MDedge Pediatrics

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

A study found that 94% of best-selling baby cleansers contain allergens, despite their hypoallergenic claims.

METHODOLOGY:

• Many baby cleansers are marketed as “hypoallergenic,” but these claims are not validated. 
• This study assessed the potential allergens and marketing claims in best-selling baby cleansers. 
• The researchers collected ingredients and marketing claims of the top 50 best-selling baby body wash products sold on Amazon on April 4, 2023. 
• Ingredient lists were checked for potential allergens using the 2020 American Contact Dermatitis Society (ACDS) core allergen series, which lists 90 common allergens for adults and children.

TAKEAWAY:

• In the 50 cleansers tested, 10 allergens were identified. Overall, 94% of the cleansers contained at least one allergen, averaging 2.9 allergens per product; cocamidopropyl betaine  (72%), fragrance (64%), and sodium benzoate (54%) were the most common allergens. 
• All cleansers had at least five marketing claims, with an average of 10.9 claims per product; the most common claims were “paraben-free” (88%), “phthalate-free” (84%), “tear-free” (74%), and “hypoallergenic” or “allergy-tested” (74%). 
• There was no significant difference in the number of allergens in the cleansers marketed as “hypoallergenic” or “allergy tested” compared with cleansers that did not have these claims (P = .843).
• Fewer allergens were found in cleansers endorsed by the National Eczema Association (P = .004) or labeled “synthetic fragrance-free” (P = .003).
• There was a positive correlation between a greater number of allergens and an increased number of marketing claims (r = 0.547, P < .001) and a negative correlation between cost and number of allergens (r = −0.450, P = .001).

IN PRACTICE:

Because marketing claims like “hypoallergenic” may be misleading, “clinicians should counsel parents to carefully examine cleanser ingredients or consider selecting cleansers” endorsed by the National Eczema Association or another international eczema organization, especially for infants and children with a history of atopic dermatitis, the authors wrote. 

SOURCE:

The study, led by Sasan D. Noveir, BA, from the University of California, Los Angeles, and coauthors from the division of dermatology at UCLA, was published online in Pediatric Dermatology.

LIMITATIONS:

The study only evaluated top-selling products from a single online source at a specific time, which may limit generalizability. Potential allergens not included in the ACDS core series may be present.

DISCLOSURES:

The study did not disclose any funding source. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A study found that 94% of best-selling baby cleansers contain allergens, despite their hypoallergenic claims.

METHODOLOGY:

• Many baby cleansers are marketed as “hypoallergenic,” but these claims are not validated. 
• This study assessed the potential allergens and marketing claims in best-selling baby cleansers. 
• The researchers collected ingredients and marketing claims of the top 50 best-selling baby body wash products sold on Amazon on April 4, 2023. 
• Ingredient lists were checked for potential allergens using the 2020 American Contact Dermatitis Society (ACDS) core allergen series, which lists 90 common allergens for adults and children.

TAKEAWAY:

• In the 50 cleansers tested, 10 allergens were identified. Overall, 94% of the cleansers contained at least one allergen, averaging 2.9 allergens per product; cocamidopropyl betaine  (72%), fragrance (64%), and sodium benzoate (54%) were the most common allergens. 
• All cleansers had at least five marketing claims, with an average of 10.9 claims per product; the most common claims were “paraben-free” (88%), “phthalate-free” (84%), “tear-free” (74%), and “hypoallergenic” or “allergy-tested” (74%). 
• There was no significant difference in the number of allergens in the cleansers marketed as “hypoallergenic” or “allergy tested” compared with cleansers that did not have these claims (P = .843).
• Fewer allergens were found in cleansers endorsed by the National Eczema Association (P = .004) or labeled “synthetic fragrance-free” (P = .003).
• There was a positive correlation between a greater number of allergens and an increased number of marketing claims (r = 0.547, P < .001) and a negative correlation between cost and number of allergens (r = −0.450, P = .001).

IN PRACTICE:

Because marketing claims like “hypoallergenic” may be misleading, “clinicians should counsel parents to carefully examine cleanser ingredients or consider selecting cleansers” endorsed by the National Eczema Association or another international eczema organization, especially for infants and children with a history of atopic dermatitis, the authors wrote. 

SOURCE:

The study, led by Sasan D. Noveir, BA, from the University of California, Los Angeles, and coauthors from the division of dermatology at UCLA, was published online in Pediatric Dermatology.

LIMITATIONS:

The study only evaluated top-selling products from a single online source at a specific time, which may limit generalizability. Potential allergens not included in the ACDS core series may be present.

DISCLOSURES:

The study did not disclose any funding source. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A study found that 94% of best-selling baby cleansers contain allergens, despite their hypoallergenic claims.

METHODOLOGY:

• Many baby cleansers are marketed as “hypoallergenic,” but these claims are not validated. 
• This study assessed the potential allergens and marketing claims in best-selling baby cleansers. 
• The researchers collected ingredients and marketing claims of the top 50 best-selling baby body wash products sold on Amazon on April 4, 2023. 
• Ingredient lists were checked for potential allergens using the 2020 American Contact Dermatitis Society (ACDS) core allergen series, which lists 90 common allergens for adults and children.

TAKEAWAY:

• In the 50 cleansers tested, 10 allergens were identified. Overall, 94% of the cleansers contained at least one allergen, averaging 2.9 allergens per product; cocamidopropyl betaine  (72%), fragrance (64%), and sodium benzoate (54%) were the most common allergens. 
• All cleansers had at least five marketing claims, with an average of 10.9 claims per product; the most common claims were “paraben-free” (88%), “phthalate-free” (84%), “tear-free” (74%), and “hypoallergenic” or “allergy-tested” (74%). 
• There was no significant difference in the number of allergens in the cleansers marketed as “hypoallergenic” or “allergy tested” compared with cleansers that did not have these claims (P = .843).
• Fewer allergens were found in cleansers endorsed by the National Eczema Association (P = .004) or labeled “synthetic fragrance-free” (P = .003).
• There was a positive correlation between a greater number of allergens and an increased number of marketing claims (r = 0.547, P < .001) and a negative correlation between cost and number of allergens (r = −0.450, P = .001).

IN PRACTICE:

Because marketing claims like “hypoallergenic” may be misleading, “clinicians should counsel parents to carefully examine cleanser ingredients or consider selecting cleansers” endorsed by the National Eczema Association or another international eczema organization, especially for infants and children with a history of atopic dermatitis, the authors wrote. 

SOURCE:

The study, led by Sasan D. Noveir, BA, from the University of California, Los Angeles, and coauthors from the division of dermatology at UCLA, was published online in Pediatric Dermatology.

LIMITATIONS:

The study only evaluated top-selling products from a single online source at a specific time, which may limit generalizability. Potential allergens not included in the ACDS core series may be present.

DISCLOSURES:

The study did not disclose any funding source. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have developed a tool that uses artificial intelligence (AI) to identify acute otitis media in children based on otoscopic videos. It may improve diagnosis of ear infections in primary care settings, the developers said.

METHODOLOGY:

• The developers relied on otoscopic videos of the tympanic membrane captured on smartphones connected to scopes.
• Their analysis focused on 1151 videos from 635 children, most younger than 3 years old, who were seen for sick or well visits at outpatient clinics in Pennsylvania from 2018 to 2023.
• The tool was trained to differentiate between patients who did and did not have acute otitis media.

TAKEAWAY:

• Out of an original pool of 1561 videos, 410 were excluded due to obstruction by cerumen. In the remaining videos, experts identified acute otitis media in 305 videos (26.5%) and no acute otitis media in 846 videos (73.5%).
• The tool achieved a sensitivity of 93.8% and specificity of 93.5%, with bulging of the tympanic membrane being the most indicative feature of acute otitis media, present in 100% of diagnosed cases, according to the researchers.
• Feedback from 60 parents was largely positive, with 80% wanting the tool to be used during future visits.

IN PRACTICE:

Based on the diagnostic accuracy of clinicians in other studies, “The algorithm exhibited higher accuracy than pediatricians, primary care physicians, and advance practice clinicians and, accordingly, could reasonably be used in these settings to aid with decisions regarding treatment,” the authors of the study wrote. “More accurate diagnosis of [acute otitis media] may help reduce unnecessary prescriptions of antimicrobials in young children,” they added.

Studies directly comparing the performance of the tool vs clinicians are still needed, however, according to an editorial accompanying the journal article.

“While the data from this study show the model’s accuracy (94%) is superior to historical accuracy of clinicians in diagnosing acute otitis media (84% or less), these data come from different studies not using the same definition for accuracy,” wrote Hojjat Salmasian, MD, MPH, PhD, and Lisa Biggs, MD, with Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. “If we assume the model is confirmed to be highly accurate and free from bias, this model could truly transform care for patients with suspected acute otitis media.”

SOURCE:

Alejandro Hoberman, MD, with the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, was the corresponding author of the study. It was published online in JAMA Pediatrics .

LIMITATIONS:

The study used convenience sampling and did not include external validation of the tool. The researchers lacked information about participant demographics and the reason for their clinic visit.

DISCLOSURES:

Three authors of the study are listed as inventors on a patent for a tool to diagnose acute otitis media. Two authors with Dcipher Analytics disclosed fees from the University of Pittsburgh for their work on an application programming interface during the study. The research was supported by the Department of Pediatrics at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have developed a tool that uses artificial intelligence (AI) to identify acute otitis media in children based on otoscopic videos. It may improve diagnosis of ear infections in primary care settings, the developers said.

METHODOLOGY:

• The developers relied on otoscopic videos of the tympanic membrane captured on smartphones connected to scopes.
• Their analysis focused on 1151 videos from 635 children, most younger than 3 years old, who were seen for sick or well visits at outpatient clinics in Pennsylvania from 2018 to 2023.
• The tool was trained to differentiate between patients who did and did not have acute otitis media.

TAKEAWAY:

• Out of an original pool of 1561 videos, 410 were excluded due to obstruction by cerumen. In the remaining videos, experts identified acute otitis media in 305 videos (26.5%) and no acute otitis media in 846 videos (73.5%).
• The tool achieved a sensitivity of 93.8% and specificity of 93.5%, with bulging of the tympanic membrane being the most indicative feature of acute otitis media, present in 100% of diagnosed cases, according to the researchers.
• Feedback from 60 parents was largely positive, with 80% wanting the tool to be used during future visits.

IN PRACTICE:

Based on the diagnostic accuracy of clinicians in other studies, “The algorithm exhibited higher accuracy than pediatricians, primary care physicians, and advance practice clinicians and, accordingly, could reasonably be used in these settings to aid with decisions regarding treatment,” the authors of the study wrote. “More accurate diagnosis of [acute otitis media] may help reduce unnecessary prescriptions of antimicrobials in young children,” they added.

Studies directly comparing the performance of the tool vs clinicians are still needed, however, according to an editorial accompanying the journal article.

“While the data from this study show the model’s accuracy (94%) is superior to historical accuracy of clinicians in diagnosing acute otitis media (84% or less), these data come from different studies not using the same definition for accuracy,” wrote Hojjat Salmasian, MD, MPH, PhD, and Lisa Biggs, MD, with Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. “If we assume the model is confirmed to be highly accurate and free from bias, this model could truly transform care for patients with suspected acute otitis media.”

SOURCE:

Alejandro Hoberman, MD, with the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, was the corresponding author of the study. It was published online in JAMA Pediatrics .

LIMITATIONS:

The study used convenience sampling and did not include external validation of the tool. The researchers lacked information about participant demographics and the reason for their clinic visit.

DISCLOSURES:

Three authors of the study are listed as inventors on a patent for a tool to diagnose acute otitis media. Two authors with Dcipher Analytics disclosed fees from the University of Pittsburgh for their work on an application programming interface during the study. The research was supported by the Department of Pediatrics at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have developed a tool that uses artificial intelligence (AI) to identify acute otitis media in children based on otoscopic videos. It may improve diagnosis of ear infections in primary care settings, the developers said.

