MDedge Dermatology

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.

Women continue to be underrepresented among the leadership ranks of dermatology training programs, although the gender gap has closed in recent years, according to a recent cross-sectional study.

Although women made up more than half of the dermatology residency program directors (53.5%), associate directors (62.6%), and assistant directors (58.3%) in 2021, those numbers fall short of women’s majority (65% in 2018) among the trainees themselves, Yasmine Abushukur of Oakland University in Rochester, Mich., and associates said in a research letter.

Advancements were “made in gender diversity within academic dermatology from 2016 to 2021, [but] women remain underrepresented, particularly in leadership of dermatopathology and dermatologic surgery fellowships,” the investigators wrote.

Data gathered from 142 dermatology residency programs accredited by the Accreditation Council for Graduate Medical Education show that progress has been made since 2016, at least among program directors (PDs), of whom 48% were women, according to a previous study. Data on associate and assistant PDs from 2016 were not available to Ms. Abushukur and associates.

At the fellowship program level, women made gains as PDs in dermatopathology (34% in 2016 and 41% in 2021) and pediatric dermatology (64% in 2016 and 76% in 2021), but not in dermatologic surgery, where the proportion held at 26% over the study period. “This disparity is reflective of the general trend in surgery and pathology leadership nationally,” the researchers noted.

Taking a couple of steps up the ladder of authority shows that 39% of dermatology chairs were women in 2021, compared with 23% in 2016. A study published in 2016 demonstrated decreased diversity among academic faculty members as faculty rank increased, and “our data mirror this sentiment by demonstrating a majority of women in assistant and associate PD positions, with a minority of women chairs,” they wrote.

The investigators said that they had no conflicts of interest and no outside funding. Ms. Abushukur’s coauthors were from the departments of dermatology at the Henry Ford Health System, Detroit, and Wayne State University, Dearborn, Mich.

Women continue to be underrepresented among the leadership ranks of dermatology training programs, although the gender gap has closed in recent years, according to a recent cross-sectional study.

Although women made up more than half of the dermatology residency program directors (53.5%), associate directors (62.6%), and assistant directors (58.3%) in 2021, those numbers fall short of women’s majority (65% in 2018) among the trainees themselves, Yasmine Abushukur of Oakland University in Rochester, Mich., and associates said in a research letter.

Advancements were “made in gender diversity within academic dermatology from 2016 to 2021, [but] women remain underrepresented, particularly in leadership of dermatopathology and dermatologic surgery fellowships,” the investigators wrote.

Data gathered from 142 dermatology residency programs accredited by the Accreditation Council for Graduate Medical Education show that progress has been made since 2016, at least among program directors (PDs), of whom 48% were women, according to a previous study. Data on associate and assistant PDs from 2016 were not available to Ms. Abushukur and associates.

At the fellowship program level, women made gains as PDs in dermatopathology (34% in 2016 and 41% in 2021) and pediatric dermatology (64% in 2016 and 76% in 2021), but not in dermatologic surgery, where the proportion held at 26% over the study period. “This disparity is reflective of the general trend in surgery and pathology leadership nationally,” the researchers noted.

Taking a couple of steps up the ladder of authority shows that 39% of dermatology chairs were women in 2021, compared with 23% in 2016. A study published in 2016 demonstrated decreased diversity among academic faculty members as faculty rank increased, and “our data mirror this sentiment by demonstrating a majority of women in assistant and associate PD positions, with a minority of women chairs,” they wrote.

The investigators said that they had no conflicts of interest and no outside funding. Ms. Abushukur’s coauthors were from the departments of dermatology at the Henry Ford Health System, Detroit, and Wayne State University, Dearborn, Mich.

Women continue to be underrepresented among the leadership ranks of dermatology training programs, although the gender gap has closed in recent years, according to a recent cross-sectional study.

Although women made up more than half of the dermatology residency program directors (53.5%), associate directors (62.6%), and assistant directors (58.3%) in 2021, those numbers fall short of women’s majority (65% in 2018) among the trainees themselves, Yasmine Abushukur of Oakland University in Rochester, Mich., and associates said in a research letter.

Advancements were “made in gender diversity within academic dermatology from 2016 to 2021, [but] women remain underrepresented, particularly in leadership of dermatopathology and dermatologic surgery fellowships,” the investigators wrote.

Data gathered from 142 dermatology residency programs accredited by the Accreditation Council for Graduate Medical Education show that progress has been made since 2016, at least among program directors (PDs), of whom 48% were women, according to a previous study. Data on associate and assistant PDs from 2016 were not available to Ms. Abushukur and associates.

At the fellowship program level, women made gains as PDs in dermatopathology (34% in 2016 and 41% in 2021) and pediatric dermatology (64% in 2016 and 76% in 2021), but not in dermatologic surgery, where the proportion held at 26% over the study period. “This disparity is reflective of the general trend in surgery and pathology leadership nationally,” the researchers noted.

Taking a couple of steps up the ladder of authority shows that 39% of dermatology chairs were women in 2021, compared with 23% in 2016. A study published in 2016 demonstrated decreased diversity among academic faculty members as faculty rank increased, and “our data mirror this sentiment by demonstrating a majority of women in assistant and associate PD positions, with a minority of women chairs,” they wrote.

The investigators said that they had no conflicts of interest and no outside funding. Ms. Abushukur’s coauthors were from the departments of dermatology at the Henry Ford Health System, Detroit, and Wayne State University, Dearborn, Mich.

Surgical site infections are one of the top causes of postoperative morbidity and death worldwide, but there is little agreement and much debate over the most effective wound dressing to improve outcomes and reduce the health care burden.

Recent clinical trials have indicated that transparent, semiocclusive films have advantages over gauze held by adhesive tape.

But current transparent film bandages may become dislodged during activities such as showering, say authors of a pilot study published in the Journal of Wound Care. Patients may not realize the bandage has been disrupted, which can lead to infection.

The paper describes a novel product called DrySee dressing (DSD), which features a liquid indicator that turns blue around the edges if moisture is present.

“Clinicians, patients, and caregivers are alerted to the loss of dressing integrity and can replace the dressing when any portion of the perimeter changes to a blue [color],” the authors explain. “In addition, the dressing turns blue when the central pad is saturated with fluid, allowing the patient or provider to change the dressing.”

DSD is indicated for wounds that have low levels of exudate.
 

Two transparent film dressings compared

Researchers recruited 20 patients from the general population in Pittsburgh, for a small pilot study to test DSD against a comparator film dressing (3M Tegaderm + Pad). The volunteers received “a small stipend,” according to the paper.

A 1.5-centimeter incision was made in both forearms of each volunteer. The forearms were randomized regarding which got which bandage. Both bandages have been cleared by the U.S. Food and Drug Administration as nonsignificant-risk devices.

Volunteers were instructed to wear the dressing and continue their typical activities of daily living.

The average age of the volunteers was 52 years (range, 20-80 years). Among the 20 volunteers, 11 reported no comorbidities, and 45% reported at least one comorbidity.

Most of the volunteers favored DSD over the comparator in a postoperative survey – 75% to 25%, according to the report.

The wear time between the two transparent dressings across all subjects was 1.4 days. There was no difference in wear time, logged by the volunteers, between the two groups.   

There were no infectious complications, the paper states.

The maker, DrySee (Houston), which holds three patents on the product, supported the research with an unrestricted grant.

DrySee CEO Brad Greer told this news organization, “With DrySee, you know when to change your dressing. All other dressings look the same wet, saturated, or dry.”

He said the study confirms what they have seen in practice, adding that the product is unique.

“No one else in the world has this technology,” Mr. Greer said.
 

Surgeons want to see more data

Heather Evans, MD, a general surgeon with the Medical University of South Carolina, MUSC Health, Charleston, who was not involved with the study, praised the color-indicator design and said she liked the bandage’s narrow indication for low-exudate wounds.

She said in an interview, “It’s a lot to put on a layperson to suddenly know how to take care of wounds when you leave the hospital.”

Giving them the confidence that their wound is safe if the blue doesn’t appear “is a really cool concept,” she said.

She said that, although the volunteers included some elderly people and people with conditions such as diabetes that could affect wound healing, the bandage needs to be tested with a bigger trial to see if it is effective outside controlled conditions.

She also said that some occlusive dressings will be more durable and stay on days longer than DSD or the comparator, which may affect the choice for some.

“The average length of dressing time in this study was less than 2 days,” she pointed out.

Jim Rickert, MD, an orthopedic surgeon with Indiana University Health Bedford, who was not involved with the study, agreed that any surgical or wound dressing, including transparent films, can become dislodged, and said, “This type of product has promise but this is a small pilot study. I would want to see results from a trial of actual surgical patients to see if this type of dressing did indeed decrease post-op infections compared to standard dressing materials.”

Not all are convinced either that there is a need to be filled or that DSD will be the right solution.

