from a phase 2 clinical trial comparing treatment with tenofovir alafenamide (25 mg once daily) with placebo in 70 treatment-naive and treatment-experienced patients aged 12-18 years weighing at least 35 kg.

The study met its primary endpoint of percentage of patients with HBV DNA levels less than 20 IU/mL at 24 weeks of therapy, Gilead Sciences said in a press release.

Overall, 10 of 47 (21%) patients treated with tenofovir alafenamide achieved HBV DNA less than 20 IU/mL at 24 weeks, compared with 0 of 23 (0%) treated with placebo.

The rates of serum ALT normalization were higher with tenofovir alafenamide than with placebo (44% vs 0%).

The mean percent changes in bone mineral density (BMD) from baseline to 24 weeks were numerically similar for tenofovir alafenamide– and placebo-treated patients (2.4% and 1.9% for lumbar spine, and 1.5% and 1.9% for whole body, respectively).

The mean changes from baseline BMD z scores were –0.03 and –0.09 for lumbar spine, and –0.05 and –0.01 for whole body, for tenofovir alafenamide and placebo groups, respectively.

The FDA initially approved the nucleoside analog reverse transcriptase inhibitor in 2016 for adults with chronic HBV.

The drug was approved in Europe in 2017 for chronic HBV infection in adults and adolescents aged 12 years and older weighing at least 35 kg.

Tenofovir alafenamide carries a boxed warning citing risks for lactic acidosis/severe hepatomegaly with steatosis and posttreatment severe acute exacerbation of HBV.

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

The Food and Drug Administration has expanded the indication for tenofovir alafenamide (Vemlidy) to children aged 12 years and older with chronic hepatitis B virus (HBV) infection with compensated liver disease, the drug’s manufacturer has announced.

The approval in the pediatric patient population was supported by 24-week data from a phase 2 clinical trial comparing treatment with tenofovir alafenamide (25 mg once daily) with placebo in 70 treatment-naive and treatment-experienced patients aged 12-18 years weighing at least 35 kg.

The study met its primary endpoint of percentage of patients with HBV DNA levels less than 20 IU/mL at 24 weeks of therapy, Gilead Sciences said in a press release.

Overall, 10 of 47 (21%) patients treated with tenofovir alafenamide achieved HBV DNA less than 20 IU/mL at 24 weeks, compared with 0 of 23 (0%) treated with placebo.

The rates of serum ALT normalization were higher with tenofovir alafenamide than with placebo (44% vs 0%).

The mean percent changes in bone mineral density (BMD) from baseline to 24 weeks were numerically similar for tenofovir alafenamide– and placebo-treated patients (2.4% and 1.9% for lumbar spine, and 1.5% and 1.9% for whole body, respectively).

The mean changes from baseline BMD z scores were –0.03 and –0.09 for lumbar spine, and –0.05 and –0.01 for whole body, for tenofovir alafenamide and placebo groups, respectively.

The FDA initially approved the nucleoside analog reverse transcriptase inhibitor in 2016 for adults with chronic HBV.

The drug was approved in Europe in 2017 for chronic HBV infection in adults and adolescents aged 12 years and older weighing at least 35 kg.

Tenofovir alafenamide carries a boxed warning citing risks for lactic acidosis/severe hepatomegaly with steatosis and posttreatment severe acute exacerbation of HBV.

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

Vaping has become the dominant form of tobacco use by adolescents in the United States immediately after waking up, according to an analysis of a survey on teen tobacco use published in JAMA Network Open.

By 2019, Stanton Glantz, PhD, and associates found, “more e-cigarette users were using their first tobacco product within 5 minutes of waking than users of cigarettes and all other tobacco products combined.” Use upon waking is an indicator of addiction.

That number changed drastically from 2014 when less than 1% of sole-e-cigarette users were using e-cigarettes first thing in the morning to 10.3% by 2021. The numbers did not change for sole cigarette smokers or sole smokeless tobacco users, but did increase by half (odds ratio per year, 1.49) for sole cigar users.

In addition, among adolescents who currently use any tobacco product, the proportion whose first tobacco product was e-cigarettes increased from 27.2% in 2014 to 78.3% in 2019 and remained close to that at 77% in 2021.

Meanwhile, the number of young people using e-cigarettes peaked in 2019 and has been declining.

By 2019, the Centers for Disease Control and Prevention estimated that 5.3 million middle and high school students were using e-cigarettes. That number dropped to 3.6 million in 2020 and to 2.1 million in 2021 during the COVID-19 pandemic.
 

Researchers suspect more addictive nicotine

This increasing intensity of use may reflect the higher nicotine delivery and addiction liability of modern e-cigarettes that use protonated nicotine, which makes nicotine easier to inhale than older versions of e-cigarettes, which used freebase nicotine, Dr. Glantz and associates wrote.

The change in nicotine came in 2015 with the introduction of Juul products, they said, “which added benzoic acid to the nicotine e-liquid to lower the pH level and form protonated nicotine.”

The researchers advised: “Clinicians should question all their patients about nicotine and tobacco product use, including e-cigarettes and other new nicotine products.”

Raghu Appasani, MD, a psychiatrist who specializes in adolescent addiction and a clinical fellow at University of California, San Francisco, said in an interview that users often misunderstand the potential health effects of e-cigarettes and mistakenly think of them as a safe alternative to cigarettes.

All medical providers have a responsibility to ask patients about nicotine and tobacco products, Dr. Appasani said.
 

‘Be curious, not judgmental’

Dr. Appasani advised: “Be curious with your approach. This may uncover that maybe they use [e-cigarettes] to fit into a social scene or have stressors at home or in school. Most likely there is an underlying issue that has led to their use. Perhaps there is untreated anxiety and/or depression. Be curious, not judgmental.”

It is also important to ask about social and psychological factors that may be contributing to use and help the user think through how the use is affecting life in their home, school, and social settings, Dr. Appasani said.

He said he was not surprised by the findings as e-cigarettes allow easy access to smoking and it’s easier to hide the habit. The flavoring often get kids hooked originally.

The authors wrote: “These findings suggest that clinicians need to be ready to address youth addiction to these new highly addictive nicotine products during many clinical encounters, and stronger regulation is needed, including comprehensive bans on the sale of flavored tobacco products.”

Just more than half of the survey respondents (51.1%) were male and average age was 14. Researchers analyzed data from the National Youth Tobacco Survey, a nationally representative survey of middle and high school students.

They used the Youth Behavioral Risk Factor Surveillance System from 2015 to 2019 as a confirmatory analysis.

This study was supported in part by grants from the National Cancer Institute. Dr. Glantz received personal fees from the World Health Organization outside the submitted work. One coauthor reported serving as a paid expert witness against the tobacco industry outside the submitted work. No other disclosures were reported. Dr. Appasani declared no relevant financial relationships.

Vaping has become the dominant form of tobacco use by adolescents in the United States immediately after waking up, according to an analysis of a survey on teen tobacco use published in JAMA Network Open.

By 2019, Stanton Glantz, PhD, and associates found, “more e-cigarette users were using their first tobacco product within 5 minutes of waking than users of cigarettes and all other tobacco products combined.” Use upon waking is an indicator of addiction.

That number changed drastically from 2014 when less than 1% of sole-e-cigarette users were using e-cigarettes first thing in the morning to 10.3% by 2021. The numbers did not change for sole cigarette smokers or sole smokeless tobacco users, but did increase by half (odds ratio per year, 1.49) for sole cigar users.

In addition, among adolescents who currently use any tobacco product, the proportion whose first tobacco product was e-cigarettes increased from 27.2% in 2014 to 78.3% in 2019 and remained close to that at 77% in 2021.

Meanwhile, the number of young people using e-cigarettes peaked in 2019 and has been declining.

By 2019, the Centers for Disease Control and Prevention estimated that 5.3 million middle and high school students were using e-cigarettes. That number dropped to 3.6 million in 2020 and to 2.1 million in 2021 during the COVID-19 pandemic.
 

Researchers suspect more addictive nicotine

This increasing intensity of use may reflect the higher nicotine delivery and addiction liability of modern e-cigarettes that use protonated nicotine, which makes nicotine easier to inhale than older versions of e-cigarettes, which used freebase nicotine, Dr. Glantz and associates wrote.

The change in nicotine came in 2015 with the introduction of Juul products, they said, “which added benzoic acid to the nicotine e-liquid to lower the pH level and form protonated nicotine.”

The researchers advised: “Clinicians should question all their patients about nicotine and tobacco product use, including e-cigarettes and other new nicotine products.”

Raghu Appasani, MD, a psychiatrist who specializes in adolescent addiction and a clinical fellow at University of California, San Francisco, said in an interview that users often misunderstand the potential health effects of e-cigarettes and mistakenly think of them as a safe alternative to cigarettes.

All medical providers have a responsibility to ask patients about nicotine and tobacco products, Dr. Appasani said.
 

‘Be curious, not judgmental’

Dr. Appasani advised: “Be curious with your approach. This may uncover that maybe they use [e-cigarettes] to fit into a social scene or have stressors at home or in school. Most likely there is an underlying issue that has led to their use. Perhaps there is untreated anxiety and/or depression. Be curious, not judgmental.”

It is also important to ask about social and psychological factors that may be contributing to use and help the user think through how the use is affecting life in their home, school, and social settings, Dr. Appasani said.

He said he was not surprised by the findings as e-cigarettes allow easy access to smoking and it’s easier to hide the habit. The flavoring often get kids hooked originally.

The authors wrote: “These findings suggest that clinicians need to be ready to address youth addiction to these new highly addictive nicotine products during many clinical encounters, and stronger regulation is needed, including comprehensive bans on the sale of flavored tobacco products.”

Just more than half of the survey respondents (51.1%) were male and average age was 14. Researchers analyzed data from the National Youth Tobacco Survey, a nationally representative survey of middle and high school students.

They used the Youth Behavioral Risk Factor Surveillance System from 2015 to 2019 as a confirmatory analysis.

This study was supported in part by grants from the National Cancer Institute. Dr. Glantz received personal fees from the World Health Organization outside the submitted work. One coauthor reported serving as a paid expert witness against the tobacco industry outside the submitted work. No other disclosures were reported. Dr. Appasani declared no relevant financial relationships.

Vaping has become the dominant form of tobacco use by adolescents in the United States immediately after waking up, according to an analysis of a survey on teen tobacco use published in JAMA Network Open.

By 2019, Stanton Glantz, PhD, and associates found, “more e-cigarette users were using their first tobacco product within 5 minutes of waking than users of cigarettes and all other tobacco products combined.” Use upon waking is an indicator of addiction.

That number changed drastically from 2014 when less than 1% of sole-e-cigarette users were using e-cigarettes first thing in the morning to 10.3% by 2021. The numbers did not change for sole cigarette smokers or sole smokeless tobacco users, but did increase by half (odds ratio per year, 1.49) for sole cigar users.

In addition, among adolescents who currently use any tobacco product, the proportion whose first tobacco product was e-cigarettes increased from 27.2% in 2014 to 78.3% in 2019 and remained close to that at 77% in 2021.

Meanwhile, the number of young people using e-cigarettes peaked in 2019 and has been declining.

By 2019, the Centers for Disease Control and Prevention estimated that 5.3 million middle and high school students were using e-cigarettes. That number dropped to 3.6 million in 2020 and to 2.1 million in 2021 during the COVID-19 pandemic.
 

Researchers suspect more addictive nicotine

This increasing intensity of use may reflect the higher nicotine delivery and addiction liability of modern e-cigarettes that use protonated nicotine, which makes nicotine easier to inhale than older versions of e-cigarettes, which used freebase nicotine, Dr. Glantz and associates wrote.

The change in nicotine came in 2015 with the introduction of Juul products, they said, “which added benzoic acid to the nicotine e-liquid to lower the pH level and form protonated nicotine.”

The researchers advised: “Clinicians should question all their patients about nicotine and tobacco product use, including e-cigarettes and other new nicotine products.”

Raghu Appasani, MD, a psychiatrist who specializes in adolescent addiction and a clinical fellow at University of California, San Francisco, said in an interview that users often misunderstand the potential health effects of e-cigarettes and mistakenly think of them as a safe alternative to cigarettes.

All medical providers have a responsibility to ask patients about nicotine and tobacco products, Dr. Appasani said.
 

‘Be curious, not judgmental’

Dr. Appasani advised: “Be curious with your approach. This may uncover that maybe they use [e-cigarettes] to fit into a social scene or have stressors at home or in school. Most likely there is an underlying issue that has led to their use. Perhaps there is untreated anxiety and/or depression. Be curious, not judgmental.”

It is also important to ask about social and psychological factors that may be contributing to use and help the user think through how the use is affecting life in their home, school, and social settings, Dr. Appasani said.

He said he was not surprised by the findings as e-cigarettes allow easy access to smoking and it’s easier to hide the habit. The flavoring often get kids hooked originally.

The authors wrote: “These findings suggest that clinicians need to be ready to address youth addiction to these new highly addictive nicotine products during many clinical encounters, and stronger regulation is needed, including comprehensive bans on the sale of flavored tobacco products.”

Just more than half of the survey respondents (51.1%) were male and average age was 14. Researchers analyzed data from the National Youth Tobacco Survey, a nationally representative survey of middle and high school students.

They used the Youth Behavioral Risk Factor Surveillance System from 2015 to 2019 as a confirmatory analysis.

This study was supported in part by grants from the National Cancer Institute. Dr. Glantz received personal fees from the World Health Organization outside the submitted work. One coauthor reported serving as a paid expert witness against the tobacco industry outside the submitted work. No other disclosures were reported. Dr. Appasani declared no relevant financial relationships.

Perineuriomas are benign, slow-growing tumors derived from perineurial cells,¹ which form the structurally supportive perineurium that surrounds individual nerve fascicles.^2,3 Perineuriomas are classified into 2 main forms: intraneural or extraneural.⁴ Intraneural perineuriomas are found within the border of the peripheral nerve,⁵ while extraneural perineuriomas usually are found in soft tissue and skin. Extraneural perineuriomas can be further classified into variants based on their histologic appearance, including reticular, sclerosing, and plexiform subtypes. Extraneural perineuriomas usually present on the extremities or trunk of young to middle-aged adults as a well-circumscribed, painless, subcutaneous masses.¹ These tumors are especially unusual in children.⁴ We present 2 extraneural perineurioma cases in children, and we review the pertinent diagnostic features of perineurioma as well as the presentation in the pediatric population.

Case Reports

Patient 1—A 10-year-old boy with a history of cerebral palsy and related comorbidities presented to the clinic for evaluation of a lesion on the thigh with no associated pain, irritation, erythema, or drainage. Physical examination revealed a soft, pedunculated, mobile nodule on the right medial thigh. An elliptical excision was performed. Gross examination demonstrated a 2.0×2.0×1.8-cm polypoid nodule. Histologic examination showed a dermal-based proliferation of bland spindle cells (Figure 1). The cytomorphology was characterized by elongated tapering nuclei and many areas with delicate bipolar cytoplasmic processes. The constituent cells were arranged in a whorled pattern in a variably myxoid to collagenous stroma. The tumor cells were multifocally positive for CD34; focally positive for smooth muscle actin (SMA); and negative for S-100, epithelial membrane antigen (EMA), GLUT1, claudin-1, STAT6, and desmin. Rb protein was intact. The CD34 immunostain highlighted the cytoplasmic processes. Electron microscopy was performed because the immunohistochemical results were nonspecific despite the favorable histologic features for perineurioma and showed pinocytic vesicles with delicate cytoplasmic processes, characteristic of perineurioma (Figure 2). Follow-up visits were related to the management of multiple comorbidities; no known recurrence of the lesion was documented.