METHODOLOGY:

• The developers relied on otoscopic videos of the tympanic membrane captured on smartphones connected to scopes.
• Their analysis focused on 1151 videos from 635 children, most younger than 3 years old, who were seen for sick or well visits at outpatient clinics in Pennsylvania from 2018 to 2023.
• The tool was trained to differentiate between patients who did and did not have acute otitis media.

TAKEAWAY:

• Out of an original pool of 1561 videos, 410 were excluded due to obstruction by cerumen. In the remaining videos, experts identified acute otitis media in 305 videos (26.5%) and no acute otitis media in 846 videos (73.5%).
• The tool achieved a sensitivity of 93.8% and specificity of 93.5%, with bulging of the tympanic membrane being the most indicative feature of acute otitis media, present in 100% of diagnosed cases, according to the researchers.
• Feedback from 60 parents was largely positive, with 80% wanting the tool to be used during future visits.

IN PRACTICE:

Based on the diagnostic accuracy of clinicians in other studies, “The algorithm exhibited higher accuracy than pediatricians, primary care physicians, and advance practice clinicians and, accordingly, could reasonably be used in these settings to aid with decisions regarding treatment,” the authors of the study wrote. “More accurate diagnosis of [acute otitis media] may help reduce unnecessary prescriptions of antimicrobials in young children,” they added.

Studies directly comparing the performance of the tool vs clinicians are still needed, however, according to an editorial accompanying the journal article.

“While the data from this study show the model’s accuracy (94%) is superior to historical accuracy of clinicians in diagnosing acute otitis media (84% or less), these data come from different studies not using the same definition for accuracy,” wrote Hojjat Salmasian, MD, MPH, PhD, and Lisa Biggs, MD, with Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. “If we assume the model is confirmed to be highly accurate and free from bias, this model could truly transform care for patients with suspected acute otitis media.”

SOURCE:

Alejandro Hoberman, MD, with the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, was the corresponding author of the study. It was published online in JAMA Pediatrics .

LIMITATIONS:

The study used convenience sampling and did not include external validation of the tool. The researchers lacked information about participant demographics and the reason for their clinic visit.

DISCLOSURES:

Three authors of the study are listed as inventors on a patent for a tool to diagnose acute otitis media. Two authors with Dcipher Analytics disclosed fees from the University of Pittsburgh for their work on an application programming interface during the study. The research was supported by the Department of Pediatrics at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A wise medical precept is attributed to Theodore Woodward, MD (1914-2005): “When you hear hoofbeats, think of horses, not zebras.” Primary care pediatricians, however, often find themselves confronting so-called rare or uncommon diseases (“zebras”) in their offices. The pressing challenge is to know when to suspect them. How can one reconcile the need to dispel uncertainty with the use of diagnostic tests that can be costly and invasive? When can the desire to reassure parents mean delaying the detection of a potentially treatable condition?

“It may seem like wordplay, but it’s not uncommon to have a rare disease,” noted Alejandro Fainboim, MD, a specialist in rare diseases and head of the Multivalent Day Hospital at the Ricardo Gutiérrez Children’s Hospital in Buenos Aires, Argentina. “And pediatricians are the first line of defense in detecting these types of pathologies. To make the diagnosis, we have to consider them. And to consider them, we must be knowledgeable. That’s why sometimes, ignorance slows down the diagnosis,” Dr. Fainboim made his remarks during an online seminar organized for the press on the eve of Rare Disease Day, which is commemorated on February 29th.

There are more than 8000 rare diseases, which generally are defined as those affecting fewer than five people per 10,000. But collectively, one in every 13 people has one of these diseases, and one in every two diagnosed patients is a child. Dr. Fainboim emphasized that most of these rare diseases are severe or very severe, hereditary, degenerative, and potentially fatal. And although they are pediatric pathologies, some manifest later in adulthood.

“The major problem we pediatricians face is that we’re handed a model from adults to solve pediatric diseases. So, signs and symptoms are described that we won’t find early on, but we have to anticipate and learn to decode some that are hidden,” he remarked.

Diagnostic delays and repeated consultations with various doctors before identification are common. Dr. Fainboim added that in industrialized countries, the diagnosis of these diseases takes between 5 and 10 years, and in low-income countries, up to 30 years or more. However, “this has improved significantly in recent years,” he said.
 

Unnoticed Signs

Specialists who treat patients with rare diseases often feel that there were obvious signs that went unnoticed and should have aroused the suspicion of the primary care physician. An example is paroxysmal nocturnal hemoglobinuria, which affects 13-14 people per million inhabitants and can appear at any age, although the incidence is higher in the third decade of life.

“In my 50 years as a doctor, I’ve seen seven or eight patients with paroxysmal nocturnal hemoglobinuria,” said Elsa Nucifora, MD, a hematologist at the Italian Hospital of Buenos Aires, Argentina. But “the diagnosis is so easy” that doctors could make it if they “were to think instead of acting automatically because they’re in a hurry,” she added. The diagnosis should be considered “every time anemia occurs in a young person, with certain characteristics, instead of giving them iron like everyone else and ‘we’ll see later’…the diagnosis is in two or three steps, so it’s not complicated.”

Similar situations occur with more than 1000 neuromuscular diseases involving mutations in more than 600 genes, including spinal muscular atrophy and muscular dystrophies.

“What are the most common manifestations? The hypotonic infant, the child who walks late, who falls frequently, who can’t climb stairs, who later may have difficulty breathing, who loses strength: These are presentations often unrecognized by doctors not in the specialty,” said Alberto Dubrovsky, MD, director of the Department of Neurology and the Neuromuscular Diseases Unit at the Favaloro University Neuroscience Institute in Buenos Aires, Argentina, during the seminar. “And considering that these diseases are diagnosed based on genetic mutations that need to be known to search for and request them, we are faced with a truly complex scenario that requires subspecialization.”

In a study recently published in the Argentine Archives of Pediatrics, Dr. Dubrovsky and colleagues interviewed 112 families of Argentine patients with molecular diagnoses of spinal muscular atrophy types I, II, and III and found that in 75%-85% of cases, the first signs of the disease (such as hypotonia, developmental delay, inability to achieve bipedal standing, or frequent falls) were recognized by parents. For type I, the most severe and early onset, in only 17.5% of cases did a neonatologist or pediatrician first notice something. Of the 72 patients with types II and III, where routine checks are less frequent than in the first months of life, only one doctor detected the first signs of the disease before parents or other relatives.

In the same study, the median time elapsed between the first sign and confirmed molecular diagnosis was 2, 10, and 31.5 months for types I, II, and III, respectively. The delay “is primarily due to the lack of clinical suspicion on the part of the intervening physician, who often dismisses or misinterprets the signs reported by parents, as reflected in the alternative diagnoses invoked,” the authors wrote.

“I don’t even ask for suspicion of a specific rare disease because that requires specialization. What I ask for is a kind of recognition or realization that something is happening and then request a consultation with the specialist to ensure proper care,” said Dr. Dubrovsky.

In another study conducted among 70 Argentine patients under age 13 years who were diagnosed with Duchenne muscular dystrophy (one of the most severe forms of muscular dystrophy), 82% of the pediatricians who were initially consulted for any problem in motor agility that parents, other relatives, or teachers had detected dismissed the observation. “They’re told to wait, that it will mature a little more,” said Dr. Dubrovsky. This explains why the time to diagnosis in Argentina from the first signs is around 2 years. The delays are unfortunate because “today we have treatments capable of interfering with the disease’s progression slope, reducing its progression, or eventually stopping it,” he said.

“Do you mind that primary care pediatricians don’t notice or dismiss signs and symptoms strongly suggestive of one of these rare diseases? Does it frustrate you?” this news organization asked asked Dr. Dubrovsky. “Sometimes it does make me angry, but many times it’s understood that there can’t be highly trained specialists everywhere to realize and request diagnostic tests. One must consider the circumstances in each case, and that’s why we work in education,” he replied.
 

Rules and Experience

In an interview, Dr. Fainboim highlighted key factors that should prompt a pediatrician’s suspicion. One is common symptoms expressed in a more intense or complicated way or when many symptoms coexist in the same patient, even if each one separately is benign or not so severe.

Dr. Fainboim also recommended establishing a therapeutic alliance with parents. “We shouldn’t undermine what parents say, especially those who have other children and already know what normal child development is like. This is a very important milestone.

“We have to strengthen the suspicion clue, and for that, we rely on standards and our experience, which we keep refining. As Wilde said, experience is the sum of our mistakes. But there’s no universal answer. Not all families are the same. Not all diseases manifest in the same way. And unless there’s an imminent risk to life or function, one can wait and take the time to evaluate it. For example, if I have a child with slowed developmental milestones, what I have to do is teach how to stimulate them or send them for stimulation with another professional. And I observe the response to this initial basic treatment. If I see no response, the alarms start to grow louder,” said Dr. Fainboim.

Pablo Barvosa, MD, the principal physician in the outpatient area of the Juan P. Garrahan Pediatric Hospital in Buenos Aires, Argentina, and a member of the Working Group on Genetics and Rare Diseases of the Argentine Society of Pediatrics, told this news organization about other factors that should be considered for detecting these pathologies. Dr. Barvosa did not participate in the online seminar.

“Patients with rare diseases have common symptoms. What needs to be done is to prioritize those symptoms that behave abnormally, that have an unusual evolution compared with normal situations. For example, children who go into a coma after a fasting episode or after eating a certain food,” he said.

Dr. Barvosa also suggested considering when patients belong to certain communities where there is a lot of endogamy, due to the higher incidence of hereditary diseases. “Attention should be heightened when parents are cousins or relatives,” he pointed out.

“My view is that doctors should think more and better, be rational, sequential. If a disease is treated and resolved, but we find out that the child had 26 previous hospitalizations in the last 2 years, something is wrong. We have to look at the patient’s and family’s life histories. If a mother had 15 miscarriages, that’s a warning sign. We have to find a common thread. Be a sharp-witted pediatrician,” said Dr. Barvosa.

The suspicion and diagnosis of a rare disease can be devastating for families and painful for the professional, but even if there is no specific treatment, “something can always be done for patients,” he added.

And in certain circumstances, identifying a rare disease can reverse the ominous “stamp” of a wrong diagnosis. Dr. Barvosa commented on the case of a 7-year-old boy he attended at the hospital in 2014. The boy presented as quadriplegic, with no mobility in his limbs, and the parents were convinced he had that condition because he had fallen from the roof of the house. Although imaging techniques did not show a spinal injury, it was assumed to be a case of spinal cord injury without radiographic abnormality. But something caught Dr. Barvosa’s attention: The boy had well-developed abdominal muscles, as if he were an athlete. So, he requested an electromyogram, and the muscle was found to be in permanent contraction.

“The patient didn’t have a spinal cord injury: He had Isaacs’ syndrome,” said Dr. Barvosa. The syndrome also is known as acquired neuromyotonia, a rare condition of hyperexcitability of peripheral nerves that activate muscle fibers. “That is treated with anticonvulsants, such as phenytoin. Within a week, he was walking again, and shortly after, he was playing soccer. When I presented the case at a conference, I cried with emotion. That’s why the pediatrician must be insistent, be like the gadfly that stings in the ear” when there are clinical elements that don’t quite fit into a clear diagnosis, he added.

In recent publications, Dr. Dubrovsky has reported receiving fees for consultations or research from PTC, Sarepta, Biogen, Sanofi Genzyme, Takeda Avexis, Novartis, Raffo, and Roche. Dr. Nucifora has received fees from Jansen LATAM. Dr. Fainboim reported receiving fees from Sanofi. Dr. Barvosa has declared no relevant financial conflicts of interest. The webinar was organized by Urban Comunicaciones.
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A wise medical precept is attributed to Theodore Woodward, MD (1914-2005): “When you hear hoofbeats, think of horses, not zebras.” Primary care pediatricians, however, often find themselves confronting so-called rare or uncommon diseases (“zebras”) in their offices. The pressing challenge is to know when to suspect them. How can one reconcile the need to dispel uncertainty with the use of diagnostic tests that can be costly and invasive? When can the desire to reassure parents mean delaying the detection of a potentially treatable condition?