Therese Duane, MD, a general surgeon with Texas Health Harris Methodist Fort Worth, who was not part of the study, said in an interview that she “has no issues with the current products.”

She added that more information is needed before considering DSD a better solution, including animal studies and use “on very sick patients.”

“Twenty volunteers with cuts on their arm is barely a start for comparison,” she said.

The authors, led by Kristy Breisinger, a research analyst with the SerenaGroup Research Foundation in Cambridge, Mass., acknowledged the limitations, including the small sample size and that the trial was conducted at only one institution. Additionally, the analysis is based on descriptive statistics.

They write that the trial design was chosen “to simulate a real-world setting that is not always achievable in animal studies.”

The research was sponsored by an unrestricted grant from the maker of DSD, DrySee Inc., in Houston.

Mr. Greer is DrySee’s CEO. The authors and Dr. Duane, Dr. Rickert, and Dr. Evans declared no relevant financial relationships.

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

Surgical site infections are one of the top causes of postoperative morbidity and death worldwide, but there is little agreement and much debate over the most effective wound dressing to improve outcomes and reduce the health care burden.

Recent clinical trials have indicated that transparent, semiocclusive films have advantages over gauze held by adhesive tape.

But current transparent film bandages may become dislodged during activities such as showering, say authors of a pilot study published in the Journal of Wound Care. Patients may not realize the bandage has been disrupted, which can lead to infection.

The paper describes a novel product called DrySee dressing (DSD), which features a liquid indicator that turns blue around the edges if moisture is present.

“Clinicians, patients, and caregivers are alerted to the loss of dressing integrity and can replace the dressing when any portion of the perimeter changes to a blue [color],” the authors explain. “In addition, the dressing turns blue when the central pad is saturated with fluid, allowing the patient or provider to change the dressing.”

DSD is indicated for wounds that have low levels of exudate.
 

Two transparent film dressings compared

Researchers recruited 20 patients from the general population in Pittsburgh, for a small pilot study to test DSD against a comparator film dressing (3M Tegaderm + Pad). The volunteers received “a small stipend,” according to the paper.

A 1.5-centimeter incision was made in both forearms of each volunteer. The forearms were randomized regarding which got which bandage. Both bandages have been cleared by the U.S. Food and Drug Administration as nonsignificant-risk devices.

Volunteers were instructed to wear the dressing and continue their typical activities of daily living.

The average age of the volunteers was 52 years (range, 20-80 years). Among the 20 volunteers, 11 reported no comorbidities, and 45% reported at least one comorbidity.

Most of the volunteers favored DSD over the comparator in a postoperative survey – 75% to 25%, according to the report.

The wear time between the two transparent dressings across all subjects was 1.4 days. There was no difference in wear time, logged by the volunteers, between the two groups.   

There were no infectious complications, the paper states.

The maker, DrySee (Houston), which holds three patents on the product, supported the research with an unrestricted grant.

DrySee CEO Brad Greer told this news organization, “With DrySee, you know when to change your dressing. All other dressings look the same wet, saturated, or dry.”

He said the study confirms what they have seen in practice, adding that the product is unique.

“No one else in the world has this technology,” Mr. Greer said.
 

Surgeons want to see more data

Heather Evans, MD, a general surgeon with the Medical University of South Carolina, MUSC Health, Charleston, who was not involved with the study, praised the color-indicator design and said she liked the bandage’s narrow indication for low-exudate wounds.

She said in an interview, “It’s a lot to put on a layperson to suddenly know how to take care of wounds when you leave the hospital.”

Giving them the confidence that their wound is safe if the blue doesn’t appear “is a really cool concept,” she said.

She said that, although the volunteers included some elderly people and people with conditions such as diabetes that could affect wound healing, the bandage needs to be tested with a bigger trial to see if it is effective outside controlled conditions.

She also said that some occlusive dressings will be more durable and stay on days longer than DSD or the comparator, which may affect the choice for some.

“The average length of dressing time in this study was less than 2 days,” she pointed out.

Jim Rickert, MD, an orthopedic surgeon with Indiana University Health Bedford, who was not involved with the study, agreed that any surgical or wound dressing, including transparent films, can become dislodged, and said, “This type of product has promise but this is a small pilot study. I would want to see results from a trial of actual surgical patients to see if this type of dressing did indeed decrease post-op infections compared to standard dressing materials.”

Not all are convinced either that there is a need to be filled or that DSD will be the right solution.

Therese Duane, MD, a general surgeon with Texas Health Harris Methodist Fort Worth, who was not part of the study, said in an interview that she “has no issues with the current products.”

She added that more information is needed before considering DSD a better solution, including animal studies and use “on very sick patients.”

“Twenty volunteers with cuts on their arm is barely a start for comparison,” she said.

The authors, led by Kristy Breisinger, a research analyst with the SerenaGroup Research Foundation in Cambridge, Mass., acknowledged the limitations, including the small sample size and that the trial was conducted at only one institution. Additionally, the analysis is based on descriptive statistics.

They write that the trial design was chosen “to simulate a real-world setting that is not always achievable in animal studies.”

The research was sponsored by an unrestricted grant from the maker of DSD, DrySee Inc., in Houston.

Mr. Greer is DrySee’s CEO. The authors and Dr. Duane, Dr. Rickert, and Dr. Evans declared no relevant financial relationships.

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

Surgical site infections are one of the top causes of postoperative morbidity and death worldwide, but there is little agreement and much debate over the most effective wound dressing to improve outcomes and reduce the health care burden.

Recent clinical trials have indicated that transparent, semiocclusive films have advantages over gauze held by adhesive tape.

But current transparent film bandages may become dislodged during activities such as showering, say authors of a pilot study published in the Journal of Wound Care. Patients may not realize the bandage has been disrupted, which can lead to infection.

The paper describes a novel product called DrySee dressing (DSD), which features a liquid indicator that turns blue around the edges if moisture is present.

“Clinicians, patients, and caregivers are alerted to the loss of dressing integrity and can replace the dressing when any portion of the perimeter changes to a blue [color],” the authors explain. “In addition, the dressing turns blue when the central pad is saturated with fluid, allowing the patient or provider to change the dressing.”

DSD is indicated for wounds that have low levels of exudate.
 

Two transparent film dressings compared

Researchers recruited 20 patients from the general population in Pittsburgh, for a small pilot study to test DSD against a comparator film dressing (3M Tegaderm + Pad). The volunteers received “a small stipend,” according to the paper.

A 1.5-centimeter incision was made in both forearms of each volunteer. The forearms were randomized regarding which got which bandage. Both bandages have been cleared by the U.S. Food and Drug Administration as nonsignificant-risk devices.

Volunteers were instructed to wear the dressing and continue their typical activities of daily living.

The average age of the volunteers was 52 years (range, 20-80 years). Among the 20 volunteers, 11 reported no comorbidities, and 45% reported at least one comorbidity.

Most of the volunteers favored DSD over the comparator in a postoperative survey – 75% to 25%, according to the report.

The wear time between the two transparent dressings across all subjects was 1.4 days. There was no difference in wear time, logged by the volunteers, between the two groups.   

There were no infectious complications, the paper states.

The maker, DrySee (Houston), which holds three patents on the product, supported the research with an unrestricted grant.

DrySee CEO Brad Greer told this news organization, “With DrySee, you know when to change your dressing. All other dressings look the same wet, saturated, or dry.”

He said the study confirms what they have seen in practice, adding that the product is unique.

“No one else in the world has this technology,” Mr. Greer said.
 

Surgeons want to see more data

Heather Evans, MD, a general surgeon with the Medical University of South Carolina, MUSC Health, Charleston, who was not involved with the study, praised the color-indicator design and said she liked the bandage’s narrow indication for low-exudate wounds.

She said in an interview, “It’s a lot to put on a layperson to suddenly know how to take care of wounds when you leave the hospital.”

Giving them the confidence that their wound is safe if the blue doesn’t appear “is a really cool concept,” she said.

She said that, although the volunteers included some elderly people and people with conditions such as diabetes that could affect wound healing, the bandage needs to be tested with a bigger trial to see if it is effective outside controlled conditions.

She also said that some occlusive dressings will be more durable and stay on days longer than DSD or the comparator, which may affect the choice for some.

“The average length of dressing time in this study was less than 2 days,” she pointed out.

Jim Rickert, MD, an orthopedic surgeon with Indiana University Health Bedford, who was not involved with the study, agreed that any surgical or wound dressing, including transparent films, can become dislodged, and said, “This type of product has promise but this is a small pilot study. I would want to see results from a trial of actual surgical patients to see if this type of dressing did indeed decrease post-op infections compared to standard dressing materials.”

Not all are convinced either that there is a need to be filled or that DSD will be the right solution.

Therese Duane, MD, a general surgeon with Texas Health Harris Methodist Fort Worth, who was not part of the study, said in an interview that she “has no issues with the current products.”