Patient 2—A 15-year-old adolescent boy with no notable medical history presented to the pediatric clinic for a bump on the right upper arm of 4 to 5 months’ duration. He did not recall an injury to the area and denied change in size, redness, bruising, or pain of the lesion. Ultrasonography demonstrated a 2.6×2.3×1.3-cm hypoechoic and slightly heterogeneous, well-circumscribed, subcutaneous mass with internal vascularity. The patient was then referred to a pediatric surgeon. The clinical differential included a lipoma, lymphadenopathy, or sebaceous cyst. An excision was performed. Gross inspection demonstrated a 7-g, 2.8×2.6×1.8-cm, homogeneous, tan-pink, rubbery nodule with minimal surrounding soft tissue. Histologic examination showed a bland proliferation of spindle cells with storiform and whorled patterns (Figure 3). No notable nuclear atypia or necrosis was identified. The tumor cells were focally positive for EMA (Figure 4), claudin-1, and CD34 and negative for S-100, SOX10, GLUT1, desmin, STAT6, pankeratin AE1/AE3, and SMA. The diagnosis of perineurioma was rendered. No recurrence of the lesion was appreciated clinically on a 6-month follow-up examination.

Comment

Characteristics of Perineuriomas—On gross evaluation, perineuriomas are firm, gray-white, and well circumscribed but not encapsulated. Histologically, perineuriomas can have a storiform, whorled, or lamellar pattern of spindle cells. Perivascular whorls can be a histologic clue. The spindle cells are bland appearing and typically are elongated and slender but can appear slightly ovoid and plump. The background stroma can be myxoid, collagenous, or mixed. There usually is no atypia, and mitotic figures are rare.^2,3,6,7 Intraneural perineuriomas vary architecturally in that they display a unique onion bulb–like appearance in which whorls of cytoplasmic material of variable sizes surround central axons.³

Diagnosis—The diagnosis of perineuriomas usually requires characteristic immunohistochemical and sometimes ultrastructural features. Perineuriomas are positive for EMA and GLUT1 and variable for CD34.⁶ Approximately 20% to 91% will be positive for claudin-1, a tight junction protein associated with perineuriomas.⁸ Of note, EMA and GLUT1 usually are positive in both neoplastic and nonneoplastic perineurial cells.^9,10 Occasionally, these tumors can be focally positive for SMA and negative for S-100 and glial fibrillary acidic protein. The bipolar, thin, delicate, cytoplasmic processes with long-tapering nuclei may be easier to appreciate on electron microscopy than on conventional light microscopy. In addition, the cells contain pinocytotic vesicles and a discontinuous external lamina, which may be helpful for diagnosis.¹⁰

Genetics—Genetic alterations in perineurioma continue to be elucidated. Although many soft tissue perineuriomas possess deletion of chromosome 22q material, this is not a consistent finding and is not pathognomonic. Notably, the NF2 tumor suppressor gene is found on chromosome 22.¹¹ For the sclerosing variant of perineurioma, rearrangements or deletions of chromosome 10q have been described. A study of 14 soft tissue/extraneural perineuriomas using whole-exome sequencing and single nucleotide polymorphism array showed 6 cases of recurrent chromosome 22q deletions containing the NF2 locus and 4 cases with a previously unreported finding of chromosome 17q deletions containing the NF1 locus that were mutually exclusive events in all but 1 case.¹² Although perineuriomas can harbor NF1 or NF2 mutations, perineuriomas are not considered to be associated with neurofibromatosis type 1 or 2 (NF1 or NF2, respectively). Patients with NF1 or NF2 and perineurioma are exceedingly rare. One pediatric patient with both soft tissue perineurioma and NF1 has been reported in the literature.¹³

Differential Diagnosis—Perineuriomas should be distinguished from other benign neural neoplasms of the skin and soft tissue. Commonly considered in the differential diagnosis is schwannoma and neurofibroma. Schwannomas are encapsulated epineurial nerve sheath tumors comprised of a neoplastic proliferation of Schwann cells. Schwannomas morphologically differ from perineuriomas because of the presence of the hypercellular Antoni A with Verocay bodies and the hypocellular myxoid Antoni B patterns of spindle cells with elongated wavy nuclei and tapered ends. Other features include hyalinized vessels, hemosiderin deposition, cystic degeneration, and/or degenerative atypia.^3,14 Importantly, the constituent cells of schwannomas are positive for S-100 and SOX10 and negative for EMA.³ Neurofibromas consist of fascicles and whorls of Schwann cells in a background myxoid stroma with scattered mast cells, lymphocytes, fibroblasts, and perineurial cells. Similar to schwannomas, neurofibromas also are positive for S-100 and negative for EMA.^3,14 Neurofibromas can have either a somatic or germline mutation of the biallelic NF1 gene on chromosome 17q11.2 with subsequent loss of protein neurofibromin activity.¹⁵ Less common but still a consideration are the hybrid peripheral nerve sheath tumors that may present with a biphasic or intermingled morphology. Combinations include neurofibroma-schwannoma, schwannoma-perineurioma, and neurofibroma-perineurioma. The hybrid schwannoma-perineurioma has a mixture of thin and plump spindle cells with tapered nuclei as well as patchy S-100 positivity corresponding to schwannian areas. Similarly, S-100 will highlight the wavy Schwann cells in neurofibroma-perineurioma as well as CD34-highlighting fibroblasts.^7,15 In both aforementioned hybrid tumors, EMA will be positive in the perineurial areas. Another potential diagnostic consideration that can occur in both pediatric and adult populations is dermatofibrosarcoma protuberans (DFSP), which is comprised of a dermal proliferation of monomorphic fusiform spindle cells. Although both perineuriomas and DFSP can have a storiform architecture, DFSP is more asymmetric and infiltrative. Dermatofibrosarcoma protuberans is recognized in areas of individual adipocyte trapping, referred to as honeycombing. Dermatofibrosarcoma protuberans typically does not express EMA, though the sclerosing variant of DFSP has been reported to sometimes demonstrate focal EMA reactivity.^11,14,16 For morphologically challenging cases, cytogenetic studies will show t(17;22) translocation fusing the COL1A1 and PDGFRB genes.¹⁶ Finally, for subcutaneous or deep-seated tumors, one also may consider other mesenchymal neoplasms, including solitary fibrous tumor, low-grade fibromyxoid sarcoma, or low-grade malignant peripheral nerve sheath tumor (MPNST).¹¹

Management—Perineuriomas are considered benign. The presence of mitotic figures, pleomorphism, and degenerative nuclear atypia akin to ancient change, as seen in ancient schwannoma, does not affect their benign clinical behavior. Treatment of a perineurioma typically is surgical excision with conservative margins and minimal chance of recurrence.^1,11 So-called malignant perineuriomas are better classified as MPNSTs with perineural differentiation or perineurial MPNST. They also are positive for EMA and may be distinguished from perineurioma by the presence of major atypia and an infiltrative growth pattern.^17,18

Considerations in the Pediatric Population—Few pediatric soft tissue perineuriomas have been reported. A clinicopathologic analysis by Hornick and Fletcher¹ of patients with soft tissue perineurioma showed that only 6 of 81 patients were younger than 20 years. The youngest reported case of perineurioma occurred as an extraneural perineurioma on the scalp in an infant.¹⁹ Only 1 soft tissue perineural MPNST has been reported in the pediatric population, arising on the face of an 11-year-old boy. In a case series of 11 pediatric perineuriomas, including extraneural and intraneural, there was no evidence of recurrence or metastasis at follow-up.⁴

Conclusion

Perineuriomas are rare benign peripheral nerve sheath tumors with unique histologic and immunohistochemical features. Soft tissue perineuriomas in the pediatric population are an important diagnostic consideration, especially for the pediatrician or dermatologist when encountering a well-circumscribed nodular soft tissue lesion of the extremity or when encountering a neural-appearing tumor in the subcutaneous tissue.

Acknowledgment—We would like to thank Christopher Fletcher, MD (Boston, Massachusetts), for his expertise in outside consultation for patient 1.

Perineuriomas are benign, slow-growing tumors derived from perineurial cells,¹ which form the structurally supportive perineurium that surrounds individual nerve fascicles.^2,3 Perineuriomas are classified into 2 main forms: intraneural or extraneural.⁴ Intraneural perineuriomas are found within the border of the peripheral nerve,⁵ while extraneural perineuriomas usually are found in soft tissue and skin. Extraneural perineuriomas can be further classified into variants based on their histologic appearance, including reticular, sclerosing, and plexiform subtypes. Extraneural perineuriomas usually present on the extremities or trunk of young to middle-aged adults as a well-circumscribed, painless, subcutaneous masses.¹ These tumors are especially unusual in children.⁴ We present 2 extraneural perineurioma cases in children, and we review the pertinent diagnostic features of perineurioma as well as the presentation in the pediatric population.

Case Reports

Patient 1—A 10-year-old boy with a history of cerebral palsy and related comorbidities presented to the clinic for evaluation of a lesion on the thigh with no associated pain, irritation, erythema, or drainage. Physical examination revealed a soft, pedunculated, mobile nodule on the right medial thigh. An elliptical excision was performed. Gross examination demonstrated a 2.0×2.0×1.8-cm polypoid nodule. Histologic examination showed a dermal-based proliferation of bland spindle cells (Figure 1). The cytomorphology was characterized by elongated tapering nuclei and many areas with delicate bipolar cytoplasmic processes. The constituent cells were arranged in a whorled pattern in a variably myxoid to collagenous stroma. The tumor cells were multifocally positive for CD34; focally positive for smooth muscle actin (SMA); and negative for S-100, epithelial membrane antigen (EMA), GLUT1, claudin-1, STAT6, and desmin. Rb protein was intact. The CD34 immunostain highlighted the cytoplasmic processes. Electron microscopy was performed because the immunohistochemical results were nonspecific despite the favorable histologic features for perineurioma and showed pinocytic vesicles with delicate cytoplasmic processes, characteristic of perineurioma (Figure 2). Follow-up visits were related to the management of multiple comorbidities; no known recurrence of the lesion was documented.

Patient 2—A 15-year-old adolescent boy with no notable medical history presented to the pediatric clinic for a bump on the right upper arm of 4 to 5 months’ duration. He did not recall an injury to the area and denied change in size, redness, bruising, or pain of the lesion. Ultrasonography demonstrated a 2.6×2.3×1.3-cm hypoechoic and slightly heterogeneous, well-circumscribed, subcutaneous mass with internal vascularity. The patient was then referred to a pediatric surgeon. The clinical differential included a lipoma, lymphadenopathy, or sebaceous cyst. An excision was performed. Gross inspection demonstrated a 7-g, 2.8×2.6×1.8-cm, homogeneous, tan-pink, rubbery nodule with minimal surrounding soft tissue. Histologic examination showed a bland proliferation of spindle cells with storiform and whorled patterns (Figure 3). No notable nuclear atypia or necrosis was identified. The tumor cells were focally positive for EMA (Figure 4), claudin-1, and CD34 and negative for S-100, SOX10, GLUT1, desmin, STAT6, pankeratin AE1/AE3, and SMA. The diagnosis of perineurioma was rendered. No recurrence of the lesion was appreciated clinically on a 6-month follow-up examination.

Comment

Characteristics of Perineuriomas—On gross evaluation, perineuriomas are firm, gray-white, and well circumscribed but not encapsulated. Histologically, perineuriomas can have a storiform, whorled, or lamellar pattern of spindle cells. Perivascular whorls can be a histologic clue. The spindle cells are bland appearing and typically are elongated and slender but can appear slightly ovoid and plump. The background stroma can be myxoid, collagenous, or mixed. There usually is no atypia, and mitotic figures are rare.^2,3,6,7 Intraneural perineuriomas vary architecturally in that they display a unique onion bulb–like appearance in which whorls of cytoplasmic material of variable sizes surround central axons.³

Diagnosis—The diagnosis of perineuriomas usually requires characteristic immunohistochemical and sometimes ultrastructural features. Perineuriomas are positive for EMA and GLUT1 and variable for CD34.⁶ Approximately 20% to 91% will be positive for claudin-1, a tight junction protein associated with perineuriomas.⁸ Of note, EMA and GLUT1 usually are positive in both neoplastic and nonneoplastic perineurial cells.^9,10 Occasionally, these tumors can be focally positive for SMA and negative for S-100 and glial fibrillary acidic protein. The bipolar, thin, delicate, cytoplasmic processes with long-tapering nuclei may be easier to appreciate on electron microscopy than on conventional light microscopy. In addition, the cells contain pinocytotic vesicles and a discontinuous external lamina, which may be helpful for diagnosis.¹⁰

Genetics—Genetic alterations in perineurioma continue to be elucidated. Although many soft tissue perineuriomas possess deletion of chromosome 22q material, this is not a consistent finding and is not pathognomonic. Notably, the NF2 tumor suppressor gene is found on chromosome 22.¹¹ For the sclerosing variant of perineurioma, rearrangements or deletions of chromosome 10q have been described. A study of 14 soft tissue/extraneural perineuriomas using whole-exome sequencing and single nucleotide polymorphism array showed 6 cases of recurrent chromosome 22q deletions containing the NF2 locus and 4 cases with a previously unreported finding of chromosome 17q deletions containing the NF1 locus that were mutually exclusive events in all but 1 case.¹² Although perineuriomas can harbor NF1 or NF2 mutations, perineuriomas are not considered to be associated with neurofibromatosis type 1 or 2 (NF1 or NF2, respectively). Patients with NF1 or NF2 and perineurioma are exceedingly rare. One pediatric patient with both soft tissue perineurioma and NF1 has been reported in the literature.¹³