“It may seem like wordplay, but it’s not uncommon to have a rare disease,” noted Alejandro Fainboim, MD, a specialist in rare diseases and head of the Multivalent Day Hospital at the Ricardo Gutiérrez Children’s Hospital in Buenos Aires, Argentina. “And pediatricians are the first line of defense in detecting these types of pathologies. To make the diagnosis, we have to consider them. And to consider them, we must be knowledgeable. That’s why sometimes, ignorance slows down the diagnosis,” Dr. Fainboim made his remarks during an online seminar organized for the press on the eve of Rare Disease Day, which is commemorated on February 29th.

There are more than 8000 rare diseases, which generally are defined as those affecting fewer than five people per 10,000. But collectively, one in every 13 people has one of these diseases, and one in every two diagnosed patients is a child. Dr. Fainboim emphasized that most of these rare diseases are severe or very severe, hereditary, degenerative, and potentially fatal. And although they are pediatric pathologies, some manifest later in adulthood.

“The major problem we pediatricians face is that we’re handed a model from adults to solve pediatric diseases. So, signs and symptoms are described that we won’t find early on, but we have to anticipate and learn to decode some that are hidden,” he remarked.

Diagnostic delays and repeated consultations with various doctors before identification are common. Dr. Fainboim added that in industrialized countries, the diagnosis of these diseases takes between 5 and 10 years, and in low-income countries, up to 30 years or more. However, “this has improved significantly in recent years,” he said.
 

Unnoticed Signs

Specialists who treat patients with rare diseases often feel that there were obvious signs that went unnoticed and should have aroused the suspicion of the primary care physician. An example is paroxysmal nocturnal hemoglobinuria, which affects 13-14 people per million inhabitants and can appear at any age, although the incidence is higher in the third decade of life.

“In my 50 years as a doctor, I’ve seen seven or eight patients with paroxysmal nocturnal hemoglobinuria,” said Elsa Nucifora, MD, a hematologist at the Italian Hospital of Buenos Aires, Argentina. But “the diagnosis is so easy” that doctors could make it if they “were to think instead of acting automatically because they’re in a hurry,” she added. The diagnosis should be considered “every time anemia occurs in a young person, with certain characteristics, instead of giving them iron like everyone else and ‘we’ll see later’…the diagnosis is in two or three steps, so it’s not complicated.”

Similar situations occur with more than 1000 neuromuscular diseases involving mutations in more than 600 genes, including spinal muscular atrophy and muscular dystrophies.

“What are the most common manifestations? The hypotonic infant, the child who walks late, who falls frequently, who can’t climb stairs, who later may have difficulty breathing, who loses strength: These are presentations often unrecognized by doctors not in the specialty,” said Alberto Dubrovsky, MD, director of the Department of Neurology and the Neuromuscular Diseases Unit at the Favaloro University Neuroscience Institute in Buenos Aires, Argentina, during the seminar. “And considering that these diseases are diagnosed based on genetic mutations that need to be known to search for and request them, we are faced with a truly complex scenario that requires subspecialization.”

In a study recently published in the Argentine Archives of Pediatrics, Dr. Dubrovsky and colleagues interviewed 112 families of Argentine patients with molecular diagnoses of spinal muscular atrophy types I, II, and III and found that in 75%-85% of cases, the first signs of the disease (such as hypotonia, developmental delay, inability to achieve bipedal standing, or frequent falls) were recognized by parents. For type I, the most severe and early onset, in only 17.5% of cases did a neonatologist or pediatrician first notice something. Of the 72 patients with types II and III, where routine checks are less frequent than in the first months of life, only one doctor detected the first signs of the disease before parents or other relatives.

In the same study, the median time elapsed between the first sign and confirmed molecular diagnosis was 2, 10, and 31.5 months for types I, II, and III, respectively. The delay “is primarily due to the lack of clinical suspicion on the part of the intervening physician, who often dismisses or misinterprets the signs reported by parents, as reflected in the alternative diagnoses invoked,” the authors wrote.

“I don’t even ask for suspicion of a specific rare disease because that requires specialization. What I ask for is a kind of recognition or realization that something is happening and then request a consultation with the specialist to ensure proper care,” said Dr. Dubrovsky.

In another study conducted among 70 Argentine patients under age 13 years who were diagnosed with Duchenne muscular dystrophy (one of the most severe forms of muscular dystrophy), 82% of the pediatricians who were initially consulted for any problem in motor agility that parents, other relatives, or teachers had detected dismissed the observation. “They’re told to wait, that it will mature a little more,” said Dr. Dubrovsky. This explains why the time to diagnosis in Argentina from the first signs is around 2 years. The delays are unfortunate because “today we have treatments capable of interfering with the disease’s progression slope, reducing its progression, or eventually stopping it,” he said.

“Do you mind that primary care pediatricians don’t notice or dismiss signs and symptoms strongly suggestive of one of these rare diseases? Does it frustrate you?” this news organization asked asked Dr. Dubrovsky. “Sometimes it does make me angry, but many times it’s understood that there can’t be highly trained specialists everywhere to realize and request diagnostic tests. One must consider the circumstances in each case, and that’s why we work in education,” he replied.
 

Rules and Experience

In an interview, Dr. Fainboim highlighted key factors that should prompt a pediatrician’s suspicion. One is common symptoms expressed in a more intense or complicated way or when many symptoms coexist in the same patient, even if each one separately is benign or not so severe.

Dr. Fainboim also recommended establishing a therapeutic alliance with parents. “We shouldn’t undermine what parents say, especially those who have other children and already know what normal child development is like. This is a very important milestone.

“We have to strengthen the suspicion clue, and for that, we rely on standards and our experience, which we keep refining. As Wilde said, experience is the sum of our mistakes. But there’s no universal answer. Not all families are the same. Not all diseases manifest in the same way. And unless there’s an imminent risk to life or function, one can wait and take the time to evaluate it. For example, if I have a child with slowed developmental milestones, what I have to do is teach how to stimulate them or send them for stimulation with another professional. And I observe the response to this initial basic treatment. If I see no response, the alarms start to grow louder,” said Dr. Fainboim.

Pablo Barvosa, MD, the principal physician in the outpatient area of the Juan P. Garrahan Pediatric Hospital in Buenos Aires, Argentina, and a member of the Working Group on Genetics and Rare Diseases of the Argentine Society of Pediatrics, told this news organization about other factors that should be considered for detecting these pathologies. Dr. Barvosa did not participate in the online seminar.

“Patients with rare diseases have common symptoms. What needs to be done is to prioritize those symptoms that behave abnormally, that have an unusual evolution compared with normal situations. For example, children who go into a coma after a fasting episode or after eating a certain food,” he said.

Dr. Barvosa also suggested considering when patients belong to certain communities where there is a lot of endogamy, due to the higher incidence of hereditary diseases. “Attention should be heightened when parents are cousins or relatives,” he pointed out.

“My view is that doctors should think more and better, be rational, sequential. If a disease is treated and resolved, but we find out that the child had 26 previous hospitalizations in the last 2 years, something is wrong. We have to look at the patient’s and family’s life histories. If a mother had 15 miscarriages, that’s a warning sign. We have to find a common thread. Be a sharp-witted pediatrician,” said Dr. Barvosa.

The suspicion and diagnosis of a rare disease can be devastating for families and painful for the professional, but even if there is no specific treatment, “something can always be done for patients,” he added.

And in certain circumstances, identifying a rare disease can reverse the ominous “stamp” of a wrong diagnosis. Dr. Barvosa commented on the case of a 7-year-old boy he attended at the hospital in 2014. The boy presented as quadriplegic, with no mobility in his limbs, and the parents were convinced he had that condition because he had fallen from the roof of the house. Although imaging techniques did not show a spinal injury, it was assumed to be a case of spinal cord injury without radiographic abnormality. But something caught Dr. Barvosa’s attention: The boy had well-developed abdominal muscles, as if he were an athlete. So, he requested an electromyogram, and the muscle was found to be in permanent contraction.

“The patient didn’t have a spinal cord injury: He had Isaacs’ syndrome,” said Dr. Barvosa. The syndrome also is known as acquired neuromyotonia, a rare condition of hyperexcitability of peripheral nerves that activate muscle fibers. “That is treated with anticonvulsants, such as phenytoin. Within a week, he was walking again, and shortly after, he was playing soccer. When I presented the case at a conference, I cried with emotion. That’s why the pediatrician must be insistent, be like the gadfly that stings in the ear” when there are clinical elements that don’t quite fit into a clear diagnosis, he added.

In recent publications, Dr. Dubrovsky has reported receiving fees for consultations or research from PTC, Sarepta, Biogen, Sanofi Genzyme, Takeda Avexis, Novartis, Raffo, and Roche. Dr. Nucifora has received fees from Jansen LATAM. Dr. Fainboim reported receiving fees from Sanofi. Dr. Barvosa has declared no relevant financial conflicts of interest. The webinar was organized by Urban Comunicaciones.
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A wise medical precept is attributed to Theodore Woodward, MD (1914-2005): “When you hear hoofbeats, think of horses, not zebras.” Primary care pediatricians, however, often find themselves confronting so-called rare or uncommon diseases (“zebras”) in their offices. The pressing challenge is to know when to suspect them. How can one reconcile the need to dispel uncertainty with the use of diagnostic tests that can be costly and invasive? When can the desire to reassure parents mean delaying the detection of a potentially treatable condition?

“It may seem like wordplay, but it’s not uncommon to have a rare disease,” noted Alejandro Fainboim, MD, a specialist in rare diseases and head of the Multivalent Day Hospital at the Ricardo Gutiérrez Children’s Hospital in Buenos Aires, Argentina. “And pediatricians are the first line of defense in detecting these types of pathologies. To make the diagnosis, we have to consider them. And to consider them, we must be knowledgeable. That’s why sometimes, ignorance slows down the diagnosis,” Dr. Fainboim made his remarks during an online seminar organized for the press on the eve of Rare Disease Day, which is commemorated on February 29th.

There are more than 8000 rare diseases, which generally are defined as those affecting fewer than five people per 10,000. But collectively, one in every 13 people has one of these diseases, and one in every two diagnosed patients is a child. Dr. Fainboim emphasized that most of these rare diseases are severe or very severe, hereditary, degenerative, and potentially fatal. And although they are pediatric pathologies, some manifest later in adulthood.

“The major problem we pediatricians face is that we’re handed a model from adults to solve pediatric diseases. So, signs and symptoms are described that we won’t find early on, but we have to anticipate and learn to decode some that are hidden,” he remarked.

Diagnostic delays and repeated consultations with various doctors before identification are common. Dr. Fainboim added that in industrialized countries, the diagnosis of these diseases takes between 5 and 10 years, and in low-income countries, up to 30 years or more. However, “this has improved significantly in recent years,” he said.
 

Unnoticed Signs

Specialists who treat patients with rare diseases often feel that there were obvious signs that went unnoticed and should have aroused the suspicion of the primary care physician. An example is paroxysmal nocturnal hemoglobinuria, which affects 13-14 people per million inhabitants and can appear at any age, although the incidence is higher in the third decade of life.

“In my 50 years as a doctor, I’ve seen seven or eight patients with paroxysmal nocturnal hemoglobinuria,” said Elsa Nucifora, MD, a hematologist at the Italian Hospital of Buenos Aires, Argentina. But “the diagnosis is so easy” that doctors could make it if they “were to think instead of acting automatically because they’re in a hurry,” she added. The diagnosis should be considered “every time anemia occurs in a young person, with certain characteristics, instead of giving them iron like everyone else and ‘we’ll see later’…the diagnosis is in two or three steps, so it’s not complicated.”

Similar situations occur with more than 1000 neuromuscular diseases involving mutations in more than 600 genes, including spinal muscular atrophy and muscular dystrophies.

“What are the most common manifestations? The hypotonic infant, the child who walks late, who falls frequently, who can’t climb stairs, who later may have difficulty breathing, who loses strength: These are presentations often unrecognized by doctors not in the specialty,” said Alberto Dubrovsky, MD, director of the Department of Neurology and the Neuromuscular Diseases Unit at the Favaloro University Neuroscience Institute in Buenos Aires, Argentina, during the seminar. “And considering that these diseases are diagnosed based on genetic mutations that need to be known to search for and request them, we are faced with a truly complex scenario that requires subspecialization.”