She added that more information is needed before considering DSD a better solution, including animal studies and use “on very sick patients.”

“Twenty volunteers with cuts on their arm is barely a start for comparison,” she said.

The authors, led by Kristy Breisinger, a research analyst with the SerenaGroup Research Foundation in Cambridge, Mass., acknowledged the limitations, including the small sample size and that the trial was conducted at only one institution. Additionally, the analysis is based on descriptive statistics.

They write that the trial design was chosen “to simulate a real-world setting that is not always achievable in animal studies.”

The research was sponsored by an unrestricted grant from the maker of DSD, DrySee Inc., in Houston.

Mr. Greer is DrySee’s CEO. The authors and Dr. Duane, Dr. Rickert, and Dr. Evans declared no relevant financial relationships.

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

Response-adapted de-escalation of immunotherapy in patients with advanced melanoma may lead to considerable savings for payers – close to $20,000 per patient – compared with standard immunotherapy, an economic analysis found.

“The rising costs of cancer therapies are becoming untenable for both patients and payers, and there is both clinical and economic benefit to finding less expensive treatment alternatives,” Wolfgang Kunz, MD, University Hospital, Ludwig Maximilian University of Munich, told this news organization.

This economic analysis “highlights that leveraging modern diagnostic capabilities can do just that: Pairing drug regimens with CT-image analysis to optimize dosages can reduce health care costs and improve clinical outcomes,” Dr. Kunz said.

The study was published online in JAMA Dermatology.

While the use of immunotherapies over the past decade has improved the prognosis for patients with advanced melanoma, these drugs come with a hefty price tag.

One potential way to help reduce costs: de-escalate therapy. The ADAPT-IT trial demonstrated similar progression-free and overall survival among patients who received response-adapted ipilimumab discontinuation and those who received standard of care.

In the current analysis, Dr. Kunz and colleagues wanted to understand whether this response-adapted approach was also cost effective.

The team applied economic modeling to data from the ADAPT-IT trial as well as CheckMate 067, in which patients received standard of care four doses of combination ipilimumab-nivolumab followed by nivolumab monotherapy. In the ADAPT-IT trial, patients also initially received the immunotherapy combination but had CT scans to determine their response after two doses; if they responded, patients discontinued ipilimumab and continued with nivolumab monotherapy.

Overall, ADAPT-IT showed that responders could forgo the additional two doses of ipilimumab plus nivolumab while maintaining similar progression-free survival and overall survival seen at 18 months in the CheckMate 067 trial.

The current economic analysis, based on 41 patients from ADAPT-IT and 314 from CheckMate 067, showed a potential reduction in health care costs of $19,891 per patient with the response-adapted approach.

Response-adapted treatment was the cost-effective option in 94% of simulated scenarios.

When extrapolated to 2019 incidence rates of distant melanoma cases, yearly national savings could reach about $58 million.

“In the relatively small space of immunotherapies in advanced melanoma, we hope this analysis motivates clinicians to consider response-adapted treatment,” Dr. Kunz told this news organization.

“On the larger scale, this analysis serves as a stepping stone to more response-guided treatment protocols,” Dr. Kunz added. “With drug costs rising and imaging capabilities growing, more frequent image-guided adjustments are a perfect fit into the personalized care model.”

When applying the cost savings noted in this analysis across all treated patients, “the economic impact may be profound,” said Joseph Skitzki, MD, surgical oncologist, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., who wasn’t involved in the study. The “financial toxicity of cancer care is increasingly recognized as a potential barrier to optimal outcomes and any measures to mitigate cost may be impactful.”

However, Dr. Skitzki said several caveats need to be considered.

One is that the data included from ADAPT-IT only included 41 patients, compared with 314 patients from CheckMate 067.

“It is possible that a larger real-world study utilizing the ADAPT-IT protocol may not be as favorable in terms of outcomes and could lessen the economic impact of de-escalation, although any form of de-escalation is likely to have a cost benefit,” Dr. Skitzki said in an interview.

A real-world response–adapted de-escalation clinical trial, with an emphasis on costs and a benchmark of similar progression-free and overall survival, should be conducted before the de-escalated option becomes “practice changing,” Dr. Skitzki said.

Jeffrey Weber, MD, PhD, deputy director, Perlmutter Cancer Center, NYU Langone Health, New York, also urged caution in interpreting the results.

“I would not base treatment decisions on a small sampling of 41 patients in the absence of a randomized comparison,” Dr. Weber told this news organization. “Without a proper comparison, I would not advocate using only two doses of ipilimumab-nivolumab to make decisions on treatment.”

Dr. Skitzki added that, while “studies like this one are desperately needed to lessen the economic impact of new and emerging combination immunotherapies,” there is likely also a “disincentive for pharmaceutical companies to conduct this type of research.”

This research had no specific funding. Dr. Kunz and Dr. Skitzki reported no relevant conflicts of interest. Dr. Weber disclosed relationships with Merck, Genentech, AstraZeneca, Pfizer, Regeneron, and GSK, among others, and holds equity in Cytomx, Biond, NexImmune, and Immunomax.

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

Response-adapted de-escalation of immunotherapy in patients with advanced melanoma may lead to considerable savings for payers – close to $20,000 per patient – compared with standard immunotherapy, an economic analysis found.

“The rising costs of cancer therapies are becoming untenable for both patients and payers, and there is both clinical and economic benefit to finding less expensive treatment alternatives,” Wolfgang Kunz, MD, University Hospital, Ludwig Maximilian University of Munich, told this news organization.

This economic analysis “highlights that leveraging modern diagnostic capabilities can do just that: Pairing drug regimens with CT-image analysis to optimize dosages can reduce health care costs and improve clinical outcomes,” Dr. Kunz said.

The study was published online in JAMA Dermatology.

While the use of immunotherapies over the past decade has improved the prognosis for patients with advanced melanoma, these drugs come with a hefty price tag.

One potential way to help reduce costs: de-escalate therapy. The ADAPT-IT trial demonstrated similar progression-free and overall survival among patients who received response-adapted ipilimumab discontinuation and those who received standard of care.

In the current analysis, Dr. Kunz and colleagues wanted to understand whether this response-adapted approach was also cost effective.

The team applied economic modeling to data from the ADAPT-IT trial as well as CheckMate 067, in which patients received standard of care four doses of combination ipilimumab-nivolumab followed by nivolumab monotherapy. In the ADAPT-IT trial, patients also initially received the immunotherapy combination but had CT scans to determine their response after two doses; if they responded, patients discontinued ipilimumab and continued with nivolumab monotherapy.

Overall, ADAPT-IT showed that responders could forgo the additional two doses of ipilimumab plus nivolumab while maintaining similar progression-free survival and overall survival seen at 18 months in the CheckMate 067 trial.

The current economic analysis, based on 41 patients from ADAPT-IT and 314 from CheckMate 067, showed a potential reduction in health care costs of $19,891 per patient with the response-adapted approach.

Response-adapted treatment was the cost-effective option in 94% of simulated scenarios.

When extrapolated to 2019 incidence rates of distant melanoma cases, yearly national savings could reach about $58 million.

“In the relatively small space of immunotherapies in advanced melanoma, we hope this analysis motivates clinicians to consider response-adapted treatment,” Dr. Kunz told this news organization.

“On the larger scale, this analysis serves as a stepping stone to more response-guided treatment protocols,” Dr. Kunz added. “With drug costs rising and imaging capabilities growing, more frequent image-guided adjustments are a perfect fit into the personalized care model.”

When applying the cost savings noted in this analysis across all treated patients, “the economic impact may be profound,” said Joseph Skitzki, MD, surgical oncologist, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., who wasn’t involved in the study. The “financial toxicity of cancer care is increasingly recognized as a potential barrier to optimal outcomes and any measures to mitigate cost may be impactful.”

However, Dr. Skitzki said several caveats need to be considered.

One is that the data included from ADAPT-IT only included 41 patients, compared with 314 patients from CheckMate 067.

“It is possible that a larger real-world study utilizing the ADAPT-IT protocol may not be as favorable in terms of outcomes and could lessen the economic impact of de-escalation, although any form of de-escalation is likely to have a cost benefit,” Dr. Skitzki said in an interview.

A real-world response–adapted de-escalation clinical trial, with an emphasis on costs and a benchmark of similar progression-free and overall survival, should be conducted before the de-escalated option becomes “practice changing,” Dr. Skitzki said.

Jeffrey Weber, MD, PhD, deputy director, Perlmutter Cancer Center, NYU Langone Health, New York, also urged caution in interpreting the results.

“I would not base treatment decisions on a small sampling of 41 patients in the absence of a randomized comparison,” Dr. Weber told this news organization. “Without a proper comparison, I would not advocate using only two doses of ipilimumab-nivolumab to make decisions on treatment.”

