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FDA to step up oversight of cosmetics, assess ‘forever chemicals’
They are also preparing to assess potential risks of so-called forever chemicals in these products.
The Food and Drug Administration last year gained new authority over cosmetics when Congress passed the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) by adding this bill to a December budget package.
“On average, consumers in the U.S. use six to 12 cosmetics products daily. But, until recently the FDA didn’t have the authority to require manufacturers to submit cosmetic product listings, including a list of ingredients used in these products, or register the facilities where they were produced,” Namandjé Bumpus, PhD, FDA’s chief scientist, said in a press release.
In the statement, the FDA announced the release of a draft guidance document that is intended to help companies comply with the transparency requirements slated to kick in this December. The agency is accepting comments on this draft guidance through Sept. 7.
“Later this year, registration and listing of cosmetic product facilities and products will become a requirement, making information about cosmetic products, including the ingredients used in products and the facilities where they are produced, readily available to the agency,” Dr. Bumpus said.
The products, according to the FDA statement, include makeup, nail polishes, shaving creams, other grooming products, perfumes, face and body cleansers, hair products, moisturizers, and other skin care items.
MoCRA “represents a sea change in how FDA regulates the cosmetics industry,” attorneys Frederick R. Ball, Alyson Walker Lotman, and Kelly A. Bonner, wrote in an article for the Food and Drug Law Institute published in spring 2023.
The FDA has called the MoCRA law “the most significant expansion” of its authority to regulate cosmetics since the Federal Food, Drug, and Cosmetic Act was passed in 1938.
The agency is in the process of expanding its staff to carry out newly authorized duties, including the tracking of adverse events. The FDA budget request for fiscal 2024, which begins Oct. 1, seeks $5 million for work needed to implement MoCRA.
PFAS, or ‘forever chemicals’
Some of the requested FDA funding is intended to prepare the agency to assess the use of per-and polyfluoroalkyl substances (PFAS) in cosmetics.
MoCRA sets a 3-year deadline for the FDA to issue an assessment of the use and potential risks of PFAS in cosmetics products. PFAS are sometimes added as ingredients in some cosmetic products, including lotions, cleansers, nail polish, shaving cream, foundation, lipstick, eyeliner, eyeshadow, and mascara, according to the FDA. Sometimes the presence of PFAS in cosmetics is unintentional and is the result of impurities in raw materials or is due to the breakdown of ingredients, the FDA said.
The FDA’s website says that so far, the available research doesn’t allow for “definitive conclusions about the potential health risks of PFAS in cosmetics.”
The Centers for Disease Control and Prevention has stated that research has suggested potential links between high levels of certain PFAS, in general, with increased cholesterol levels, changes in liver enzyme levels, increased risk of hypertension or preeclampsia in pregnant women, and increased risk of kidney or testicular cancer.
PFAS compounds often are used to resist grease, oil, water, and heat in industrial settings. They are used in thousands of products, from nonstick cookware to firefighting foams and protective gear, because they can reduce friction, according to a National Academies of Sciences, Engineering, and Medicine report on PFAS that was issued last year.
PFAS are known as “forever chemicals” because they contain a carbon-fluorine bond, which does not break naturally. Even when PFAS are transformed in the body, they can assume other forms of PFAS that preserve the troublesome carbon-fluorine bond. With PFAS, the human body is confronted with a substance it doesn’t have the tools to process.
This is in contrast to proteins and carbohydrates, which are in a sense prepackaged for relatively easy disassembly in the human body. Many of these compounds have weak links that enzymes and stomach acid can take apart, such as sulfur-to-sulfur (disulfide) bonds. That’s why protein-based biotech drugs are injected instead of administered as pills. The ultimate goal of this digestion is for the body to gain energy from these compounds.
But with PFAS, the body faces the challenge of carbon-fluorine bonds that are very hard to break down, and there is no payoff for these efforts, Graham F. Peaslee, PhD, professor of physics at the University of Notre Dame (Indiana), told this news organization.
“Nothing will naturally eat it because when you break the bond, it’s like eating celery,” he said. “You use more calories to eat the celery than you gain back from it.”
Interest from a U.S. senator
Dr. Peaslee was one of the authors of a 2021 article about PFAS in cosmetics that appeared in the journal Environmental Science and Technology Letters.
In the article, Dr. Peaslee and colleagues reported on their screening of 231 cosmetic products purchased in the United States and Canada using particle-induced gamma-ray emission spectroscopy. They found cases of undisclosed PFAS in cosmetic products. Foundations, mascaras, and lip products were noted as being especially problematic.
Sen. Susan Collins (R-ME) cited Dr. Peaslee’s article in a 2021 floor speech as she argued for having the FDA ban the intentional addition of PFAS to cosmetics.
“The findings of this study are particularly alarming, as many of these products are subject to direct human exposure,” Sen. Collins said. “For example, lipstick is often inadvertently ingested, and mascara is sometimes absorbed through tear ducts.”
In addition, workers at cosmetics plants may be exposed to PFAS and discarded cosmetics that have these compounds, which could potentially contaminate drinking water, Sen. Collins said. In 2021, she introduced legislation seeking a ban on PFAS that are intentionally added to cosmetics. That legislation did not advance through the Senate.
But the Senate Appropriations Committee, on which Sen. Collins is the ranking Republican, wants the FDA to keep a ban on PFAS in mind.
The Senate Agriculture Appropriations subcommittee, which oversees the FDA’s budget, raised the issue of PFAS and cosmetics in a June report. The FDA should develop a plan outlining research needed to inform “regulatory decision making, including potential development of a proposed rule to ban intentionally added PFAS substances in cosmetics,” the subcommittee said.
A version of this article first appeared on Medscape.com.
They are also preparing to assess potential risks of so-called forever chemicals in these products.
The Food and Drug Administration last year gained new authority over cosmetics when Congress passed the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) by adding this bill to a December budget package.
“On average, consumers in the U.S. use six to 12 cosmetics products daily. But, until recently the FDA didn’t have the authority to require manufacturers to submit cosmetic product listings, including a list of ingredients used in these products, or register the facilities where they were produced,” Namandjé Bumpus, PhD, FDA’s chief scientist, said in a press release.
In the statement, the FDA announced the release of a draft guidance document that is intended to help companies comply with the transparency requirements slated to kick in this December. The agency is accepting comments on this draft guidance through Sept. 7.
“Later this year, registration and listing of cosmetic product facilities and products will become a requirement, making information about cosmetic products, including the ingredients used in products and the facilities where they are produced, readily available to the agency,” Dr. Bumpus said.
The products, according to the FDA statement, include makeup, nail polishes, shaving creams, other grooming products, perfumes, face and body cleansers, hair products, moisturizers, and other skin care items.
MoCRA “represents a sea change in how FDA regulates the cosmetics industry,” attorneys Frederick R. Ball, Alyson Walker Lotman, and Kelly A. Bonner, wrote in an article for the Food and Drug Law Institute published in spring 2023.
The FDA has called the MoCRA law “the most significant expansion” of its authority to regulate cosmetics since the Federal Food, Drug, and Cosmetic Act was passed in 1938.
The agency is in the process of expanding its staff to carry out newly authorized duties, including the tracking of adverse events. The FDA budget request for fiscal 2024, which begins Oct. 1, seeks $5 million for work needed to implement MoCRA.
PFAS, or ‘forever chemicals’
Some of the requested FDA funding is intended to prepare the agency to assess the use of per-and polyfluoroalkyl substances (PFAS) in cosmetics.
MoCRA sets a 3-year deadline for the FDA to issue an assessment of the use and potential risks of PFAS in cosmetics products. PFAS are sometimes added as ingredients in some cosmetic products, including lotions, cleansers, nail polish, shaving cream, foundation, lipstick, eyeliner, eyeshadow, and mascara, according to the FDA. Sometimes the presence of PFAS in cosmetics is unintentional and is the result of impurities in raw materials or is due to the breakdown of ingredients, the FDA said.
The FDA’s website says that so far, the available research doesn’t allow for “definitive conclusions about the potential health risks of PFAS in cosmetics.”
The Centers for Disease Control and Prevention has stated that research has suggested potential links between high levels of certain PFAS, in general, with increased cholesterol levels, changes in liver enzyme levels, increased risk of hypertension or preeclampsia in pregnant women, and increased risk of kidney or testicular cancer.
PFAS compounds often are used to resist grease, oil, water, and heat in industrial settings. They are used in thousands of products, from nonstick cookware to firefighting foams and protective gear, because they can reduce friction, according to a National Academies of Sciences, Engineering, and Medicine report on PFAS that was issued last year.
PFAS are known as “forever chemicals” because they contain a carbon-fluorine bond, which does not break naturally. Even when PFAS are transformed in the body, they can assume other forms of PFAS that preserve the troublesome carbon-fluorine bond. With PFAS, the human body is confronted with a substance it doesn’t have the tools to process.
This is in contrast to proteins and carbohydrates, which are in a sense prepackaged for relatively easy disassembly in the human body. Many of these compounds have weak links that enzymes and stomach acid can take apart, such as sulfur-to-sulfur (disulfide) bonds. That’s why protein-based biotech drugs are injected instead of administered as pills. The ultimate goal of this digestion is for the body to gain energy from these compounds.
But with PFAS, the body faces the challenge of carbon-fluorine bonds that are very hard to break down, and there is no payoff for these efforts, Graham F. Peaslee, PhD, professor of physics at the University of Notre Dame (Indiana), told this news organization.
“Nothing will naturally eat it because when you break the bond, it’s like eating celery,” he said. “You use more calories to eat the celery than you gain back from it.”
Interest from a U.S. senator
Dr. Peaslee was one of the authors of a 2021 article about PFAS in cosmetics that appeared in the journal Environmental Science and Technology Letters.
In the article, Dr. Peaslee and colleagues reported on their screening of 231 cosmetic products purchased in the United States and Canada using particle-induced gamma-ray emission spectroscopy. They found cases of undisclosed PFAS in cosmetic products. Foundations, mascaras, and lip products were noted as being especially problematic.
Sen. Susan Collins (R-ME) cited Dr. Peaslee’s article in a 2021 floor speech as she argued for having the FDA ban the intentional addition of PFAS to cosmetics.
“The findings of this study are particularly alarming, as many of these products are subject to direct human exposure,” Sen. Collins said. “For example, lipstick is often inadvertently ingested, and mascara is sometimes absorbed through tear ducts.”
In addition, workers at cosmetics plants may be exposed to PFAS and discarded cosmetics that have these compounds, which could potentially contaminate drinking water, Sen. Collins said. In 2021, she introduced legislation seeking a ban on PFAS that are intentionally added to cosmetics. That legislation did not advance through the Senate.
But the Senate Appropriations Committee, on which Sen. Collins is the ranking Republican, wants the FDA to keep a ban on PFAS in mind.
The Senate Agriculture Appropriations subcommittee, which oversees the FDA’s budget, raised the issue of PFAS and cosmetics in a June report. The FDA should develop a plan outlining research needed to inform “regulatory decision making, including potential development of a proposed rule to ban intentionally added PFAS substances in cosmetics,” the subcommittee said.
A version of this article first appeared on Medscape.com.
They are also preparing to assess potential risks of so-called forever chemicals in these products.
The Food and Drug Administration last year gained new authority over cosmetics when Congress passed the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) by adding this bill to a December budget package.
“On average, consumers in the U.S. use six to 12 cosmetics products daily. But, until recently the FDA didn’t have the authority to require manufacturers to submit cosmetic product listings, including a list of ingredients used in these products, or register the facilities where they were produced,” Namandjé Bumpus, PhD, FDA’s chief scientist, said in a press release.
In the statement, the FDA announced the release of a draft guidance document that is intended to help companies comply with the transparency requirements slated to kick in this December. The agency is accepting comments on this draft guidance through Sept. 7.
“Later this year, registration and listing of cosmetic product facilities and products will become a requirement, making information about cosmetic products, including the ingredients used in products and the facilities where they are produced, readily available to the agency,” Dr. Bumpus said.
The products, according to the FDA statement, include makeup, nail polishes, shaving creams, other grooming products, perfumes, face and body cleansers, hair products, moisturizers, and other skin care items.
MoCRA “represents a sea change in how FDA regulates the cosmetics industry,” attorneys Frederick R. Ball, Alyson Walker Lotman, and Kelly A. Bonner, wrote in an article for the Food and Drug Law Institute published in spring 2023.
The FDA has called the MoCRA law “the most significant expansion” of its authority to regulate cosmetics since the Federal Food, Drug, and Cosmetic Act was passed in 1938.
The agency is in the process of expanding its staff to carry out newly authorized duties, including the tracking of adverse events. The FDA budget request for fiscal 2024, which begins Oct. 1, seeks $5 million for work needed to implement MoCRA.
PFAS, or ‘forever chemicals’
Some of the requested FDA funding is intended to prepare the agency to assess the use of per-and polyfluoroalkyl substances (PFAS) in cosmetics.
MoCRA sets a 3-year deadline for the FDA to issue an assessment of the use and potential risks of PFAS in cosmetics products. PFAS are sometimes added as ingredients in some cosmetic products, including lotions, cleansers, nail polish, shaving cream, foundation, lipstick, eyeliner, eyeshadow, and mascara, according to the FDA. Sometimes the presence of PFAS in cosmetics is unintentional and is the result of impurities in raw materials or is due to the breakdown of ingredients, the FDA said.