In a study recently published in the Argentine Archives of Pediatrics, Dr. Dubrovsky and colleagues interviewed 112 families of Argentine patients with molecular diagnoses of spinal muscular atrophy types I, II, and III and found that in 75%-85% of cases, the first signs of the disease (such as hypotonia, developmental delay, inability to achieve bipedal standing, or frequent falls) were recognized by parents. For type I, the most severe and early onset, in only 17.5% of cases did a neonatologist or pediatrician first notice something. Of the 72 patients with types II and III, where routine checks are less frequent than in the first months of life, only one doctor detected the first signs of the disease before parents or other relatives.

In the same study, the median time elapsed between the first sign and confirmed molecular diagnosis was 2, 10, and 31.5 months for types I, II, and III, respectively. The delay “is primarily due to the lack of clinical suspicion on the part of the intervening physician, who often dismisses or misinterprets the signs reported by parents, as reflected in the alternative diagnoses invoked,” the authors wrote.

“I don’t even ask for suspicion of a specific rare disease because that requires specialization. What I ask for is a kind of recognition or realization that something is happening and then request a consultation with the specialist to ensure proper care,” said Dr. Dubrovsky.

In another study conducted among 70 Argentine patients under age 13 years who were diagnosed with Duchenne muscular dystrophy (one of the most severe forms of muscular dystrophy), 82% of the pediatricians who were initially consulted for any problem in motor agility that parents, other relatives, or teachers had detected dismissed the observation. “They’re told to wait, that it will mature a little more,” said Dr. Dubrovsky. This explains why the time to diagnosis in Argentina from the first signs is around 2 years. The delays are unfortunate because “today we have treatments capable of interfering with the disease’s progression slope, reducing its progression, or eventually stopping it,” he said.

“Do you mind that primary care pediatricians don’t notice or dismiss signs and symptoms strongly suggestive of one of these rare diseases? Does it frustrate you?” this news organization asked asked Dr. Dubrovsky. “Sometimes it does make me angry, but many times it’s understood that there can’t be highly trained specialists everywhere to realize and request diagnostic tests. One must consider the circumstances in each case, and that’s why we work in education,” he replied.
 

Rules and Experience

In an interview, Dr. Fainboim highlighted key factors that should prompt a pediatrician’s suspicion. One is common symptoms expressed in a more intense or complicated way or when many symptoms coexist in the same patient, even if each one separately is benign or not so severe.

Dr. Fainboim also recommended establishing a therapeutic alliance with parents. “We shouldn’t undermine what parents say, especially those who have other children and already know what normal child development is like. This is a very important milestone.

“We have to strengthen the suspicion clue, and for that, we rely on standards and our experience, which we keep refining. As Wilde said, experience is the sum of our mistakes. But there’s no universal answer. Not all families are the same. Not all diseases manifest in the same way. And unless there’s an imminent risk to life or function, one can wait and take the time to evaluate it. For example, if I have a child with slowed developmental milestones, what I have to do is teach how to stimulate them or send them for stimulation with another professional. And I observe the response to this initial basic treatment. If I see no response, the alarms start to grow louder,” said Dr. Fainboim.

Pablo Barvosa, MD, the principal physician in the outpatient area of the Juan P. Garrahan Pediatric Hospital in Buenos Aires, Argentina, and a member of the Working Group on Genetics and Rare Diseases of the Argentine Society of Pediatrics, told this news organization about other factors that should be considered for detecting these pathologies. Dr. Barvosa did not participate in the online seminar.

“Patients with rare diseases have common symptoms. What needs to be done is to prioritize those symptoms that behave abnormally, that have an unusual evolution compared with normal situations. For example, children who go into a coma after a fasting episode or after eating a certain food,” he said.

Dr. Barvosa also suggested considering when patients belong to certain communities where there is a lot of endogamy, due to the higher incidence of hereditary diseases. “Attention should be heightened when parents are cousins or relatives,” he pointed out.

“My view is that doctors should think more and better, be rational, sequential. If a disease is treated and resolved, but we find out that the child had 26 previous hospitalizations in the last 2 years, something is wrong. We have to look at the patient’s and family’s life histories. If a mother had 15 miscarriages, that’s a warning sign. We have to find a common thread. Be a sharp-witted pediatrician,” said Dr. Barvosa.

The suspicion and diagnosis of a rare disease can be devastating for families and painful for the professional, but even if there is no specific treatment, “something can always be done for patients,” he added.

And in certain circumstances, identifying a rare disease can reverse the ominous “stamp” of a wrong diagnosis. Dr. Barvosa commented on the case of a 7-year-old boy he attended at the hospital in 2014. The boy presented as quadriplegic, with no mobility in his limbs, and the parents were convinced he had that condition because he had fallen from the roof of the house. Although imaging techniques did not show a spinal injury, it was assumed to be a case of spinal cord injury without radiographic abnormality. But something caught Dr. Barvosa’s attention: The boy had well-developed abdominal muscles, as if he were an athlete. So, he requested an electromyogram, and the muscle was found to be in permanent contraction.

“The patient didn’t have a spinal cord injury: He had Isaacs’ syndrome,” said Dr. Barvosa. The syndrome also is known as acquired neuromyotonia, a rare condition of hyperexcitability of peripheral nerves that activate muscle fibers. “That is treated with anticonvulsants, such as phenytoin. Within a week, he was walking again, and shortly after, he was playing soccer. When I presented the case at a conference, I cried with emotion. That’s why the pediatrician must be insistent, be like the gadfly that stings in the ear” when there are clinical elements that don’t quite fit into a clear diagnosis, he added.

In recent publications, Dr. Dubrovsky has reported receiving fees for consultations or research from PTC, Sarepta, Biogen, Sanofi Genzyme, Takeda Avexis, Novartis, Raffo, and Roche. Dr. Nucifora has received fees from Jansen LATAM. Dr. Fainboim reported receiving fees from Sanofi. Dr. Barvosa has declared no relevant financial conflicts of interest. The webinar was organized by Urban Comunicaciones.
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Topical calcineurin inhibitors (TCIs), topical corticosteroids (TCSs), and topical Janus kinase (JAK) inhibitors are supported as mainstay treatments in new expert recommendations on the use of topical therapeutics in children, adolescents, and young adults with vitiligo.

METHODOLOGY:

• While half of all vitiligo cases manifest within the initial two decades of life, no guidelines specifically address the management of vitiligo in children, adolescents, and young adults with vitiligo.
• A protocol was established to formulate consensus recommendations addressing questions related to pediatric vitiligo.
• Overall, 50 articles on topical corticosteroids and/or topical calcineurin inhibitors, five on topical Janus kinase inhibitors, and two each on pseudocatalase and microdermabrasion were included.
• The participants recorded their agreement levels with the formulated statements, using a 5-point Likert scale.

TAKEAWAY:

• TCIs, TCSs, JAK inhibitors, and phototherapy, specifically narrowband ultraviolet (UV)-B light therapy, are mainstay treatments; the combination of UV-B light and topical therapy may enhance initial repigmentation.
• Long-term monitoring for skin cancers is advised, and short outdoor UV exposure is suggested for pediatric patients.
• TCIs, such as tacrolimus and pimecrolimus, are recommended as first-line therapy, particularly on the face, applied twice daily for ≥ 3 months; continued use for 6-12 additional months is recommended if repigmentation is observed.
• The choice of TCS class depends on the site and planned usage duration. Short-term use or overlap with TCIs is recommended because of the risk for atrophy with long-term TCS use. Class 5-6 agents are another option.
• For areas with thin skin, TCSs can be considered second-line treatments.
• Topical JAK inhibitors, specifically topical 1.5% ruxolitinib cream, are recommended for patients aged ≥ 12 years, as first- or second-line therapy. Limitation to 10% body surface area is recommended to minimize systemic absorption. Limited evidence exists for children aged < 12 years.

IN PRACTICE:

“Effective therapy requires a focus on long-term therapeutic interventions to maximize the local gain and retention of pigmentation with a trial period of twice-weekly application. Counseling should include discussion of the chronicity of vitiligo and the need for long-term care,” the authors wrote.

LIMITATIONS:

Some of the recommendations were opinion-based because of the scarcity of evidence-based literature.

SOURCE:

The consensus statement was published on March 13 in JAMA Dermatology.

DISCLOSURES:

This work was supported by grants from Vitiligo Research Foundation and Incyte Pharmaceuticals. The majority of authors disclosed financial relationships outside this work; several reported no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Topical calcineurin inhibitors (TCIs), topical corticosteroids (TCSs), and topical Janus kinase (JAK) inhibitors are supported as mainstay treatments in new expert recommendations on the use of topical therapeutics in children, adolescents, and young adults with vitiligo.

METHODOLOGY:

• While half of all vitiligo cases manifest within the initial two decades of life, no guidelines specifically address the management of vitiligo in children, adolescents, and young adults with vitiligo.
• A protocol was established to formulate consensus recommendations addressing questions related to pediatric vitiligo.
• Overall, 50 articles on topical corticosteroids and/or topical calcineurin inhibitors, five on topical Janus kinase inhibitors, and two each on pseudocatalase and microdermabrasion were included.
• The participants recorded their agreement levels with the formulated statements, using a 5-point Likert scale.

TAKEAWAY:

• TCIs, TCSs, JAK inhibitors, and phototherapy, specifically narrowband ultraviolet (UV)-B light therapy, are mainstay treatments; the combination of UV-B light and topical therapy may enhance initial repigmentation.
• Long-term monitoring for skin cancers is advised, and short outdoor UV exposure is suggested for pediatric patients.
• TCIs, such as tacrolimus and pimecrolimus, are recommended as first-line therapy, particularly on the face, applied twice daily for ≥ 3 months; continued use for 6-12 additional months is recommended if repigmentation is observed.
• The choice of TCS class depends on the site and planned usage duration. Short-term use or overlap with TCIs is recommended because of the risk for atrophy with long-term TCS use. Class 5-6 agents are another option.
• For areas with thin skin, TCSs can be considered second-line treatments.
• Topical JAK inhibitors, specifically topical 1.5% ruxolitinib cream, are recommended for patients aged ≥ 12 years, as first- or second-line therapy. Limitation to 10% body surface area is recommended to minimize systemic absorption. Limited evidence exists for children aged < 12 years.

IN PRACTICE:

“Effective therapy requires a focus on long-term therapeutic interventions to maximize the local gain and retention of pigmentation with a trial period of twice-weekly application. Counseling should include discussion of the chronicity of vitiligo and the need for long-term care,” the authors wrote.

LIMITATIONS:

Some of the recommendations were opinion-based because of the scarcity of evidence-based literature.

SOURCE:

The consensus statement was published on March 13 in JAMA Dermatology.

DISCLOSURES:

This work was supported by grants from Vitiligo Research Foundation and Incyte Pharmaceuticals. The majority of authors disclosed financial relationships outside this work; several reported no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Topical calcineurin inhibitors (TCIs), topical corticosteroids (TCSs), and topical Janus kinase (JAK) inhibitors are supported as mainstay treatments in new expert recommendations on the use of topical therapeutics in children, adolescents, and young adults with vitiligo.

METHODOLOGY:

• While half of all vitiligo cases manifest within the initial two decades of life, no guidelines specifically address the management of vitiligo in children, adolescents, and young adults with vitiligo.
• A protocol was established to formulate consensus recommendations addressing questions related to pediatric vitiligo.
• Overall, 50 articles on topical corticosteroids and/or topical calcineurin inhibitors, five on topical Janus kinase inhibitors, and two each on pseudocatalase and microdermabrasion were included.
• The participants recorded their agreement levels with the formulated statements, using a 5-point Likert scale.