Dr. Skitzki added that, while “studies like this one are desperately needed to lessen the economic impact of new and emerging combination immunotherapies,” there is likely also a “disincentive for pharmaceutical companies to conduct this type of research.”

This research had no specific funding. Dr. Kunz and Dr. Skitzki reported no relevant conflicts of interest. Dr. Weber disclosed relationships with Merck, Genentech, AstraZeneca, Pfizer, Regeneron, and GSK, among others, and holds equity in Cytomx, Biond, NexImmune, and Immunomax.

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

Response-adapted de-escalation of immunotherapy in patients with advanced melanoma may lead to considerable savings for payers – close to $20,000 per patient – compared with standard immunotherapy, an economic analysis found.

“The rising costs of cancer therapies are becoming untenable for both patients and payers, and there is both clinical and economic benefit to finding less expensive treatment alternatives,” Wolfgang Kunz, MD, University Hospital, Ludwig Maximilian University of Munich, told this news organization.

This economic analysis “highlights that leveraging modern diagnostic capabilities can do just that: Pairing drug regimens with CT-image analysis to optimize dosages can reduce health care costs and improve clinical outcomes,” Dr. Kunz said.

The study was published online in JAMA Dermatology.

While the use of immunotherapies over the past decade has improved the prognosis for patients with advanced melanoma, these drugs come with a hefty price tag.

One potential way to help reduce costs: de-escalate therapy. The ADAPT-IT trial demonstrated similar progression-free and overall survival among patients who received response-adapted ipilimumab discontinuation and those who received standard of care.

In the current analysis, Dr. Kunz and colleagues wanted to understand whether this response-adapted approach was also cost effective.

The team applied economic modeling to data from the ADAPT-IT trial as well as CheckMate 067, in which patients received standard of care four doses of combination ipilimumab-nivolumab followed by nivolumab monotherapy. In the ADAPT-IT trial, patients also initially received the immunotherapy combination but had CT scans to determine their response after two doses; if they responded, patients discontinued ipilimumab and continued with nivolumab monotherapy.

Overall, ADAPT-IT showed that responders could forgo the additional two doses of ipilimumab plus nivolumab while maintaining similar progression-free survival and overall survival seen at 18 months in the CheckMate 067 trial.

The current economic analysis, based on 41 patients from ADAPT-IT and 314 from CheckMate 067, showed a potential reduction in health care costs of $19,891 per patient with the response-adapted approach.

Response-adapted treatment was the cost-effective option in 94% of simulated scenarios.

When extrapolated to 2019 incidence rates of distant melanoma cases, yearly national savings could reach about $58 million.

“In the relatively small space of immunotherapies in advanced melanoma, we hope this analysis motivates clinicians to consider response-adapted treatment,” Dr. Kunz told this news organization.

“On the larger scale, this analysis serves as a stepping stone to more response-guided treatment protocols,” Dr. Kunz added. “With drug costs rising and imaging capabilities growing, more frequent image-guided adjustments are a perfect fit into the personalized care model.”

When applying the cost savings noted in this analysis across all treated patients, “the economic impact may be profound,” said Joseph Skitzki, MD, surgical oncologist, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., who wasn’t involved in the study. The “financial toxicity of cancer care is increasingly recognized as a potential barrier to optimal outcomes and any measures to mitigate cost may be impactful.”

However, Dr. Skitzki said several caveats need to be considered.

One is that the data included from ADAPT-IT only included 41 patients, compared with 314 patients from CheckMate 067.

“It is possible that a larger real-world study utilizing the ADAPT-IT protocol may not be as favorable in terms of outcomes and could lessen the economic impact of de-escalation, although any form of de-escalation is likely to have a cost benefit,” Dr. Skitzki said in an interview.

A real-world response–adapted de-escalation clinical trial, with an emphasis on costs and a benchmark of similar progression-free and overall survival, should be conducted before the de-escalated option becomes “practice changing,” Dr. Skitzki said.

Jeffrey Weber, MD, PhD, deputy director, Perlmutter Cancer Center, NYU Langone Health, New York, also urged caution in interpreting the results.

“I would not base treatment decisions on a small sampling of 41 patients in the absence of a randomized comparison,” Dr. Weber told this news organization. “Without a proper comparison, I would not advocate using only two doses of ipilimumab-nivolumab to make decisions on treatment.”

Dr. Skitzki added that, while “studies like this one are desperately needed to lessen the economic impact of new and emerging combination immunotherapies,” there is likely also a “disincentive for pharmaceutical companies to conduct this type of research.”

This research had no specific funding. Dr. Kunz and Dr. Skitzki reported no relevant conflicts of interest. Dr. Weber disclosed relationships with Merck, Genentech, AstraZeneca, Pfizer, Regeneron, and GSK, among others, and holds equity in Cytomx, Biond, NexImmune, and Immunomax.

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

Medicare’s recently announced 2023 physician payment rule likely trims doctors’ pay even as it aims to expand patients’ access to behavioral health services, chronic pain management, and hearing screening. The rule also seeks to ease financial and administrative burdens on accountable care organizations (ACOs).

But physician groups’ initial reactions centered on what the American Medical Association describes as a “damaging across-the-board reduction” of 4.4% in a base calculation, known as a conversion factor.

The reduction is only one of the current threats to physician’s finances, Jack Resneck Jr, MD, AMA’s president, said in a statement. Medicare payment rates also fail to account for inflation in practice costs and COVID-related challenges. Physician’s Medicare payments could be cut by nearly 8.5% in 2023, factoring in other budget cuts, Dr. Resneck said in the statement.

That “would severely impede patient access to care due to the forced closure of physician practices and put further strain on those that remained open during the pandemic,” he said.

A key driver of these cuts is a law that was intended to resolve budget battles between Congress and physicians, while also transitioning Medicare away from fee-for-service payments and pegging reimbursement to judgments about value of care provided. The Centers for Medicare & Medicaid Services thus had little choice about cuts mandated by the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015.

For AMA and other physician groups, the finalization of the Medicare rule served as a rallying point to build support for pending legislation intended to stave off at least some payment cuts.

Federal officials should act soon to block the expected cuts before this season of Congress ends in January, said Anders Gilberg, senior vice president for government affairs at the Medical Group Management Association, in a statement.

“This cannot wait until next Congress – there are claims-processing implications for retroactively applying these policies,” Mr. Gilberg said.

He said MGMA would work with Congress and CMS “to mitigate these cuts and develop sustainable payment policies to allow physician practices to focus on treating patients instead of scrambling to keep their doors open.”
 

Chronic budget battles

Once seen as a promising resolution to chronic annual budget battles between physicians and Medicare, MACRA has proven a near-universal disappointment. A federal advisory commission in 2018 recommended that Congress scrap MACRA’s  Merit-based Incentive Payment System (MIPS) and replace it with a new approach for attempting to tie reimbursement to judgments about the quality of medical care.

MACRA replaced an earlier budgeting approach on Medicare physician pay, known as the sustainable growth rate (SGR). Physician groups successfully lobbied Congress for many years to block threatened Medicare payment cuts. Between 2003 and April 2014, Congress passed 17 laws overriding the cuts to physician pay that the lawmakers earlier mandated through the SGR.

A similar pattern has emerged as Congress now acts on short-term fixes to stave off MACRA-mandated cuts. A law passed last December postponed cuts in physician pay from MACRA and federal budget laws.

And more than 70 members of the House support a bill (HR 8800) intended to block a slated 4.4% MACRA-related cut in physician pay for 2023. Two physicians, Rep. Ami Bera, MD, (D-CA) and Rep. Larry Bucshon (R-IN) sponsored the bill.

Among the groups backing the bill are the AMA, American Academy of Family Physicians, and American College of Physicians. The lawmakers may try to attach this bill to a large spending measure, known as an omnibus, that Congress will try to clear in December to avoid a partial government shutdown.

In a statement, Tochi Iroku-Malize, MD, MPH, MBA, the president of AAFP, urged Congress to factor in inflation in setting physician reimbursement and to reconsider Medicare’s approach to paying physicians.

“It’s past time to end the untenable physician payment cuts – which have now become an annual threat to the stability of physician practices – caused by Medicare budget neutrality requirements and the ongoing freeze in annual payment updates,” Dr. Iroku-Malize said.

Congress also needs to retool its approach to alternative payment models (APMs) intended to improve the quality of patient care, Dr. Iroku-Malize said.

“Physicians in APMs are better equipped to address unmet social needs and provide other enhanced services that are not supported by fee-for-service payment rates,” Dr. Iroku-Malize said. “However, insufficient Medicare fee-for-service payment rates, inadequate support, and burdensome timelines are undermining the move to value-based care and exacerbating our nation’s underinvestment in primary care.”
 

Policy changes

But the new rule did have some good news for family physicians, Dr. Iroku-Malize told this news organization in an email.