The FDA’s website says that so far, the available research doesn’t allow for “definitive conclusions about the potential health risks of PFAS in cosmetics.”
The Centers for Disease Control and Prevention has stated that research has suggested potential links between high levels of certain PFAS, in general, with increased cholesterol levels, changes in liver enzyme levels, increased risk of hypertension or preeclampsia in pregnant women, and increased risk of kidney or testicular cancer.
PFAS compounds often are used to resist grease, oil, water, and heat in industrial settings. They are used in thousands of products, from nonstick cookware to firefighting foams and protective gear, because they can reduce friction, according to a National Academies of Sciences, Engineering, and Medicine report on PFAS that was issued last year.
PFAS are known as “forever chemicals” because they contain a carbon-fluorine bond, which does not break naturally. Even when PFAS are transformed in the body, they can assume other forms of PFAS that preserve the troublesome carbon-fluorine bond. With PFAS, the human body is confronted with a substance it doesn’t have the tools to process.
This is in contrast to proteins and carbohydrates, which are in a sense prepackaged for relatively easy disassembly in the human body. Many of these compounds have weak links that enzymes and stomach acid can take apart, such as sulfur-to-sulfur (disulfide) bonds. That’s why protein-based biotech drugs are injected instead of administered as pills. The ultimate goal of this digestion is for the body to gain energy from these compounds.
But with PFAS, the body faces the challenge of carbon-fluorine bonds that are very hard to break down, and there is no payoff for these efforts, Graham F. Peaslee, PhD, professor of physics at the University of Notre Dame (Indiana), told this news organization.
“Nothing will naturally eat it because when you break the bond, it’s like eating celery,” he said. “You use more calories to eat the celery than you gain back from it.”
Interest from a U.S. senator
Dr. Peaslee was one of the authors of a 2021 article about PFAS in cosmetics that appeared in the journal Environmental Science and Technology Letters.
In the article, Dr. Peaslee and colleagues reported on their screening of 231 cosmetic products purchased in the United States and Canada using particle-induced gamma-ray emission spectroscopy. They found cases of undisclosed PFAS in cosmetic products. Foundations, mascaras, and lip products were noted as being especially problematic.
Sen. Susan Collins (R-ME) cited Dr. Peaslee’s article in a 2021 floor speech as she argued for having the FDA ban the intentional addition of PFAS to cosmetics.
“The findings of this study are particularly alarming, as many of these products are subject to direct human exposure,” Sen. Collins said. “For example, lipstick is often inadvertently ingested, and mascara is sometimes absorbed through tear ducts.”
In addition, workers at cosmetics plants may be exposed to PFAS and discarded cosmetics that have these compounds, which could potentially contaminate drinking water, Sen. Collins said. In 2021, she introduced legislation seeking a ban on PFAS that are intentionally added to cosmetics. That legislation did not advance through the Senate.
But the Senate Appropriations Committee, on which Sen. Collins is the ranking Republican, wants the FDA to keep a ban on PFAS in mind.
The Senate Agriculture Appropriations subcommittee, which oversees the FDA’s budget, raised the issue of PFAS and cosmetics in a June report. The FDA should develop a plan outlining research needed to inform “regulatory decision making, including potential development of a proposed rule to ban intentionally added PFAS substances in cosmetics,” the subcommittee said.
A version of this article first appeared on Medscape.com.
Inner lip erosions
The patient was having a flare of pemphigus vulgaris (PV), a rare and sometimes life-threatening acquired autoimmune blistering disease that affects the skin and/or mucosa. Ashkenazi Jewish patients and patients from Mediterranean and Middle Eastern countries are more likely to be affected.
In PV, acquired autoantibodies target the desmosomes that connect epithelial cells together, weakening the intercellular adhesion. It can affect skin, mucosa, or both. Patients present with fragile bullae or ulcers. The connections between the cells are often so damaged that rubbing on the skin creates a new blister called “Nikolsky sign.” In the mouth, bullae erode rapidly. Look for disease affecting the ocular conjunctiva or sclera, as well. PV can also occasionally affect the nasopharynx and esophagus, usually manifesting as hemoptysis, dysphagia, and nosebleeds with ulcer seen on endoscopy or otolaryngoscopy.
Although PV is often severe (and can warrant hospitalization when significant body surface area is involved), some patients may have few active lesions and can be managed safely as outpatients.
The diagnosis requires 2 biopsies and serum for indirect immunofluorescence. One biopsy (either by punch or shave to the upper dermis) is taken from the edge of a bulla or ulcer. Another biopsy (by punch or shave) is taken from nearby normal-looking skin or mucosa for testing the direct immunofluorescence pattern. In the mucosa, a punch biopsy may be left open or closed with absorbable sutures. A serum sample is taken for indirect immunofluorescence to differentiate pemphigus vulgaris from other forms of pemphigus.1
PV is treated by suppressing the immune system. Focal disease may be treated with super-potent topical steroids, including clobetasol 0.05% ointment. Even in the mouth, topical clobetasol 0.05% may be used off-label twice daily until control is achieved. When topical treatment is used in the mouth, advise patients to apply the clobetasol ointment to a piece of gauze and place the gauze (ointment side down) over affected areas for 20 to 30 minutes twice daily.
Patients with widespread or severe disease should be hospitalized. In severe cases, supportive wound care is provided, and treatment is aimed at immunosuppression. Systemic options include high-dose prednisone 0.5 to 1 mg/kg daily until clear, a steroid-sparing immunosuppressant such as mycophenolate mofetil up to 1000 mg bid, or rituximab in 1 of several regimens.
Three years prior to this patient’s visit, she had been successfully treated for PV with a course of rituximab. To treat the current flare, she was started on prednisone 60 mg/d. In addition, the plan was for her to complete 2 infusions of 1000 mg rituximab 2 weeks apart.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, Maine.
1. Didona, D, Schmidt, MF, Maglie, R, et al. Pemphigus and pemphigoids: clinical presentation, diagnosis and therapy. J Dtsch Dermatol Ges. 2023;1-20. doi: 10.1111/ddg.15174
The patient was having a flare of pemphigus vulgaris (PV), a rare and sometimes life-threatening acquired autoimmune blistering disease that affects the skin and/or mucosa. Ashkenazi Jewish patients and patients from Mediterranean and Middle Eastern countries are more likely to be affected.
In PV, acquired autoantibodies target the desmosomes that connect epithelial cells together, weakening the intercellular adhesion. It can affect skin, mucosa, or both. Patients present with fragile bullae or ulcers. The connections between the cells are often so damaged that rubbing on the skin creates a new blister called “Nikolsky sign.” In the mouth, bullae erode rapidly. Look for disease affecting the ocular conjunctiva or sclera, as well. PV can also occasionally affect the nasopharynx and esophagus, usually manifesting as hemoptysis, dysphagia, and nosebleeds with ulcer seen on endoscopy or otolaryngoscopy.
Although PV is often severe (and can warrant hospitalization when significant body surface area is involved), some patients may have few active lesions and can be managed safely as outpatients.
The diagnosis requires 2 biopsies and serum for indirect immunofluorescence. One biopsy (either by punch or shave to the upper dermis) is taken from the edge of a bulla or ulcer. Another biopsy (by punch or shave) is taken from nearby normal-looking skin or mucosa for testing the direct immunofluorescence pattern. In the mucosa, a punch biopsy may be left open or closed with absorbable sutures. A serum sample is taken for indirect immunofluorescence to differentiate pemphigus vulgaris from other forms of pemphigus.1
PV is treated by suppressing the immune system. Focal disease may be treated with super-potent topical steroids, including clobetasol 0.05% ointment. Even in the mouth, topical clobetasol 0.05% may be used off-label twice daily until control is achieved. When topical treatment is used in the mouth, advise patients to apply the clobetasol ointment to a piece of gauze and place the gauze (ointment side down) over affected areas for 20 to 30 minutes twice daily.
Patients with widespread or severe disease should be hospitalized. In severe cases, supportive wound care is provided, and treatment is aimed at immunosuppression. Systemic options include high-dose prednisone 0.5 to 1 mg/kg daily until clear, a steroid-sparing immunosuppressant such as mycophenolate mofetil up to 1000 mg bid, or rituximab in 1 of several regimens.
Three years prior to this patient’s visit, she had been successfully treated for PV with a course of rituximab. To treat the current flare, she was started on prednisone 60 mg/d. In addition, the plan was for her to complete 2 infusions of 1000 mg rituximab 2 weeks apart.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, Maine.
The patient was having a flare of pemphigus vulgaris (PV), a rare and sometimes life-threatening acquired autoimmune blistering disease that affects the skin and/or mucosa. Ashkenazi Jewish patients and patients from Mediterranean and Middle Eastern countries are more likely to be affected.
In PV, acquired autoantibodies target the desmosomes that connect epithelial cells together, weakening the intercellular adhesion. It can affect skin, mucosa, or both. Patients present with fragile bullae or ulcers. The connections between the cells are often so damaged that rubbing on the skin creates a new blister called “Nikolsky sign.” In the mouth, bullae erode rapidly. Look for disease affecting the ocular conjunctiva or sclera, as well. PV can also occasionally affect the nasopharynx and esophagus, usually manifesting as hemoptysis, dysphagia, and nosebleeds with ulcer seen on endoscopy or otolaryngoscopy.
Although PV is often severe (and can warrant hospitalization when significant body surface area is involved), some patients may have few active lesions and can be managed safely as outpatients.
The diagnosis requires 2 biopsies and serum for indirect immunofluorescence. One biopsy (either by punch or shave to the upper dermis) is taken from the edge of a bulla or ulcer. Another biopsy (by punch or shave) is taken from nearby normal-looking skin or mucosa for testing the direct immunofluorescence pattern. In the mucosa, a punch biopsy may be left open or closed with absorbable sutures. A serum sample is taken for indirect immunofluorescence to differentiate pemphigus vulgaris from other forms of pemphigus.1
PV is treated by suppressing the immune system. Focal disease may be treated with super-potent topical steroids, including clobetasol 0.05% ointment. Even in the mouth, topical clobetasol 0.05% may be used off-label twice daily until control is achieved. When topical treatment is used in the mouth, advise patients to apply the clobetasol ointment to a piece of gauze and place the gauze (ointment side down) over affected areas for 20 to 30 minutes twice daily.
Patients with widespread or severe disease should be hospitalized. In severe cases, supportive wound care is provided, and treatment is aimed at immunosuppression. Systemic options include high-dose prednisone 0.5 to 1 mg/kg daily until clear, a steroid-sparing immunosuppressant such as mycophenolate mofetil up to 1000 mg bid, or rituximab in 1 of several regimens.
Three years prior to this patient’s visit, she had been successfully treated for PV with a course of rituximab. To treat the current flare, she was started on prednisone 60 mg/d. In addition, the plan was for her to complete 2 infusions of 1000 mg rituximab 2 weeks apart.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, Maine.
1. Didona, D, Schmidt, MF, Maglie, R, et al. Pemphigus and pemphigoids: clinical presentation, diagnosis and therapy. J Dtsch Dermatol Ges. 2023;1-20. doi: 10.1111/ddg.15174
1. Didona, D, Schmidt, MF, Maglie, R, et al. Pemphigus and pemphigoids: clinical presentation, diagnosis and therapy. J Dtsch Dermatol Ges. 2023;1-20. doi: 10.1111/ddg.15174
Atopic dermatitis may be a risk factor for GBS colonization in pregnancy
suggest.
“The rate of GBS colonization among pregnant females with a history of AD has not been previously reported, but AD could be a risk factor for maternal carriage of GBS,” corresponding author David J. Margolis, MD, PhD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and colleagues wrote in the study, which was published as a letter to the editor online in the Journal of Investigative Dermatology. “GBS reporting in a large administrative database represents a unique opportunity to conduct a population-based evaluation of GBS carriage with AD. Understanding this association could expand our understanding of microbial changes associated with AD,” they noted.
To determine if an association between GBS and AD in pregnant women exists, the researchers performed a cross-sectional study using a random sample from an Optum administrative database of pregnant women who had vaginal deliveries between May of 2007 and September 2021. The primary outcome of interest was the presence of GBS based on American College of Obstetricians and Gynecologists–recommended codes for GBS during 36 0/7 to 37 6/7 weeks of pregnancy. They used descriptive statistics to summarize categorical and continuous variables as proportions and means, and logistic regression to examine the association between AD and GBS status.
The cohort included 566,467 pregnant women with an average age of 38.8 years. Of these, 2.9% had a diagnosis of AD or a history of AD, and 24.9% had diagnoses of asthma, seasonal allergies, or both. Women with AD had an increased odds ratio of asthma (OR, 2.55), seasonal allergies (OR, 3.39), or both (OR, 5.35), compared with those without AD.
GBS was reported in 20.6% of the cohort. The median time of follow-up for those with and without GBS was 494 days and 468 days, respectively (P = .134). Among the women with AD, 24.1% had GBS, compared with 20.51% of the women without AD (P <.0001), which translated into an OR of 1.23 (95% confidence interval, 1.18-1.27).