TAKEAWAY:

• TCIs, TCSs, JAK inhibitors, and phototherapy, specifically narrowband ultraviolet (UV)-B light therapy, are mainstay treatments; the combination of UV-B light and topical therapy may enhance initial repigmentation.
• Long-term monitoring for skin cancers is advised, and short outdoor UV exposure is suggested for pediatric patients.
• TCIs, such as tacrolimus and pimecrolimus, are recommended as first-line therapy, particularly on the face, applied twice daily for ≥ 3 months; continued use for 6-12 additional months is recommended if repigmentation is observed.
• The choice of TCS class depends on the site and planned usage duration. Short-term use or overlap with TCIs is recommended because of the risk for atrophy with long-term TCS use. Class 5-6 agents are another option.
• For areas with thin skin, TCSs can be considered second-line treatments.
• Topical JAK inhibitors, specifically topical 1.5% ruxolitinib cream, are recommended for patients aged ≥ 12 years, as first- or second-line therapy. Limitation to 10% body surface area is recommended to minimize systemic absorption. Limited evidence exists for children aged < 12 years.

IN PRACTICE:

“Effective therapy requires a focus on long-term therapeutic interventions to maximize the local gain and retention of pigmentation with a trial period of twice-weekly application. Counseling should include discussion of the chronicity of vitiligo and the need for long-term care,” the authors wrote.

LIMITATIONS:

Some of the recommendations were opinion-based because of the scarcity of evidence-based literature.

SOURCE:

The consensus statement was published on March 13 in JAMA Dermatology.

DISCLOSURES:

This work was supported by grants from Vitiligo Research Foundation and Incyte Pharmaceuticals. The majority of authors disclosed financial relationships outside this work; several reported no disclosures.

A version of this article appeared on Medscape.com.

Sublingual immunotherapy (SLIT) is as safe and effective for high-risk older children and adolescents as oral immunotherapy (OIT) is for infants and preschoolers, according to new research.

Preliminary data from a study of more than 180 pediatric patients with multiple food allergies showed that while most patients had mild symptoms, none experienced a severe grade 4 reaction during the buildup and maintenance phase of SLIT.

In addition, 70% of those tested at the end of the treatment protocol were able to tolerate 300 mg of their allergen, a success rate nearly as high as that for OIT.

The study was published in The Journal of Allergy and Clinical Immunology: In Practice.

SLIT has been used successfully in the treatment of environmental allergens such as grass and tree pollen and dust mites. In this study, researchers decided to test SLIT’s effectiveness and safety in the treatment of food allergies in older children.

“We knew that OIT is very effective and safe in infants and toddlers, but there was literature illustrating that for older, school-age kids and adolescents, OIT is not safe enough, as those older age groups tend to have higher risk of severe reaction during treatment,” senior author Edmond Chan, MD, clinical professor of allergy at the University of British Columbia and pediatric allergist at BC Children’s Hospital, both in Vancouver, British Columbia, Canada, told this news organization. “With that knowledge, we decided to explore SLIT as another first-phase therapy for the older kids.”

The investigators recruited 188 high-risk older children aged 4-18 years for multifood SLIT. Most (61.7%) participants had multiple food allergies. Approximately 68% were male, and the population’s median age was 11.3 years.

Nearly half (48.4%) of participants had atopic dermatitis, 45.2% had asthma, 58.0% had allergic rhinitis, and 2.66% had preexisting eosinophilic esophagitis.

Most (75.0%) of the children were classified as higher risk, and 23 had a history of a grade 3 or 4 reaction before beginning SLIT.

Of the 188 children who were initially enrolled in the study, 173 (92.0%) finished their SLIT buildup phase.

Because the study started when COVID-19 pandemic restrictions were in place, the SLIT protocol mandated that patients be seen virtually. The patients’ caregivers learned how to mix and administer the required doses at home using recipes specially developed by the research team that used products bought at the grocery store.

A wide variety of food allergens were treated, including peanut, other legumes, tree nuts, sesame, other seeds, egg, cow’s milk, fish, wheat, shrimp, and other allergens.

The children built up to 2-mg protein SLIT maintenance over the course of three to five visits under nurse supervision.

After 1-2 years of daily SLIT maintenance, patients were offered a low-dose oral food challenge (OFC; cumulative dose: 300 mg of protein) with the goal of bypassing OIT buildup.

Nearly all patients (93.1%) had symptoms during SLIT buildup, but most were mild grade 1 (52.1%) or 2 (40.4%) reactions. Only one patient had a grade 3 reaction. None of the patients experienced a severe grade 4 reaction.

The most common grade 1 reaction was oral itch, an expected symptom of SLIT, which occurred in 82.7% of the patients.

Four patients (2.10%) received epinephrine during buildup and went to the emergency department. All these patients returned to continue SLIT without further need for epinephrine.

To test the effectiveness of SLIT, the researchers performed 50 low-dose OFCs in 20 patients. Of these food challenges, 35 (70%) were successful, and patients were asked to start daily 300-mg OIT maintenance, thus bypassing OIT buildup.

An additional nine OFCs that were unsuccessful were counseled to self-escalate from 80 mg or higher to 300 mg at home with medical guidance as needed.

“Our preliminary data of 20 patients and 50 low-dose oral food challenges suggest that an initial phase of 1-2 years of 2-mg daily SLIT therapy may be a safe and effective way to bypass the OIT buildup phase without the need for dozens of in-person visits with an allergist,” said Dr. Chan.

“So now we have the best of both worlds. We harness the safety of SLIT for the first 1-2 years, with the effectiveness of OIT for the remainder of the treatment period,” he said.
 

Adds to Evidence

Commenting on the study for this news organization, Julia Upton, MD, associate professor of pediatrics at the University of Toronto, Toronto, Ontario, Canada, said, “This study adds to the evidence that consistent, low exposure to food drives meaningful desensitization far above the daily dose.” Upton did not participate in the research.

“Prior prospective studies in SLIT demonstrated that small single-digit-milligram doses and time greatly increased the threshold of reaction. This real-world report suggests that a way to utilize that threshold increase is by switching to a commonly used maintenance dose of OIT,” said Dr. Upton.

“Although few patients have been assessed for the 300-mg challenge, this study is notable for the age group of 4-18 years, and that many of the patients had reacted to low doses in the past. It also shows that many families are capable of diluting and mixing their own immunotherapy solutions with store-bought foods under the guidance of an experienced allergy clinic,” she added.

“Overall, evidence is building that by various routes, initial small amounts with minimal updoses, plus the tincture of time, may be preferred to multiple frequent updosing from multiple perspectives, including safety, feasibility, cost, and medical resources. It will also be important to understand the preferences and goals of the patient and family as various regimens become more available,” Dr. Upton concluded.

The study was funded by BC Children’s Hospital Foundation. Dr. Chan reported receiving research support from DVB Technologies; has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi, Genzyme, Bausch Health, Avir Pharma, AstraZeneca, ALK, and Alladapt; and was a colead of the CSACI OIT guidelines. Dr. Upton reported research support/grants from Novartis, Regeneron, Sanofi, ALK Abello, DBV Technologies, CIHR, and SickKids Food Allergy and Anaphylaxis Program and fees from Pfizer, ALK Abello, Bausch Health, Astra Zeneca, and Pharming. She serves as an associate editor for Allergy, Asthma & Clinical Immunology and is on the Board of Directors of Canadian Society of Allergy and Clinical Immunology and the Healthcare Advisory Board of Food Allergy Canada.

A version of this article appeared on Medscape.com .

Sublingual immunotherapy (SLIT) is as safe and effective for high-risk older children and adolescents as oral immunotherapy (OIT) is for infants and preschoolers, according to new research.

Preliminary data from a study of more than 180 pediatric patients with multiple food allergies showed that while most patients had mild symptoms, none experienced a severe grade 4 reaction during the buildup and maintenance phase of SLIT.

In addition, 70% of those tested at the end of the treatment protocol were able to tolerate 300 mg of their allergen, a success rate nearly as high as that for OIT.

The study was published in The Journal of Allergy and Clinical Immunology: In Practice.

SLIT has been used successfully in the treatment of environmental allergens such as grass and tree pollen and dust mites. In this study, researchers decided to test SLIT’s effectiveness and safety in the treatment of food allergies in older children.

“We knew that OIT is very effective and safe in infants and toddlers, but there was literature illustrating that for older, school-age kids and adolescents, OIT is not safe enough, as those older age groups tend to have higher risk of severe reaction during treatment,” senior author Edmond Chan, MD, clinical professor of allergy at the University of British Columbia and pediatric allergist at BC Children’s Hospital, both in Vancouver, British Columbia, Canada, told this news organization. “With that knowledge, we decided to explore SLIT as another first-phase therapy for the older kids.”

The investigators recruited 188 high-risk older children aged 4-18 years for multifood SLIT. Most (61.7%) participants had multiple food allergies. Approximately 68% were male, and the population’s median age was 11.3 years.

Nearly half (48.4%) of participants had atopic dermatitis, 45.2% had asthma, 58.0% had allergic rhinitis, and 2.66% had preexisting eosinophilic esophagitis.

Most (75.0%) of the children were classified as higher risk, and 23 had a history of a grade 3 or 4 reaction before beginning SLIT.

Of the 188 children who were initially enrolled in the study, 173 (92.0%) finished their SLIT buildup phase.

Because the study started when COVID-19 pandemic restrictions were in place, the SLIT protocol mandated that patients be seen virtually. The patients’ caregivers learned how to mix and administer the required doses at home using recipes specially developed by the research team that used products bought at the grocery store.

A wide variety of food allergens were treated, including peanut, other legumes, tree nuts, sesame, other seeds, egg, cow’s milk, fish, wheat, shrimp, and other allergens.

The children built up to 2-mg protein SLIT maintenance over the course of three to five visits under nurse supervision.

After 1-2 years of daily SLIT maintenance, patients were offered a low-dose oral food challenge (OFC; cumulative dose: 300 mg of protein) with the goal of bypassing OIT buildup.

Nearly all patients (93.1%) had symptoms during SLIT buildup, but most were mild grade 1 (52.1%) or 2 (40.4%) reactions. Only one patient had a grade 3 reaction. None of the patients experienced a severe grade 4 reaction.

The most common grade 1 reaction was oral itch, an expected symptom of SLIT, which occurred in 82.7% of the patients.

Four patients (2.10%) received epinephrine during buildup and went to the emergency department. All these patients returned to continue SLIT without further need for epinephrine.

To test the effectiveness of SLIT, the researchers performed 50 low-dose OFCs in 20 patients. Of these food challenges, 35 (70%) were successful, and patients were asked to start daily 300-mg OIT maintenance, thus bypassing OIT buildup.

An additional nine OFCs that were unsuccessful were counseled to self-escalate from 80 mg or higher to 300 mg at home with medical guidance as needed.

“Our preliminary data of 20 patients and 50 low-dose oral food challenges suggest that an initial phase of 1-2 years of 2-mg daily SLIT therapy may be a safe and effective way to bypass the OIT buildup phase without the need for dozens of in-person visits with an allergist,” said Dr. Chan.

“So now we have the best of both worlds. We harness the safety of SLIT for the first 1-2 years, with the effectiveness of OIT for the remainder of the treatment period,” he said.
 

Adds to Evidence

Commenting on the study for this news organization, Julia Upton, MD, associate professor of pediatrics at the University of Toronto, Toronto, Ontario, Canada, said, “This study adds to the evidence that consistent, low exposure to food drives meaningful desensitization far above the daily dose.” Upton did not participate in the research.

“Prior prospective studies in SLIT demonstrated that small single-digit-milligram doses and time greatly increased the threshold of reaction. This real-world report suggests that a way to utilize that threshold increase is by switching to a commonly used maintenance dose of OIT,” said Dr. Upton.

“Although few patients have been assessed for the 300-mg challenge, this study is notable for the age group of 4-18 years, and that many of the patients had reacted to low doses in the past. It also shows that many families are capable of diluting and mixing their own immunotherapy solutions with store-bought foods under the guidance of an experienced allergy clinic,” she added.

“Overall, evidence is building that by various routes, initial small amounts with minimal updoses, plus the tincture of time, may be preferred to multiple frequent updosing from multiple perspectives, including safety, feasibility, cost, and medical resources. It will also be important to understand the preferences and goals of the patient and family as various regimens become more available,” Dr. Upton concluded.