CMS said it will pay psychologists and social workers to help manage behavioral health needs as part of the primary care team, in addition to their own services. This change will give primary care practices more flexibility to coordinate with behavioral health professionals, Dr. Iroku-Malize noted.

“We know that primary care physicians are the first point of contact for many patients, and behavioral health integration increases critical access to mental health care, decreases stigma for patients, and can prevent more severe medical and behavioral health events,” she wrote.

CMS also eased a supervision requirement for nonphysicians providing behavioral health services.

It intends to allow certain health professionals to provide this care without requiring that a supervising physician or nurse practitioner be physically on site. This shift from direct supervision to what’s called general supervision applies to marriage and family therapists, licensed professional counselors, addiction counselors, certified peer recovery specialists, and behavioral health specialists, CMS said.

Other major policy changes include:

Medicare will pay for telehealth opioid treatment programs allowing patients to initiate treatment with buprenorphine. CMS also clarified that certain programs can bill for opioid use disorder treatment services provided through mobile units, such as vans.

Medicare enrollees may see audiologists for nonacute hearing conditions without an order from a physician or nurse practitioner. The policy is meant to allow audiologists to examine patients to prescribe, fit, or change hearing aids, or to provide hearing tests unrelated to disequilibrium.

CMS created new reimbursement codes for chronic pain management and treatment services to encourage clinicians to see patients with this condition. The codes also are meant to encourage practitioners already treating Medicare patients with chronic pain to spend more time helping them manage their condition “within a trusting, supportive, and ongoing care partnership,” CMS said.

CMS also made changes to the Medicare Shared Savings Program (MSSP) intended to reduce administrative burdens and offer more financial support to practices involved in ACOs. These steps include expanding opportunities for certain low-revenue ACOs to share in savings even if they do not meet a target rate.

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

Medicare’s recently announced 2023 physician payment rule likely trims doctors’ pay even as it aims to expand patients’ access to behavioral health services, chronic pain management, and hearing screening. The rule also seeks to ease financial and administrative burdens on accountable care organizations (ACOs).

But physician groups’ initial reactions centered on what the American Medical Association describes as a “damaging across-the-board reduction” of 4.4% in a base calculation, known as a conversion factor.

The reduction is only one of the current threats to physician’s finances, Jack Resneck Jr, MD, AMA’s president, said in a statement. Medicare payment rates also fail to account for inflation in practice costs and COVID-related challenges. Physician’s Medicare payments could be cut by nearly 8.5% in 2023, factoring in other budget cuts, Dr. Resneck said in the statement.

That “would severely impede patient access to care due to the forced closure of physician practices and put further strain on those that remained open during the pandemic,” he said.

A key driver of these cuts is a law that was intended to resolve budget battles between Congress and physicians, while also transitioning Medicare away from fee-for-service payments and pegging reimbursement to judgments about value of care provided. The Centers for Medicare & Medicaid Services thus had little choice about cuts mandated by the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015.

For AMA and other physician groups, the finalization of the Medicare rule served as a rallying point to build support for pending legislation intended to stave off at least some payment cuts.

Federal officials should act soon to block the expected cuts before this season of Congress ends in January, said Anders Gilberg, senior vice president for government affairs at the Medical Group Management Association, in a statement.

“This cannot wait until next Congress – there are claims-processing implications for retroactively applying these policies,” Mr. Gilberg said.

He said MGMA would work with Congress and CMS “to mitigate these cuts and develop sustainable payment policies to allow physician practices to focus on treating patients instead of scrambling to keep their doors open.”
 

Chronic budget battles

Once seen as a promising resolution to chronic annual budget battles between physicians and Medicare, MACRA has proven a near-universal disappointment. A federal advisory commission in 2018 recommended that Congress scrap MACRA’s  Merit-based Incentive Payment System (MIPS) and replace it with a new approach for attempting to tie reimbursement to judgments about the quality of medical care.

MACRA replaced an earlier budgeting approach on Medicare physician pay, known as the sustainable growth rate (SGR). Physician groups successfully lobbied Congress for many years to block threatened Medicare payment cuts. Between 2003 and April 2014, Congress passed 17 laws overriding the cuts to physician pay that the lawmakers earlier mandated through the SGR.

A similar pattern has emerged as Congress now acts on short-term fixes to stave off MACRA-mandated cuts. A law passed last December postponed cuts in physician pay from MACRA and federal budget laws.

And more than 70 members of the House support a bill (HR 8800) intended to block a slated 4.4% MACRA-related cut in physician pay for 2023. Two physicians, Rep. Ami Bera, MD, (D-CA) and Rep. Larry Bucshon (R-IN) sponsored the bill.

Among the groups backing the bill are the AMA, American Academy of Family Physicians, and American College of Physicians. The lawmakers may try to attach this bill to a large spending measure, known as an omnibus, that Congress will try to clear in December to avoid a partial government shutdown.

In a statement, Tochi Iroku-Malize, MD, MPH, MBA, the president of AAFP, urged Congress to factor in inflation in setting physician reimbursement and to reconsider Medicare’s approach to paying physicians.

“It’s past time to end the untenable physician payment cuts – which have now become an annual threat to the stability of physician practices – caused by Medicare budget neutrality requirements and the ongoing freeze in annual payment updates,” Dr. Iroku-Malize said.

Congress also needs to retool its approach to alternative payment models (APMs) intended to improve the quality of patient care, Dr. Iroku-Malize said.

“Physicians in APMs are better equipped to address unmet social needs and provide other enhanced services that are not supported by fee-for-service payment rates,” Dr. Iroku-Malize said. “However, insufficient Medicare fee-for-service payment rates, inadequate support, and burdensome timelines are undermining the move to value-based care and exacerbating our nation’s underinvestment in primary care.”
 

Policy changes

But the new rule did have some good news for family physicians, Dr. Iroku-Malize told this news organization in an email.

CMS said it will pay psychologists and social workers to help manage behavioral health needs as part of the primary care team, in addition to their own services. This change will give primary care practices more flexibility to coordinate with behavioral health professionals, Dr. Iroku-Malize noted.

“We know that primary care physicians are the first point of contact for many patients, and behavioral health integration increases critical access to mental health care, decreases stigma for patients, and can prevent more severe medical and behavioral health events,” she wrote.

CMS also eased a supervision requirement for nonphysicians providing behavioral health services.

It intends to allow certain health professionals to provide this care without requiring that a supervising physician or nurse practitioner be physically on site. This shift from direct supervision to what’s called general supervision applies to marriage and family therapists, licensed professional counselors, addiction counselors, certified peer recovery specialists, and behavioral health specialists, CMS said.

Other major policy changes include:

Medicare will pay for telehealth opioid treatment programs allowing patients to initiate treatment with buprenorphine. CMS also clarified that certain programs can bill for opioid use disorder treatment services provided through mobile units, such as vans.

Medicare enrollees may see audiologists for nonacute hearing conditions without an order from a physician or nurse practitioner. The policy is meant to allow audiologists to examine patients to prescribe, fit, or change hearing aids, or to provide hearing tests unrelated to disequilibrium.

CMS created new reimbursement codes for chronic pain management and treatment services to encourage clinicians to see patients with this condition. The codes also are meant to encourage practitioners already treating Medicare patients with chronic pain to spend more time helping them manage their condition “within a trusting, supportive, and ongoing care partnership,” CMS said.

CMS also made changes to the Medicare Shared Savings Program (MSSP) intended to reduce administrative burdens and offer more financial support to practices involved in ACOs. These steps include expanding opportunities for certain low-revenue ACOs to share in savings even if they do not meet a target rate.

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

Medicare’s recently announced 2023 physician payment rule likely trims doctors’ pay even as it aims to expand patients’ access to behavioral health services, chronic pain management, and hearing screening. The rule also seeks to ease financial and administrative burdens on accountable care organizations (ACOs).

But physician groups’ initial reactions centered on what the American Medical Association describes as a “damaging across-the-board reduction” of 4.4% in a base calculation, known as a conversion factor.

The reduction is only one of the current threats to physician’s finances, Jack Resneck Jr, MD, AMA’s president, said in a statement. Medicare payment rates also fail to account for inflation in practice costs and COVID-related challenges. Physician’s Medicare payments could be cut by nearly 8.5% in 2023, factoring in other budget cuts, Dr. Resneck said in the statement.

That “would severely impede patient access to care due to the forced closure of physician practices and put further strain on those that remained open during the pandemic,” he said.

A key driver of these cuts is a law that was intended to resolve budget battles between Congress and physicians, while also transitioning Medicare away from fee-for-service payments and pegging reimbursement to judgments about value of care provided. The Centers for Medicare & Medicaid Services thus had little choice about cuts mandated by the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015.

For AMA and other physician groups, the finalization of the Medicare rule served as a rallying point to build support for pending legislation intended to stave off at least some payment cuts.

Federal officials should act soon to block the expected cuts before this season of Congress ends in January, said Anders Gilberg, senior vice president for government affairs at the Medical Group Management Association, in a statement.