Among the women with GBS, the OR of asthma was 1.08 (95% CI, 1.06-1.10) and was 1.07 (95% CI, 1.05-1.09) among those with seasonal allergies. When adjusted for potential confounders, these findings did not change substantively.
“It is not apparent why pregnant females with AD are more likely to specifically carry GBS,” the authors wrote. “However, several studies have shown that individuals with AD are more likely to carry [Staphylococcus] aureus and that individuals with AD might be deficient in host defenses against S. aureus and other pathogens,” they added.
“Individuals with AD frequently receive antibiotics as part of their AD treatment and this might alter their resident microbiome. Carriage rates may be enhanced by the inhibition of an important barrier protein called filaggrin (FLG) and FLG loss of function genetic variation is known to decrease barrier proteins thought to inhibit the colonization of S. aureus and other pathogens,” the researchers wrote.
They acknowledged certain limitations of their study, including its reliance on an administrative database that does not contain information on past disease.
Asked to comment on the results, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was not involved with the study, characterized AD as “the poster child for cutaneous dysbiosis – an altered petri dish, so to speak, [that] facilitates survival of the few, leading to decreased microbial diversity that can both enable potential pathogen invasion and immune dysregulation.”
Though it’s not surprising that pregnant AD patients have dysbiosis, the focus on GBS, “which can be a bad actor in the perinatal period, is an interesting connection,” he said. “Will this change practices? Pregnant women should be screened for GBS regardless, but maybe more attention or counseling can be offered to AD patients about the importance of screening. Would decolonization regimens be employed early in pregnancy? This study can’t answer that but certainly raises good questions.”
Dr. Margolis disclosed that he is or recently has been a consultant for Pfizer, Leo, and Sanofi with respect to studies of atopic dermatitis and served on an advisory board for the National Eczema Association. Another author disclosed receiving grants from companies related to work with AD; other authors had no disclosures. Dr. Friedman reported having no relevant disclosures.
suggest.
“The rate of GBS colonization among pregnant females with a history of AD has not been previously reported, but AD could be a risk factor for maternal carriage of GBS,” corresponding author David J. Margolis, MD, PhD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and colleagues wrote in the study, which was published as a letter to the editor online in the Journal of Investigative Dermatology. “GBS reporting in a large administrative database represents a unique opportunity to conduct a population-based evaluation of GBS carriage with AD. Understanding this association could expand our understanding of microbial changes associated with AD,” they noted.
To determine if an association between GBS and AD in pregnant women exists, the researchers performed a cross-sectional study using a random sample from an Optum administrative database of pregnant women who had vaginal deliveries between May of 2007 and September 2021. The primary outcome of interest was the presence of GBS based on American College of Obstetricians and Gynecologists–recommended codes for GBS during 36 0/7 to 37 6/7 weeks of pregnancy. They used descriptive statistics to summarize categorical and continuous variables as proportions and means, and logistic regression to examine the association between AD and GBS status.
The cohort included 566,467 pregnant women with an average age of 38.8 years. Of these, 2.9% had a diagnosis of AD or a history of AD, and 24.9% had diagnoses of asthma, seasonal allergies, or both. Women with AD had an increased odds ratio of asthma (OR, 2.55), seasonal allergies (OR, 3.39), or both (OR, 5.35), compared with those without AD.
GBS was reported in 20.6% of the cohort. The median time of follow-up for those with and without GBS was 494 days and 468 days, respectively (P = .134). Among the women with AD, 24.1% had GBS, compared with 20.51% of the women without AD (P <.0001), which translated into an OR of 1.23 (95% confidence interval, 1.18-1.27).
Among the women with GBS, the OR of asthma was 1.08 (95% CI, 1.06-1.10) and was 1.07 (95% CI, 1.05-1.09) among those with seasonal allergies. When adjusted for potential confounders, these findings did not change substantively.
“It is not apparent why pregnant females with AD are more likely to specifically carry GBS,” the authors wrote. “However, several studies have shown that individuals with AD are more likely to carry [Staphylococcus] aureus and that individuals with AD might be deficient in host defenses against S. aureus and other pathogens,” they added.
“Individuals with AD frequently receive antibiotics as part of their AD treatment and this might alter their resident microbiome. Carriage rates may be enhanced by the inhibition of an important barrier protein called filaggrin (FLG) and FLG loss of function genetic variation is known to decrease barrier proteins thought to inhibit the colonization of S. aureus and other pathogens,” the researchers wrote.
They acknowledged certain limitations of their study, including its reliance on an administrative database that does not contain information on past disease.
Asked to comment on the results, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was not involved with the study, characterized AD as “the poster child for cutaneous dysbiosis – an altered petri dish, so to speak, [that] facilitates survival of the few, leading to decreased microbial diversity that can both enable potential pathogen invasion and immune dysregulation.”
Though it’s not surprising that pregnant AD patients have dysbiosis, the focus on GBS, “which can be a bad actor in the perinatal period, is an interesting connection,” he said. “Will this change practices? Pregnant women should be screened for GBS regardless, but maybe more attention or counseling can be offered to AD patients about the importance of screening. Would decolonization regimens be employed early in pregnancy? This study can’t answer that but certainly raises good questions.”
Dr. Margolis disclosed that he is or recently has been a consultant for Pfizer, Leo, and Sanofi with respect to studies of atopic dermatitis and served on an advisory board for the National Eczema Association. Another author disclosed receiving grants from companies related to work with AD; other authors had no disclosures. Dr. Friedman reported having no relevant disclosures.
suggest.
“The rate of GBS colonization among pregnant females with a history of AD has not been previously reported, but AD could be a risk factor for maternal carriage of GBS,” corresponding author David J. Margolis, MD, PhD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and colleagues wrote in the study, which was published as a letter to the editor online in the Journal of Investigative Dermatology. “GBS reporting in a large administrative database represents a unique opportunity to conduct a population-based evaluation of GBS carriage with AD. Understanding this association could expand our understanding of microbial changes associated with AD,” they noted.
To determine if an association between GBS and AD in pregnant women exists, the researchers performed a cross-sectional study using a random sample from an Optum administrative database of pregnant women who had vaginal deliveries between May of 2007 and September 2021. The primary outcome of interest was the presence of GBS based on American College of Obstetricians and Gynecologists–recommended codes for GBS during 36 0/7 to 37 6/7 weeks of pregnancy. They used descriptive statistics to summarize categorical and continuous variables as proportions and means, and logistic regression to examine the association between AD and GBS status.
The cohort included 566,467 pregnant women with an average age of 38.8 years. Of these, 2.9% had a diagnosis of AD or a history of AD, and 24.9% had diagnoses of asthma, seasonal allergies, or both. Women with AD had an increased odds ratio of asthma (OR, 2.55), seasonal allergies (OR, 3.39), or both (OR, 5.35), compared with those without AD.
GBS was reported in 20.6% of the cohort. The median time of follow-up for those with and without GBS was 494 days and 468 days, respectively (P = .134). Among the women with AD, 24.1% had GBS, compared with 20.51% of the women without AD (P <.0001), which translated into an OR of 1.23 (95% confidence interval, 1.18-1.27).
Among the women with GBS, the OR of asthma was 1.08 (95% CI, 1.06-1.10) and was 1.07 (95% CI, 1.05-1.09) among those with seasonal allergies. When adjusted for potential confounders, these findings did not change substantively.
“It is not apparent why pregnant females with AD are more likely to specifically carry GBS,” the authors wrote. “However, several studies have shown that individuals with AD are more likely to carry [Staphylococcus] aureus and that individuals with AD might be deficient in host defenses against S. aureus and other pathogens,” they added.
“Individuals with AD frequently receive antibiotics as part of their AD treatment and this might alter their resident microbiome. Carriage rates may be enhanced by the inhibition of an important barrier protein called filaggrin (FLG) and FLG loss of function genetic variation is known to decrease barrier proteins thought to inhibit the colonization of S. aureus and other pathogens,” the researchers wrote.
They acknowledged certain limitations of their study, including its reliance on an administrative database that does not contain information on past disease.
Asked to comment on the results, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was not involved with the study, characterized AD as “the poster child for cutaneous dysbiosis – an altered petri dish, so to speak, [that] facilitates survival of the few, leading to decreased microbial diversity that can both enable potential pathogen invasion and immune dysregulation.”
Though it’s not surprising that pregnant AD patients have dysbiosis, the focus on GBS, “which can be a bad actor in the perinatal period, is an interesting connection,” he said. “Will this change practices? Pregnant women should be screened for GBS regardless, but maybe more attention or counseling can be offered to AD patients about the importance of screening. Would decolonization regimens be employed early in pregnancy? This study can’t answer that but certainly raises good questions.”
Dr. Margolis disclosed that he is or recently has been a consultant for Pfizer, Leo, and Sanofi with respect to studies of atopic dermatitis and served on an advisory board for the National Eczema Association. Another author disclosed receiving grants from companies related to work with AD; other authors had no disclosures. Dr. Friedman reported having no relevant disclosures.
FROM THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
Mohs found to confer survival benefit in localized Merkel cell carcinoma
results from a national retrospective cohort study suggest.
The study found that, in patients with pathologically confirmed, localized T1/T2 MCC, “treatment with MMS was associated with an approximately 40% reduction in hazard of death compared with WLE,” reported John A. Carucci, MD, PhD, and colleagues in the department of dermatology at NYU Langone Health, New York. The results provide “preliminary data suggesting that treatment of localized, early-stage MCC with MMS may result in the most optimal patient survival outcomes for this aggressive form of skin cancer,” they added. The study was published online in JAMA Dermatology.
“Although data for keratinocytic nonmelanoma skin cancers have been definitive in demonstrating the advantage of peripheral and deep en face margin assessment over conventional WLE or NME [narrow-margin excision], the data for MCC, likely because of the disease’s rarity and limitations of available data sets, have been mixed,” they wrote.
Results from national studies published in the Journal of the National Cancer Institute and the Journal of the American Academy of Dermatology found no difference in survival among patients with localized MCC treated with WLE versus MMS. “However, these studies did not have confirmed pathologic node status, a substantial limitation considering that clinically node-negative cases of localized MCC have sentinel lymph node positivity rates ranging from 25% to 40%,” the authors noted.
To evaluate the association of the surgical excision modality and patient survival for pathologically confirmed localized T1/T2 MCC, Dr. Carucci and coauthors examined a cohort of 2,313 patients from the National Cancer Database with T1/T2 MCC diagnosed between Jan. 1, 2004, and Dec. 31, 2018, with pathologically confirmed, negative regional lymph nodes and treated with surgery. Their mean age was 71 years and 57.9% were male. Of the 2,313 patients, 1,452 underwent WLE, 104 underwent MMS, and 757 underwent NME.
The unadjusted analysis revealed that, compared with WLE, excision with MMS had the best unadjusted mean survival rates: 87.4% versus 86.1%, respectively, at 3 years, 84.5% versus 76.9% at 5 years, and 81.8% versus 60.9% at 10 years. Patients treated with NME had similar mean survival rates as those treated with WLE: 84.8% at 3 years, 78.3% at 5 years, and 60.8% at 10 years.
Multivariable survival analysis demonstrated that treatment with MMS was associated with significantly improved survival, compared with WLE (hazard ratio, 0.59; 95% CI, 0.36-0.97; P = .04).
“These data suggest that MMS may provide a survival benefit in the treatment of localized MCC, although further prospective work studying this issue is required,” the authors concluded. “Future directions may also focus on elucidating the benefit of adjuvant radiotherapy in localized cases treated with MMS.”
They acknowledged certain limitations of the study, including the fewer numbers of patients receiving MMS surgery, lack of randomization, and potential for selection bias.
In an interview, Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, who was asked to comment on the study, said that the field of MCC “has undergone rapid and robust transformation over the past 20 years. These changes encompass advancements in diagnosing the condition, identifying linked viruses, and developing systemic treatments.”
The study findings “imply that comprehensive assessment of histologic margins might offer advantages beyond minimizing scars, minimizing functional impact, and reducing the likelihood of local recurrence,” he said.
“It’s beyond doubt,” he added, that the study “furnishes us with yet another set of real-world insights that will undoubtedly influence patient outcomes. These insights serve to bring clarity to the ways in which we can deliver precisely targeted surgical treatment with durable outcomes for localized MCC.”
Patricia M. Richey, MD, director of Mohs surgery at Boston University, who was also asked to comment on the study, added that, because of the nature of the National Cancer Database, “the authors of this study were unfortunately unable to report disease-specific survival or immunosuppression status. That being said, the preliminary data presented are convincing and should result in us further exploring this topic, as well as readdressing and questioning related issues such as whether or not adjuvant radiotherapy is truly beneficial in cases with histologic clearance via Mohs.”
Dr. Carucci reported receiving grant funding from Regeneron for investigator-initiated basic research. No other author disclosures were reported. Neither Dr. Blalock nor Dr. Richey had relevant disclosures.
results from a national retrospective cohort study suggest.
The study found that, in patients with pathologically confirmed, localized T1/T2 MCC, “treatment with MMS was associated with an approximately 40% reduction in hazard of death compared with WLE,” reported John A. Carucci, MD, PhD, and colleagues in the department of dermatology at NYU Langone Health, New York. The results provide “preliminary data suggesting that treatment of localized, early-stage MCC with MMS may result in the most optimal patient survival outcomes for this aggressive form of skin cancer,” they added. The study was published online in JAMA Dermatology.