The study was funded by BC Children’s Hospital Foundation. Dr. Chan reported receiving research support from DVB Technologies; has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi, Genzyme, Bausch Health, Avir Pharma, AstraZeneca, ALK, and Alladapt; and was a colead of the CSACI OIT guidelines. Dr. Upton reported research support/grants from Novartis, Regeneron, Sanofi, ALK Abello, DBV Technologies, CIHR, and SickKids Food Allergy and Anaphylaxis Program and fees from Pfizer, ALK Abello, Bausch Health, Astra Zeneca, and Pharming. She serves as an associate editor for Allergy, Asthma & Clinical Immunology and is on the Board of Directors of Canadian Society of Allergy and Clinical Immunology and the Healthcare Advisory Board of Food Allergy Canada.

A version of this article appeared on Medscape.com .

Sublingual immunotherapy (SLIT) is as safe and effective for high-risk older children and adolescents as oral immunotherapy (OIT) is for infants and preschoolers, according to new research.

Preliminary data from a study of more than 180 pediatric patients with multiple food allergies showed that while most patients had mild symptoms, none experienced a severe grade 4 reaction during the buildup and maintenance phase of SLIT.

In addition, 70% of those tested at the end of the treatment protocol were able to tolerate 300 mg of their allergen, a success rate nearly as high as that for OIT.

The study was published in The Journal of Allergy and Clinical Immunology: In Practice.

SLIT has been used successfully in the treatment of environmental allergens such as grass and tree pollen and dust mites. In this study, researchers decided to test SLIT’s effectiveness and safety in the treatment of food allergies in older children.

“We knew that OIT is very effective and safe in infants and toddlers, but there was literature illustrating that for older, school-age kids and adolescents, OIT is not safe enough, as those older age groups tend to have higher risk of severe reaction during treatment,” senior author Edmond Chan, MD, clinical professor of allergy at the University of British Columbia and pediatric allergist at BC Children’s Hospital, both in Vancouver, British Columbia, Canada, told this news organization. “With that knowledge, we decided to explore SLIT as another first-phase therapy for the older kids.”

The investigators recruited 188 high-risk older children aged 4-18 years for multifood SLIT. Most (61.7%) participants had multiple food allergies. Approximately 68% were male, and the population’s median age was 11.3 years.

Nearly half (48.4%) of participants had atopic dermatitis, 45.2% had asthma, 58.0% had allergic rhinitis, and 2.66% had preexisting eosinophilic esophagitis.

Most (75.0%) of the children were classified as higher risk, and 23 had a history of a grade 3 or 4 reaction before beginning SLIT.

Of the 188 children who were initially enrolled in the study, 173 (92.0%) finished their SLIT buildup phase.

Because the study started when COVID-19 pandemic restrictions were in place, the SLIT protocol mandated that patients be seen virtually. The patients’ caregivers learned how to mix and administer the required doses at home using recipes specially developed by the research team that used products bought at the grocery store.

A wide variety of food allergens were treated, including peanut, other legumes, tree nuts, sesame, other seeds, egg, cow’s milk, fish, wheat, shrimp, and other allergens.

The children built up to 2-mg protein SLIT maintenance over the course of three to five visits under nurse supervision.

After 1-2 years of daily SLIT maintenance, patients were offered a low-dose oral food challenge (OFC; cumulative dose: 300 mg of protein) with the goal of bypassing OIT buildup.

Nearly all patients (93.1%) had symptoms during SLIT buildup, but most were mild grade 1 (52.1%) or 2 (40.4%) reactions. Only one patient had a grade 3 reaction. None of the patients experienced a severe grade 4 reaction.

The most common grade 1 reaction was oral itch, an expected symptom of SLIT, which occurred in 82.7% of the patients.

Four patients (2.10%) received epinephrine during buildup and went to the emergency department. All these patients returned to continue SLIT without further need for epinephrine.

To test the effectiveness of SLIT, the researchers performed 50 low-dose OFCs in 20 patients. Of these food challenges, 35 (70%) were successful, and patients were asked to start daily 300-mg OIT maintenance, thus bypassing OIT buildup.

An additional nine OFCs that were unsuccessful were counseled to self-escalate from 80 mg or higher to 300 mg at home with medical guidance as needed.

“Our preliminary data of 20 patients and 50 low-dose oral food challenges suggest that an initial phase of 1-2 years of 2-mg daily SLIT therapy may be a safe and effective way to bypass the OIT buildup phase without the need for dozens of in-person visits with an allergist,” said Dr. Chan.

“So now we have the best of both worlds. We harness the safety of SLIT for the first 1-2 years, with the effectiveness of OIT for the remainder of the treatment period,” he said.
 

Adds to Evidence

Commenting on the study for this news organization, Julia Upton, MD, associate professor of pediatrics at the University of Toronto, Toronto, Ontario, Canada, said, “This study adds to the evidence that consistent, low exposure to food drives meaningful desensitization far above the daily dose.” Upton did not participate in the research.

“Prior prospective studies in SLIT demonstrated that small single-digit-milligram doses and time greatly increased the threshold of reaction. This real-world report suggests that a way to utilize that threshold increase is by switching to a commonly used maintenance dose of OIT,” said Dr. Upton.

“Although few patients have been assessed for the 300-mg challenge, this study is notable for the age group of 4-18 years, and that many of the patients had reacted to low doses in the past. It also shows that many families are capable of diluting and mixing their own immunotherapy solutions with store-bought foods under the guidance of an experienced allergy clinic,” she added.

“Overall, evidence is building that by various routes, initial small amounts with minimal updoses, plus the tincture of time, may be preferred to multiple frequent updosing from multiple perspectives, including safety, feasibility, cost, and medical resources. It will also be important to understand the preferences and goals of the patient and family as various regimens become more available,” Dr. Upton concluded.

The study was funded by BC Children’s Hospital Foundation. Dr. Chan reported receiving research support from DVB Technologies; has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi, Genzyme, Bausch Health, Avir Pharma, AstraZeneca, ALK, and Alladapt; and was a colead of the CSACI OIT guidelines. Dr. Upton reported research support/grants from Novartis, Regeneron, Sanofi, ALK Abello, DBV Technologies, CIHR, and SickKids Food Allergy and Anaphylaxis Program and fees from Pfizer, ALK Abello, Bausch Health, Astra Zeneca, and Pharming. She serves as an associate editor for Allergy, Asthma & Clinical Immunology and is on the Board of Directors of Canadian Society of Allergy and Clinical Immunology and the Healthcare Advisory Board of Food Allergy Canada.

A version of this article appeared on Medscape.com .

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

TOPLINE:

Changes in plasma growth hormone mediators such as growth hormone receptor (GHR) and insulin-like growth factor-binding protein 1 (IGFBP-1) were associated with glycemic failure in youth-onset type 2 diabetes (T2D), an analysis of the TODAY trial showed.

METHODOLOGY:

• In youth, T2D often occurs during or after puberty, hinting at hormonal influences in the development and/or progression of the disease.
• This secondary analysis assessed the role of growth hormone mediators including insulin-like growth factor-1 (IGF-1), GHR, and IGFBP-1 in glycemic failure in a subset of 398 youths, aged 10-17 years, with a T2D duration of less than 2 years (62% girls; 21% White).
• The participants were followed up for a mean of 3.9 years.
• The primary outcomes included glycemic failure, defined as an A1c level of 8% or more for 6 months, or acute metabolic decompensation requiring insulin.
• Other assessments included baseline and 36-month measures of glycemia, insulin sensitivity, high molecular weight adiponectin, and beta cell function.

TAKEAWAY:

• Of 398 participants, 182 (46%) experienced glycemic failure, while 216 (54%) retained glycemic control.
• At 36 months, youths with glycemic failure had lower IGF-1 levels (P < .001) and higher log₂ GHR (P = .03) and log₂ IGFBP-1 (P = .009) levels than those who maintained glycemic control.
• A greater increase in IGF-1 level at 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995; P < .001).
• Increased levels of log₂ GHR and log₂ IGFBP-1 were associated with higher odds of glycemic failure (OR, 1.75; P = .04 and OR, 1.37; P = .007, respectively). Results were adjusted for body mass index (BMI), suggesting that associations between GHR level and glycemic outcomes exist independent of BMI.
• Interhormonal correlations suggested an association between glucose metabolism and growth hormone signaling or a shared process leading to changes in both processes.

IN PRACTICE:

“Our study has identified GHR level as a novel biomarker of decrease in glycemic control in youths with T2D,” the study authors wrote. Future research is needed, with an emphasis on assessing alterations in growth hormone mediators which may contribute to diabetes complications in youth.

SOURCE:

The study, published online in JAMA Network Open, was led by Chang Lu, MD, Division of Endocrinology, Boston Children’s Hospital, and Joslin Diabetes Center at Harvard Medical School, Boston, Massachusetts.

LIMITATIONS:

The study did not include a control group (individuals without diabetes). The cohort largely included youth in late puberty or after puberty, affecting subgroup analysis. Moreover, only circulating growth hormone mediators were measured, limiting the identity of the source tissue of the hormone and the target organs.

DISCLOSURES:

Some authors reported receiving grants from the National Institutes of Health and National Institute of Diabetes and Digestive and Kidney Diseases while conducting the study. Also, certain authors reported receiving grants and personal fees from various trusts as well as pharmaceutical, healthcare, and medical technology companies outside the submitted work.

TOPLINE:

Changes in plasma growth hormone mediators such as growth hormone receptor (GHR) and insulin-like growth factor-binding protein 1 (IGFBP-1) were associated with glycemic failure in youth-onset type 2 diabetes (T2D), an analysis of the TODAY trial showed.

METHODOLOGY:

• In youth, T2D often occurs during or after puberty, hinting at hormonal influences in the development and/or progression of the disease.
• This secondary analysis assessed the role of growth hormone mediators including insulin-like growth factor-1 (IGF-1), GHR, and IGFBP-1 in glycemic failure in a subset of 398 youths, aged 10-17 years, with a T2D duration of less than 2 years (62% girls; 21% White).
• The participants were followed up for a mean of 3.9 years.
• The primary outcomes included glycemic failure, defined as an A1c level of 8% or more for 6 months, or acute metabolic decompensation requiring insulin.
• Other assessments included baseline and 36-month measures of glycemia, insulin sensitivity, high molecular weight adiponectin, and beta cell function.

TAKEAWAY:

• Of 398 participants, 182 (46%) experienced glycemic failure, while 216 (54%) retained glycemic control.
• At 36 months, youths with glycemic failure had lower IGF-1 levels (P < .001) and higher log₂ GHR (P = .03) and log₂ IGFBP-1 (P = .009) levels than those who maintained glycemic control.
• A greater increase in IGF-1 level at 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995; P < .001).
• Increased levels of log₂ GHR and log₂ IGFBP-1 were associated with higher odds of glycemic failure (OR, 1.75; P = .04 and OR, 1.37; P = .007, respectively). Results were adjusted for body mass index (BMI), suggesting that associations between GHR level and glycemic outcomes exist independent of BMI.
• Interhormonal correlations suggested an association between glucose metabolism and growth hormone signaling or a shared process leading to changes in both processes.

IN PRACTICE:

“Our study has identified GHR level as a novel biomarker of decrease in glycemic control in youths with T2D,” the study authors wrote. Future research is needed, with an emphasis on assessing alterations in growth hormone mediators which may contribute to diabetes complications in youth.

SOURCE:

The study, published online in JAMA Network Open, was led by Chang Lu, MD, Division of Endocrinology, Boston Children’s Hospital, and Joslin Diabetes Center at Harvard Medical School, Boston, Massachusetts.

LIMITATIONS:

The study did not include a control group (individuals without diabetes). The cohort largely included youth in late puberty or after puberty, affecting subgroup analysis. Moreover, only circulating growth hormone mediators were measured, limiting the identity of the source tissue of the hormone and the target organs.

DISCLOSURES:

Some authors reported receiving grants from the National Institutes of Health and National Institute of Diabetes and Digestive and Kidney Diseases while conducting the study. Also, certain authors reported receiving grants and personal fees from various trusts as well as pharmaceutical, healthcare, and medical technology companies outside the submitted work.