Differential Diagnosis—Perineuriomas should be distinguished from other benign neural neoplasms of the skin and soft tissue. Commonly considered in the differential diagnosis is schwannoma and neurofibroma. Schwannomas are encapsulated epineurial nerve sheath tumors comprised of a neoplastic proliferation of Schwann cells. Schwannomas morphologically differ from perineuriomas because of the presence of the hypercellular Antoni A with Verocay bodies and the hypocellular myxoid Antoni B patterns of spindle cells with elongated wavy nuclei and tapered ends. Other features include hyalinized vessels, hemosiderin deposition, cystic degeneration, and/or degenerative atypia.^3,14 Importantly, the constituent cells of schwannomas are positive for S-100 and SOX10 and negative for EMA.³ Neurofibromas consist of fascicles and whorls of Schwann cells in a background myxoid stroma with scattered mast cells, lymphocytes, fibroblasts, and perineurial cells. Similar to schwannomas, neurofibromas also are positive for S-100 and negative for EMA.^3,14 Neurofibromas can have either a somatic or germline mutation of the biallelic NF1 gene on chromosome 17q11.2 with subsequent loss of protein neurofibromin activity.¹⁵ Less common but still a consideration are the hybrid peripheral nerve sheath tumors that may present with a biphasic or intermingled morphology. Combinations include neurofibroma-schwannoma, schwannoma-perineurioma, and neurofibroma-perineurioma. The hybrid schwannoma-perineurioma has a mixture of thin and plump spindle cells with tapered nuclei as well as patchy S-100 positivity corresponding to schwannian areas. Similarly, S-100 will highlight the wavy Schwann cells in neurofibroma-perineurioma as well as CD34-highlighting fibroblasts.^7,15 In both aforementioned hybrid tumors, EMA will be positive in the perineurial areas. Another potential diagnostic consideration that can occur in both pediatric and adult populations is dermatofibrosarcoma protuberans (DFSP), which is comprised of a dermal proliferation of monomorphic fusiform spindle cells. Although both perineuriomas and DFSP can have a storiform architecture, DFSP is more asymmetric and infiltrative. Dermatofibrosarcoma protuberans is recognized in areas of individual adipocyte trapping, referred to as honeycombing. Dermatofibrosarcoma protuberans typically does not express EMA, though the sclerosing variant of DFSP has been reported to sometimes demonstrate focal EMA reactivity.^11,14,16 For morphologically challenging cases, cytogenetic studies will show t(17;22) translocation fusing the COL1A1 and PDGFRB genes.¹⁶ Finally, for subcutaneous or deep-seated tumors, one also may consider other mesenchymal neoplasms, including solitary fibrous tumor, low-grade fibromyxoid sarcoma, or low-grade malignant peripheral nerve sheath tumor (MPNST).¹¹

Management—Perineuriomas are considered benign. The presence of mitotic figures, pleomorphism, and degenerative nuclear atypia akin to ancient change, as seen in ancient schwannoma, does not affect their benign clinical behavior. Treatment of a perineurioma typically is surgical excision with conservative margins and minimal chance of recurrence.^1,11 So-called malignant perineuriomas are better classified as MPNSTs with perineural differentiation or perineurial MPNST. They also are positive for EMA and may be distinguished from perineurioma by the presence of major atypia and an infiltrative growth pattern.^17,18

Considerations in the Pediatric Population—Few pediatric soft tissue perineuriomas have been reported. A clinicopathologic analysis by Hornick and Fletcher¹ of patients with soft tissue perineurioma showed that only 6 of 81 patients were younger than 20 years. The youngest reported case of perineurioma occurred as an extraneural perineurioma on the scalp in an infant.¹⁹ Only 1 soft tissue perineural MPNST has been reported in the pediatric population, arising on the face of an 11-year-old boy. In a case series of 11 pediatric perineuriomas, including extraneural and intraneural, there was no evidence of recurrence or metastasis at follow-up.⁴

Conclusion

Perineuriomas are rare benign peripheral nerve sheath tumors with unique histologic and immunohistochemical features. Soft tissue perineuriomas in the pediatric population are an important diagnostic consideration, especially for the pediatrician or dermatologist when encountering a well-circumscribed nodular soft tissue lesion of the extremity or when encountering a neural-appearing tumor in the subcutaneous tissue.

Acknowledgment—We would like to thank Christopher Fletcher, MD (Boston, Massachusetts), for his expertise in outside consultation for patient 1.

Perineuriomas are benign, slow-growing tumors derived from perineurial cells,¹ which form the structurally supportive perineurium that surrounds individual nerve fascicles.^2,3 Perineuriomas are classified into 2 main forms: intraneural or extraneural.⁴ Intraneural perineuriomas are found within the border of the peripheral nerve,⁵ while extraneural perineuriomas usually are found in soft tissue and skin. Extraneural perineuriomas can be further classified into variants based on their histologic appearance, including reticular, sclerosing, and plexiform subtypes. Extraneural perineuriomas usually present on the extremities or trunk of young to middle-aged adults as a well-circumscribed, painless, subcutaneous masses.¹ These tumors are especially unusual in children.⁴ We present 2 extraneural perineurioma cases in children, and we review the pertinent diagnostic features of perineurioma as well as the presentation in the pediatric population.

Case Reports

Patient 1—A 10-year-old boy with a history of cerebral palsy and related comorbidities presented to the clinic for evaluation of a lesion on the thigh with no associated pain, irritation, erythema, or drainage. Physical examination revealed a soft, pedunculated, mobile nodule on the right medial thigh. An elliptical excision was performed. Gross examination demonstrated a 2.0×2.0×1.8-cm polypoid nodule. Histologic examination showed a dermal-based proliferation of bland spindle cells (Figure 1). The cytomorphology was characterized by elongated tapering nuclei and many areas with delicate bipolar cytoplasmic processes. The constituent cells were arranged in a whorled pattern in a variably myxoid to collagenous stroma. The tumor cells were multifocally positive for CD34; focally positive for smooth muscle actin (SMA); and negative for S-100, epithelial membrane antigen (EMA), GLUT1, claudin-1, STAT6, and desmin. Rb protein was intact. The CD34 immunostain highlighted the cytoplasmic processes. Electron microscopy was performed because the immunohistochemical results were nonspecific despite the favorable histologic features for perineurioma and showed pinocytic vesicles with delicate cytoplasmic processes, characteristic of perineurioma (Figure 2). Follow-up visits were related to the management of multiple comorbidities; no known recurrence of the lesion was documented.

Patient 2—A 15-year-old adolescent boy with no notable medical history presented to the pediatric clinic for a bump on the right upper arm of 4 to 5 months’ duration. He did not recall an injury to the area and denied change in size, redness, bruising, or pain of the lesion. Ultrasonography demonstrated a 2.6×2.3×1.3-cm hypoechoic and slightly heterogeneous, well-circumscribed, subcutaneous mass with internal vascularity. The patient was then referred to a pediatric surgeon. The clinical differential included a lipoma, lymphadenopathy, or sebaceous cyst. An excision was performed. Gross inspection demonstrated a 7-g, 2.8×2.6×1.8-cm, homogeneous, tan-pink, rubbery nodule with minimal surrounding soft tissue. Histologic examination showed a bland proliferation of spindle cells with storiform and whorled patterns (Figure 3). No notable nuclear atypia or necrosis was identified. The tumor cells were focally positive for EMA (Figure 4), claudin-1, and CD34 and negative for S-100, SOX10, GLUT1, desmin, STAT6, pankeratin AE1/AE3, and SMA. The diagnosis of perineurioma was rendered. No recurrence of the lesion was appreciated clinically on a 6-month follow-up examination.

Comment

Characteristics of Perineuriomas—On gross evaluation, perineuriomas are firm, gray-white, and well circumscribed but not encapsulated. Histologically, perineuriomas can have a storiform, whorled, or lamellar pattern of spindle cells. Perivascular whorls can be a histologic clue. The spindle cells are bland appearing and typically are elongated and slender but can appear slightly ovoid and plump. The background stroma can be myxoid, collagenous, or mixed. There usually is no atypia, and mitotic figures are rare.^2,3,6,7 Intraneural perineuriomas vary architecturally in that they display a unique onion bulb–like appearance in which whorls of cytoplasmic material of variable sizes surround central axons.³

Diagnosis—The diagnosis of perineuriomas usually requires characteristic immunohistochemical and sometimes ultrastructural features. Perineuriomas are positive for EMA and GLUT1 and variable for CD34.⁶ Approximately 20% to 91% will be positive for claudin-1, a tight junction protein associated with perineuriomas.⁸ Of note, EMA and GLUT1 usually are positive in both neoplastic and nonneoplastic perineurial cells.^9,10 Occasionally, these tumors can be focally positive for SMA and negative for S-100 and glial fibrillary acidic protein. The bipolar, thin, delicate, cytoplasmic processes with long-tapering nuclei may be easier to appreciate on electron microscopy than on conventional light microscopy. In addition, the cells contain pinocytotic vesicles and a discontinuous external lamina, which may be helpful for diagnosis.¹⁰

Genetics—Genetic alterations in perineurioma continue to be elucidated. Although many soft tissue perineuriomas possess deletion of chromosome 22q material, this is not a consistent finding and is not pathognomonic. Notably, the NF2 tumor suppressor gene is found on chromosome 22.¹¹ For the sclerosing variant of perineurioma, rearrangements or deletions of chromosome 10q have been described. A study of 14 soft tissue/extraneural perineuriomas using whole-exome sequencing and single nucleotide polymorphism array showed 6 cases of recurrent chromosome 22q deletions containing the NF2 locus and 4 cases with a previously unreported finding of chromosome 17q deletions containing the NF1 locus that were mutually exclusive events in all but 1 case.¹² Although perineuriomas can harbor NF1 or NF2 mutations, perineuriomas are not considered to be associated with neurofibromatosis type 1 or 2 (NF1 or NF2, respectively). Patients with NF1 or NF2 and perineurioma are exceedingly rare. One pediatric patient with both soft tissue perineurioma and NF1 has been reported in the literature.¹³

Differential Diagnosis—Perineuriomas should be distinguished from other benign neural neoplasms of the skin and soft tissue. Commonly considered in the differential diagnosis is schwannoma and neurofibroma. Schwannomas are encapsulated epineurial nerve sheath tumors comprised of a neoplastic proliferation of Schwann cells. Schwannomas morphologically differ from perineuriomas because of the presence of the hypercellular Antoni A with Verocay bodies and the hypocellular myxoid Antoni B patterns of spindle cells with elongated wavy nuclei and tapered ends. Other features include hyalinized vessels, hemosiderin deposition, cystic degeneration, and/or degenerative atypia.^3,14 Importantly, the constituent cells of schwannomas are positive for S-100 and SOX10 and negative for EMA.³ Neurofibromas consist of fascicles and whorls of Schwann cells in a background myxoid stroma with scattered mast cells, lymphocytes, fibroblasts, and perineurial cells. Similar to schwannomas, neurofibromas also are positive for S-100 and negative for EMA.^3,14 Neurofibromas can have either a somatic or germline mutation of the biallelic NF1 gene on chromosome 17q11.2 with subsequent loss of protein neurofibromin activity.¹⁵ Less common but still a consideration are the hybrid peripheral nerve sheath tumors that may present with a biphasic or intermingled morphology. Combinations include neurofibroma-schwannoma, schwannoma-perineurioma, and neurofibroma-perineurioma. The hybrid schwannoma-perineurioma has a mixture of thin and plump spindle cells with tapered nuclei as well as patchy S-100 positivity corresponding to schwannian areas. Similarly, S-100 will highlight the wavy Schwann cells in neurofibroma-perineurioma as well as CD34-highlighting fibroblasts.^7,15 In both aforementioned hybrid tumors, EMA will be positive in the perineurial areas. Another potential diagnostic consideration that can occur in both pediatric and adult populations is dermatofibrosarcoma protuberans (DFSP), which is comprised of a dermal proliferation of monomorphic fusiform spindle cells. Although both perineuriomas and DFSP can have a storiform architecture, DFSP is more asymmetric and infiltrative. Dermatofibrosarcoma protuberans is recognized in areas of individual adipocyte trapping, referred to as honeycombing. Dermatofibrosarcoma protuberans typically does not express EMA, though the sclerosing variant of DFSP has been reported to sometimes demonstrate focal EMA reactivity.^11,14,16 For morphologically challenging cases, cytogenetic studies will show t(17;22) translocation fusing the COL1A1 and PDGFRB genes.¹⁶ Finally, for subcutaneous or deep-seated tumors, one also may consider other mesenchymal neoplasms, including solitary fibrous tumor, low-grade fibromyxoid sarcoma, or low-grade malignant peripheral nerve sheath tumor (MPNST).¹¹

Management—Perineuriomas are considered benign. The presence of mitotic figures, pleomorphism, and degenerative nuclear atypia akin to ancient change, as seen in ancient schwannoma, does not affect their benign clinical behavior. Treatment of a perineurioma typically is surgical excision with conservative margins and minimal chance of recurrence.^1,11 So-called malignant perineuriomas are better classified as MPNSTs with perineural differentiation or perineurial MPNST. They also are positive for EMA and may be distinguished from perineurioma by the presence of major atypia and an infiltrative growth pattern.^17,18

Considerations in the Pediatric Population—Few pediatric soft tissue perineuriomas have been reported. A clinicopathologic analysis by Hornick and Fletcher¹ of patients with soft tissue perineurioma showed that only 6 of 81 patients were younger than 20 years. The youngest reported case of perineurioma occurred as an extraneural perineurioma on the scalp in an infant.¹⁹ Only 1 soft tissue perineural MPNST has been reported in the pediatric population, arising on the face of an 11-year-old boy. In a case series of 11 pediatric perineuriomas, including extraneural and intraneural, there was no evidence of recurrence or metastasis at follow-up.⁴

Conclusion

Perineuriomas are rare benign peripheral nerve sheath tumors with unique histologic and immunohistochemical features. Soft tissue perineuriomas in the pediatric population are an important diagnostic consideration, especially for the pediatrician or dermatologist when encountering a well-circumscribed nodular soft tissue lesion of the extremity or when encountering a neural-appearing tumor in the subcutaneous tissue.

Acknowledgment—We would like to thank Christopher Fletcher, MD (Boston, Massachusetts), for his expertise in outside consultation for patient 1.

Atopic dermatitis (AD), or eczema, is a common inflammatory skin disease notorious for its chronic, relapsing, and often frustrating disease course. Although as many as 25% of children in the United States are affected by this condition and its impact on the quality of life of affected patients and families is profound,^1-3 therapeutic advances in the pediatric population have been fairly limited until recently.

Over the last 10 years, there has been robust investigation into pediatric AD therapeutics, with many topical and systemic medications either recently approved or under clinical investigation. These developments are changing the landscape of the management of pediatric AD and raise a set of fascinating questions about how early and aggressive intervention might change the course of this disease. We discuss current limitations in the field that may be addressed with additional research.

New Topical Medications

In the last several years, there has been a rapid increase in efforts to develop new topical agents to manage AD. Until the beginning of the 21st century, the dermatologist’s arsenal was limited to topical corticosteroids (TCs). In the early 2000s, attention shifted to topical calcineurin inhibitors as nonsteroidal alternatives when the US Food and Drug Administration (FDA) approved topical tacrolimus and pimecrolimus for AD. In 2016, crisaborole (a phosphodiesterase-4 [PDE4] inhibitor) was approved by the FDA for use in mild to moderate AD in patients 2 years and older, marking a new age of development for topical AD therapies. In 2021, the FDA approved ruxolitinib (a topical Janus kinase [JAK] 1/2 inhibitor) for use in mild to moderate AD in patients 12 years and older.