“Although data for keratinocytic nonmelanoma skin cancers have been definitive in demonstrating the advantage of peripheral and deep en face margin assessment over conventional WLE or NME [narrow-margin excision], the data for MCC, likely because of the disease’s rarity and limitations of available data sets, have been mixed,” they wrote.
Results from national studies published in the Journal of the National Cancer Institute and the Journal of the American Academy of Dermatology found no difference in survival among patients with localized MCC treated with WLE versus MMS. “However, these studies did not have confirmed pathologic node status, a substantial limitation considering that clinically node-negative cases of localized MCC have sentinel lymph node positivity rates ranging from 25% to 40%,” the authors noted.
To evaluate the association of the surgical excision modality and patient survival for pathologically confirmed localized T1/T2 MCC, Dr. Carucci and coauthors examined a cohort of 2,313 patients from the National Cancer Database with T1/T2 MCC diagnosed between Jan. 1, 2004, and Dec. 31, 2018, with pathologically confirmed, negative regional lymph nodes and treated with surgery. Their mean age was 71 years and 57.9% were male. Of the 2,313 patients, 1,452 underwent WLE, 104 underwent MMS, and 757 underwent NME.
The unadjusted analysis revealed that, compared with WLE, excision with MMS had the best unadjusted mean survival rates: 87.4% versus 86.1%, respectively, at 3 years, 84.5% versus 76.9% at 5 years, and 81.8% versus 60.9% at 10 years. Patients treated with NME had similar mean survival rates as those treated with WLE: 84.8% at 3 years, 78.3% at 5 years, and 60.8% at 10 years.
Multivariable survival analysis demonstrated that treatment with MMS was associated with significantly improved survival, compared with WLE (hazard ratio, 0.59; 95% CI, 0.36-0.97; P = .04).
“These data suggest that MMS may provide a survival benefit in the treatment of localized MCC, although further prospective work studying this issue is required,” the authors concluded. “Future directions may also focus on elucidating the benefit of adjuvant radiotherapy in localized cases treated with MMS.”
They acknowledged certain limitations of the study, including the fewer numbers of patients receiving MMS surgery, lack of randomization, and potential for selection bias.
In an interview, Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, who was asked to comment on the study, said that the field of MCC “has undergone rapid and robust transformation over the past 20 years. These changes encompass advancements in diagnosing the condition, identifying linked viruses, and developing systemic treatments.”
The study findings “imply that comprehensive assessment of histologic margins might offer advantages beyond minimizing scars, minimizing functional impact, and reducing the likelihood of local recurrence,” he said.
“It’s beyond doubt,” he added, that the study “furnishes us with yet another set of real-world insights that will undoubtedly influence patient outcomes. These insights serve to bring clarity to the ways in which we can deliver precisely targeted surgical treatment with durable outcomes for localized MCC.”
Patricia M. Richey, MD, director of Mohs surgery at Boston University, who was also asked to comment on the study, added that, because of the nature of the National Cancer Database, “the authors of this study were unfortunately unable to report disease-specific survival or immunosuppression status. That being said, the preliminary data presented are convincing and should result in us further exploring this topic, as well as readdressing and questioning related issues such as whether or not adjuvant radiotherapy is truly beneficial in cases with histologic clearance via Mohs.”
Dr. Carucci reported receiving grant funding from Regeneron for investigator-initiated basic research. No other author disclosures were reported. Neither Dr. Blalock nor Dr. Richey had relevant disclosures.
results from a national retrospective cohort study suggest.
The study found that, in patients with pathologically confirmed, localized T1/T2 MCC, “treatment with MMS was associated with an approximately 40% reduction in hazard of death compared with WLE,” reported John A. Carucci, MD, PhD, and colleagues in the department of dermatology at NYU Langone Health, New York. The results provide “preliminary data suggesting that treatment of localized, early-stage MCC with MMS may result in the most optimal patient survival outcomes for this aggressive form of skin cancer,” they added. The study was published online in JAMA Dermatology.
“Although data for keratinocytic nonmelanoma skin cancers have been definitive in demonstrating the advantage of peripheral and deep en face margin assessment over conventional WLE or NME [narrow-margin excision], the data for MCC, likely because of the disease’s rarity and limitations of available data sets, have been mixed,” they wrote.
Results from national studies published in the Journal of the National Cancer Institute and the Journal of the American Academy of Dermatology found no difference in survival among patients with localized MCC treated with WLE versus MMS. “However, these studies did not have confirmed pathologic node status, a substantial limitation considering that clinically node-negative cases of localized MCC have sentinel lymph node positivity rates ranging from 25% to 40%,” the authors noted.
To evaluate the association of the surgical excision modality and patient survival for pathologically confirmed localized T1/T2 MCC, Dr. Carucci and coauthors examined a cohort of 2,313 patients from the National Cancer Database with T1/T2 MCC diagnosed between Jan. 1, 2004, and Dec. 31, 2018, with pathologically confirmed, negative regional lymph nodes and treated with surgery. Their mean age was 71 years and 57.9% were male. Of the 2,313 patients, 1,452 underwent WLE, 104 underwent MMS, and 757 underwent NME.
The unadjusted analysis revealed that, compared with WLE, excision with MMS had the best unadjusted mean survival rates: 87.4% versus 86.1%, respectively, at 3 years, 84.5% versus 76.9% at 5 years, and 81.8% versus 60.9% at 10 years. Patients treated with NME had similar mean survival rates as those treated with WLE: 84.8% at 3 years, 78.3% at 5 years, and 60.8% at 10 years.
Multivariable survival analysis demonstrated that treatment with MMS was associated with significantly improved survival, compared with WLE (hazard ratio, 0.59; 95% CI, 0.36-0.97; P = .04).
“These data suggest that MMS may provide a survival benefit in the treatment of localized MCC, although further prospective work studying this issue is required,” the authors concluded. “Future directions may also focus on elucidating the benefit of adjuvant radiotherapy in localized cases treated with MMS.”
They acknowledged certain limitations of the study, including the fewer numbers of patients receiving MMS surgery, lack of randomization, and potential for selection bias.
In an interview, Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, who was asked to comment on the study, said that the field of MCC “has undergone rapid and robust transformation over the past 20 years. These changes encompass advancements in diagnosing the condition, identifying linked viruses, and developing systemic treatments.”
The study findings “imply that comprehensive assessment of histologic margins might offer advantages beyond minimizing scars, minimizing functional impact, and reducing the likelihood of local recurrence,” he said.
“It’s beyond doubt,” he added, that the study “furnishes us with yet another set of real-world insights that will undoubtedly influence patient outcomes. These insights serve to bring clarity to the ways in which we can deliver precisely targeted surgical treatment with durable outcomes for localized MCC.”
Patricia M. Richey, MD, director of Mohs surgery at Boston University, who was also asked to comment on the study, added that, because of the nature of the National Cancer Database, “the authors of this study were unfortunately unable to report disease-specific survival or immunosuppression status. That being said, the preliminary data presented are convincing and should result in us further exploring this topic, as well as readdressing and questioning related issues such as whether or not adjuvant radiotherapy is truly beneficial in cases with histologic clearance via Mohs.”
Dr. Carucci reported receiving grant funding from Regeneron for investigator-initiated basic research. No other author disclosures were reported. Neither Dr. Blalock nor Dr. Richey had relevant disclosures.
FROM JAMA DERMATOLOGY
Consider housing insecurity, other issues when managing challenging skin diseases in children, expert says
ASHEVILLE, N.C. – , according to a pediatric dermatologist who addressed the annual meeting of the Society for Pediatric Dermatology.
As a general principle for treating chronic skin conditions in children who are not doing well, it is reasonable to draw out information about a patient’s access to adequate housing, nutrition, and other basic needs, George Hightower, MD, PhD, of the division of pediatric and adolescent dermatology, University of California, San Diego, said at the meeting.
“We need conversations about where patients play, learn, and rest their heads at night,” said Dr. Hightower, who conducts research in this area. Fundamental components of well-being, such as stable housing and secure access to nutrition “are inseparable” from a child’s health, he noted.
“What are the stakes?” he asked. For many children, these factors might mean the difference between effective and poor control of the diseases for which the patient is seeking care.
To illustrate the point, Dr. Hightower used hidradenitis suppurativa (HS), a disease that appears to be on the rise among adolescents, as an example of why patient circumstances matter and should be considered. A complex disorder that is more prevalent in resource-poor communities, HS is difficult to control, often requiring extended periods of treatment with medications that can involve complex dosing or regular infusions.
“There is a need for medical providers to help the patient plan for this chronic illness,” said Dr. Hightower, referring to the importance of close follow-up. In adolescents, HS can be sufficiently disruptive from both the physical and psychological perspective that poor control can “derail future aspirations” by complicating educational endeavors and social interactions.
Dr. Hightower acknowledged that simply documenting housing insecurity or other issues does not solve these problems, but he does believe that developing a sensitivity to these obstacles to health care is a first step. It is a process that should permeate into medical training, health care research, and strategies to improve outcomes.
“The connections between fair housing and clinical practice may appear tenuous and inconsequential to the care provided by medical specialists,” Dr. Hightower said, but he emphasized that there are clear consequences when these factors contribute to inadequate control of such diseases as HS. As a source of missed appointments and disjointed care, an unstable home life can be an important barrier to disease control – and because of scarring nodules, fistulae, pain, school absences, and social isolation, complications can be dire.
Solutions to insecure housing are not typically available to an individual clinician, but the awareness that this can be a factor can help both physicians and patients begin to think about the role this plays in impairing recovery and what solutions might be found to modify the impact. Awareness not just among individual clinicians but a broader consortium of those working to improve health care outcomes is needed to “challenge the way we are doing medicine,” he said.
While conversations about the social determinants of health, including access to resources within patients’ neighborhoods, schools, and environment, can demonstrate concern about how to address obstacles, it can also be part of a reorientation to think beyond treatment for the underlying pathology alone. Eliciting trust and emphasizing the importance of environmental barriers to adequate care can be positive steps on the path to solutions.
Participatory action research
Relevant to this orientation, Dr. Hightower spoke about participatory action research (PAR), which provides a framework for patients to participate in the planning of clinical studies to effect change, not just serve as subjects in these studies.
The assumption of PAR is that “all people have valuable knowledge about their lives and experiences,” Dr. Hightower said. From this assumption, individuals who have been historically marginalized by race, income, or other factors can help define the problems from the patient’s perspective and, from there, create studies to seek solutions.
PAR is consistent with a patient-centered approach to medical care, which Dr. Hightower called “the future of medicine.” It involves a big-picture approach to look beyond disease pathology and symptoms to factors that might be creating susceptibility to disease and undermining health care.
Organized medicine alone cannot solve the cause of social inequities leading to disparate risks for disease and risks of inadequate health care, but Dr. Hightower argued that these inequities should not be ignored. He believes medical trainees should learn how to elicit information about the barriers to adequate health care and be aware of solutions, such as fair housing policies.
While he believes that PAR is an example of a pathway to problem solving, he suggested that a comprehensive approach requires an effective method of communication between providers and patients that would lead to a collaborative and mutually reinforcing approach.
“How do we ensure that individuals from communities most impacted by health disparities are treated fairly and empowered to address these disparities?” Dr. Hightower asked. He said that this is the direction of his own research and the issues that inhibit adequate treatment of many dermatologic diseases, as well as other types of disease, in childhood.
Craig Burkhart, MD, director of a private pediatric and adolescent dermatology practice in Cary, N.C., said that Dr. Hightower’s message is relevant. The value of considering and addressing the psychological well-being of patients of any age is not a new concept, but he acknowledged that he, for one, has not routinely inquired about obstacles to follow-up care if there is a signal that this might be an issue.
“As dermatologists, we focus on the acute complaints. We want to make the patient better,” said Dr. Burkhart, who moderated the session in which Dr. Hightower spoke. He agreed with Dr. Hightower that environmental factors make a difference on the road to recovery for a patient, and his presentation was a good reminder, he said, to consider the patient’s circumstances when response to treatment is inadequate, particularly in chronic diseases like HS, for which comprehensive care and close follow-up are needed.
Dr. Hightower and Dr. Burkhart report no potential conflicts of interest.
ASHEVILLE, N.C. – , according to a pediatric dermatologist who addressed the annual meeting of the Society for Pediatric Dermatology.
As a general principle for treating chronic skin conditions in children who are not doing well, it is reasonable to draw out information about a patient’s access to adequate housing, nutrition, and other basic needs, George Hightower, MD, PhD, of the division of pediatric and adolescent dermatology, University of California, San Diego, said at the meeting.
“We need conversations about where patients play, learn, and rest their heads at night,” said Dr. Hightower, who conducts research in this area. Fundamental components of well-being, such as stable housing and secure access to nutrition “are inseparable” from a child’s health, he noted.
“What are the stakes?” he asked. For many children, these factors might mean the difference between effective and poor control of the diseases for which the patient is seeking care.
To illustrate the point, Dr. Hightower used hidradenitis suppurativa (HS), a disease that appears to be on the rise among adolescents, as an example of why patient circumstances matter and should be considered. A complex disorder that is more prevalent in resource-poor communities, HS is difficult to control, often requiring extended periods of treatment with medications that can involve complex dosing or regular infusions.