“This cannot wait until next Congress – there are claims-processing implications for retroactively applying these policies,” Mr. Gilberg said.

He said MGMA would work with Congress and CMS “to mitigate these cuts and develop sustainable payment policies to allow physician practices to focus on treating patients instead of scrambling to keep their doors open.”
 

Chronic budget battles

Once seen as a promising resolution to chronic annual budget battles between physicians and Medicare, MACRA has proven a near-universal disappointment. A federal advisory commission in 2018 recommended that Congress scrap MACRA’s  Merit-based Incentive Payment System (MIPS) and replace it with a new approach for attempting to tie reimbursement to judgments about the quality of medical care.

MACRA replaced an earlier budgeting approach on Medicare physician pay, known as the sustainable growth rate (SGR). Physician groups successfully lobbied Congress for many years to block threatened Medicare payment cuts. Between 2003 and April 2014, Congress passed 17 laws overriding the cuts to physician pay that the lawmakers earlier mandated through the SGR.

A similar pattern has emerged as Congress now acts on short-term fixes to stave off MACRA-mandated cuts. A law passed last December postponed cuts in physician pay from MACRA and federal budget laws.

And more than 70 members of the House support a bill (HR 8800) intended to block a slated 4.4% MACRA-related cut in physician pay for 2023. Two physicians, Rep. Ami Bera, MD, (D-CA) and Rep. Larry Bucshon (R-IN) sponsored the bill.

Among the groups backing the bill are the AMA, American Academy of Family Physicians, and American College of Physicians. The lawmakers may try to attach this bill to a large spending measure, known as an omnibus, that Congress will try to clear in December to avoid a partial government shutdown.

In a statement, Tochi Iroku-Malize, MD, MPH, MBA, the president of AAFP, urged Congress to factor in inflation in setting physician reimbursement and to reconsider Medicare’s approach to paying physicians.

“It’s past time to end the untenable physician payment cuts – which have now become an annual threat to the stability of physician practices – caused by Medicare budget neutrality requirements and the ongoing freeze in annual payment updates,” Dr. Iroku-Malize said.

Congress also needs to retool its approach to alternative payment models (APMs) intended to improve the quality of patient care, Dr. Iroku-Malize said.

“Physicians in APMs are better equipped to address unmet social needs and provide other enhanced services that are not supported by fee-for-service payment rates,” Dr. Iroku-Malize said. “However, insufficient Medicare fee-for-service payment rates, inadequate support, and burdensome timelines are undermining the move to value-based care and exacerbating our nation’s underinvestment in primary care.”
 

Policy changes

But the new rule did have some good news for family physicians, Dr. Iroku-Malize told this news organization in an email.

CMS said it will pay psychologists and social workers to help manage behavioral health needs as part of the primary care team, in addition to their own services. This change will give primary care practices more flexibility to coordinate with behavioral health professionals, Dr. Iroku-Malize noted.

“We know that primary care physicians are the first point of contact for many patients, and behavioral health integration increases critical access to mental health care, decreases stigma for patients, and can prevent more severe medical and behavioral health events,” she wrote.

CMS also eased a supervision requirement for nonphysicians providing behavioral health services.

It intends to allow certain health professionals to provide this care without requiring that a supervising physician or nurse practitioner be physically on site. This shift from direct supervision to what’s called general supervision applies to marriage and family therapists, licensed professional counselors, addiction counselors, certified peer recovery specialists, and behavioral health specialists, CMS said.

Other major policy changes include:

Medicare will pay for telehealth opioid treatment programs allowing patients to initiate treatment with buprenorphine. CMS also clarified that certain programs can bill for opioid use disorder treatment services provided through mobile units, such as vans.

Medicare enrollees may see audiologists for nonacute hearing conditions without an order from a physician or nurse practitioner. The policy is meant to allow audiologists to examine patients to prescribe, fit, or change hearing aids, or to provide hearing tests unrelated to disequilibrium.

CMS created new reimbursement codes for chronic pain management and treatment services to encourage clinicians to see patients with this condition. The codes also are meant to encourage practitioners already treating Medicare patients with chronic pain to spend more time helping them manage their condition “within a trusting, supportive, and ongoing care partnership,” CMS said.

CMS also made changes to the Medicare Shared Savings Program (MSSP) intended to reduce administrative burdens and offer more financial support to practices involved in ACOs. These steps include expanding opportunities for certain low-revenue ACOs to share in savings even if they do not meet a target rate.

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

LAS VEGAS – Acne is a barrier-deficient disorder, and good skin care with over-the-counter products can improve this barrier and increase adherence to prescription medications, Hilary E. Baldwin, MD, of Rutgers Robert Wood Johnson Medical Center, New Brunswick, N.J., said in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

In some cases, the use of good-quality over-the -counter skin care products can improve acne without prescription treatment, said Dr. Baldwin, who is medical director of the Acne Treatment and Research Center, New York. Good skin care can enhance the effects of prescription medication by decreasing side effects such as inflammation, pain, and erythema, and improving compliance; and use of OTC products has not been shown to interfere with the efficacy of prescription products, she noted.

However, patient education about OTC products is key, she said. In particular, “cleansers are a double-edged sword,” Dr. Baldwin emphasized.

Cleansing is important to preserve barrier function, but “there is a risk of skin damage” if cleansers are too harsh, she said. The goal is to remove dirt, oils, and bacteria without disrupting the lipids, proteins, and normal flora that keep skin healthy, and to avoid altering pH, she added.

Key considerations for OTC cleansers include surfactants, pH, and patient preferences, Dr. Baldwin said.

Surfactants, the main components of OTC cleansers, can do more harm than good in some cases. Surfactants break down impurities on the skin surface, but not all are created equal, and some may cause skin irritation, she explained.

Surfactants fall into four categories: nonionic (no charge), anionic (negative charge), cationic (positive charge), and amphoteric (dual charge). Of these, cationic surfactants have the highest level of antimicrobial activity.

Many patients with acne seek out antibacterial cleansers, but many of these products have a high pH, which can inhibit healthy skin function and promote inflammation, Dr. Baldwin noted.

The right OTC skin care products can normalize pH, which promotes repair of the skin barrier and reduces inflammation, she said. While some products are labeled as “gentle,” they may have a high pH, and many products don’t list a pH, Dr. Baldwin pointed out. Many antibacterial products have pH levels in the 10-12 range, while true soaps fall in the 9-10 range, and hydrating liquid cleansers often land in the 5-7 range, she said.

“Most of our patients don’t know what ingredients to look for” in a cleanser, she noted. However, data show that a majority of patients prefer a foaming cleanser, enjoy the face-washing experience – and wash their faces at least twice a day, with a range of products including bath soap, said Dr. Baldwin. Consequently, “educate your patient about moisturizing,” she advised.

For patients with greasy or oily skin, Dr. Baldwin recommends lipid-free foaming cleansers, such as those with ceramides or glycerin. For patients with dry, irritated acne, she advises once-daily washing only, without cleansing devices, which includes washcloths, she said. Look for hydrating cleansers that are nonfoaming or slightly foaming for these patients, she added.

Another tip for patients is to remind them that “sebum is not a moisturizer,” said Dr. Baldwin. Acne patients may still need moisturizers, especially if they experience dry skin as a side effect of their acne medication, but finding the right fit can be a challenge requiring some trial and error, she noted.

OTC products for rosacea

Dr. Baldwin also addressed the use of OTC products for patients with rosacea. For cleansers, she recommends the same hydrating, nonfoaming categories as for her acne patients, with a once-daily, no-device regimen. She advises rosacea patients to avoid pure humectants for moisturizing and noted that silicone-based products are often the least irritating.

Seek moisturizers with ceramides, hyaluronic acid, glycerin, or niacinamide, she said. Data have shown that effective moisturization improves the ability of patients with rosacea to use and adhere to their prescription medications, Dr. Baldwin emphasized. Moisturizers also can make the medication more effective by enhancing the penetration of products such as azelaic acid, she added.

No acne or rosacea visit is complete until overall skin care has been discussed, Dr. Baldwin said.

Dr. Baldwin disclosed serving as a consultant or adviser for Almirall, EPI Health, Galderma, La Roche Posay, Ortho Dermatologics, Sun, and Vyne; and serving as a speaker or member of the speakers’ bureau for Almirall, Galderma, La Roche Posay, Ortho Dermatologics, and Sun. MedscapeLive and this news organization are owned by the same parent company.

LAS VEGAS – Acne is a barrier-deficient disorder, and good skin care with over-the-counter products can improve this barrier and increase adherence to prescription medications, Hilary E. Baldwin, MD, of Rutgers Robert Wood Johnson Medical Center, New Brunswick, N.J., said in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

In some cases, the use of good-quality over-the -counter skin care products can improve acne without prescription treatment, said Dr. Baldwin, who is medical director of the Acne Treatment and Research Center, New York. Good skin care can enhance the effects of prescription medication by decreasing side effects such as inflammation, pain, and erythema, and improving compliance; and use of OTC products has not been shown to interfere with the efficacy of prescription products, she noted.