Roflumilast (ARQ-151) and difamilast (OPA-15406)(members of the PDE4 inhibitor class) are undergoing investigation for pediatric AD. A phase 3 clinical trial for roflumilast for AD is underway (ClinicalTrial.gov Identifier: NCT04845620); it is already approved for psoriasis in patients 12 years and older. A phase 3 trial of difamilast (NCT03911401) was recently completed, with results supporting the drug’s safety and efficacy in AD management.⁴ Efforts to synthesize new better-targeted PDE4 inhibitors are ongoing.⁵

Tapinarof (a novel aryl hydrocarbon receptor-modulating agent) is approved for psoriasis in adults, and a phase 3 trial for management of pediatric AD is underway (NCT05032859) after phase 2 trials revealed promising results.⁶

Lastly, the microbiome is a target for AD topical therapies. A recently completed phase 1 trial of bacteriotherapy with Staphylococcus hominis A9 transplant lotion showed promising results (NCT03151148).⁷ Although this bacteriotherapy technique is early in development and has been studied only in adult patients, results are exciting because they represent a gateway to a largely unexplored realm of potential future therapies.

Standard of Care—How will these new topical therapies impact our standard of care for pediatric AD patients? Topical corticosteroids are still a pillar of topical AD therapy, but the potential for nonsteroidal topical agents as alternatives and used in combination therapeutic regimens has expanded exponentially. It is uncertain how we might individualize regimens tailored to patient-specific factors because the standard approach has been to test drugs as monotherapy, with vehicle comparisons or with reference medications in Europe.

Newer topical nonsteroidal agents may offer several opportunities. First, they may help avoid local and systemic adverse effects that often limit the use of current standard therapy.⁸ This capability may prove essential in bridging TC treatments and serving as long-term maintenance therapies to decrease the frequency of eczema flares. Second, they can alleviate the need for different medication strengths for different body regions, thereby allowing for simplification of regimens and potentially increased adherence and decreased disease burden—a boon to affected patients and caregivers.

Although the efficacy and long-term safety profile of these new drugs require further study, it does not seem unreasonable to look forward to achieving levels of optimization and individualization with topical regimens for AD in the near future that makes flares in patients with mild to moderate AD a phenomenon of the past.

Advances in Systemic Therapy

Systemic therapeutics in pediatric AD also recently entered an exciting era of development. Traditional systemic agents, including cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil, have existed for decades but have not been widely utilized for moderate to severe AD in the United States, especially in the pediatric population, likely because these drugs lacked FDA approval and they can cause a range of adverse effects, including notable immunosuppression.⁹

Introduction and approval of dupilumab in 2017 by the FDA was revolutionary in this field. As a monoclonal antibody targeted against IL-4 and IL-13, dupilumab has consistently demonstrated strong long-term efficacy for pediatric AD and has an acceptable safety profile in children and adolescents.^10-14 Expansion of the label to include children as young as 6 months with moderate to severe AD seems an important milestone in pediatric AD care.

Since the approval of dupilumab for adolescents and children aged 6 to 12 years, global experience has supported expanded use of systemic agents for patients who have an inadequate response to TCs and previously approved nonsteroidal topical agents. How expansive the use of systemics will be in younger children depends on how their long-term use impacts the disease course, whether therapy is disease modifying, and whether early use can curb the development of comorbidities.

Investigations into targeted systemic therapeutics for eczematous dermatitis are not limited to dupilumab. In a study of adolescents as young as 12 years, tralokinumab (an IL-13 pathway inhibitor) demonstrated an Eczema Area Severity Index-75 of 27.8% to 28.6% and a mean decrease in the SCORing Atopic Dermatitis index of 27.5 to 29.1, with minimal adverse effects.¹⁵ Lebrikizumab, another biologic IL-13 inhibitor with strong published safety and efficacy data in adults, has completed short- and longer-term studies in adolescents (NCT04178967 and NCT04146363).¹⁶ The drug received FDA Fast Track designation for moderate to severe AD in patients 12 years and older after showing positive data.¹⁷

This push to targeted therapy stretches beyond monoclonal antibodies. In the last few years, oral JAK inhibitors have emerged as a new class of systemic therapy for eczematous dermatitis. Upadacitinib, a JAK1 selective inhibitor, was approved by the FDA in 2022 for patients 12 years and older with AD and has data that supports its efficacy in adolescents and adults.¹⁸ Other JAK inhibitors including the selective JAK1 inhibitor abrocitinib and the combined JAK1/2 inhibitor baricitinib are being studied for pediatric AD (NCT04564755, NCT03422822, and NCT03952559), with most evidence to date supporting their safety and efficacy, at least over the short-term.¹⁹

The study of these and other advanced systemic therapies for eczematous dermatitis is transforming the toolbox for pediatric AD care. Although long-term data are lacking for some of these medications, it is possible that newer agents may decrease reliance on older immunosuppressants, such as systemic corticosteroids, cyclosporine, and methotrexate. Unanswered questions include: How and which systemic medications may alter the course of the disease? What is the disease modification for AD? What is the impact on comorbidities over time?

What’s Missing?

The field of pediatric AD has experienced exciting new developments with the emergence of targeted therapeutics, but those new agents require more long-term study, though we already have longer-term data on crisaborole and dupilumab.^10-14,20 Studies of the long-term use of these new treatments on comorbidities of pediatric AD—mental health outcomes, cardiovascular disease, effects on the family, and other allergic conditions—are needed.²¹ Furthermore, clinical guidelines that address indications, timing of use, tapering, and discontinuation of new treatments depend on long-term experience and data collection.

Therefore, it is prudent that investigators, companies, payers, patients, and families support phase 4, long-term extension, and registry studies, which will expand our knowledge of AD medications and their impact on the disease over time.

Final Thoughts

Medications to treat AD are reaching a new level of advancement—from topical agents that target novel pathways to revolutionary biologics and systemic medications. Although there are knowledge gaps on these new therapeutics, the standard of care is already rapidly changing as the expectations of clinicians, patients, and families advance with each addition to the provider’s toolbox.

Atopic dermatitis (AD), or eczema, is a common inflammatory skin disease notorious for its chronic, relapsing, and often frustrating disease course. Although as many as 25% of children in the United States are affected by this condition and its impact on the quality of life of affected patients and families is profound,^1-3 therapeutic advances in the pediatric population have been fairly limited until recently.

Over the last 10 years, there has been robust investigation into pediatric AD therapeutics, with many topical and systemic medications either recently approved or under clinical investigation. These developments are changing the landscape of the management of pediatric AD and raise a set of fascinating questions about how early and aggressive intervention might change the course of this disease. We discuss current limitations in the field that may be addressed with additional research.

New Topical Medications

In the last several years, there has been a rapid increase in efforts to develop new topical agents to manage AD. Until the beginning of the 21st century, the dermatologist’s arsenal was limited to topical corticosteroids (TCs). In the early 2000s, attention shifted to topical calcineurin inhibitors as nonsteroidal alternatives when the US Food and Drug Administration (FDA) approved topical tacrolimus and pimecrolimus for AD. In 2016, crisaborole (a phosphodiesterase-4 [PDE4] inhibitor) was approved by the FDA for use in mild to moderate AD in patients 2 years and older, marking a new age of development for topical AD therapies. In 2021, the FDA approved ruxolitinib (a topical Janus kinase [JAK] 1/2 inhibitor) for use in mild to moderate AD in patients 12 years and older.

Roflumilast (ARQ-151) and difamilast (OPA-15406)(members of the PDE4 inhibitor class) are undergoing investigation for pediatric AD. A phase 3 clinical trial for roflumilast for AD is underway (ClinicalTrial.gov Identifier: NCT04845620); it is already approved for psoriasis in patients 12 years and older. A phase 3 trial of difamilast (NCT03911401) was recently completed, with results supporting the drug’s safety and efficacy in AD management.⁴ Efforts to synthesize new better-targeted PDE4 inhibitors are ongoing.⁵

Tapinarof (a novel aryl hydrocarbon receptor-modulating agent) is approved for psoriasis in adults, and a phase 3 trial for management of pediatric AD is underway (NCT05032859) after phase 2 trials revealed promising results.⁶

Lastly, the microbiome is a target for AD topical therapies. A recently completed phase 1 trial of bacteriotherapy with Staphylococcus hominis A9 transplant lotion showed promising results (NCT03151148).⁷ Although this bacteriotherapy technique is early in development and has been studied only in adult patients, results are exciting because they represent a gateway to a largely unexplored realm of potential future therapies.

Standard of Care—How will these new topical therapies impact our standard of care for pediatric AD patients? Topical corticosteroids are still a pillar of topical AD therapy, but the potential for nonsteroidal topical agents as alternatives and used in combination therapeutic regimens has expanded exponentially. It is uncertain how we might individualize regimens tailored to patient-specific factors because the standard approach has been to test drugs as monotherapy, with vehicle comparisons or with reference medications in Europe.

Newer topical nonsteroidal agents may offer several opportunities. First, they may help avoid local and systemic adverse effects that often limit the use of current standard therapy.⁸ This capability may prove essential in bridging TC treatments and serving as long-term maintenance therapies to decrease the frequency of eczema flares. Second, they can alleviate the need for different medication strengths for different body regions, thereby allowing for simplification of regimens and potentially increased adherence and decreased disease burden—a boon to affected patients and caregivers.

Although the efficacy and long-term safety profile of these new drugs require further study, it does not seem unreasonable to look forward to achieving levels of optimization and individualization with topical regimens for AD in the near future that makes flares in patients with mild to moderate AD a phenomenon of the past.

Advances in Systemic Therapy

Systemic therapeutics in pediatric AD also recently entered an exciting era of development. Traditional systemic agents, including cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil, have existed for decades but have not been widely utilized for moderate to severe AD in the United States, especially in the pediatric population, likely because these drugs lacked FDA approval and they can cause a range of adverse effects, including notable immunosuppression.⁹

Introduction and approval of dupilumab in 2017 by the FDA was revolutionary in this field. As a monoclonal antibody targeted against IL-4 and IL-13, dupilumab has consistently demonstrated strong long-term efficacy for pediatric AD and has an acceptable safety profile in children and adolescents.^10-14 Expansion of the label to include children as young as 6 months with moderate to severe AD seems an important milestone in pediatric AD care.

Since the approval of dupilumab for adolescents and children aged 6 to 12 years, global experience has supported expanded use of systemic agents for patients who have an inadequate response to TCs and previously approved nonsteroidal topical agents. How expansive the use of systemics will be in younger children depends on how their long-term use impacts the disease course, whether therapy is disease modifying, and whether early use can curb the development of comorbidities.

Investigations into targeted systemic therapeutics for eczematous dermatitis are not limited to dupilumab. In a study of adolescents as young as 12 years, tralokinumab (an IL-13 pathway inhibitor) demonstrated an Eczema Area Severity Index-75 of 27.8% to 28.6% and a mean decrease in the SCORing Atopic Dermatitis index of 27.5 to 29.1, with minimal adverse effects.¹⁵ Lebrikizumab, another biologic IL-13 inhibitor with strong published safety and efficacy data in adults, has completed short- and longer-term studies in adolescents (NCT04178967 and NCT04146363).¹⁶ The drug received FDA Fast Track designation for moderate to severe AD in patients 12 years and older after showing positive data.¹⁷

This push to targeted therapy stretches beyond monoclonal antibodies. In the last few years, oral JAK inhibitors have emerged as a new class of systemic therapy for eczematous dermatitis. Upadacitinib, a JAK1 selective inhibitor, was approved by the FDA in 2022 for patients 12 years and older with AD and has data that supports its efficacy in adolescents and adults.¹⁸ Other JAK inhibitors including the selective JAK1 inhibitor abrocitinib and the combined JAK1/2 inhibitor baricitinib are being studied for pediatric AD (NCT04564755, NCT03422822, and NCT03952559), with most evidence to date supporting their safety and efficacy, at least over the short-term.¹⁹

The study of these and other advanced systemic therapies for eczematous dermatitis is transforming the toolbox for pediatric AD care. Although long-term data are lacking for some of these medications, it is possible that newer agents may decrease reliance on older immunosuppressants, such as systemic corticosteroids, cyclosporine, and methotrexate. Unanswered questions include: How and which systemic medications may alter the course of the disease? What is the disease modification for AD? What is the impact on comorbidities over time?

What’s Missing?

The field of pediatric AD has experienced exciting new developments with the emergence of targeted therapeutics, but those new agents require more long-term study, though we already have longer-term data on crisaborole and dupilumab.^10-14,20 Studies of the long-term use of these new treatments on comorbidities of pediatric AD—mental health outcomes, cardiovascular disease, effects on the family, and other allergic conditions—are needed.²¹ Furthermore, clinical guidelines that address indications, timing of use, tapering, and discontinuation of new treatments depend on long-term experience and data collection.

Therefore, it is prudent that investigators, companies, payers, patients, and families support phase 4, long-term extension, and registry studies, which will expand our knowledge of AD medications and their impact on the disease over time.

Final Thoughts

Medications to treat AD are reaching a new level of advancement—from topical agents that target novel pathways to revolutionary biologics and systemic medications. Although there are knowledge gaps on these new therapeutics, the standard of care is already rapidly changing as the expectations of clinicians, patients, and families advance with each addition to the provider’s toolbox.

Atopic dermatitis (AD), or eczema, is a common inflammatory skin disease notorious for its chronic, relapsing, and often frustrating disease course. Although as many as 25% of children in the United States are affected by this condition and its impact on the quality of life of affected patients and families is profound,^1-3 therapeutic advances in the pediatric population have been fairly limited until recently.

Over the last 10 years, there has been robust investigation into pediatric AD therapeutics, with many topical and systemic medications either recently approved or under clinical investigation. These developments are changing the landscape of the management of pediatric AD and raise a set of fascinating questions about how early and aggressive intervention might change the course of this disease. We discuss current limitations in the field that may be addressed with additional research.

New Topical Medications

In the last several years, there has been a rapid increase in efforts to develop new topical agents to manage AD. Until the beginning of the 21st century, the dermatologist’s arsenal was limited to topical corticosteroids (TCs). In the early 2000s, attention shifted to topical calcineurin inhibitors as nonsteroidal alternatives when the US Food and Drug Administration (FDA) approved topical tacrolimus and pimecrolimus for AD. In 2016, crisaborole (a phosphodiesterase-4 [PDE4] inhibitor) was approved by the FDA for use in mild to moderate AD in patients 2 years and older, marking a new age of development for topical AD therapies. In 2021, the FDA approved ruxolitinib (a topical Janus kinase [JAK] 1/2 inhibitor) for use in mild to moderate AD in patients 12 years and older.

Roflumilast (ARQ-151) and difamilast (OPA-15406)(members of the PDE4 inhibitor class) are undergoing investigation for pediatric AD. A phase 3 clinical trial for roflumilast for AD is underway (ClinicalTrial.gov Identifier: NCT04845620); it is already approved for psoriasis in patients 12 years and older. A phase 3 trial of difamilast (NCT03911401) was recently completed, with results supporting the drug’s safety and efficacy in AD management.⁴ Efforts to synthesize new better-targeted PDE4 inhibitors are ongoing.⁵

Tapinarof (a novel aryl hydrocarbon receptor-modulating agent) is approved for psoriasis in adults, and a phase 3 trial for management of pediatric AD is underway (NCT05032859) after phase 2 trials revealed promising results.⁶

Lastly, the microbiome is a target for AD topical therapies. A recently completed phase 1 trial of bacteriotherapy with Staphylococcus hominis A9 transplant lotion showed promising results (NCT03151148).⁷ Although this bacteriotherapy technique is early in development and has been studied only in adult patients, results are exciting because they represent a gateway to a largely unexplored realm of potential future therapies.