“There is a need for medical providers to help the patient plan for this chronic illness,” said Dr. Hightower, referring to the importance of close follow-up. In adolescents, HS can be sufficiently disruptive from both the physical and psychological perspective that poor control can “derail future aspirations” by complicating educational endeavors and social interactions.
Dr. Hightower acknowledged that simply documenting housing insecurity or other issues does not solve these problems, but he does believe that developing a sensitivity to these obstacles to health care is a first step. It is a process that should permeate into medical training, health care research, and strategies to improve outcomes.
“The connections between fair housing and clinical practice may appear tenuous and inconsequential to the care provided by medical specialists,” Dr. Hightower said, but he emphasized that there are clear consequences when these factors contribute to inadequate control of such diseases as HS. As a source of missed appointments and disjointed care, an unstable home life can be an important barrier to disease control – and because of scarring nodules, fistulae, pain, school absences, and social isolation, complications can be dire.
Solutions to insecure housing are not typically available to an individual clinician, but the awareness that this can be a factor can help both physicians and patients begin to think about the role this plays in impairing recovery and what solutions might be found to modify the impact. Awareness not just among individual clinicians but a broader consortium of those working to improve health care outcomes is needed to “challenge the way we are doing medicine,” he said.
While conversations about the social determinants of health, including access to resources within patients’ neighborhoods, schools, and environment, can demonstrate concern about how to address obstacles, it can also be part of a reorientation to think beyond treatment for the underlying pathology alone. Eliciting trust and emphasizing the importance of environmental barriers to adequate care can be positive steps on the path to solutions.
Participatory action research
Relevant to this orientation, Dr. Hightower spoke about participatory action research (PAR), which provides a framework for patients to participate in the planning of clinical studies to effect change, not just serve as subjects in these studies.
The assumption of PAR is that “all people have valuable knowledge about their lives and experiences,” Dr. Hightower said. From this assumption, individuals who have been historically marginalized by race, income, or other factors can help define the problems from the patient’s perspective and, from there, create studies to seek solutions.
PAR is consistent with a patient-centered approach to medical care, which Dr. Hightower called “the future of medicine.” It involves a big-picture approach to look beyond disease pathology and symptoms to factors that might be creating susceptibility to disease and undermining health care.
Organized medicine alone cannot solve the cause of social inequities leading to disparate risks for disease and risks of inadequate health care, but Dr. Hightower argued that these inequities should not be ignored. He believes medical trainees should learn how to elicit information about the barriers to adequate health care and be aware of solutions, such as fair housing policies.
While he believes that PAR is an example of a pathway to problem solving, he suggested that a comprehensive approach requires an effective method of communication between providers and patients that would lead to a collaborative and mutually reinforcing approach.
“How do we ensure that individuals from communities most impacted by health disparities are treated fairly and empowered to address these disparities?” Dr. Hightower asked. He said that this is the direction of his own research and the issues that inhibit adequate treatment of many dermatologic diseases, as well as other types of disease, in childhood.
Craig Burkhart, MD, director of a private pediatric and adolescent dermatology practice in Cary, N.C., said that Dr. Hightower’s message is relevant. The value of considering and addressing the psychological well-being of patients of any age is not a new concept, but he acknowledged that he, for one, has not routinely inquired about obstacles to follow-up care if there is a signal that this might be an issue.
“As dermatologists, we focus on the acute complaints. We want to make the patient better,” said Dr. Burkhart, who moderated the session in which Dr. Hightower spoke. He agreed with Dr. Hightower that environmental factors make a difference on the road to recovery for a patient, and his presentation was a good reminder, he said, to consider the patient’s circumstances when response to treatment is inadequate, particularly in chronic diseases like HS, for which comprehensive care and close follow-up are needed.
Dr. Hightower and Dr. Burkhart report no potential conflicts of interest.
ASHEVILLE, N.C. – , according to a pediatric dermatologist who addressed the annual meeting of the Society for Pediatric Dermatology.
As a general principle for treating chronic skin conditions in children who are not doing well, it is reasonable to draw out information about a patient’s access to adequate housing, nutrition, and other basic needs, George Hightower, MD, PhD, of the division of pediatric and adolescent dermatology, University of California, San Diego, said at the meeting.
“We need conversations about where patients play, learn, and rest their heads at night,” said Dr. Hightower, who conducts research in this area. Fundamental components of well-being, such as stable housing and secure access to nutrition “are inseparable” from a child’s health, he noted.
“What are the stakes?” he asked. For many children, these factors might mean the difference between effective and poor control of the diseases for which the patient is seeking care.
To illustrate the point, Dr. Hightower used hidradenitis suppurativa (HS), a disease that appears to be on the rise among adolescents, as an example of why patient circumstances matter and should be considered. A complex disorder that is more prevalent in resource-poor communities, HS is difficult to control, often requiring extended periods of treatment with medications that can involve complex dosing or regular infusions.
“There is a need for medical providers to help the patient plan for this chronic illness,” said Dr. Hightower, referring to the importance of close follow-up. In adolescents, HS can be sufficiently disruptive from both the physical and psychological perspective that poor control can “derail future aspirations” by complicating educational endeavors and social interactions.
Dr. Hightower acknowledged that simply documenting housing insecurity or other issues does not solve these problems, but he does believe that developing a sensitivity to these obstacles to health care is a first step. It is a process that should permeate into medical training, health care research, and strategies to improve outcomes.
“The connections between fair housing and clinical practice may appear tenuous and inconsequential to the care provided by medical specialists,” Dr. Hightower said, but he emphasized that there are clear consequences when these factors contribute to inadequate control of such diseases as HS. As a source of missed appointments and disjointed care, an unstable home life can be an important barrier to disease control – and because of scarring nodules, fistulae, pain, school absences, and social isolation, complications can be dire.
Solutions to insecure housing are not typically available to an individual clinician, but the awareness that this can be a factor can help both physicians and patients begin to think about the role this plays in impairing recovery and what solutions might be found to modify the impact. Awareness not just among individual clinicians but a broader consortium of those working to improve health care outcomes is needed to “challenge the way we are doing medicine,” he said.
While conversations about the social determinants of health, including access to resources within patients’ neighborhoods, schools, and environment, can demonstrate concern about how to address obstacles, it can also be part of a reorientation to think beyond treatment for the underlying pathology alone. Eliciting trust and emphasizing the importance of environmental barriers to adequate care can be positive steps on the path to solutions.
Participatory action research
Relevant to this orientation, Dr. Hightower spoke about participatory action research (PAR), which provides a framework for patients to participate in the planning of clinical studies to effect change, not just serve as subjects in these studies.
The assumption of PAR is that “all people have valuable knowledge about their lives and experiences,” Dr. Hightower said. From this assumption, individuals who have been historically marginalized by race, income, or other factors can help define the problems from the patient’s perspective and, from there, create studies to seek solutions.
PAR is consistent with a patient-centered approach to medical care, which Dr. Hightower called “the future of medicine.” It involves a big-picture approach to look beyond disease pathology and symptoms to factors that might be creating susceptibility to disease and undermining health care.
Organized medicine alone cannot solve the cause of social inequities leading to disparate risks for disease and risks of inadequate health care, but Dr. Hightower argued that these inequities should not be ignored. He believes medical trainees should learn how to elicit information about the barriers to adequate health care and be aware of solutions, such as fair housing policies.
While he believes that PAR is an example of a pathway to problem solving, he suggested that a comprehensive approach requires an effective method of communication between providers and patients that would lead to a collaborative and mutually reinforcing approach.
“How do we ensure that individuals from communities most impacted by health disparities are treated fairly and empowered to address these disparities?” Dr. Hightower asked. He said that this is the direction of his own research and the issues that inhibit adequate treatment of many dermatologic diseases, as well as other types of disease, in childhood.
Craig Burkhart, MD, director of a private pediatric and adolescent dermatology practice in Cary, N.C., said that Dr. Hightower’s message is relevant. The value of considering and addressing the psychological well-being of patients of any age is not a new concept, but he acknowledged that he, for one, has not routinely inquired about obstacles to follow-up care if there is a signal that this might be an issue.
“As dermatologists, we focus on the acute complaints. We want to make the patient better,” said Dr. Burkhart, who moderated the session in which Dr. Hightower spoke. He agreed with Dr. Hightower that environmental factors make a difference on the road to recovery for a patient, and his presentation was a good reminder, he said, to consider the patient’s circumstances when response to treatment is inadequate, particularly in chronic diseases like HS, for which comprehensive care and close follow-up are needed.
Dr. Hightower and Dr. Burkhart report no potential conflicts of interest.
AT SPD 2023
Dupilumab gains off-label uses as clinicians turn to drug for more indications
.
The drug, marketed as Dupixent, is currently approved in the United States to treat atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis in adults. Dupilumab is also approved to treat eosinophilic esophagitis in patients aged 12 years and older and atopic dermatitis and asthma in some patients as young as age 6 months.
As the roster of approved and off-label indications grows, skin specialists said, pediatricians and other primary care providers should become familiar with the drug – given the increasing likelihood that their patients may be taking the medication.
The U.S. Food and Drug Administration first approved dupilumab in 2017 for eczema and has continued to add new treatment indications, the most recent being for prurigo nodularis, in 2022. Sanofi, which markets the drug with Regeneron, announced in April 2022 that some 430,000 patients worldwide were taking the drug – a figure it hoped to raise by 1.5 million by 2025.
A well-tolerated – if expensive – drug
Dupilumab, an interleukin-4 (IL-4) receptor alpha-antagonist biologic, blocks both IL-4 and IL-13 signaling, Marlys Fassett, MD, PhD, associate professor of dermatology at the University of California, San Francisco, told this news organization.
Dr. Fassett said she prescribes the drug off label for chronic idiopathic urticaria, including in older patients, and finds that the side effects in older patients are similar to those in younger people. The medication costs $36,000 per year, although some patients can get it more cheaply.
“Dupixent is a super-safe drug because it doesn’t immunosuppress any other part of the immune system, so you still have good antibacterial, antiviral, and antifungal immunity,” she added. “That makes perfect sense as a biological mechanism, and it’s been found safe in clinical trials.”
Case reports of potential adverse reactions to dupilumab have included ocular surface disease, lichen planus, and rash on the face and neck.
“We’re still learning about complications and are watching patients carefully,” said Marissa J. Perman, MD, section chief of dermatology at Children’s Hospital of Philadelphia.
Many people with atopic dermatitis also have other allergic conditions, such as contact dermatitis, asthma, prurigo nodularis, allergic rhinitis, and seasonal allergies. Each of these conditions has a pathway that depends on IL-4 receptors, Dr. Fassett said.
“It’s amazing how many conditions Dupixent improves. Sometimes we prescribe on-label Dupixent for atopic dermatitis, and inadvertently, the drug also improves that patient’s other, off-label conditions,” Dr. Fassett said. “I think that’s the best evidence that Dupixent works in these off-label cases.”
Lindsay C. Strowd, MD, associate professor of dermatology at Wake Forest University, Winston-Salem, N.C., said she uses off-label dupilumab to treat bullous pemphigoid and intense pruritus of unknown etiology.
“And several times I have treated drug reaction with eosinophilia and systemic symptoms, a rare adverse drug reaction that causes a rash and eosinophilia,” Dr. Strowd added.
Tissa Hata, MD, professor of medicine and clinical service chief at the University of California, San Diego, mainly treats elderly patients. She uses dupilumab to treat bullous pemphigoid and chronic pruritus. “There have been reports of using Dupixent to treat adult alopecia areata, chronic urticaria, localized scleroderma, and even keloids,” she told this news organization.
As a pediatric dermatologist, Dr. Perman treats children with atopic dermatitis as young as 3 months of age. She also uses dupilumab for alopecia areata, graft vs. host disease, and pruritus not otherwise specified.
Conjunctivitis and facial redness are two side effects Dr. Fassett sometimes sees with dupilumab. They occur similarly with all conditions and in all age groups. “We don’t know why they occur, and we don’t always know how to alleviate them,” she said. “So a small number of patients stop using Dupixent because they can’t tolerate those two side effects.
“We’re not worried about infection risk,” Dr. Fassett said. “Your patients may have heard of dupilumab as an immunosuppressant, but its immunosuppression is very focused. You can reassure them that they’re not at increased risk for viral or bacterial infections when they’re on this drug.”
“I don’t think there are any different safety signals to watch for with on-label vs. off-label Dupixent use,” Dr. Strowd added. “In general, the medicine is very safe.”
Dr. Hata said she is impressed with dupilumab’s safety in her elderly patients. All her patients older than 85 years who have taken the drug for bullous pemphigoid have tolerated it well, she said.
“Dupixent seems to be a safe alternative for elderly patients with pruritus because they often cannot tolerate sedating antihistamines due to the risk of falling,” Dr. Hata said. “And UV therapy may be difficult for elderly patients due to problems with transport.”
Although some of Dr. Hata’s elderly patients with atopic dermatitis have discontinued use of the drug after developing conjunctivitis, none taking the drug off label have discontinued it because of side effects, she noted.
“Dupixent manages the condition, but it is not a cure,” Dr. Fassett noted. “Based on the current data, we think it’s safe and effective to take long term, potentially for life.”