However, patient education about OTC products is key, she said. In particular, “cleansers are a double-edged sword,” Dr. Baldwin emphasized.

Cleansing is important to preserve barrier function, but “there is a risk of skin damage” if cleansers are too harsh, she said. The goal is to remove dirt, oils, and bacteria without disrupting the lipids, proteins, and normal flora that keep skin healthy, and to avoid altering pH, she added.

Key considerations for OTC cleansers include surfactants, pH, and patient preferences, Dr. Baldwin said.

Surfactants, the main components of OTC cleansers, can do more harm than good in some cases. Surfactants break down impurities on the skin surface, but not all are created equal, and some may cause skin irritation, she explained.

Surfactants fall into four categories: nonionic (no charge), anionic (negative charge), cationic (positive charge), and amphoteric (dual charge). Of these, cationic surfactants have the highest level of antimicrobial activity.

Many patients with acne seek out antibacterial cleansers, but many of these products have a high pH, which can inhibit healthy skin function and promote inflammation, Dr. Baldwin noted.

The right OTC skin care products can normalize pH, which promotes repair of the skin barrier and reduces inflammation, she said. While some products are labeled as “gentle,” they may have a high pH, and many products don’t list a pH, Dr. Baldwin pointed out. Many antibacterial products have pH levels in the 10-12 range, while true soaps fall in the 9-10 range, and hydrating liquid cleansers often land in the 5-7 range, she said.

“Most of our patients don’t know what ingredients to look for” in a cleanser, she noted. However, data show that a majority of patients prefer a foaming cleanser, enjoy the face-washing experience – and wash their faces at least twice a day, with a range of products including bath soap, said Dr. Baldwin. Consequently, “educate your patient about moisturizing,” she advised.

For patients with greasy or oily skin, Dr. Baldwin recommends lipid-free foaming cleansers, such as those with ceramides or glycerin. For patients with dry, irritated acne, she advises once-daily washing only, without cleansing devices, which includes washcloths, she said. Look for hydrating cleansers that are nonfoaming or slightly foaming for these patients, she added.

Another tip for patients is to remind them that “sebum is not a moisturizer,” said Dr. Baldwin. Acne patients may still need moisturizers, especially if they experience dry skin as a side effect of their acne medication, but finding the right fit can be a challenge requiring some trial and error, she noted.

OTC products for rosacea

Dr. Baldwin also addressed the use of OTC products for patients with rosacea. For cleansers, she recommends the same hydrating, nonfoaming categories as for her acne patients, with a once-daily, no-device regimen. She advises rosacea patients to avoid pure humectants for moisturizing and noted that silicone-based products are often the least irritating.

Seek moisturizers with ceramides, hyaluronic acid, glycerin, or niacinamide, she said. Data have shown that effective moisturization improves the ability of patients with rosacea to use and adhere to their prescription medications, Dr. Baldwin emphasized. Moisturizers also can make the medication more effective by enhancing the penetration of products such as azelaic acid, she added.

No acne or rosacea visit is complete until overall skin care has been discussed, Dr. Baldwin said.

Dr. Baldwin disclosed serving as a consultant or adviser for Almirall, EPI Health, Galderma, La Roche Posay, Ortho Dermatologics, Sun, and Vyne; and serving as a speaker or member of the speakers’ bureau for Almirall, Galderma, La Roche Posay, Ortho Dermatologics, and Sun. MedscapeLive and this news organization are owned by the same parent company.

LAS VEGAS – Acne is a barrier-deficient disorder, and good skin care with over-the-counter products can improve this barrier and increase adherence to prescription medications, Hilary E. Baldwin, MD, of Rutgers Robert Wood Johnson Medical Center, New Brunswick, N.J., said in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

In some cases, the use of good-quality over-the -counter skin care products can improve acne without prescription treatment, said Dr. Baldwin, who is medical director of the Acne Treatment and Research Center, New York. Good skin care can enhance the effects of prescription medication by decreasing side effects such as inflammation, pain, and erythema, and improving compliance; and use of OTC products has not been shown to interfere with the efficacy of prescription products, she noted.

However, patient education about OTC products is key, she said. In particular, “cleansers are a double-edged sword,” Dr. Baldwin emphasized.

Cleansing is important to preserve barrier function, but “there is a risk of skin damage” if cleansers are too harsh, she said. The goal is to remove dirt, oils, and bacteria without disrupting the lipids, proteins, and normal flora that keep skin healthy, and to avoid altering pH, she added.

Key considerations for OTC cleansers include surfactants, pH, and patient preferences, Dr. Baldwin said.

Surfactants, the main components of OTC cleansers, can do more harm than good in some cases. Surfactants break down impurities on the skin surface, but not all are created equal, and some may cause skin irritation, she explained.

Surfactants fall into four categories: nonionic (no charge), anionic (negative charge), cationic (positive charge), and amphoteric (dual charge). Of these, cationic surfactants have the highest level of antimicrobial activity.

Many patients with acne seek out antibacterial cleansers, but many of these products have a high pH, which can inhibit healthy skin function and promote inflammation, Dr. Baldwin noted.

The right OTC skin care products can normalize pH, which promotes repair of the skin barrier and reduces inflammation, she said. While some products are labeled as “gentle,” they may have a high pH, and many products don’t list a pH, Dr. Baldwin pointed out. Many antibacterial products have pH levels in the 10-12 range, while true soaps fall in the 9-10 range, and hydrating liquid cleansers often land in the 5-7 range, she said.

“Most of our patients don’t know what ingredients to look for” in a cleanser, she noted. However, data show that a majority of patients prefer a foaming cleanser, enjoy the face-washing experience – and wash their faces at least twice a day, with a range of products including bath soap, said Dr. Baldwin. Consequently, “educate your patient about moisturizing,” she advised.

For patients with greasy or oily skin, Dr. Baldwin recommends lipid-free foaming cleansers, such as those with ceramides or glycerin. For patients with dry, irritated acne, she advises once-daily washing only, without cleansing devices, which includes washcloths, she said. Look for hydrating cleansers that are nonfoaming or slightly foaming for these patients, she added.

Another tip for patients is to remind them that “sebum is not a moisturizer,” said Dr. Baldwin. Acne patients may still need moisturizers, especially if they experience dry skin as a side effect of their acne medication, but finding the right fit can be a challenge requiring some trial and error, she noted.

OTC products for rosacea

Dr. Baldwin also addressed the use of OTC products for patients with rosacea. For cleansers, she recommends the same hydrating, nonfoaming categories as for her acne patients, with a once-daily, no-device regimen. She advises rosacea patients to avoid pure humectants for moisturizing and noted that silicone-based products are often the least irritating.

Seek moisturizers with ceramides, hyaluronic acid, glycerin, or niacinamide, she said. Data have shown that effective moisturization improves the ability of patients with rosacea to use and adhere to their prescription medications, Dr. Baldwin emphasized. Moisturizers also can make the medication more effective by enhancing the penetration of products such as azelaic acid, she added.

No acne or rosacea visit is complete until overall skin care has been discussed, Dr. Baldwin said.

Dr. Baldwin disclosed serving as a consultant or adviser for Almirall, EPI Health, Galderma, La Roche Posay, Ortho Dermatologics, Sun, and Vyne; and serving as a speaker or member of the speakers’ bureau for Almirall, Galderma, La Roche Posay, Ortho Dermatologics, and Sun. MedscapeLive and this news organization are owned by the same parent company.

When compared with the general population, hairdressers experience an excess risk of contact allergy linked to hair cosmetic ingredients, a systematic review suggests.

“Research has shown that up to 70% of hairdressers suffer from work-related skin damage, mostly hand dermatitis, at some point during their career,” write Wolfgang Uter of Friedrich-Alexander University Erlangen-Nürnberg and coauthors. In general, they write, occupational skin diseases such as hand dermatitis represent up to 35% of reported occupational diseases. The study was published online in Contact Dermatitis.

Wet work and skin contact with detergents and hairdressing chemicals are top risk factors for developing occupational skin disease in this population, according to the researchers.

To further understand the burden of occupational contact allergy in hairdressers, the investigators gathered evidence published since 2000 on contact allergies to hair cosmetic chemicals. They searched the literature for nine substances selected beforehand by experts and stakeholders. The researchers also examined the prevalence of sensitization between hairdressers and other individuals given skin patch tests.
 

Substance by substance

Common potentially sensitizing cosmetic ingredients reported across studies included p-phenylenediamine (PPD), persulfates (mostly ammonium persulfate [APS]), glyceryl thioglycolate (GMTG), and ammonium thioglycolate (ATG).