Standard of Care—How will these new topical therapies impact our standard of care for pediatric AD patients? Topical corticosteroids are still a pillar of topical AD therapy, but the potential for nonsteroidal topical agents as alternatives and used in combination therapeutic regimens has expanded exponentially. It is uncertain how we might individualize regimens tailored to patient-specific factors because the standard approach has been to test drugs as monotherapy, with vehicle comparisons or with reference medications in Europe.

Newer topical nonsteroidal agents may offer several opportunities. First, they may help avoid local and systemic adverse effects that often limit the use of current standard therapy.⁸ This capability may prove essential in bridging TC treatments and serving as long-term maintenance therapies to decrease the frequency of eczema flares. Second, they can alleviate the need for different medication strengths for different body regions, thereby allowing for simplification of regimens and potentially increased adherence and decreased disease burden—a boon to affected patients and caregivers.

Although the efficacy and long-term safety profile of these new drugs require further study, it does not seem unreasonable to look forward to achieving levels of optimization and individualization with topical regimens for AD in the near future that makes flares in patients with mild to moderate AD a phenomenon of the past.

Advances in Systemic Therapy

Systemic therapeutics in pediatric AD also recently entered an exciting era of development. Traditional systemic agents, including cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil, have existed for decades but have not been widely utilized for moderate to severe AD in the United States, especially in the pediatric population, likely because these drugs lacked FDA approval and they can cause a range of adverse effects, including notable immunosuppression.⁹

Introduction and approval of dupilumab in 2017 by the FDA was revolutionary in this field. As a monoclonal antibody targeted against IL-4 and IL-13, dupilumab has consistently demonstrated strong long-term efficacy for pediatric AD and has an acceptable safety profile in children and adolescents.^10-14 Expansion of the label to include children as young as 6 months with moderate to severe AD seems an important milestone in pediatric AD care.

Since the approval of dupilumab for adolescents and children aged 6 to 12 years, global experience has supported expanded use of systemic agents for patients who have an inadequate response to TCs and previously approved nonsteroidal topical agents. How expansive the use of systemics will be in younger children depends on how their long-term use impacts the disease course, whether therapy is disease modifying, and whether early use can curb the development of comorbidities.

Investigations into targeted systemic therapeutics for eczematous dermatitis are not limited to dupilumab. In a study of adolescents as young as 12 years, tralokinumab (an IL-13 pathway inhibitor) demonstrated an Eczema Area Severity Index-75 of 27.8% to 28.6% and a mean decrease in the SCORing Atopic Dermatitis index of 27.5 to 29.1, with minimal adverse effects.¹⁵ Lebrikizumab, another biologic IL-13 inhibitor with strong published safety and efficacy data in adults, has completed short- and longer-term studies in adolescents (NCT04178967 and NCT04146363).¹⁶ The drug received FDA Fast Track designation for moderate to severe AD in patients 12 years and older after showing positive data.¹⁷

This push to targeted therapy stretches beyond monoclonal antibodies. In the last few years, oral JAK inhibitors have emerged as a new class of systemic therapy for eczematous dermatitis. Upadacitinib, a JAK1 selective inhibitor, was approved by the FDA in 2022 for patients 12 years and older with AD and has data that supports its efficacy in adolescents and adults.¹⁸ Other JAK inhibitors including the selective JAK1 inhibitor abrocitinib and the combined JAK1/2 inhibitor baricitinib are being studied for pediatric AD (NCT04564755, NCT03422822, and NCT03952559), with most evidence to date supporting their safety and efficacy, at least over the short-term.¹⁹

The study of these and other advanced systemic therapies for eczematous dermatitis is transforming the toolbox for pediatric AD care. Although long-term data are lacking for some of these medications, it is possible that newer agents may decrease reliance on older immunosuppressants, such as systemic corticosteroids, cyclosporine, and methotrexate. Unanswered questions include: How and which systemic medications may alter the course of the disease? What is the disease modification for AD? What is the impact on comorbidities over time?

What’s Missing?

The field of pediatric AD has experienced exciting new developments with the emergence of targeted therapeutics, but those new agents require more long-term study, though we already have longer-term data on crisaborole and dupilumab.^10-14,20 Studies of the long-term use of these new treatments on comorbidities of pediatric AD—mental health outcomes, cardiovascular disease, effects on the family, and other allergic conditions—are needed.²¹ Furthermore, clinical guidelines that address indications, timing of use, tapering, and discontinuation of new treatments depend on long-term experience and data collection.

Therefore, it is prudent that investigators, companies, payers, patients, and families support phase 4, long-term extension, and registry studies, which will expand our knowledge of AD medications and their impact on the disease over time.

Final Thoughts

Medications to treat AD are reaching a new level of advancement—from topical agents that target novel pathways to revolutionary biologics and systemic medications. Although there are knowledge gaps on these new therapeutics, the standard of care is already rapidly changing as the expectations of clinicians, patients, and families advance with each addition to the provider’s toolbox.

Acrodermatitis enteropathica (AE) is a rare disorder of zinc metabolism that typically presents in infancy.¹ Although it is clinically characterized by acral and periorificial dermatitis, alopecia, and diarrhea, only 20% of cases present with this triad.² Zinc deficiency in AE can either be acquired or inborn (congenital). Acquired forms can occur from dietary inadequacy or malabsorption, whereas genetic causes are related to an autosomal-recessive disorder affecting zinc transporters.¹ We report a case of a 3-month-old female infant with acquired AE who was successfully treated with zinc supplementation over the course of 3 weeks.

Case Report

A 3-month-old female infant presented to the emergency department with a rash of 2 weeks’ duration. She was born full term with no birth complications. The patient’s mother reported that the rash started on the cheeks, then enlarged and spread to the neck, back, and perineum. The patient also had been having diarrhea during this time. She previously had received mupirocin and cephalexin with no response to treatment. Maternal history was negative for lupus, and the mother’s diet consisted of a variety of foods but not many vegetables. The patient was exclusively breastfed, and there was no pertinent history of similar rashes occurring in other family members.

Physical examination revealed the patient had annular and polycyclic, hyperkeratotic, crusted papules and plaques on the cheeks, neck, back, and axillae, as well as the perineum/groin and perianal regions (Figure 1). The differential diagnosis at the time included neonatal lupus, zinc deficiency, and syphilis. Relevant laboratory testing and a shave biopsy of the left axilla were obtained.

Comment

Etiology of AE—Acrodermatitis enteropathica was first identified in 1942 as an acral rash associated with diarrhea³; in 1973, Barnes and Moynahan⁴ discovered zinc deficiency as a causal agent for these findings. The causes of AE are further subclassified as either an acquired or inborn etiology. Congenital causes commonly are seen in infants within the first few months of life, whereas acquired forms are seen at any age. Acquired forms in infants can occur from failure of the mother to secrete zinc in breast milk, low maternal serum zinc levels, or other reasons causing low nutritional intake. A single mutation in the SLC30A2 gene has been found to markedly reduce zinc concentrations in breast milk, thus causing zinc deficiency in breastfed infants.⁵ Other acquired forms can be caused by malabsorption, sometimes after surgery such as intestinal bypass or from intravenous nutrition without sufficient zinc.¹ The congenital form of AE is an autosomal-recessive disorder occurring from mutations in the SLC39A4 gene located on band 8q24.3. Affected individuals have a decreased ability to absorb zinc in the small intestine because of defects in zinc transporters ZIP and ZnT.⁶ Based on our patient’s laboratory findings and history, it is believed that the zinc deficiency was acquired, as the condition normalized with repletion and has not required any supplementation in the year of follow-up. In addition, the absence of a pertinent family history supported an acquired diagnosis, which has various etiologies, whereas the congenital form primarily is a genetic disease.

Diagnosis of AE—The characteristic clinical features of AE include erythematous, dry, scaly papules and plaques that may evolve into crusted, erosive, pustular lesions. These lesions typically are distributed in a periorificial and acral pattern.^1,2 Although AE includes the clinical triad of acral and periorificial dermatitis, alopecia, and diarrhea, most cases present with only partial features of this syndrome, as seen in our patient, who presented with only 2 symptoms—dermatitis and diarrhea. The diagnosis of AE is based on clinical and laboratory abnormalities, especially a low serum zinc level. Low levels of zinc-dependent enzymes, such as alkaline phosphatase, may support the diagnosis, as seen in our patient. Histologic evaluation is characteristic but is not diagnostic, as the same findings can be seen in other nutritional disorders. Such findings include confluent parakeratosis associated with a reduced granular layer in early lesions and subsequent ballooning of subcorneal keratinocytes, upper epidermal pallor, and intraepidermal clefts. Late lesions exhibit psoriasiform hyperplasia of the epidermis with less epidermal pallor.⁷

Acrodermatitis enteropathica (AE) is a rare disorder of zinc metabolism that typically presents in infancy.¹ Although it is clinically characterized by acral and periorificial dermatitis, alopecia, and diarrhea, only 20% of cases present with this triad.² Zinc deficiency in AE can either be acquired or inborn (congenital). Acquired forms can occur from dietary inadequacy or malabsorption, whereas genetic causes are related to an autosomal-recessive disorder affecting zinc transporters.¹ We report a case of a 3-month-old female infant with acquired AE who was successfully treated with zinc supplementation over the course of 3 weeks.

Case Report

A 3-month-old female infant presented to the emergency department with a rash of 2 weeks’ duration. She was born full term with no birth complications. The patient’s mother reported that the rash started on the cheeks, then enlarged and spread to the neck, back, and perineum. The patient also had been having diarrhea during this time. She previously had received mupirocin and cephalexin with no response to treatment. Maternal history was negative for lupus, and the mother’s diet consisted of a variety of foods but not many vegetables. The patient was exclusively breastfed, and there was no pertinent history of similar rashes occurring in other family members.

Physical examination revealed the patient had annular and polycyclic, hyperkeratotic, crusted papules and plaques on the cheeks, neck, back, and axillae, as well as the perineum/groin and perianal regions (Figure 1). The differential diagnosis at the time included neonatal lupus, zinc deficiency, and syphilis. Relevant laboratory testing and a shave biopsy of the left axilla were obtained.

Comment

Etiology of AE—Acrodermatitis enteropathica was first identified in 1942 as an acral rash associated with diarrhea³; in 1973, Barnes and Moynahan⁴ discovered zinc deficiency as a causal agent for these findings. The causes of AE are further subclassified as either an acquired or inborn etiology. Congenital causes commonly are seen in infants within the first few months of life, whereas acquired forms are seen at any age. Acquired forms in infants can occur from failure of the mother to secrete zinc in breast milk, low maternal serum zinc levels, or other reasons causing low nutritional intake. A single mutation in the SLC30A2 gene has been found to markedly reduce zinc concentrations in breast milk, thus causing zinc deficiency in breastfed infants.⁵ Other acquired forms can be caused by malabsorption, sometimes after surgery such as intestinal bypass or from intravenous nutrition without sufficient zinc.¹ The congenital form of AE is an autosomal-recessive disorder occurring from mutations in the SLC39A4 gene located on band 8q24.3. Affected individuals have a decreased ability to absorb zinc in the small intestine because of defects in zinc transporters ZIP and ZnT.⁶ Based on our patient’s laboratory findings and history, it is believed that the zinc deficiency was acquired, as the condition normalized with repletion and has not required any supplementation in the year of follow-up. In addition, the absence of a pertinent family history supported an acquired diagnosis, which has various etiologies, whereas the congenital form primarily is a genetic disease.

Diagnosis of AE—The characteristic clinical features of AE include erythematous, dry, scaly papules and plaques that may evolve into crusted, erosive, pustular lesions. These lesions typically are distributed in a periorificial and acral pattern.^1,2 Although AE includes the clinical triad of acral and periorificial dermatitis, alopecia, and diarrhea, most cases present with only partial features of this syndrome, as seen in our patient, who presented with only 2 symptoms—dermatitis and diarrhea. The diagnosis of AE is based on clinical and laboratory abnormalities, especially a low serum zinc level. Low levels of zinc-dependent enzymes, such as alkaline phosphatase, may support the diagnosis, as seen in our patient. Histologic evaluation is characteristic but is not diagnostic, as the same findings can be seen in other nutritional disorders. Such findings include confluent parakeratosis associated with a reduced granular layer in early lesions and subsequent ballooning of subcorneal keratinocytes, upper epidermal pallor, and intraepidermal clefts. Late lesions exhibit psoriasiform hyperplasia of the epidermis with less epidermal pallor.⁷

Acrodermatitis enteropathica (AE) is a rare disorder of zinc metabolism that typically presents in infancy.¹ Although it is clinically characterized by acral and periorificial dermatitis, alopecia, and diarrhea, only 20% of cases present with this triad.² Zinc deficiency in AE can either be acquired or inborn (congenital). Acquired forms can occur from dietary inadequacy or malabsorption, whereas genetic causes are related to an autosomal-recessive disorder affecting zinc transporters.¹ We report a case of a 3-month-old female infant with acquired AE who was successfully treated with zinc supplementation over the course of 3 weeks.

Case Report

A 3-month-old female infant presented to the emergency department with a rash of 2 weeks’ duration. She was born full term with no birth complications. The patient’s mother reported that the rash started on the cheeks, then enlarged and spread to the neck, back, and perineum. The patient also had been having diarrhea during this time. She previously had received mupirocin and cephalexin with no response to treatment. Maternal history was negative for lupus, and the mother’s diet consisted of a variety of foods but not many vegetables. The patient was exclusively breastfed, and there was no pertinent history of similar rashes occurring in other family members.

Physical examination revealed the patient had annular and polycyclic, hyperkeratotic, crusted papules and plaques on the cheeks, neck, back, and axillae, as well as the perineum/groin and perianal regions (Figure 1). The differential diagnosis at the time included neonatal lupus, zinc deficiency, and syphilis. Relevant laboratory testing and a shave biopsy of the left axilla were obtained.

Comment

Etiology of AE—Acrodermatitis enteropathica was first identified in 1942 as an acral rash associated with diarrhea³; in 1973, Barnes and Moynahan⁴ discovered zinc deficiency as a causal agent for these findings. The causes of AE are further subclassified as either an acquired or inborn etiology. Congenital causes commonly are seen in infants within the first few months of life, whereas acquired forms are seen at any age. Acquired forms in infants can occur from failure of the mother to secrete zinc in breast milk, low maternal serum zinc levels, or other reasons causing low nutritional intake. A single mutation in the SLC30A2 gene has been found to markedly reduce zinc concentrations in breast milk, thus causing zinc deficiency in breastfed infants.⁵ Other acquired forms can be caused by malabsorption, sometimes after surgery such as intestinal bypass or from intravenous nutrition without sufficient zinc.¹ The congenital form of AE is an autosomal-recessive disorder occurring from mutations in the SLC39A4 gene located on band 8q24.3. Affected individuals have a decreased ability to absorb zinc in the small intestine because of defects in zinc transporters ZIP and ZnT.⁶ Based on our patient’s laboratory findings and history, it is believed that the zinc deficiency was acquired, as the condition normalized with repletion and has not required any supplementation in the year of follow-up. In addition, the absence of a pertinent family history supported an acquired diagnosis, which has various etiologies, whereas the congenital form primarily is a genetic disease.