TOPLINE:

Changes in plasma growth hormone mediators such as growth hormone receptor (GHR) and insulin-like growth factor-binding protein 1 (IGFBP-1) were associated with glycemic failure in youth-onset type 2 diabetes (T2D), an analysis of the TODAY trial showed.

METHODOLOGY:

• In youth, T2D often occurs during or after puberty, hinting at hormonal influences in the development and/or progression of the disease.
• This secondary analysis assessed the role of growth hormone mediators including insulin-like growth factor-1 (IGF-1), GHR, and IGFBP-1 in glycemic failure in a subset of 398 youths, aged 10-17 years, with a T2D duration of less than 2 years (62% girls; 21% White).
• The participants were followed up for a mean of 3.9 years.
• The primary outcomes included glycemic failure, defined as an A1c level of 8% or more for 6 months, or acute metabolic decompensation requiring insulin.
• Other assessments included baseline and 36-month measures of glycemia, insulin sensitivity, high molecular weight adiponectin, and beta cell function.

TAKEAWAY:

• Of 398 participants, 182 (46%) experienced glycemic failure, while 216 (54%) retained glycemic control.
• At 36 months, youths with glycemic failure had lower IGF-1 levels (P < .001) and higher log₂ GHR (P = .03) and log₂ IGFBP-1 (P = .009) levels than those who maintained glycemic control.
• A greater increase in IGF-1 level at 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995; P < .001).
• Increased levels of log₂ GHR and log₂ IGFBP-1 were associated with higher odds of glycemic failure (OR, 1.75; P = .04 and OR, 1.37; P = .007, respectively). Results were adjusted for body mass index (BMI), suggesting that associations between GHR level and glycemic outcomes exist independent of BMI.
• Interhormonal correlations suggested an association between glucose metabolism and growth hormone signaling or a shared process leading to changes in both processes.

IN PRACTICE:

“Our study has identified GHR level as a novel biomarker of decrease in glycemic control in youths with T2D,” the study authors wrote. Future research is needed, with an emphasis on assessing alterations in growth hormone mediators which may contribute to diabetes complications in youth.

SOURCE:

The study, published online in JAMA Network Open, was led by Chang Lu, MD, Division of Endocrinology, Boston Children’s Hospital, and Joslin Diabetes Center at Harvard Medical School, Boston, Massachusetts.

LIMITATIONS:

The study did not include a control group (individuals without diabetes). The cohort largely included youth in late puberty or after puberty, affecting subgroup analysis. Moreover, only circulating growth hormone mediators were measured, limiting the identity of the source tissue of the hormone and the target organs.

DISCLOSURES:

Some authors reported receiving grants from the National Institutes of Health and National Institute of Diabetes and Digestive and Kidney Diseases while conducting the study. Also, certain authors reported receiving grants and personal fees from various trusts as well as pharmaceutical, healthcare, and medical technology companies outside the submitted work.

Nearly 18 months after the US Food and Drug Administration (FDA) first acknowledged a national shortage of Adderall, the most common drug used to treat attention-deficit/hyperactivity disorder (ADHD), there is now a widespread scarcity of other stimulant medications — with no end in sight. How did this crisis develop and what measures are underway to address it?

The first shortage of immediate release formulations of amphetamine mixed salts (Adderall, Adderall IR) was reported by the FDA in October 2022. Now, the list includes Focalin, Ritalin, and Vyvanse, among others.

Adding to the ongoing crisis, the FDA announced in early February that Azurity Pharmaceuticals was voluntarily withdrawing one lot of its Zenzedi (dextroamphetamine sulfate) 30 mg tablets because of contamination with the antihistamine, carbinoxamine.

For the roughly 10 million adults and 6 million children in the United States grappling with ADHD, getting a prescription filled with the exact medication ordered by a physician is dictated by geographic location, insurance formularies, and pharmacy supply chains. It’s particularly challenging for those who live in rural or underserved areas with limited access to nearby pharmacies.

“Not a day goes by when I don’t hear from a number of unfortunately struggling patients about this shortage,” said Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, Baltimore, Maryland.

The ADHD drug shortage is now well into its second year, and clinicians and advocates alike say there is no apparent end in sight.

How Did We Get Here?

Manufacturers and federal agencies blame the shortage on rising demand and each other, while clinicians say that insurers, drug distributors, and middlemen are also playing a role in keeping medications out of patients’ hands.

In August 2023, the Drug Enforcement Administration (DEA), which sets quotas for the production of controlled substances, and the FDA publicly blamed manufacturers for the shortages, claiming they were not using up their allocations.

At the time, the DEA said manufacturers made and sold only 70% of their quota, nearly 1 billion doses short of what they were allowed to produce and ship that year.

The agencies also noted a record-high number of prescriptions for stimulants from 2012 to 2021. Driven in part by telehealth, the demand intensified during the pandemic. One recent study reported a 14% increase in ADHD stimulant prescriptions between 2020 and 2022.

Insurers also play a role in the shortage, David Goodman, MD, an assistant professor of psychiatry and behavioral sciences also at Johns Hopkins University, told this news organization.

Stepped therapy — in which patients must try one, two, or three medications before they are authorized to receive a more expensive or newer drug — contributes to the problem, Dr. Goodman said. Demand for such medications is high and supply low. In addition, some insurers only provide coverage for in-network pharmacies, regardless of the ability of other providers outside such networks to fill prescriptions.

“If the insurance dictates where you get your pills, and that pharmacy doesn’t have the pills or that pharmacy chain in your area doesn’t have those pills, you’re out of luck,” Dr. Goodman said.

Patients as Detectives

To get prescriptions filled, patients must “turn into detectives,” Laurie Kulikosky, CEO of Children and Adults with Attention-Deficit/Hyperactivity Disorder, told this news organization. “It’s a huge stressor.”

Tracking which ADHD medications are available, on back order, or discontinued requires frequent checking of the FDA’s drug shortages website.

Some manufacturers of generic versions of mixed amphetamine salts are only fulfilling orders for existing contracts, while others say new product won’t be available until at least April or as late as September. All blame the delay on the shortage of active ingredients.

Teva, which makes both the brand and generic of Adderall, reported on the FDA’s site that its manufacturing and distribution is at record-high levels, but demand continues to rise.

The branded Concerta is available, but some makers of generic methylphenidate reported supplies won’t be available until July.

Lisdexamfetamine dimesylate in almost all dosages is either unavailable, available in restricted quantities, or on extended back order. However, the branded product Vyvanse is available.

Industry, Government Respond

In a November 2023 statement, the DEA reported that 17 of 18 drug manufacturers the agency contacted planned to use their full DEA quota and increase production for that year. The agency said it had made it easier for manufacturers to request changes in allocations and that periodically updating quotas was a possibility.

This news organization asked the DEA whether any manufacturers had not met their 2023 quotas, but an agency spokesperson said it would not comment.

An FDA spokesperson said it could help manufacturers ask for bigger quotas and to increase production, noting that in 2023, the DEA increased the quota for methylphenidate following an FDA request.

“The FDA is in frequent communication with the manufacturers of ADHD stimulant medications and the DEA, and we will continue to monitor supply,” the spokesperson said.

For 2024, the FDA told the DEA that it predicted a 3.1% increase in use of amphetamine, methylphenidate (including dexmethylphenidate), and lisdexamfetamine. The DEA took that into account when it issued its final quotas for 2024. Whether those amounts will be enough remains to be seen.

With many drugs — not just those for ADHD — in short supply, in February, the US Department of Health and Human Services (HHS) and the Federal Trade Commission opened an inquiry of sorts, seeking comments on how middlemen and others were influencing pricing and supply of generic drugs.

“When you’re prescribed an important medication by your doctor and you learn the drug is out of stock, your heart sinks,” HHS Secretary Xavier Becerra said in a statement. “This devastating reality is the case for too many Americans who need generic drugs for ADHD, cancer, and other conditions.”

On the comments site, which is open until April 15, many of the 4000-plus complaints filed to-date are from individuals with ADHD.

Dr. Pawar said clinicians can’t know what’s going on between the FDA, the DEA, and manufacturers, adding that, “they need to sit together and figure something out.”

Even Members of Congress have had trouble getting answers. In October, Rep. Abigail Spanberger (D-Virginia) and a dozen colleagues wrote to the FDA and DEA seeking information on how the agencies were responding to stimulant shortages. The DEA has still not replied.

Workarounds the Only Option?

In the past, physicians would prescribe the optimal medication for individual patients based on clinical factors. Now, one of the major factors in determining drug choice is the agent that has “the highest likelihood of benefit and the lowest likelihood of administrative demand or burden,” Dr. Goodman said.

With so many medications in short supply, clinicians have figured out workarounds to get prescriptions filled, but they don’t often pan out.

If a patient needs a 60-mg daily dose of a medication and the pharmacy doesn’t have any 60-mg pills, Dr. Goodman said he might write a prescription for a 30-mg pill to be taken twice a day. However, insurers often will cover only 30 pills for a month, which can thwart this strategy.

Dr. Pawar said he sometimes prescribes Journay PM in lieu of Concerta because it is often available. But insurers may deny coverage of Journay PM because it is a newer medication, he said. When prescribing ADHD medications, he also provides his patients with a list of potential substitutes so they can ask the pharmacist if any are in stock.

With no end to the shortage in sight, clinicians must often prescribe multiple medications until their patients are able to find one that’s available. In addition, patients are burdened with making calls and visits to multiple pharmacies until they find one that can fill their prescription.

Meanwhile, the ripple effects to the ADHD drug shortage continue to spread. Extended periods without treatment can lead to declining job performance or job loss, fractured relationships, and even financial distress, Dr. Goodman said.

“If you go without your pills for a month and you’re not performing, your work declines and you lose your job as a result, that’s not on you — that’s on the fact that you can’t get your treatment,” he noted. “The shortage is no longer an inconvenience.”

Dr. Goodman, Dr. Pawar, and Ms. Kulikosky reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Nearly 18 months after the US Food and Drug Administration (FDA) first acknowledged a national shortage of Adderall, the most common drug used to treat attention-deficit/hyperactivity disorder (ADHD), there is now a widespread scarcity of other stimulant medications — with no end in sight. How did this crisis develop and what measures are underway to address it?

The first shortage of immediate release formulations of amphetamine mixed salts (Adderall, Adderall IR) was reported by the FDA in October 2022. Now, the list includes Focalin, Ritalin, and Vyvanse, among others.

Adding to the ongoing crisis, the FDA announced in early February that Azurity Pharmaceuticals was voluntarily withdrawing one lot of its Zenzedi (dextroamphetamine sulfate) 30 mg tablets because of contamination with the antihistamine, carbinoxamine.

For the roughly 10 million adults and 6 million children in the United States grappling with ADHD, getting a prescription filled with the exact medication ordered by a physician is dictated by geographic location, insurance formularies, and pharmacy supply chains. It’s particularly challenging for those who live in rural or underserved areas with limited access to nearby pharmacies.

“Not a day goes by when I don’t hear from a number of unfortunately struggling patients about this shortage,” said Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, Baltimore, Maryland.

The ADHD drug shortage is now well into its second year, and clinicians and advocates alike say there is no apparent end in sight.

How Did We Get Here?

Manufacturers and federal agencies blame the shortage on rising demand and each other, while clinicians say that insurers, drug distributors, and middlemen are also playing a role in keeping medications out of patients’ hands.

In August 2023, the Drug Enforcement Administration (DEA), which sets quotas for the production of controlled substances, and the FDA publicly blamed manufacturers for the shortages, claiming they were not using up their allocations.

At the time, the DEA said manufacturers made and sold only 70% of their quota, nearly 1 billion doses short of what they were allowed to produce and ship that year.

The agencies also noted a record-high number of prescriptions for stimulants from 2012 to 2021. Driven in part by telehealth, the demand intensified during the pandemic. One recent study reported a 14% increase in ADHD stimulant prescriptions between 2020 and 2022.

Insurers also play a role in the shortage, David Goodman, MD, an assistant professor of psychiatry and behavioral sciences also at Johns Hopkins University, told this news organization.