Making injections less bothersome
Dupilumab is injected subcutaneously from a single-dose prefilled syringe or a prefilled pen (syringe hidden in an opaque sheath), typically in the thigh, arm, abdomen, or buttocks. According to Sanofi and Regeneron, patients receive dupilumab injections every 2 to 4 weeks in doses based on their age and weight.
“The medication is somewhat viscous, so taking the syringe or pen out of the refrigerator ahead of time to warm it up can make the experience less painful,” Dr. Strowd advised. “For pediatric patients, I sometimes prescribe topical lidocaine applied 30 minutes before injection.”
Dr. Hata suggested icing the skin prior to injecting or distracting the patient by tapping a different area of the skin.
For her pediatric patients, Dr. Perman said she uses “lots of distraction, EMLA cream, and having one person hold the child while a second person injects.”
Clinic and pharmacy staff may show patients how to inject properly, Dr. Fassett added; and the product website provides injection tutorials.
Off-label dupixent can be expensive, difficult to obtain
The list price per injection, regardless of dose, is around $1,800. But according to the company’s website, most patients have health insurance or qualify for other assistance, so “very few patients pay the list price.”
Even so, “due to cost and insurance coverage hurdles, obtaining Dupixent for off-label use can be difficult,” Dr. Strowd said.
“In academic medicine, we can obtain drugs for our patients that community doctors may not get approval for,” Dr. Fassett added. “Community doctors can use information in the medical literature and in news articles to press insurance companies to spend money to provide their patients with Dupixent.”
The experts who commented have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
.
The drug, marketed as Dupixent, is currently approved in the United States to treat atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis in adults. Dupilumab is also approved to treat eosinophilic esophagitis in patients aged 12 years and older and atopic dermatitis and asthma in some patients as young as age 6 months.
As the roster of approved and off-label indications grows, skin specialists said, pediatricians and other primary care providers should become familiar with the drug – given the increasing likelihood that their patients may be taking the medication.
The U.S. Food and Drug Administration first approved dupilumab in 2017 for eczema and has continued to add new treatment indications, the most recent being for prurigo nodularis, in 2022. Sanofi, which markets the drug with Regeneron, announced in April 2022 that some 430,000 patients worldwide were taking the drug – a figure it hoped to raise by 1.5 million by 2025.
A well-tolerated – if expensive – drug
Dupilumab, an interleukin-4 (IL-4) receptor alpha-antagonist biologic, blocks both IL-4 and IL-13 signaling, Marlys Fassett, MD, PhD, associate professor of dermatology at the University of California, San Francisco, told this news organization.
Dr. Fassett said she prescribes the drug off label for chronic idiopathic urticaria, including in older patients, and finds that the side effects in older patients are similar to those in younger people. The medication costs $36,000 per year, although some patients can get it more cheaply.
“Dupixent is a super-safe drug because it doesn’t immunosuppress any other part of the immune system, so you still have good antibacterial, antiviral, and antifungal immunity,” she added. “That makes perfect sense as a biological mechanism, and it’s been found safe in clinical trials.”
Case reports of potential adverse reactions to dupilumab have included ocular surface disease, lichen planus, and rash on the face and neck.
“We’re still learning about complications and are watching patients carefully,” said Marissa J. Perman, MD, section chief of dermatology at Children’s Hospital of Philadelphia.
Many people with atopic dermatitis also have other allergic conditions, such as contact dermatitis, asthma, prurigo nodularis, allergic rhinitis, and seasonal allergies. Each of these conditions has a pathway that depends on IL-4 receptors, Dr. Fassett said.
“It’s amazing how many conditions Dupixent improves. Sometimes we prescribe on-label Dupixent for atopic dermatitis, and inadvertently, the drug also improves that patient’s other, off-label conditions,” Dr. Fassett said. “I think that’s the best evidence that Dupixent works in these off-label cases.”
Lindsay C. Strowd, MD, associate professor of dermatology at Wake Forest University, Winston-Salem, N.C., said she uses off-label dupilumab to treat bullous pemphigoid and intense pruritus of unknown etiology.
“And several times I have treated drug reaction with eosinophilia and systemic symptoms, a rare adverse drug reaction that causes a rash and eosinophilia,” Dr. Strowd added.
Tissa Hata, MD, professor of medicine and clinical service chief at the University of California, San Diego, mainly treats elderly patients. She uses dupilumab to treat bullous pemphigoid and chronic pruritus. “There have been reports of using Dupixent to treat adult alopecia areata, chronic urticaria, localized scleroderma, and even keloids,” she told this news organization.
As a pediatric dermatologist, Dr. Perman treats children with atopic dermatitis as young as 3 months of age. She also uses dupilumab for alopecia areata, graft vs. host disease, and pruritus not otherwise specified.
Conjunctivitis and facial redness are two side effects Dr. Fassett sometimes sees with dupilumab. They occur similarly with all conditions and in all age groups. “We don’t know why they occur, and we don’t always know how to alleviate them,” she said. “So a small number of patients stop using Dupixent because they can’t tolerate those two side effects.
“We’re not worried about infection risk,” Dr. Fassett said. “Your patients may have heard of dupilumab as an immunosuppressant, but its immunosuppression is very focused. You can reassure them that they’re not at increased risk for viral or bacterial infections when they’re on this drug.”
“I don’t think there are any different safety signals to watch for with on-label vs. off-label Dupixent use,” Dr. Strowd added. “In general, the medicine is very safe.”
Dr. Hata said she is impressed with dupilumab’s safety in her elderly patients. All her patients older than 85 years who have taken the drug for bullous pemphigoid have tolerated it well, she said.
“Dupixent seems to be a safe alternative for elderly patients with pruritus because they often cannot tolerate sedating antihistamines due to the risk of falling,” Dr. Hata said. “And UV therapy may be difficult for elderly patients due to problems with transport.”
Although some of Dr. Hata’s elderly patients with atopic dermatitis have discontinued use of the drug after developing conjunctivitis, none taking the drug off label have discontinued it because of side effects, she noted.
“Dupixent manages the condition, but it is not a cure,” Dr. Fassett noted. “Based on the current data, we think it’s safe and effective to take long term, potentially for life.”
Making injections less bothersome
Dupilumab is injected subcutaneously from a single-dose prefilled syringe or a prefilled pen (syringe hidden in an opaque sheath), typically in the thigh, arm, abdomen, or buttocks. According to Sanofi and Regeneron, patients receive dupilumab injections every 2 to 4 weeks in doses based on their age and weight.
“The medication is somewhat viscous, so taking the syringe or pen out of the refrigerator ahead of time to warm it up can make the experience less painful,” Dr. Strowd advised. “For pediatric patients, I sometimes prescribe topical lidocaine applied 30 minutes before injection.”
Dr. Hata suggested icing the skin prior to injecting or distracting the patient by tapping a different area of the skin.
For her pediatric patients, Dr. Perman said she uses “lots of distraction, EMLA cream, and having one person hold the child while a second person injects.”
Clinic and pharmacy staff may show patients how to inject properly, Dr. Fassett added; and the product website provides injection tutorials.
Off-label dupixent can be expensive, difficult to obtain
The list price per injection, regardless of dose, is around $1,800. But according to the company’s website, most patients have health insurance or qualify for other assistance, so “very few patients pay the list price.”
Even so, “due to cost and insurance coverage hurdles, obtaining Dupixent for off-label use can be difficult,” Dr. Strowd said.
“In academic medicine, we can obtain drugs for our patients that community doctors may not get approval for,” Dr. Fassett added. “Community doctors can use information in the medical literature and in news articles to press insurance companies to spend money to provide their patients with Dupixent.”
The experts who commented have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
.
The drug, marketed as Dupixent, is currently approved in the United States to treat atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis in adults. Dupilumab is also approved to treat eosinophilic esophagitis in patients aged 12 years and older and atopic dermatitis and asthma in some patients as young as age 6 months.
As the roster of approved and off-label indications grows, skin specialists said, pediatricians and other primary care providers should become familiar with the drug – given the increasing likelihood that their patients may be taking the medication.
The U.S. Food and Drug Administration first approved dupilumab in 2017 for eczema and has continued to add new treatment indications, the most recent being for prurigo nodularis, in 2022. Sanofi, which markets the drug with Regeneron, announced in April 2022 that some 430,000 patients worldwide were taking the drug – a figure it hoped to raise by 1.5 million by 2025.
A well-tolerated – if expensive – drug
Dupilumab, an interleukin-4 (IL-4) receptor alpha-antagonist biologic, blocks both IL-4 and IL-13 signaling, Marlys Fassett, MD, PhD, associate professor of dermatology at the University of California, San Francisco, told this news organization.
Dr. Fassett said she prescribes the drug off label for chronic idiopathic urticaria, including in older patients, and finds that the side effects in older patients are similar to those in younger people. The medication costs $36,000 per year, although some patients can get it more cheaply.
“Dupixent is a super-safe drug because it doesn’t immunosuppress any other part of the immune system, so you still have good antibacterial, antiviral, and antifungal immunity,” she added. “That makes perfect sense as a biological mechanism, and it’s been found safe in clinical trials.”
Case reports of potential adverse reactions to dupilumab have included ocular surface disease, lichen planus, and rash on the face and neck.
“We’re still learning about complications and are watching patients carefully,” said Marissa J. Perman, MD, section chief of dermatology at Children’s Hospital of Philadelphia.
Many people with atopic dermatitis also have other allergic conditions, such as contact dermatitis, asthma, prurigo nodularis, allergic rhinitis, and seasonal allergies. Each of these conditions has a pathway that depends on IL-4 receptors, Dr. Fassett said.
“It’s amazing how many conditions Dupixent improves. Sometimes we prescribe on-label Dupixent for atopic dermatitis, and inadvertently, the drug also improves that patient’s other, off-label conditions,” Dr. Fassett said. “I think that’s the best evidence that Dupixent works in these off-label cases.”
Lindsay C. Strowd, MD, associate professor of dermatology at Wake Forest University, Winston-Salem, N.C., said she uses off-label dupilumab to treat bullous pemphigoid and intense pruritus of unknown etiology.
“And several times I have treated drug reaction with eosinophilia and systemic symptoms, a rare adverse drug reaction that causes a rash and eosinophilia,” Dr. Strowd added.
Tissa Hata, MD, professor of medicine and clinical service chief at the University of California, San Diego, mainly treats elderly patients. She uses dupilumab to treat bullous pemphigoid and chronic pruritus. “There have been reports of using Dupixent to treat adult alopecia areata, chronic urticaria, localized scleroderma, and even keloids,” she told this news organization.
As a pediatric dermatologist, Dr. Perman treats children with atopic dermatitis as young as 3 months of age. She also uses dupilumab for alopecia areata, graft vs. host disease, and pruritus not otherwise specified.
Conjunctivitis and facial redness are two side effects Dr. Fassett sometimes sees with dupilumab. They occur similarly with all conditions and in all age groups. “We don’t know why they occur, and we don’t always know how to alleviate them,” she said. “So a small number of patients stop using Dupixent because they can’t tolerate those two side effects.
“We’re not worried about infection risk,” Dr. Fassett said. “Your patients may have heard of dupilumab as an immunosuppressant, but its immunosuppression is very focused. You can reassure them that they’re not at increased risk for viral or bacterial infections when they’re on this drug.”
“I don’t think there are any different safety signals to watch for with on-label vs. off-label Dupixent use,” Dr. Strowd added. “In general, the medicine is very safe.”
Dr. Hata said she is impressed with dupilumab’s safety in her elderly patients. All her patients older than 85 years who have taken the drug for bullous pemphigoid have tolerated it well, she said.
“Dupixent seems to be a safe alternative for elderly patients with pruritus because they often cannot tolerate sedating antihistamines due to the risk of falling,” Dr. Hata said. “And UV therapy may be difficult for elderly patients due to problems with transport.”
Although some of Dr. Hata’s elderly patients with atopic dermatitis have discontinued use of the drug after developing conjunctivitis, none taking the drug off label have discontinued it because of side effects, she noted.
“Dupixent manages the condition, but it is not a cure,” Dr. Fassett noted. “Based on the current data, we think it’s safe and effective to take long term, potentially for life.”
Making injections less bothersome
Dupilumab is injected subcutaneously from a single-dose prefilled syringe or a prefilled pen (syringe hidden in an opaque sheath), typically in the thigh, arm, abdomen, or buttocks. According to Sanofi and Regeneron, patients receive dupilumab injections every 2 to 4 weeks in doses based on their age and weight.
“The medication is somewhat viscous, so taking the syringe or pen out of the refrigerator ahead of time to warm it up can make the experience less painful,” Dr. Strowd advised. “For pediatric patients, I sometimes prescribe topical lidocaine applied 30 minutes before injection.”
Dr. Hata suggested icing the skin prior to injecting or distracting the patient by tapping a different area of the skin.
For her pediatric patients, Dr. Perman said she uses “lots of distraction, EMLA cream, and having one person hold the child while a second person injects.”
Clinic and pharmacy staff may show patients how to inject properly, Dr. Fassett added; and the product website provides injection tutorials.
Off-label dupixent can be expensive, difficult to obtain
The list price per injection, regardless of dose, is around $1,800. But according to the company’s website, most patients have health insurance or qualify for other assistance, so “very few patients pay the list price.”