Diagnosis of AE—The characteristic clinical features of AE include erythematous, dry, scaly papules and plaques that may evolve into crusted, erosive, pustular lesions. These lesions typically are distributed in a periorificial and acral pattern.^1,2 Although AE includes the clinical triad of acral and periorificial dermatitis, alopecia, and diarrhea, most cases present with only partial features of this syndrome, as seen in our patient, who presented with only 2 symptoms—dermatitis and diarrhea. The diagnosis of AE is based on clinical and laboratory abnormalities, especially a low serum zinc level. Low levels of zinc-dependent enzymes, such as alkaline phosphatase, may support the diagnosis, as seen in our patient. Histologic evaluation is characteristic but is not diagnostic, as the same findings can be seen in other nutritional disorders. Such findings include confluent parakeratosis associated with a reduced granular layer in early lesions and subsequent ballooning of subcorneal keratinocytes, upper epidermal pallor, and intraepidermal clefts. Late lesions exhibit psoriasiform hyperplasia of the epidermis with less epidermal pallor.⁷

Tinea capitis (TC) most often is caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Noninflammatory TC typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated areas of alopecia with fine scale studded with broken-off hairs at the scalp surface, resulting in a black dot appearance. Inflammatory variants of TC include kerion and favus.¹ Herein, updates on diagnosis, treatment, and monitoring of TC are provided, as well as a discussion of changes in the fungal microbiome associated with TC. Lastly, insights to some queries that practitioners may encounter when treating children with TC are provided.

Genetic Susceptibility

Molecular techniques have identified a number of macrophage regulator, leukocyte activation and migration, and cutaneous permeability genes associated with susceptibility to TC. These findings indicate that genetically determined deficiency in adaptive immune responses may affect the predisposition to dermatophyte infections.²

Clinical Varieties of Infection

Dermatophytes causing ringworm are capable of invading the hair shafts and can simultaneously invade smooth or glabrous skin (eg, T tonsurans, Trichophyton schoenleinii, Trichophyton violaceum). Some causative dermatophytes can even penetrate the nails (eg, Trichophyton soudanense). The clinical presentation is dependent on 3 main patterns of hair invasion³:

• Ectothrix: A mid-follicular pattern of invasion with hyphae growing down to the hair bulb that commonly is caused by Microsporum species. It clinically presents with scaling and inflammation with hair shafts breaking 2 to 3 mm above the scalp level.

• Endothrix: This pattern is nonfluorescent on Wood lamp examination, and hairs often break at the scalp level (black dot type). Trichophyton tonsurans, T soudanense, Trichophyton rubrum, and T violaceum are common causes.

• Favus: In this pattern, T schoenleinii is a common cause, and hairs grow to considerable lengths above the scalp with less damage than the other patterns. The hair shafts present with characteristic air spaces, and hyphae form clusters at the level of the epidermis.

Diagnosis

Optimal treatment of TC relies on proper identification of the causative agent. Fungal culture remains the gold standard of mycologic diagnosis regardless of its delayed results, which may take up to 4 weeks for proper identification of the fungal colonies and require ample expertise to interpret the morphologic features of the grown colonies.⁴

Other tests such as the potassium hydroxide preparation are nonspecific and do not identify the dermatophyte species. Although this method has been reported to have 5% to 15% false-negative results in routine practice depending on the skill of the observer and the quality of sampling, microscopic examination is essential, as it may allow the clinician to start treatment sooner pending culture results. The use of a Wood lamp is not suitable for definitive species identification, as this technique primarily is useful for observing fluorescence in ectothrix infection caused by Microsporum species, with the exception of T schoenleinii; otherwise, Trichophyton species, which cause endothrix infections, do not fluoresce.⁵Polymerase chain reaction is a sensitive technique that can help identify both the genus and species of common dermatophytes. Common target sequences include the ribosomal internal transcribed spacer and translation elongation factor 1α. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also has become popular for dermatophyte identification.⁶Trichoscopic diagnosis of TC, which is simple and noninvasive, is becoming increasingly popular. Features such as short, broken, black dot, comma, corkscrew, and/or zigzag hairs, as well as perifollicular scaling, are helpful for diagnosing TC (Figure). Moreover, trichoscopy can be useful for differentiating other common causes of hair loss, such as trichotillomania and alopecia areata. It had been reported that the trichoscopic features of TC can be seen as early as 2 weeks after starting treatment and therefore this can be a reliable period in which to follow-up with the patient to evaluate progress. The disappearance of black dots and comma hairs can be appreciated from 2 weeks onwards by trichoscopic evaluation.⁴

Treatment

The common recommendation for first-line treatment of TC is the use of systemic antifungals with the use of a topical agent as an adjuvant to prevent the spread of fungal spores. For almost 6 decades, griseofulvin had been the gold-standard fungistatic used for treating TC in patients older than 2 years until the 2007 US Food and Drug Administration (FDA) approval of terbinafine fungicidal oral granules for treatment of TC in patients older than 4 years.⁷

Meta-analyses have demonstrated comparable efficacy for a 4-week course of terbinafine compared to 6 weeks of griseofulvin for TC based on the infectious organism. Terbinafine demonstrated superiority in treating T tonsurans and a similar efficacy in treating T violaceum, while griseofulvin was superior in treating M canis and other Microsporum species.^8,9

The off-label use of fluconazole and itraconazole to treat TC is gaining popularity, with limited trials showing increased evidence of their effectiveness. There is not much clinical evidence to support the use of other oral antifungals, including the newer azoles such as voriconazole or posaconazole.⁹

Newer limited evidence has shown the off-label use of photodynamic therapy to be a promising alternative to systemic antifungal therapy in treating TC, pending validation by larger sample trials.¹⁰In my practice, I have found that severe cases of TC demonstrating inflammation or possible widespread id reactions are better treated with oral steroids. Ketoconazole shampoo or selenium sulfide used 2 to 3 times weekly to prevent spread in the early phases of therapy is a good adjunct to systemic treatment. Cases with kerions should be assessed for the possibility of a coexisting bacterial infection under the crusts, and if confirmed, antibiotics should be started.⁹The commonly used systemic antifungals generally are safe with a low side-effect profile, but there is a risk for hepatotoxicity. The FDA recommends that baseline alanine transaminase and aspartate transaminase levels should be obtained prior to beginning a terbinafine-based treatment regimen.¹¹ The American Academy of Pediatrics has specifically stated that laboratory testing of serum hepatic enzymes is not a requirement if a griseofulvin-based regimen does not exceed 8 weeks; however, transaminase levels (alanine transaminase and aspartate transaminase) should be considered in patients using terbinafine at baseline or if treatment is prolonged beyond 4 to 6 weeks.¹² In agreement with the FDA guidelines, the Canadian Pediatric Society has suggested that liver enzymes should be periodically monitored in patients being treated with terbinafine beyond 4 to 6 weeks.¹³

Changes in the Fungal Microbiome

Research has shown that changes in the fungal microbiome were associated with an altered bacterial community in patients with TC. During fungal infection, the relative abundances of Cutibacterium and Corynebacterium increased, and the relative abundance of Streptococcus decreased. In addition, some uncommon bacterial genera such as Herbaspirillum and Methylorubrum were detected on the scalp in TC.¹⁴

Carrier State

Carrier state is determined for those siblings and contacts of cases with a clinically normal scalp that are positive on culture. Those individuals could represent a potential reservoir responsible for contamination (or recontamination) of the patient as well as treatment failure. Opinions remain divided as to whether to use oral antifungal therapy in these carriers or maintain therapy on antifungal shampoos containing ketoconazole or povidone-iodine. Due to the paucity of available data, my experience has shown that it is sufficient to use antifungal shampoos for such carriers. In zoophilic infections, it is important to identify and treat the animal source.^6-9

Final Thoughts

Successful treatment of TC requires accurate identification of the pathogen, which commonly is achieved via fungal culture. Despite its practical value, the conventional identification of dermatophytes based on morphologic features can be highly challenging due to the low positive rate and delayed results. Trichoscopy is a quick, handy, and noninvasive tool that can better indicate the diagnosis and also is helpful for follow-up on treatment progress. Due to better understanding of the immunology and genetic susceptibility associated with TC spread, the current treatment pipeline holds more insight into better control of this condition. Increased surveillance, prompt diagnosis, and early onset of systemic treatment are the key to proper prevention of spread of TC.

Tinea capitis (TC) most often is caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Noninflammatory TC typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated areas of alopecia with fine scale studded with broken-off hairs at the scalp surface, resulting in a black dot appearance. Inflammatory variants of TC include kerion and favus.¹ Herein, updates on diagnosis, treatment, and monitoring of TC are provided, as well as a discussion of changes in the fungal microbiome associated with TC. Lastly, insights to some queries that practitioners may encounter when treating children with TC are provided.

Genetic Susceptibility

Molecular techniques have identified a number of macrophage regulator, leukocyte activation and migration, and cutaneous permeability genes associated with susceptibility to TC. These findings indicate that genetically determined deficiency in adaptive immune responses may affect the predisposition to dermatophyte infections.²

Clinical Varieties of Infection

Dermatophytes causing ringworm are capable of invading the hair shafts and can simultaneously invade smooth or glabrous skin (eg, T tonsurans, Trichophyton schoenleinii, Trichophyton violaceum). Some causative dermatophytes can even penetrate the nails (eg, Trichophyton soudanense). The clinical presentation is dependent on 3 main patterns of hair invasion³:

• Ectothrix: A mid-follicular pattern of invasion with hyphae growing down to the hair bulb that commonly is caused by Microsporum species. It clinically presents with scaling and inflammation with hair shafts breaking 2 to 3 mm above the scalp level.

• Endothrix: This pattern is nonfluorescent on Wood lamp examination, and hairs often break at the scalp level (black dot type). Trichophyton tonsurans, T soudanense, Trichophyton rubrum, and T violaceum are common causes.

• Favus: In this pattern, T schoenleinii is a common cause, and hairs grow to considerable lengths above the scalp with less damage than the other patterns. The hair shafts present with characteristic air spaces, and hyphae form clusters at the level of the epidermis.

Diagnosis

Optimal treatment of TC relies on proper identification of the causative agent. Fungal culture remains the gold standard of mycologic diagnosis regardless of its delayed results, which may take up to 4 weeks for proper identification of the fungal colonies and require ample expertise to interpret the morphologic features of the grown colonies.⁴

Other tests such as the potassium hydroxide preparation are nonspecific and do not identify the dermatophyte species. Although this method has been reported to have 5% to 15% false-negative results in routine practice depending on the skill of the observer and the quality of sampling, microscopic examination is essential, as it may allow the clinician to start treatment sooner pending culture results. The use of a Wood lamp is not suitable for definitive species identification, as this technique primarily is useful for observing fluorescence in ectothrix infection caused by Microsporum species, with the exception of T schoenleinii; otherwise, Trichophyton species, which cause endothrix infections, do not fluoresce.⁵Polymerase chain reaction is a sensitive technique that can help identify both the genus and species of common dermatophytes. Common target sequences include the ribosomal internal transcribed spacer and translation elongation factor 1α. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also has become popular for dermatophyte identification.⁶Trichoscopic diagnosis of TC, which is simple and noninvasive, is becoming increasingly popular. Features such as short, broken, black dot, comma, corkscrew, and/or zigzag hairs, as well as perifollicular scaling, are helpful for diagnosing TC (Figure). Moreover, trichoscopy can be useful for differentiating other common causes of hair loss, such as trichotillomania and alopecia areata. It had been reported that the trichoscopic features of TC can be seen as early as 2 weeks after starting treatment and therefore this can be a reliable period in which to follow-up with the patient to evaluate progress. The disappearance of black dots and comma hairs can be appreciated from 2 weeks onwards by trichoscopic evaluation.⁴

Treatment

The common recommendation for first-line treatment of TC is the use of systemic antifungals with the use of a topical agent as an adjuvant to prevent the spread of fungal spores. For almost 6 decades, griseofulvin had been the gold-standard fungistatic used for treating TC in patients older than 2 years until the 2007 US Food and Drug Administration (FDA) approval of terbinafine fungicidal oral granules for treatment of TC in patients older than 4 years.⁷

Meta-analyses have demonstrated comparable efficacy for a 4-week course of terbinafine compared to 6 weeks of griseofulvin for TC based on the infectious organism. Terbinafine demonstrated superiority in treating T tonsurans and a similar efficacy in treating T violaceum, while griseofulvin was superior in treating M canis and other Microsporum species.^8,9

The off-label use of fluconazole and itraconazole to treat TC is gaining popularity, with limited trials showing increased evidence of their effectiveness. There is not much clinical evidence to support the use of other oral antifungals, including the newer azoles such as voriconazole or posaconazole.⁹

Newer limited evidence has shown the off-label use of photodynamic therapy to be a promising alternative to systemic antifungal therapy in treating TC, pending validation by larger sample trials.¹⁰In my practice, I have found that severe cases of TC demonstrating inflammation or possible widespread id reactions are better treated with oral steroids. Ketoconazole shampoo or selenium sulfide used 2 to 3 times weekly to prevent spread in the early phases of therapy is a good adjunct to systemic treatment. Cases with kerions should be assessed for the possibility of a coexisting bacterial infection under the crusts, and if confirmed, antibiotics should be started.⁹The commonly used systemic antifungals generally are safe with a low side-effect profile, but there is a risk for hepatotoxicity. The FDA recommends that baseline alanine transaminase and aspartate transaminase levels should be obtained prior to beginning a terbinafine-based treatment regimen.¹¹ The American Academy of Pediatrics has specifically stated that laboratory testing of serum hepatic enzymes is not a requirement if a griseofulvin-based regimen does not exceed 8 weeks; however, transaminase levels (alanine transaminase and aspartate transaminase) should be considered in patients using terbinafine at baseline or if treatment is prolonged beyond 4 to 6 weeks.¹² In agreement with the FDA guidelines, the Canadian Pediatric Society has suggested that liver enzymes should be periodically monitored in patients being treated with terbinafine beyond 4 to 6 weeks.¹³

Changes in the Fungal Microbiome

Research has shown that changes in the fungal microbiome were associated with an altered bacterial community in patients with TC. During fungal infection, the relative abundances of Cutibacterium and Corynebacterium increased, and the relative abundance of Streptococcus decreased. In addition, some uncommon bacterial genera such as Herbaspirillum and Methylorubrum were detected on the scalp in TC.¹⁴

Carrier State

Carrier state is determined for those siblings and contacts of cases with a clinically normal scalp that are positive on culture. Those individuals could represent a potential reservoir responsible for contamination (or recontamination) of the patient as well as treatment failure. Opinions remain divided as to whether to use oral antifungal therapy in these carriers or maintain therapy on antifungal shampoos containing ketoconazole or povidone-iodine. Due to the paucity of available data, my experience has shown that it is sufficient to use antifungal shampoos for such carriers. In zoophilic infections, it is important to identify and treat the animal source.^6-9

Final Thoughts

Successful treatment of TC requires accurate identification of the pathogen, which commonly is achieved via fungal culture. Despite its practical value, the conventional identification of dermatophytes based on morphologic features can be highly challenging due to the low positive rate and delayed results. Trichoscopy is a quick, handy, and noninvasive tool that can better indicate the diagnosis and also is helpful for follow-up on treatment progress. Due to better understanding of the immunology and genetic susceptibility associated with TC spread, the current treatment pipeline holds more insight into better control of this condition. Increased surveillance, prompt diagnosis, and early onset of systemic treatment are the key to proper prevention of spread of TC.