In a pooled analysis, the overall prevalence of contact allergy to PPD was 4.3% in consecutively patch-tested patients, but in hairdressers specifically, the overall prevalence of contact allergy to this ingredient was 28.6%, reviewers reported.

The pooled prevalence of contact allergy to APS was 5.5% in consumers and 17.2% in hairdressers. In other review studies, contact allergy risks to APS, GMTG, and ATG were also elevated in hairdressers compared with all controls.

The calculated relative risk (RR) of contact allergy to PPD was approximately 5.4 higher for hairdressers, while the RR for ATG sensitization was 3.4 in hairdressers compared with consumers.

Commenting on these findings, James A. Yiannias, MD, professor of dermatology at the Mayo Medical School, Phoenix, told this news organization in an email that many providers and patients are concerned only about hair dye molecules such as PPD and aminophenol, as well as permanent, wave, and straightening chemicals such as GMTG.

“Although these are common allergens in hairdressers, allergens such as fragrances and some preservatives found in daily hair care products such as shampoos, conditioners, and hair sprays are also common causes of contact dermatitis,” said Dr. Yiannias, who wasn’t involved in the research.

Consequences of exposure

Dr. Yiannias explained that progressive worsening of the dermatitis can occur with ongoing allergen exposure and, if not properly mitigated, can lead to bigger issues. “Initial nuisances of mild irritation and hyperkeratosis can evolve to a state of fissuring with the risk of bleeding and significant pain,” he said.

But once severe and untreated dermatitis occurs, Dr. Yiannias said that hairdressers “may need to change careers” or at least face short- or long-term unemployment.

The researchers suggest reducing exposure to the allergen is key for prevention of symptoms, adding that adequate guidance on the safe use of new products is needed. Also, the researchers suggested that vocational schools should more rigorously implement education for hairdressers that addresses how to protect the skin appropriately at work.

“Hairdressers are taught during their training to be cautious about allergen exposure by avoiding touching high-risk ingredients such as hair dyes,” Dr. Yiannias added. “However, in practice, this is very difficult since the wearing of gloves can impair the tactile sensations that hairdressers often feel is essential in performing their job.”

The study received no industry funding. Dr. Yiannias reports no relevant financial relationships.

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

When compared with the general population, hairdressers experience an excess risk of contact allergy linked to hair cosmetic ingredients, a systematic review suggests.

“Research has shown that up to 70% of hairdressers suffer from work-related skin damage, mostly hand dermatitis, at some point during their career,” write Wolfgang Uter of Friedrich-Alexander University Erlangen-Nürnberg and coauthors. In general, they write, occupational skin diseases such as hand dermatitis represent up to 35% of reported occupational diseases. The study was published online in Contact Dermatitis.

Wet work and skin contact with detergents and hairdressing chemicals are top risk factors for developing occupational skin disease in this population, according to the researchers.

To further understand the burden of occupational contact allergy in hairdressers, the investigators gathered evidence published since 2000 on contact allergies to hair cosmetic chemicals. They searched the literature for nine substances selected beforehand by experts and stakeholders. The researchers also examined the prevalence of sensitization between hairdressers and other individuals given skin patch tests.
 

Substance by substance

Common potentially sensitizing cosmetic ingredients reported across studies included p-phenylenediamine (PPD), persulfates (mostly ammonium persulfate [APS]), glyceryl thioglycolate (GMTG), and ammonium thioglycolate (ATG).

In a pooled analysis, the overall prevalence of contact allergy to PPD was 4.3% in consecutively patch-tested patients, but in hairdressers specifically, the overall prevalence of contact allergy to this ingredient was 28.6%, reviewers reported.

The pooled prevalence of contact allergy to APS was 5.5% in consumers and 17.2% in hairdressers. In other review studies, contact allergy risks to APS, GMTG, and ATG were also elevated in hairdressers compared with all controls.

The calculated relative risk (RR) of contact allergy to PPD was approximately 5.4 higher for hairdressers, while the RR for ATG sensitization was 3.4 in hairdressers compared with consumers.

Commenting on these findings, James A. Yiannias, MD, professor of dermatology at the Mayo Medical School, Phoenix, told this news organization in an email that many providers and patients are concerned only about hair dye molecules such as PPD and aminophenol, as well as permanent, wave, and straightening chemicals such as GMTG.

“Although these are common allergens in hairdressers, allergens such as fragrances and some preservatives found in daily hair care products such as shampoos, conditioners, and hair sprays are also common causes of contact dermatitis,” said Dr. Yiannias, who wasn’t involved in the research.

Consequences of exposure

Dr. Yiannias explained that progressive worsening of the dermatitis can occur with ongoing allergen exposure and, if not properly mitigated, can lead to bigger issues. “Initial nuisances of mild irritation and hyperkeratosis can evolve to a state of fissuring with the risk of bleeding and significant pain,” he said.

But once severe and untreated dermatitis occurs, Dr. Yiannias said that hairdressers “may need to change careers” or at least face short- or long-term unemployment.

The researchers suggest reducing exposure to the allergen is key for prevention of symptoms, adding that adequate guidance on the safe use of new products is needed. Also, the researchers suggested that vocational schools should more rigorously implement education for hairdressers that addresses how to protect the skin appropriately at work.

“Hairdressers are taught during their training to be cautious about allergen exposure by avoiding touching high-risk ingredients such as hair dyes,” Dr. Yiannias added. “However, in practice, this is very difficult since the wearing of gloves can impair the tactile sensations that hairdressers often feel is essential in performing their job.”

The study received no industry funding. Dr. Yiannias reports no relevant financial relationships.

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

When compared with the general population, hairdressers experience an excess risk of contact allergy linked to hair cosmetic ingredients, a systematic review suggests.

“Research has shown that up to 70% of hairdressers suffer from work-related skin damage, mostly hand dermatitis, at some point during their career,” write Wolfgang Uter of Friedrich-Alexander University Erlangen-Nürnberg and coauthors. In general, they write, occupational skin diseases such as hand dermatitis represent up to 35% of reported occupational diseases. The study was published online in Contact Dermatitis.

Wet work and skin contact with detergents and hairdressing chemicals are top risk factors for developing occupational skin disease in this population, according to the researchers.

To further understand the burden of occupational contact allergy in hairdressers, the investigators gathered evidence published since 2000 on contact allergies to hair cosmetic chemicals. They searched the literature for nine substances selected beforehand by experts and stakeholders. The researchers also examined the prevalence of sensitization between hairdressers and other individuals given skin patch tests.
 

Substance by substance

Common potentially sensitizing cosmetic ingredients reported across studies included p-phenylenediamine (PPD), persulfates (mostly ammonium persulfate [APS]), glyceryl thioglycolate (GMTG), and ammonium thioglycolate (ATG).

In a pooled analysis, the overall prevalence of contact allergy to PPD was 4.3% in consecutively patch-tested patients, but in hairdressers specifically, the overall prevalence of contact allergy to this ingredient was 28.6%, reviewers reported.

The pooled prevalence of contact allergy to APS was 5.5% in consumers and 17.2% in hairdressers. In other review studies, contact allergy risks to APS, GMTG, and ATG were also elevated in hairdressers compared with all controls.

The calculated relative risk (RR) of contact allergy to PPD was approximately 5.4 higher for hairdressers, while the RR for ATG sensitization was 3.4 in hairdressers compared with consumers.

Commenting on these findings, James A. Yiannias, MD, professor of dermatology at the Mayo Medical School, Phoenix, told this news organization in an email that many providers and patients are concerned only about hair dye molecules such as PPD and aminophenol, as well as permanent, wave, and straightening chemicals such as GMTG.

“Although these are common allergens in hairdressers, allergens such as fragrances and some preservatives found in daily hair care products such as shampoos, conditioners, and hair sprays are also common causes of contact dermatitis,” said Dr. Yiannias, who wasn’t involved in the research.

Consequences of exposure

Dr. Yiannias explained that progressive worsening of the dermatitis can occur with ongoing allergen exposure and, if not properly mitigated, can lead to bigger issues. “Initial nuisances of mild irritation and hyperkeratosis can evolve to a state of fissuring with the risk of bleeding and significant pain,” he said.

But once severe and untreated dermatitis occurs, Dr. Yiannias said that hairdressers “may need to change careers” or at least face short- or long-term unemployment.

The researchers suggest reducing exposure to the allergen is key for prevention of symptoms, adding that adequate guidance on the safe use of new products is needed. Also, the researchers suggested that vocational schools should more rigorously implement education for hairdressers that addresses how to protect the skin appropriately at work.

“Hairdressers are taught during their training to be cautious about allergen exposure by avoiding touching high-risk ingredients such as hair dyes,” Dr. Yiannias added. “However, in practice, this is very difficult since the wearing of gloves can impair the tactile sensations that hairdressers often feel is essential in performing their job.”

The study received no industry funding. Dr. Yiannias reports no relevant financial relationships.

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

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