Even so, “due to cost and insurance coverage hurdles, obtaining Dupixent for off-label use can be difficult,” Dr. Strowd said.
“In academic medicine, we can obtain drugs for our patients that community doctors may not get approval for,” Dr. Fassett added. “Community doctors can use information in the medical literature and in news articles to press insurance companies to spend money to provide their patients with Dupixent.”
The experts who commented have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Diffuse Annular Plaques in an Infant
The Diagnosis: Neonatal Lupus Erythematosus
A review of the medical records of the patient’s mother from her first pregnancy revealed positive anti-Ro/SSA (Sjögren syndrome A) (>8.0 U [reference range <1.0 U]) and anti-La/SSB (Sjögren syndrome B) antibodies (>8.0 U [reference range <1.0 U]), which were reconfirmed during her pregnancy with our patient (the second child). The patient’s older brother was diagnosed with neonatal lupus erythematosus (NLE) 2 years prior at 1 month of age; therefore, the mother took hydroxychloroquine during the pregnancy with the second child to help prevent heart block if the child was diagnosed with NLE. Given the family history, positive antibodies in the mother, and clinical presentation, our patient was diagnosed with NLE. He was referred to a pediatric cardiologist and pediatrician to continue the workup of systemic manifestations of NLE and to rule out the presence of congenital heart block. The rash resolved 6 months after the initial presentation, and he did not develop any systemic manifestations of NLE.
Neonatal lupus erythematosus is a rare acquired autoimmune disorder caused by the placental transfer of anti-Ro/SSA and anti-La/SSB antibodies and less commonly anti-U1 ribonucleoprotein antinuclear autoantibodies.1,2 Approximately 1% to 2% of mothers with these positive antibodies will have infants affected with NLE.2 The annual prevalence of NLE in the United States is approximately 1 in 20,000 live births. Mothers of children with NLE most commonly have clinical Sjögren syndrome; however, anti-Ro/SSA and anti-LA/SSB antibodies may be present in 0.1% to 1.5% of healthy women, and 25% to 60% of women with autoimmune disease may be asymptomatic.1 As demonstrated in our case, when there is a family history of NLE in an infant from an earlier pregnancy, the risk for NLE increases to 17% to 20% in subsequent pregnancies1,3 and up to 25% in subsequent pregnancies if the initial child was diagnosed with a congenital heart block in the setting of NLE.1
Neonatal lupus erythematosus classically presents as annular erythematous macules and plaques with central scaling, telangictasia, atrophy, and pigmentary changes. It may start on the scalp and face and spread caudally.1,2 Patients may develop these lesions after UV exposure, and 80% of infants may not have dermatologic findings at birth. Importantly, 40% to 60% of mothers may be asymptomatic at the time of presentation of their child’s NLE.1 The diagnosis can be confirmed via antibody testing in the mother and/or infant. If performed, a punch biopsy shows interface dermatitis, vacuolar degeneration, and possible periadnexal lymphocytic infiltrates on histopathology.1,2
Management of cutaneous NLE includes sun protection (eg, application of sunscreen) and topical corticosteroids. Most dermatologic manifestations of NLE are transient, resolving after clearance of maternal IgG antibodies in 6 to 9 months; however, some telangiectasia, dyspigmentation, and atrophic scarring may persist.1-3
Neonatal lupus erythematosus also may have hepatobiliary, cardiac, hematologic, and less commonly neurologic manifestations. Hepatobiliary manifestations usually present as hepatomegaly or asymptomatic elevated transaminases or γ-glutamyl transferase.1,3 Approximately 10% to 20% of infants with NLE may present with transient anemia and thrombocytopenia.1 Cardiac manifestations are permanent and may require pacemaker implantation.1,3 The incidence of a congenital heart block in infants with NLE is 15% to 30%.3 Cardiac NLE most commonly injures the conductive tissue, leading to a congenital atrioventricular block. The development of a congenital heart block develops in the 18th to 24th week of gestation. Manifestations of a more advanced condition can include dilation of the ascending aorta and dilated cardiomyopathy.1 As such, patients need to be followed by a pediatric cardiologist for monitoring and treatment of any cardiac manifestations.
The overall prognosis of infants affected with NLE varies. Cardiac involvement is associated with a poor prognosis, while isolated cutaneous involvement requires little treatment and portends a favorable prognosis. It is critical for dermatologists to recognize NLE to refer patients to appropriate specialists to investigate and further monitor possible extracutaneous manifestations. With an understanding of the increased risk for a congenital heart block and NLE in subsequent pregnancies, mothers with positive anti-Ro/La antibodies should receive timely counseling and screening. In expectant mothers with suspected autoimmune disease, testing for antinuclear antibodies and SSA and SSB antibodies can be considered, as administration of hydroxychloroquine or prenatal systemic corticosteroids has proven to be effective in preventing a congenital heart block.1 Our patient was followed by pediatric cardiology and was not found to have a congenital heart block.
The differential diagnosis includes other causes of annular erythema in infants, as NLE can mimic several conditions. Tinea corporis may present as scaly annular plaques with central clearing; however, it rarely is encountered fulminantly in neonates.4 Erythema multiforme is a mucocutaneous hypersensitivy reaction distinguished by targetoid morphology.5 It is an exceedingly rare diagnosis in neonates; the average pediatric age of onset is 5.6 years.6 Erythema multiforme often is associated with an infection, most commonly herpes simplex virus,5 and mucosal involvement is common.6 Urticaria multiforme (also known as acute annular urticaria) is a benign disease that appears between 2 months to 3 years of age with blanchable urticarial plaques that likely are triggered by viral or bacterial infections, antibiotics, or vaccines.6 Specific lesions usually will resolve within 24 hours. Annular erythema of infancy is a benign and asymptomatic gyrate erythema that presents as annular plaques with palpable borders that spread centrifugally in patients younger than 1 year. Notably, lesions should periodically fade and may reappear cyclically for months to years. Evaluation for underlying disease usually is negative.6
- Derdulska JM, Rudnicka L, Szykut-Badaczewska A, et al. Neonatal lupus erythematosus—practical guidelines. J Perinat Med. 2021;49:529-538. doi:10.1515/jpm-2020-0543
- Wu J, Berk-Krauss J, Glick SA. Neonatal lupus erythematosus. JAMA Dermatol. 2021;157:590. doi:10.1001/jamadermatol.2021.0041
- Hon KL, Leung AK. Neonatal lupus erythematosus. Autoimmune Dis. 2012;2012:301274. doi:10.1155/2012/301274
- Khare AK, Gupta LK, Mittal A, et al. Neonatal tinea corporis. Indian J Dermatol. 2010;55:201. doi:10.4103/0019-5154.6274
- Ang-Tiu CU, Nicolas ME. Erythema multiforme in a 25-day old neonate. Pediatr Dermatol. 2013;30:E118-E120. doi:10.1111 /j.1525-1470.2012.01873.x
- Agnihotri G, Tsoukas MM. Annular skin lesions in infancy [published online February 3, 2022]. Clin Dermatol. 2022;40:505-512. doi:10.1016/j.clindermatol.2021.12.011
The Diagnosis: Neonatal Lupus Erythematosus
A review of the medical records of the patient’s mother from her first pregnancy revealed positive anti-Ro/SSA (Sjögren syndrome A) (>8.0 U [reference range <1.0 U]) and anti-La/SSB (Sjögren syndrome B) antibodies (>8.0 U [reference range <1.0 U]), which were reconfirmed during her pregnancy with our patient (the second child). The patient’s older brother was diagnosed with neonatal lupus erythematosus (NLE) 2 years prior at 1 month of age; therefore, the mother took hydroxychloroquine during the pregnancy with the second child to help prevent heart block if the child was diagnosed with NLE. Given the family history, positive antibodies in the mother, and clinical presentation, our patient was diagnosed with NLE. He was referred to a pediatric cardiologist and pediatrician to continue the workup of systemic manifestations of NLE and to rule out the presence of congenital heart block. The rash resolved 6 months after the initial presentation, and he did not develop any systemic manifestations of NLE.
Neonatal lupus erythematosus is a rare acquired autoimmune disorder caused by the placental transfer of anti-Ro/SSA and anti-La/SSB antibodies and less commonly anti-U1 ribonucleoprotein antinuclear autoantibodies.1,2 Approximately 1% to 2% of mothers with these positive antibodies will have infants affected with NLE.2 The annual prevalence of NLE in the United States is approximately 1 in 20,000 live births. Mothers of children with NLE most commonly have clinical Sjögren syndrome; however, anti-Ro/SSA and anti-LA/SSB antibodies may be present in 0.1% to 1.5% of healthy women, and 25% to 60% of women with autoimmune disease may be asymptomatic.1 As demonstrated in our case, when there is a family history of NLE in an infant from an earlier pregnancy, the risk for NLE increases to 17% to 20% in subsequent pregnancies1,3 and up to 25% in subsequent pregnancies if the initial child was diagnosed with a congenital heart block in the setting of NLE.1
Neonatal lupus erythematosus classically presents as annular erythematous macules and plaques with central scaling, telangictasia, atrophy, and pigmentary changes. It may start on the scalp and face and spread caudally.1,2 Patients may develop these lesions after UV exposure, and 80% of infants may not have dermatologic findings at birth. Importantly, 40% to 60% of mothers may be asymptomatic at the time of presentation of their child’s NLE.1 The diagnosis can be confirmed via antibody testing in the mother and/or infant. If performed, a punch biopsy shows interface dermatitis, vacuolar degeneration, and possible periadnexal lymphocytic infiltrates on histopathology.1,2
Management of cutaneous NLE includes sun protection (eg, application of sunscreen) and topical corticosteroids. Most dermatologic manifestations of NLE are transient, resolving after clearance of maternal IgG antibodies in 6 to 9 months; however, some telangiectasia, dyspigmentation, and atrophic scarring may persist.1-3
Neonatal lupus erythematosus also may have hepatobiliary, cardiac, hematologic, and less commonly neurologic manifestations. Hepatobiliary manifestations usually present as hepatomegaly or asymptomatic elevated transaminases or γ-glutamyl transferase.1,3 Approximately 10% to 20% of infants with NLE may present with transient anemia and thrombocytopenia.1 Cardiac manifestations are permanent and may require pacemaker implantation.1,3 The incidence of a congenital heart block in infants with NLE is 15% to 30%.3 Cardiac NLE most commonly injures the conductive tissue, leading to a congenital atrioventricular block. The development of a congenital heart block develops in the 18th to 24th week of gestation. Manifestations of a more advanced condition can include dilation of the ascending aorta and dilated cardiomyopathy.1 As such, patients need to be followed by a pediatric cardiologist for monitoring and treatment of any cardiac manifestations.
The overall prognosis of infants affected with NLE varies. Cardiac involvement is associated with a poor prognosis, while isolated cutaneous involvement requires little treatment and portends a favorable prognosis. It is critical for dermatologists to recognize NLE to refer patients to appropriate specialists to investigate and further monitor possible extracutaneous manifestations. With an understanding of the increased risk for a congenital heart block and NLE in subsequent pregnancies, mothers with positive anti-Ro/La antibodies should receive timely counseling and screening. In expectant mothers with suspected autoimmune disease, testing for antinuclear antibodies and SSA and SSB antibodies can be considered, as administration of hydroxychloroquine or prenatal systemic corticosteroids has proven to be effective in preventing a congenital heart block.1 Our patient was followed by pediatric cardiology and was not found to have a congenital heart block.
The differential diagnosis includes other causes of annular erythema in infants, as NLE can mimic several conditions. Tinea corporis may present as scaly annular plaques with central clearing; however, it rarely is encountered fulminantly in neonates.4 Erythema multiforme is a mucocutaneous hypersensitivy reaction distinguished by targetoid morphology.5 It is an exceedingly rare diagnosis in neonates; the average pediatric age of onset is 5.6 years.6 Erythema multiforme often is associated with an infection, most commonly herpes simplex virus,5 and mucosal involvement is common.6 Urticaria multiforme (also known as acute annular urticaria) is a benign disease that appears between 2 months to 3 years of age with blanchable urticarial plaques that likely are triggered by viral or bacterial infections, antibiotics, or vaccines.6 Specific lesions usually will resolve within 24 hours. Annular erythema of infancy is a benign and asymptomatic gyrate erythema that presents as annular plaques with palpable borders that spread centrifugally in patients younger than 1 year. Notably, lesions should periodically fade and may reappear cyclically for months to years. Evaluation for underlying disease usually is negative.6
The Diagnosis: Neonatal Lupus Erythematosus
A review of the medical records of the patient’s mother from her first pregnancy revealed positive anti-Ro/SSA (Sjögren syndrome A) (>8.0 U [reference range <1.0 U]) and anti-La/SSB (Sjögren syndrome B) antibodies (>8.0 U [reference range <1.0 U]), which were reconfirmed during her pregnancy with our patient (the second child). The patient’s older brother was diagnosed with neonatal lupus erythematosus (NLE) 2 years prior at 1 month of age; therefore, the mother took hydroxychloroquine during the pregnancy with the second child to help prevent heart block if the child was diagnosed with NLE. Given the family history, positive antibodies in the mother, and clinical presentation, our patient was diagnosed with NLE. He was referred to a pediatric cardiologist and pediatrician to continue the workup of systemic manifestations of NLE and to rule out the presence of congenital heart block. The rash resolved 6 months after the initial presentation, and he did not develop any systemic manifestations of NLE.