Tinea capitis (TC) most often is caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Noninflammatory TC typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated areas of alopecia with fine scale studded with broken-off hairs at the scalp surface, resulting in a black dot appearance. Inflammatory variants of TC include kerion and favus.¹ Herein, updates on diagnosis, treatment, and monitoring of TC are provided, as well as a discussion of changes in the fungal microbiome associated with TC. Lastly, insights to some queries that practitioners may encounter when treating children with TC are provided.

Genetic Susceptibility

Molecular techniques have identified a number of macrophage regulator, leukocyte activation and migration, and cutaneous permeability genes associated with susceptibility to TC. These findings indicate that genetically determined deficiency in adaptive immune responses may affect the predisposition to dermatophyte infections.²

Clinical Varieties of Infection

Dermatophytes causing ringworm are capable of invading the hair shafts and can simultaneously invade smooth or glabrous skin (eg, T tonsurans, Trichophyton schoenleinii, Trichophyton violaceum). Some causative dermatophytes can even penetrate the nails (eg, Trichophyton soudanense). The clinical presentation is dependent on 3 main patterns of hair invasion³:

• Ectothrix: A mid-follicular pattern of invasion with hyphae growing down to the hair bulb that commonly is caused by Microsporum species. It clinically presents with scaling and inflammation with hair shafts breaking 2 to 3 mm above the scalp level.

• Endothrix: This pattern is nonfluorescent on Wood lamp examination, and hairs often break at the scalp level (black dot type). Trichophyton tonsurans, T soudanense, Trichophyton rubrum, and T violaceum are common causes.

• Favus: In this pattern, T schoenleinii is a common cause, and hairs grow to considerable lengths above the scalp with less damage than the other patterns. The hair shafts present with characteristic air spaces, and hyphae form clusters at the level of the epidermis.

Diagnosis

Optimal treatment of TC relies on proper identification of the causative agent. Fungal culture remains the gold standard of mycologic diagnosis regardless of its delayed results, which may take up to 4 weeks for proper identification of the fungal colonies and require ample expertise to interpret the morphologic features of the grown colonies.⁴

Other tests such as the potassium hydroxide preparation are nonspecific and do not identify the dermatophyte species. Although this method has been reported to have 5% to 15% false-negative results in routine practice depending on the skill of the observer and the quality of sampling, microscopic examination is essential, as it may allow the clinician to start treatment sooner pending culture results. The use of a Wood lamp is not suitable for definitive species identification, as this technique primarily is useful for observing fluorescence in ectothrix infection caused by Microsporum species, with the exception of T schoenleinii; otherwise, Trichophyton species, which cause endothrix infections, do not fluoresce.⁵Polymerase chain reaction is a sensitive technique that can help identify both the genus and species of common dermatophytes. Common target sequences include the ribosomal internal transcribed spacer and translation elongation factor 1α. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also has become popular for dermatophyte identification.⁶Trichoscopic diagnosis of TC, which is simple and noninvasive, is becoming increasingly popular. Features such as short, broken, black dot, comma, corkscrew, and/or zigzag hairs, as well as perifollicular scaling, are helpful for diagnosing TC (Figure). Moreover, trichoscopy can be useful for differentiating other common causes of hair loss, such as trichotillomania and alopecia areata. It had been reported that the trichoscopic features of TC can be seen as early as 2 weeks after starting treatment and therefore this can be a reliable period in which to follow-up with the patient to evaluate progress. The disappearance of black dots and comma hairs can be appreciated from 2 weeks onwards by trichoscopic evaluation.⁴

Treatment

The common recommendation for first-line treatment of TC is the use of systemic antifungals with the use of a topical agent as an adjuvant to prevent the spread of fungal spores. For almost 6 decades, griseofulvin had been the gold-standard fungistatic used for treating TC in patients older than 2 years until the 2007 US Food and Drug Administration (FDA) approval of terbinafine fungicidal oral granules for treatment of TC in patients older than 4 years.⁷

Meta-analyses have demonstrated comparable efficacy for a 4-week course of terbinafine compared to 6 weeks of griseofulvin for TC based on the infectious organism. Terbinafine demonstrated superiority in treating T tonsurans and a similar efficacy in treating T violaceum, while griseofulvin was superior in treating M canis and other Microsporum species.^8,9

The off-label use of fluconazole and itraconazole to treat TC is gaining popularity, with limited trials showing increased evidence of their effectiveness. There is not much clinical evidence to support the use of other oral antifungals, including the newer azoles such as voriconazole or posaconazole.⁹

Newer limited evidence has shown the off-label use of photodynamic therapy to be a promising alternative to systemic antifungal therapy in treating TC, pending validation by larger sample trials.¹⁰In my practice, I have found that severe cases of TC demonstrating inflammation or possible widespread id reactions are better treated with oral steroids. Ketoconazole shampoo or selenium sulfide used 2 to 3 times weekly to prevent spread in the early phases of therapy is a good adjunct to systemic treatment. Cases with kerions should be assessed for the possibility of a coexisting bacterial infection under the crusts, and if confirmed, antibiotics should be started.⁹The commonly used systemic antifungals generally are safe with a low side-effect profile, but there is a risk for hepatotoxicity. The FDA recommends that baseline alanine transaminase and aspartate transaminase levels should be obtained prior to beginning a terbinafine-based treatment regimen.¹¹ The American Academy of Pediatrics has specifically stated that laboratory testing of serum hepatic enzymes is not a requirement if a griseofulvin-based regimen does not exceed 8 weeks; however, transaminase levels (alanine transaminase and aspartate transaminase) should be considered in patients using terbinafine at baseline or if treatment is prolonged beyond 4 to 6 weeks.¹² In agreement with the FDA guidelines, the Canadian Pediatric Society has suggested that liver enzymes should be periodically monitored in patients being treated with terbinafine beyond 4 to 6 weeks.¹³

Changes in the Fungal Microbiome

Research has shown that changes in the fungal microbiome were associated with an altered bacterial community in patients with TC. During fungal infection, the relative abundances of Cutibacterium and Corynebacterium increased, and the relative abundance of Streptococcus decreased. In addition, some uncommon bacterial genera such as Herbaspirillum and Methylorubrum were detected on the scalp in TC.¹⁴

Carrier State

Carrier state is determined for those siblings and contacts of cases with a clinically normal scalp that are positive on culture. Those individuals could represent a potential reservoir responsible for contamination (or recontamination) of the patient as well as treatment failure. Opinions remain divided as to whether to use oral antifungal therapy in these carriers or maintain therapy on antifungal shampoos containing ketoconazole or povidone-iodine. Due to the paucity of available data, my experience has shown that it is sufficient to use antifungal shampoos for such carriers. In zoophilic infections, it is important to identify and treat the animal source.^6-9

Final Thoughts

Successful treatment of TC requires accurate identification of the pathogen, which commonly is achieved via fungal culture. Despite its practical value, the conventional identification of dermatophytes based on morphologic features can be highly challenging due to the low positive rate and delayed results. Trichoscopy is a quick, handy, and noninvasive tool that can better indicate the diagnosis and also is helpful for follow-up on treatment progress. Due to better understanding of the immunology and genetic susceptibility associated with TC spread, the current treatment pipeline holds more insight into better control of this condition. Increased surveillance, prompt diagnosis, and early onset of systemic treatment are the key to proper prevention of spread of TC.

Attendees at ObesityWeek® 2022 listened with much excitement to the results of the STEP TEENS phase 3 trial of once-weekly subcutaneous semaglutide 2.4 mg (Wegovy) in adolescents aged 12 up to 18 years old with obesity.

When a session panel member said that clinical trials of weight-loss medications for adolescents with obesity should henceforth stop using placebo controls – implying that comparison with the once-weekly injection semaglutide would be more informative – the audience applauded.

The results were also simultaneously published in the New England Journal of Medicine to coincide with the presentation.  

The research “gives hope” to adolescents with obesity, their parents, and their doctors, the trial’s principal investigator, Daniel Weghuber, MD, said in an interview.

“Many of them have been struggling for such a long time – both the parents and the kids themselves,” said Dr. Weghuber, from the department of pediatrics, Paracelsus Medical University, Salzburg, Austria.

“It’s not an issue of lack of willpower,” he stressed. “That’s a major misunderstanding.”

“This drug [semaglutide] seems to enable people who are living with obesity to adhere to the recommendations that they may have been following for years and years but were [still] not able to achieve their goal,” he said. It “enables people to achieve their goals.”

Asked about any potential negative impact on normal growth, Dr. Weghuber pointed out that the average weight of study participants was 107 kg (236 lb). “I’m really not afraid of a 15-year-old with 107 kg losing 10%, 15%, 20%” of their weight, he said. There was no indication of a problem regarding normal growth or development in the study.

The research showed that “there is the combination of lifestyle plus in the future anti-obesity medications that will open up a new chapter” for treating adolescents with obesity, he summarized.

Senior study author, Silva Arslanian, MD, who holds the Richard L. Day Endowed Chair in Pediatrics at the University of Pittsburgh, agreed. “The results are amazing,” said Dr. Arslanian in a press release issued by the University of Pittsburgh. “For a person who is 5 foot, 5 inches tall and weighs 240 pounds, the average reduction in BMI equates to shedding about 40 pounds.”
 

‘Mind-blowing, awesome’ results

The session at ObesityWeek® 2022, the annual meeting of the Obesity Society, was chaired by Aaron S. Kelly, PhD, professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota, Minneapolis.

Dr. Kelly led the SCALE TEENS clinical trial of liraglutide (Saxenda), also a glucagon-like peptide (GLP-1) agonist like semaglutide, for adolescents aged 12 up to 18 years with obesity, which assigned 125 participants to the daily injectable liraglutide group and 126 to the placebo group. SCALE TEENS was presented and published in May 2020, leading to the approval of liraglutide for obesity in this age group, in December 2020.

Dr. Kelly called on two experts who were not involved in the research to offer their comments, starting with Claudia K. Fox, MD, MPH.

“These results are mind-blowing,” said Dr. Fox, who is associate professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota.

“We are getting close to bariatric surgery results” in these adolescent patients with obesity, added Dr. Fox, who is an American Board of Obesity Medicine diplomate. To have 40% of patients attain normal weight, “that’s massive” and “life-changing,” she said. And improvement in quality of life is what families care most about. “I am super excited,” she commented.

Next, Dr. Kelly called on Sarah C. Armstrong, MD, director of the Duke Children’s Healthy Lifestyles Program, Duke University, Durham, N.C.

Dr. Armstrong is a member of the executive committee for the American Academy of Pediatrics Section on Obesity and a coauthor of the upcoming clinical practice guidelines that are being published.

Looking at more than 16,000 abstracts at the meeting shows that “watchful waiting is not effective,” Dr. Armstrong said.
 

200 teens with obesity, only 1 with overweight

Obesity affects almost one in five children and adolescents worldwide. The chronic disease is linked with decreased life expectancy and higher risk of developing serious health problems such as type 2 diabetes, heart disease, nonalcoholic fatty liver disease, sleep apnea, and certain cancers. Teenagers with obesity are also more likely to have depression, anxiety, poor self-esteem, and other psychological issues.

STEP TEENS enrolled 201 adolescents aged 12 up to 18 years with obesity (body mass index [BMI] ≥ 95th percentile) or overweight (BMI ≥ 85th percentile) plus at least one weight-related comorbidity.

Only one recruited patient fit the latter category; the rest had obesity.

Most patients (62%) were female. They had a mean age of 15.4 years, a mean BMI of 37 kg/m², and a mean waist circumference of 110 cm (43 inches).

Patients were randomized 2:1 to receive a once-weekly 2.4-mg subcutaneous injection of semaglutide or placebo for 68 weeks, plus lifestyle intervention.

Dr. Weghuber noted that 89.6% of patients in the semaglutide group completed treatment.

The primary endpoint, mean change in BMI from baseline to week 68, was −16.1% with semaglutide and +0.6% with placebo (estimated difference, −16.7 percentage points; P < .001).

A second confirmatory endpoint, at least 5% weight loss at week 68, was met by 73% of patients in the semaglutide group versus 18% of patients in the placebo group (P < .001).

Reductions in body weight and improvements in waist circumference, A1c, lipids (except HDL cholesterol), and the liver enzyme alanine aminotransferase were greater with semaglutide than placebo.

The Impact of Weight on Quality of Life – Kids (IWQOL-Kids) questionnaire total score as well as scores for body esteem, family relation, physical comfort, and social life were better in the semaglutide group.

However, the incidence of gastrointestinal adverse events was greater with semaglutide than placebo (62% versus 42%).

Five participants (4%) in the semaglutide group and none in the placebo group developed gallstones (cholelithiasis).

Serious adverse events were reported in 11% of patients in the semaglutide group and 9% of patients in the placebo group.
 

‘Big change’ coming in guidelines for obesity in teens

Commenting on the upcoming new recommendations for adolescents, Dr. Armstrong noted “there’s going to be a strong recommendation” for therapy in the new guidelines for pediatric obesity. “That’s a big change,” she said.

In the lively question-and-answer session that followed, a clinician wanted to know what explained the very high rate of study completion during the COVID-19 pandemic (when STEP TEENS was conducted). “What can we learn?” he asked.

“The bottom line is the relationship” and “close communication” between study investigators and patients, Dr. Weghuber replied.

“The fast track is likely to lead to approval in adolescents,” another member of the audience noted. He wanted to know if the company is planning a trial of semaglutide in younger children.

They are, Dr. Weghuber replied, and one with liraglutide is already underway.

The SCALE KIDS clinical trial of liraglutide is randomizing 78 participants aged 6 up to 12 years for 56 weeks of treatment and 26 weeks of follow-up, with an estimated primary completion date of July 7, 2023.

The last words went to Dr. Fox. The current results “are indeed very awesome,” she said, yet “thousands of providers are hesitant” to prescribe medications for adolescents with obesity.