Stepped therapy — in which patients must try one, two, or three medications before they are authorized to receive a more expensive or newer drug — contributes to the problem, Dr. Goodman said. Demand for such medications is high and supply low. In addition, some insurers only provide coverage for in-network pharmacies, regardless of the ability of other providers outside such networks to fill prescriptions.

“If the insurance dictates where you get your pills, and that pharmacy doesn’t have the pills or that pharmacy chain in your area doesn’t have those pills, you’re out of luck,” Dr. Goodman said.

Patients as Detectives

To get prescriptions filled, patients must “turn into detectives,” Laurie Kulikosky, CEO of Children and Adults with Attention-Deficit/Hyperactivity Disorder, told this news organization. “It’s a huge stressor.”

Tracking which ADHD medications are available, on back order, or discontinued requires frequent checking of the FDA’s drug shortages website.

Some manufacturers of generic versions of mixed amphetamine salts are only fulfilling orders for existing contracts, while others say new product won’t be available until at least April or as late as September. All blame the delay on the shortage of active ingredients.

Teva, which makes both the brand and generic of Adderall, reported on the FDA’s site that its manufacturing and distribution is at record-high levels, but demand continues to rise.

The branded Concerta is available, but some makers of generic methylphenidate reported supplies won’t be available until July.

Lisdexamfetamine dimesylate in almost all dosages is either unavailable, available in restricted quantities, or on extended back order. However, the branded product Vyvanse is available.

Industry, Government Respond

In a November 2023 statement, the DEA reported that 17 of 18 drug manufacturers the agency contacted planned to use their full DEA quota and increase production for that year. The agency said it had made it easier for manufacturers to request changes in allocations and that periodically updating quotas was a possibility.

This news organization asked the DEA whether any manufacturers had not met their 2023 quotas, but an agency spokesperson said it would not comment.

An FDA spokesperson said it could help manufacturers ask for bigger quotas and to increase production, noting that in 2023, the DEA increased the quota for methylphenidate following an FDA request.

“The FDA is in frequent communication with the manufacturers of ADHD stimulant medications and the DEA, and we will continue to monitor supply,” the spokesperson said.

For 2024, the FDA told the DEA that it predicted a 3.1% increase in use of amphetamine, methylphenidate (including dexmethylphenidate), and lisdexamfetamine. The DEA took that into account when it issued its final quotas for 2024. Whether those amounts will be enough remains to be seen.

With many drugs — not just those for ADHD — in short supply, in February, the US Department of Health and Human Services (HHS) and the Federal Trade Commission opened an inquiry of sorts, seeking comments on how middlemen and others were influencing pricing and supply of generic drugs.

“When you’re prescribed an important medication by your doctor and you learn the drug is out of stock, your heart sinks,” HHS Secretary Xavier Becerra said in a statement. “This devastating reality is the case for too many Americans who need generic drugs for ADHD, cancer, and other conditions.”

On the comments site, which is open until April 15, many of the 4000-plus complaints filed to-date are from individuals with ADHD.

Dr. Pawar said clinicians can’t know what’s going on between the FDA, the DEA, and manufacturers, adding that, “they need to sit together and figure something out.”

Even Members of Congress have had trouble getting answers. In October, Rep. Abigail Spanberger (D-Virginia) and a dozen colleagues wrote to the FDA and DEA seeking information on how the agencies were responding to stimulant shortages. The DEA has still not replied.

Workarounds the Only Option?

In the past, physicians would prescribe the optimal medication for individual patients based on clinical factors. Now, one of the major factors in determining drug choice is the agent that has “the highest likelihood of benefit and the lowest likelihood of administrative demand or burden,” Dr. Goodman said.

With so many medications in short supply, clinicians have figured out workarounds to get prescriptions filled, but they don’t often pan out.

If a patient needs a 60-mg daily dose of a medication and the pharmacy doesn’t have any 60-mg pills, Dr. Goodman said he might write a prescription for a 30-mg pill to be taken twice a day. However, insurers often will cover only 30 pills for a month, which can thwart this strategy.

Dr. Pawar said he sometimes prescribes Journay PM in lieu of Concerta because it is often available. But insurers may deny coverage of Journay PM because it is a newer medication, he said. When prescribing ADHD medications, he also provides his patients with a list of potential substitutes so they can ask the pharmacist if any are in stock.

With no end to the shortage in sight, clinicians must often prescribe multiple medications until their patients are able to find one that’s available. In addition, patients are burdened with making calls and visits to multiple pharmacies until they find one that can fill their prescription.

Meanwhile, the ripple effects to the ADHD drug shortage continue to spread. Extended periods without treatment can lead to declining job performance or job loss, fractured relationships, and even financial distress, Dr. Goodman said.

“If you go without your pills for a month and you’re not performing, your work declines and you lose your job as a result, that’s not on you — that’s on the fact that you can’t get your treatment,” he noted. “The shortage is no longer an inconvenience.”

Dr. Goodman, Dr. Pawar, and Ms. Kulikosky reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Nearly 18 months after the US Food and Drug Administration (FDA) first acknowledged a national shortage of Adderall, the most common drug used to treat attention-deficit/hyperactivity disorder (ADHD), there is now a widespread scarcity of other stimulant medications — with no end in sight. How did this crisis develop and what measures are underway to address it?

The first shortage of immediate release formulations of amphetamine mixed salts (Adderall, Adderall IR) was reported by the FDA in October 2022. Now, the list includes Focalin, Ritalin, and Vyvanse, among others.

Adding to the ongoing crisis, the FDA announced in early February that Azurity Pharmaceuticals was voluntarily withdrawing one lot of its Zenzedi (dextroamphetamine sulfate) 30 mg tablets because of contamination with the antihistamine, carbinoxamine.

For the roughly 10 million adults and 6 million children in the United States grappling with ADHD, getting a prescription filled with the exact medication ordered by a physician is dictated by geographic location, insurance formularies, and pharmacy supply chains. It’s particularly challenging for those who live in rural or underserved areas with limited access to nearby pharmacies.

“Not a day goes by when I don’t hear from a number of unfortunately struggling patients about this shortage,” said Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, Baltimore, Maryland.

The ADHD drug shortage is now well into its second year, and clinicians and advocates alike say there is no apparent end in sight.

How Did We Get Here?

Manufacturers and federal agencies blame the shortage on rising demand and each other, while clinicians say that insurers, drug distributors, and middlemen are also playing a role in keeping medications out of patients’ hands.

In August 2023, the Drug Enforcement Administration (DEA), which sets quotas for the production of controlled substances, and the FDA publicly blamed manufacturers for the shortages, claiming they were not using up their allocations.

At the time, the DEA said manufacturers made and sold only 70% of their quota, nearly 1 billion doses short of what they were allowed to produce and ship that year.

The agencies also noted a record-high number of prescriptions for stimulants from 2012 to 2021. Driven in part by telehealth, the demand intensified during the pandemic. One recent study reported a 14% increase in ADHD stimulant prescriptions between 2020 and 2022.

Insurers also play a role in the shortage, David Goodman, MD, an assistant professor of psychiatry and behavioral sciences also at Johns Hopkins University, told this news organization.

Stepped therapy — in which patients must try one, two, or three medications before they are authorized to receive a more expensive or newer drug — contributes to the problem, Dr. Goodman said. Demand for such medications is high and supply low. In addition, some insurers only provide coverage for in-network pharmacies, regardless of the ability of other providers outside such networks to fill prescriptions.

“If the insurance dictates where you get your pills, and that pharmacy doesn’t have the pills or that pharmacy chain in your area doesn’t have those pills, you’re out of luck,” Dr. Goodman said.

Patients as Detectives

To get prescriptions filled, patients must “turn into detectives,” Laurie Kulikosky, CEO of Children and Adults with Attention-Deficit/Hyperactivity Disorder, told this news organization. “It’s a huge stressor.”

Tracking which ADHD medications are available, on back order, or discontinued requires frequent checking of the FDA’s drug shortages website.

Some manufacturers of generic versions of mixed amphetamine salts are only fulfilling orders for existing contracts, while others say new product won’t be available until at least April or as late as September. All blame the delay on the shortage of active ingredients.

Teva, which makes both the brand and generic of Adderall, reported on the FDA’s site that its manufacturing and distribution is at record-high levels, but demand continues to rise.

The branded Concerta is available, but some makers of generic methylphenidate reported supplies won’t be available until July.

Lisdexamfetamine dimesylate in almost all dosages is either unavailable, available in restricted quantities, or on extended back order. However, the branded product Vyvanse is available.

Industry, Government Respond

In a November 2023 statement, the DEA reported that 17 of 18 drug manufacturers the agency contacted planned to use their full DEA quota and increase production for that year. The agency said it had made it easier for manufacturers to request changes in allocations and that periodically updating quotas was a possibility.

This news organization asked the DEA whether any manufacturers had not met their 2023 quotas, but an agency spokesperson said it would not comment.

An FDA spokesperson said it could help manufacturers ask for bigger quotas and to increase production, noting that in 2023, the DEA increased the quota for methylphenidate following an FDA request.

“The FDA is in frequent communication with the manufacturers of ADHD stimulant medications and the DEA, and we will continue to monitor supply,” the spokesperson said.

For 2024, the FDA told the DEA that it predicted a 3.1% increase in use of amphetamine, methylphenidate (including dexmethylphenidate), and lisdexamfetamine. The DEA took that into account when it issued its final quotas for 2024. Whether those amounts will be enough remains to be seen.

With many drugs — not just those for ADHD — in short supply, in February, the US Department of Health and Human Services (HHS) and the Federal Trade Commission opened an inquiry of sorts, seeking comments on how middlemen and others were influencing pricing and supply of generic drugs.

“When you’re prescribed an important medication by your doctor and you learn the drug is out of stock, your heart sinks,” HHS Secretary Xavier Becerra said in a statement. “This devastating reality is the case for too many Americans who need generic drugs for ADHD, cancer, and other conditions.”

On the comments site, which is open until April 15, many of the 4000-plus complaints filed to-date are from individuals with ADHD.

Dr. Pawar said clinicians can’t know what’s going on between the FDA, the DEA, and manufacturers, adding that, “they need to sit together and figure something out.”

Even Members of Congress have had trouble getting answers. In October, Rep. Abigail Spanberger (D-Virginia) and a dozen colleagues wrote to the FDA and DEA seeking information on how the agencies were responding to stimulant shortages. The DEA has still not replied.

Workarounds the Only Option?

In the past, physicians would prescribe the optimal medication for individual patients based on clinical factors. Now, one of the major factors in determining drug choice is the agent that has “the highest likelihood of benefit and the lowest likelihood of administrative demand or burden,” Dr. Goodman said.

With so many medications in short supply, clinicians have figured out workarounds to get prescriptions filled, but they don’t often pan out.

If a patient needs a 60-mg daily dose of a medication and the pharmacy doesn’t have any 60-mg pills, Dr. Goodman said he might write a prescription for a 30-mg pill to be taken twice a day. However, insurers often will cover only 30 pills for a month, which can thwart this strategy.

Dr. Pawar said he sometimes prescribes Journay PM in lieu of Concerta because it is often available. But insurers may deny coverage of Journay PM because it is a newer medication, he said. When prescribing ADHD medications, he also provides his patients with a list of potential substitutes so they can ask the pharmacist if any are in stock.

With no end to the shortage in sight, clinicians must often prescribe multiple medications until their patients are able to find one that’s available. In addition, patients are burdened with making calls and visits to multiple pharmacies until they find one that can fill their prescription.

Meanwhile, the ripple effects to the ADHD drug shortage continue to spread. Extended periods without treatment can lead to declining job performance or job loss, fractured relationships, and even financial distress, Dr. Goodman said.

“If you go without your pills for a month and you’re not performing, your work declines and you lose your job as a result, that’s not on you — that’s on the fact that you can’t get your treatment,” he noted. “The shortage is no longer an inconvenience.”

Dr. Goodman, Dr. Pawar, and Ms. Kulikosky reported no relevant financial relationships.

A version of this article appeared on Medscape.com.