The trial was funded by Novo Nordisk. Dr. Weghuber has reported being a consultant for Novo Nordisk and member of the Global Pediatric Obesity Expert Panel for the company. Disclosures for the other authors are listed with the article. Dr. Kelly has reported receiving donated drugs from AstraZeneca and travel support from Novo Nordisk and serving as an unpaid consultant for Novo Nordisk, Orexigen Therapeutics, VIVUS, and WW (formerly Weight Watchers).

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

Attendees at ObesityWeek® 2022 listened with much excitement to the results of the STEP TEENS phase 3 trial of once-weekly subcutaneous semaglutide 2.4 mg (Wegovy) in adolescents aged 12 up to 18 years old with obesity.

When a session panel member said that clinical trials of weight-loss medications for adolescents with obesity should henceforth stop using placebo controls – implying that comparison with the once-weekly injection semaglutide would be more informative – the audience applauded.

The results were also simultaneously published in the New England Journal of Medicine to coincide with the presentation.  

The research “gives hope” to adolescents with obesity, their parents, and their doctors, the trial’s principal investigator, Daniel Weghuber, MD, said in an interview.

“Many of them have been struggling for such a long time – both the parents and the kids themselves,” said Dr. Weghuber, from the department of pediatrics, Paracelsus Medical University, Salzburg, Austria.

“It’s not an issue of lack of willpower,” he stressed. “That’s a major misunderstanding.”

“This drug [semaglutide] seems to enable people who are living with obesity to adhere to the recommendations that they may have been following for years and years but were [still] not able to achieve their goal,” he said. It “enables people to achieve their goals.”

Asked about any potential negative impact on normal growth, Dr. Weghuber pointed out that the average weight of study participants was 107 kg (236 lb). “I’m really not afraid of a 15-year-old with 107 kg losing 10%, 15%, 20%” of their weight, he said. There was no indication of a problem regarding normal growth or development in the study.

The research showed that “there is the combination of lifestyle plus in the future anti-obesity medications that will open up a new chapter” for treating adolescents with obesity, he summarized.

Senior study author, Silva Arslanian, MD, who holds the Richard L. Day Endowed Chair in Pediatrics at the University of Pittsburgh, agreed. “The results are amazing,” said Dr. Arslanian in a press release issued by the University of Pittsburgh. “For a person who is 5 foot, 5 inches tall and weighs 240 pounds, the average reduction in BMI equates to shedding about 40 pounds.”
 

‘Mind-blowing, awesome’ results

The session at ObesityWeek® 2022, the annual meeting of the Obesity Society, was chaired by Aaron S. Kelly, PhD, professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota, Minneapolis.

Dr. Kelly led the SCALE TEENS clinical trial of liraglutide (Saxenda), also a glucagon-like peptide (GLP-1) agonist like semaglutide, for adolescents aged 12 up to 18 years with obesity, which assigned 125 participants to the daily injectable liraglutide group and 126 to the placebo group. SCALE TEENS was presented and published in May 2020, leading to the approval of liraglutide for obesity in this age group, in December 2020.

Dr. Kelly called on two experts who were not involved in the research to offer their comments, starting with Claudia K. Fox, MD, MPH.

“These results are mind-blowing,” said Dr. Fox, who is associate professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota.

“We are getting close to bariatric surgery results” in these adolescent patients with obesity, added Dr. Fox, who is an American Board of Obesity Medicine diplomate. To have 40% of patients attain normal weight, “that’s massive” and “life-changing,” she said. And improvement in quality of life is what families care most about. “I am super excited,” she commented.

Next, Dr. Kelly called on Sarah C. Armstrong, MD, director of the Duke Children’s Healthy Lifestyles Program, Duke University, Durham, N.C.

Dr. Armstrong is a member of the executive committee for the American Academy of Pediatrics Section on Obesity and a coauthor of the upcoming clinical practice guidelines that are being published.

Looking at more than 16,000 abstracts at the meeting shows that “watchful waiting is not effective,” Dr. Armstrong said.
 

200 teens with obesity, only 1 with overweight

Obesity affects almost one in five children and adolescents worldwide. The chronic disease is linked with decreased life expectancy and higher risk of developing serious health problems such as type 2 diabetes, heart disease, nonalcoholic fatty liver disease, sleep apnea, and certain cancers. Teenagers with obesity are also more likely to have depression, anxiety, poor self-esteem, and other psychological issues.

STEP TEENS enrolled 201 adolescents aged 12 up to 18 years with obesity (body mass index [BMI] ≥ 95th percentile) or overweight (BMI ≥ 85th percentile) plus at least one weight-related comorbidity.

Only one recruited patient fit the latter category; the rest had obesity.

Most patients (62%) were female. They had a mean age of 15.4 years, a mean BMI of 37 kg/m², and a mean waist circumference of 110 cm (43 inches).

Patients were randomized 2:1 to receive a once-weekly 2.4-mg subcutaneous injection of semaglutide or placebo for 68 weeks, plus lifestyle intervention.

Dr. Weghuber noted that 89.6% of patients in the semaglutide group completed treatment.

The primary endpoint, mean change in BMI from baseline to week 68, was −16.1% with semaglutide and +0.6% with placebo (estimated difference, −16.7 percentage points; P < .001).

A second confirmatory endpoint, at least 5% weight loss at week 68, was met by 73% of patients in the semaglutide group versus 18% of patients in the placebo group (P < .001).

Reductions in body weight and improvements in waist circumference, A1c, lipids (except HDL cholesterol), and the liver enzyme alanine aminotransferase were greater with semaglutide than placebo.

The Impact of Weight on Quality of Life – Kids (IWQOL-Kids) questionnaire total score as well as scores for body esteem, family relation, physical comfort, and social life were better in the semaglutide group.

However, the incidence of gastrointestinal adverse events was greater with semaglutide than placebo (62% versus 42%).

Five participants (4%) in the semaglutide group and none in the placebo group developed gallstones (cholelithiasis).

Serious adverse events were reported in 11% of patients in the semaglutide group and 9% of patients in the placebo group.
 

‘Big change’ coming in guidelines for obesity in teens

Commenting on the upcoming new recommendations for adolescents, Dr. Armstrong noted “there’s going to be a strong recommendation” for therapy in the new guidelines for pediatric obesity. “That’s a big change,” she said.

In the lively question-and-answer session that followed, a clinician wanted to know what explained the very high rate of study completion during the COVID-19 pandemic (when STEP TEENS was conducted). “What can we learn?” he asked.

“The bottom line is the relationship” and “close communication” between study investigators and patients, Dr. Weghuber replied.

“The fast track is likely to lead to approval in adolescents,” another member of the audience noted. He wanted to know if the company is planning a trial of semaglutide in younger children.

They are, Dr. Weghuber replied, and one with liraglutide is already underway.

The SCALE KIDS clinical trial of liraglutide is randomizing 78 participants aged 6 up to 12 years for 56 weeks of treatment and 26 weeks of follow-up, with an estimated primary completion date of July 7, 2023.

The last words went to Dr. Fox. The current results “are indeed very awesome,” she said, yet “thousands of providers are hesitant” to prescribe medications for adolescents with obesity.

The trial was funded by Novo Nordisk. Dr. Weghuber has reported being a consultant for Novo Nordisk and member of the Global Pediatric Obesity Expert Panel for the company. Disclosures for the other authors are listed with the article. Dr. Kelly has reported receiving donated drugs from AstraZeneca and travel support from Novo Nordisk and serving as an unpaid consultant for Novo Nordisk, Orexigen Therapeutics, VIVUS, and WW (formerly Weight Watchers).

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

Attendees at ObesityWeek® 2022 listened with much excitement to the results of the STEP TEENS phase 3 trial of once-weekly subcutaneous semaglutide 2.4 mg (Wegovy) in adolescents aged 12 up to 18 years old with obesity.

When a session panel member said that clinical trials of weight-loss medications for adolescents with obesity should henceforth stop using placebo controls – implying that comparison with the once-weekly injection semaglutide would be more informative – the audience applauded.

The results were also simultaneously published in the New England Journal of Medicine to coincide with the presentation.  

The research “gives hope” to adolescents with obesity, their parents, and their doctors, the trial’s principal investigator, Daniel Weghuber, MD, said in an interview.

“Many of them have been struggling for such a long time – both the parents and the kids themselves,” said Dr. Weghuber, from the department of pediatrics, Paracelsus Medical University, Salzburg, Austria.

“It’s not an issue of lack of willpower,” he stressed. “That’s a major misunderstanding.”

“This drug [semaglutide] seems to enable people who are living with obesity to adhere to the recommendations that they may have been following for years and years but were [still] not able to achieve their goal,” he said. It “enables people to achieve their goals.”

Asked about any potential negative impact on normal growth, Dr. Weghuber pointed out that the average weight of study participants was 107 kg (236 lb). “I’m really not afraid of a 15-year-old with 107 kg losing 10%, 15%, 20%” of their weight, he said. There was no indication of a problem regarding normal growth or development in the study.

The research showed that “there is the combination of lifestyle plus in the future anti-obesity medications that will open up a new chapter” for treating adolescents with obesity, he summarized.

Senior study author, Silva Arslanian, MD, who holds the Richard L. Day Endowed Chair in Pediatrics at the University of Pittsburgh, agreed. “The results are amazing,” said Dr. Arslanian in a press release issued by the University of Pittsburgh. “For a person who is 5 foot, 5 inches tall and weighs 240 pounds, the average reduction in BMI equates to shedding about 40 pounds.”
 

‘Mind-blowing, awesome’ results

The session at ObesityWeek® 2022, the annual meeting of the Obesity Society, was chaired by Aaron S. Kelly, PhD, professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota, Minneapolis.

Dr. Kelly led the SCALE TEENS clinical trial of liraglutide (Saxenda), also a glucagon-like peptide (GLP-1) agonist like semaglutide, for adolescents aged 12 up to 18 years with obesity, which assigned 125 participants to the daily injectable liraglutide group and 126 to the placebo group. SCALE TEENS was presented and published in May 2020, leading to the approval of liraglutide for obesity in this age group, in December 2020.

Dr. Kelly called on two experts who were not involved in the research to offer their comments, starting with Claudia K. Fox, MD, MPH.

“These results are mind-blowing,” said Dr. Fox, who is associate professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota.

“We are getting close to bariatric surgery results” in these adolescent patients with obesity, added Dr. Fox, who is an American Board of Obesity Medicine diplomate. To have 40% of patients attain normal weight, “that’s massive” and “life-changing,” she said. And improvement in quality of life is what families care most about. “I am super excited,” she commented.

Next, Dr. Kelly called on Sarah C. Armstrong, MD, director of the Duke Children’s Healthy Lifestyles Program, Duke University, Durham, N.C.

Dr. Armstrong is a member of the executive committee for the American Academy of Pediatrics Section on Obesity and a coauthor of the upcoming clinical practice guidelines that are being published.

Looking at more than 16,000 abstracts at the meeting shows that “watchful waiting is not effective,” Dr. Armstrong said.
 

200 teens with obesity, only 1 with overweight

Obesity affects almost one in five children and adolescents worldwide. The chronic disease is linked with decreased life expectancy and higher risk of developing serious health problems such as type 2 diabetes, heart disease, nonalcoholic fatty liver disease, sleep apnea, and certain cancers. Teenagers with obesity are also more likely to have depression, anxiety, poor self-esteem, and other psychological issues.

STEP TEENS enrolled 201 adolescents aged 12 up to 18 years with obesity (body mass index [BMI] ≥ 95th percentile) or overweight (BMI ≥ 85th percentile) plus at least one weight-related comorbidity.

Only one recruited patient fit the latter category; the rest had obesity.

Most patients (62%) were female. They had a mean age of 15.4 years, a mean BMI of 37 kg/m², and a mean waist circumference of 110 cm (43 inches).

Patients were randomized 2:1 to receive a once-weekly 2.4-mg subcutaneous injection of semaglutide or placebo for 68 weeks, plus lifestyle intervention.

Dr. Weghuber noted that 89.6% of patients in the semaglutide group completed treatment.

The primary endpoint, mean change in BMI from baseline to week 68, was −16.1% with semaglutide and +0.6% with placebo (estimated difference, −16.7 percentage points; P < .001).

A second confirmatory endpoint, at least 5% weight loss at week 68, was met by 73% of patients in the semaglutide group versus 18% of patients in the placebo group (P < .001).

Reductions in body weight and improvements in waist circumference, A1c, lipids (except HDL cholesterol), and the liver enzyme alanine aminotransferase were greater with semaglutide than placebo.

The Impact of Weight on Quality of Life – Kids (IWQOL-Kids) questionnaire total score as well as scores for body esteem, family relation, physical comfort, and social life were better in the semaglutide group.

However, the incidence of gastrointestinal adverse events was greater with semaglutide than placebo (62% versus 42%).

Five participants (4%) in the semaglutide group and none in the placebo group developed gallstones (cholelithiasis).

Serious adverse events were reported in 11% of patients in the semaglutide group and 9% of patients in the placebo group.
 

‘Big change’ coming in guidelines for obesity in teens

Commenting on the upcoming new recommendations for adolescents, Dr. Armstrong noted “there’s going to be a strong recommendation” for therapy in the new guidelines for pediatric obesity. “That’s a big change,” she said.

In the lively question-and-answer session that followed, a clinician wanted to know what explained the very high rate of study completion during the COVID-19 pandemic (when STEP TEENS was conducted). “What can we learn?” he asked.

“The bottom line is the relationship” and “close communication” between study investigators and patients, Dr. Weghuber replied.

“The fast track is likely to lead to approval in adolescents,” another member of the audience noted. He wanted to know if the company is planning a trial of semaglutide in younger children.

They are, Dr. Weghuber replied, and one with liraglutide is already underway.

The SCALE KIDS clinical trial of liraglutide is randomizing 78 participants aged 6 up to 12 years for 56 weeks of treatment and 26 weeks of follow-up, with an estimated primary completion date of July 7, 2023.

The last words went to Dr. Fox. The current results “are indeed very awesome,” she said, yet “thousands of providers are hesitant” to prescribe medications for adolescents with obesity.

The trial was funded by Novo Nordisk. Dr. Weghuber has reported being a consultant for Novo Nordisk and member of the Global Pediatric Obesity Expert Panel for the company. Disclosures for the other authors are listed with the article. Dr. Kelly has reported receiving donated drugs from AstraZeneca and travel support from Novo Nordisk and serving as an unpaid consultant for Novo Nordisk, Orexigen Therapeutics, VIVUS, and WW (formerly Weight Watchers).

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

New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.

Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.

Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.

Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)

RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.

RSV is the leading cause of hospitalization for infants, the Post noted.

The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.

The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.

Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.

For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.

“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.

“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”

As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.

Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.

“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”

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

New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.

Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.

Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.

Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)

RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.

RSV is the leading cause of hospitalization for infants, the Post noted.

The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.

The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.

Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.

For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.

“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.

“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”

As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.

Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.

“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”

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

New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.

Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.

Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.

Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)

RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.

RSV is the leading cause of hospitalization for infants, the Post noted.

The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.

The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.

Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.

For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.

“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.

“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”

As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.

Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.

“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”

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