Neonatal lupus erythematosus is a rare acquired autoimmune disorder caused by the placental transfer of anti-Ro/SSA and anti-La/SSB antibodies and less commonly anti-U1 ribonucleoprotein antinuclear autoantibodies.1,2 Approximately 1% to 2% of mothers with these positive antibodies will have infants affected with NLE.2 The annual prevalence of NLE in the United States is approximately 1 in 20,000 live births. Mothers of children with NLE most commonly have clinical Sjögren syndrome; however, anti-Ro/SSA and anti-LA/SSB antibodies may be present in 0.1% to 1.5% of healthy women, and 25% to 60% of women with autoimmune disease may be asymptomatic.1 As demonstrated in our case, when there is a family history of NLE in an infant from an earlier pregnancy, the risk for NLE increases to 17% to 20% in subsequent pregnancies1,3 and up to 25% in subsequent pregnancies if the initial child was diagnosed with a congenital heart block in the setting of NLE.1
Neonatal lupus erythematosus classically presents as annular erythematous macules and plaques with central scaling, telangictasia, atrophy, and pigmentary changes. It may start on the scalp and face and spread caudally.1,2 Patients may develop these lesions after UV exposure, and 80% of infants may not have dermatologic findings at birth. Importantly, 40% to 60% of mothers may be asymptomatic at the time of presentation of their child’s NLE.1 The diagnosis can be confirmed via antibody testing in the mother and/or infant. If performed, a punch biopsy shows interface dermatitis, vacuolar degeneration, and possible periadnexal lymphocytic infiltrates on histopathology.1,2
Management of cutaneous NLE includes sun protection (eg, application of sunscreen) and topical corticosteroids. Most dermatologic manifestations of NLE are transient, resolving after clearance of maternal IgG antibodies in 6 to 9 months; however, some telangiectasia, dyspigmentation, and atrophic scarring may persist.1-3
Neonatal lupus erythematosus also may have hepatobiliary, cardiac, hematologic, and less commonly neurologic manifestations. Hepatobiliary manifestations usually present as hepatomegaly or asymptomatic elevated transaminases or γ-glutamyl transferase.1,3 Approximately 10% to 20% of infants with NLE may present with transient anemia and thrombocytopenia.1 Cardiac manifestations are permanent and may require pacemaker implantation.1,3 The incidence of a congenital heart block in infants with NLE is 15% to 30%.3 Cardiac NLE most commonly injures the conductive tissue, leading to a congenital atrioventricular block. The development of a congenital heart block develops in the 18th to 24th week of gestation. Manifestations of a more advanced condition can include dilation of the ascending aorta and dilated cardiomyopathy.1 As such, patients need to be followed by a pediatric cardiologist for monitoring and treatment of any cardiac manifestations.
The overall prognosis of infants affected with NLE varies. Cardiac involvement is associated with a poor prognosis, while isolated cutaneous involvement requires little treatment and portends a favorable prognosis. It is critical for dermatologists to recognize NLE to refer patients to appropriate specialists to investigate and further monitor possible extracutaneous manifestations. With an understanding of the increased risk for a congenital heart block and NLE in subsequent pregnancies, mothers with positive anti-Ro/La antibodies should receive timely counseling and screening. In expectant mothers with suspected autoimmune disease, testing for antinuclear antibodies and SSA and SSB antibodies can be considered, as administration of hydroxychloroquine or prenatal systemic corticosteroids has proven to be effective in preventing a congenital heart block.1 Our patient was followed by pediatric cardiology and was not found to have a congenital heart block.
The differential diagnosis includes other causes of annular erythema in infants, as NLE can mimic several conditions. Tinea corporis may present as scaly annular plaques with central clearing; however, it rarely is encountered fulminantly in neonates.4 Erythema multiforme is a mucocutaneous hypersensitivy reaction distinguished by targetoid morphology.5 It is an exceedingly rare diagnosis in neonates; the average pediatric age of onset is 5.6 years.6 Erythema multiforme often is associated with an infection, most commonly herpes simplex virus,5 and mucosal involvement is common.6 Urticaria multiforme (also known as acute annular urticaria) is a benign disease that appears between 2 months to 3 years of age with blanchable urticarial plaques that likely are triggered by viral or bacterial infections, antibiotics, or vaccines.6 Specific lesions usually will resolve within 24 hours. Annular erythema of infancy is a benign and asymptomatic gyrate erythema that presents as annular plaques with palpable borders that spread centrifugally in patients younger than 1 year. Notably, lesions should periodically fade and may reappear cyclically for months to years. Evaluation for underlying disease usually is negative.6
- Derdulska JM, Rudnicka L, Szykut-Badaczewska A, et al. Neonatal lupus erythematosus—practical guidelines. J Perinat Med. 2021;49:529-538. doi:10.1515/jpm-2020-0543
- Wu J, Berk-Krauss J, Glick SA. Neonatal lupus erythematosus. JAMA Dermatol. 2021;157:590. doi:10.1001/jamadermatol.2021.0041
- Hon KL, Leung AK. Neonatal lupus erythematosus. Autoimmune Dis. 2012;2012:301274. doi:10.1155/2012/301274
- Khare AK, Gupta LK, Mittal A, et al. Neonatal tinea corporis. Indian J Dermatol. 2010;55:201. doi:10.4103/0019-5154.6274
- Ang-Tiu CU, Nicolas ME. Erythema multiforme in a 25-day old neonate. Pediatr Dermatol. 2013;30:E118-E120. doi:10.1111 /j.1525-1470.2012.01873.x
- Agnihotri G, Tsoukas MM. Annular skin lesions in infancy [published online February 3, 2022]. Clin Dermatol. 2022;40:505-512. doi:10.1016/j.clindermatol.2021.12.011
- Derdulska JM, Rudnicka L, Szykut-Badaczewska A, et al. Neonatal lupus erythematosus—practical guidelines. J Perinat Med. 2021;49:529-538. doi:10.1515/jpm-2020-0543
- Wu J, Berk-Krauss J, Glick SA. Neonatal lupus erythematosus. JAMA Dermatol. 2021;157:590. doi:10.1001/jamadermatol.2021.0041
- Hon KL, Leung AK. Neonatal lupus erythematosus. Autoimmune Dis. 2012;2012:301274. doi:10.1155/2012/301274
- Khare AK, Gupta LK, Mittal A, et al. Neonatal tinea corporis. Indian J Dermatol. 2010;55:201. doi:10.4103/0019-5154.6274
- Ang-Tiu CU, Nicolas ME. Erythema multiforme in a 25-day old neonate. Pediatr Dermatol. 2013;30:E118-E120. doi:10.1111 /j.1525-1470.2012.01873.x
- Agnihotri G, Tsoukas MM. Annular skin lesions in infancy [published online February 3, 2022]. Clin Dermatol. 2022;40:505-512. doi:10.1016/j.clindermatol.2021.12.011
A 5-week-old infant boy presented with a rash at birth (left). The pregnancy was full term without complications, and he was otherwise healthy. A family history revealed that his older brother developed a similar rash 2 weeks after birth (right). Physical examination revealed polycyclic annular patches with an erythematous border and central clearing diffusely located on the trunk, extremities, scalp, and face with periorbital edema.
EMA validates marketing authorization application for delgocitinib cream
The which marks the beginning of the review process for the treatment by the EMA’s Committee for Medicinal Products for Human Use.
Delgocitinib is an investigational topical pan–Janus kinase inhibitor that inhibits activation of the JAK-STAT pathway.
The development follows results reported from two phase 3 clinical trials known as DELTA 1 and DELTA 2, which evaluated the safety and efficacy of delgocitinib cream applications twice per day compared with a vehicle cream in adults with mild to severe chronic hand eczema. Results of DELTA 1 were presented at the 2023 annual meeting of the American Academy of Dermatology. A multisite, open-label extension trial known as DELTA 3 is still in progress.
According to a press release from LEO Pharma, which is developing the product, the efficacy and safety of delgocitinib cream have not been evaluated by any regulatory authority. In 2020, the drug was granted fast-track designation by the Food and Drug Administration for the potential treatment of adults with moderate to severe chronic hand eczema. There are currently no treatment options available in the United States specifically approved for treating the condition.
The which marks the beginning of the review process for the treatment by the EMA’s Committee for Medicinal Products for Human Use.
Delgocitinib is an investigational topical pan–Janus kinase inhibitor that inhibits activation of the JAK-STAT pathway.
The development follows results reported from two phase 3 clinical trials known as DELTA 1 and DELTA 2, which evaluated the safety and efficacy of delgocitinib cream applications twice per day compared with a vehicle cream in adults with mild to severe chronic hand eczema. Results of DELTA 1 were presented at the 2023 annual meeting of the American Academy of Dermatology. A multisite, open-label extension trial known as DELTA 3 is still in progress.
According to a press release from LEO Pharma, which is developing the product, the efficacy and safety of delgocitinib cream have not been evaluated by any regulatory authority. In 2020, the drug was granted fast-track designation by the Food and Drug Administration for the potential treatment of adults with moderate to severe chronic hand eczema. There are currently no treatment options available in the United States specifically approved for treating the condition.
The which marks the beginning of the review process for the treatment by the EMA’s Committee for Medicinal Products for Human Use.
Delgocitinib is an investigational topical pan–Janus kinase inhibitor that inhibits activation of the JAK-STAT pathway.
The development follows results reported from two phase 3 clinical trials known as DELTA 1 and DELTA 2, which evaluated the safety and efficacy of delgocitinib cream applications twice per day compared with a vehicle cream in adults with mild to severe chronic hand eczema. Results of DELTA 1 were presented at the 2023 annual meeting of the American Academy of Dermatology. A multisite, open-label extension trial known as DELTA 3 is still in progress.
According to a press release from LEO Pharma, which is developing the product, the efficacy and safety of delgocitinib cream have not been evaluated by any regulatory authority. In 2020, the drug was granted fast-track designation by the Food and Drug Administration for the potential treatment of adults with moderate to severe chronic hand eczema. There are currently no treatment options available in the United States specifically approved for treating the condition.
Low-dose oral minoxidil for female pattern hair loss: Benefits, impact on BP, heart rate evaluated
results from a small retrospective analysis showed.
“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.
At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)
To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.
The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.
Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.
The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).
The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.
At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”
He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.
The researchers reported having no relevant disclosures, and there was no funding source for the study.
results from a small retrospective analysis showed.
“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.
At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)
To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.
The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.
Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.
The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).
The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.
At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”
He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.
The researchers reported having no relevant disclosures, and there was no funding source for the study.
results from a small retrospective analysis showed.
“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.
At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)
To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.
The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.
Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.
The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).
The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.
At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”
He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.
The researchers reported having no relevant disclosures, and there was no funding source for the study.
FROM JAAD INTERNATIONAL
What's the diagnosis?
At the week follow-up, the lesions were unchanged and the swelling on the left lateral eyebrow was worsening. A biopsy of the yellow lesion on the back and one of the scaly papules on the abdomen was performed. A fungal and bacterial cultures were also ordered.
He was referred to ophthalmology for evaluation of the eyelid swelling and an ultrasound was requested.
The skin biopsy showed a clonal proliferation of reniform histiocytes with eosinophils within the dermis. The cells were positive for S100, CD207 (langerin), and CD1a and negative for pancytokeratin and Melan-A, supportive of the diagnosis of Langerhans cell histiocytosis (LCH).
Diagnosis
The patient was admitted to the hospital, where a skeletal survey was performed, which showed an asymmetric lucency involving the left frontal calvarium extending to the superior lateral orbital rim. The brain MRI demonstrated a destructive avidly enhancing soft-tissue process which involved the superior left orbital rim likely with some degree of intracranial extension. This lesion exerts mass effect upon surrounding structures to the left ocular globe. With the skin and skeletal findings, the patient was diagnosed with LCH. His blood count was significant for thrombocytopenia. His liver and kidney function were normal. His electrolytes were also with in normal range. He was started on chemotherapy with vinblastine and systemic corticosteroids with resolution of the rash and decrease on the size of the lesion on the orbit within a few weeks.
Infantile LCH is a rare neoplastic disorder of hematopoietic myeloid precursor cells caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway, particularly BRAF-V600E mutation. White male children are mostly affected, with a peak incidence of 1-3 years of age. Nine out of 10 children with cutaneous involvement also have multisystemic disease, such as the case of our patient. LCH is classified as single or multisystem organ disease. Two-thirds of the cases present with single system involvement. Organs most commonly affected include the bone (the skull being the most commonly affected), skin, and high-risk organs like the liver, spleen, and bone marrow, and less commonly the lungs, lymph nodes, and central nervous system. Some patients can present with fever, lethargy, and weight loss. None were noted in our patient.
Skin findings of LCH can have multiple morphologies and presentations and often described as a big mimicker. In young infants like our patient, the seborrheic dermatitis–mimicking type is often seen. In other cases, the skin lesions can appear eczematous, petechial, with scabbing, crusting, or purpura. Xanthoma-like lesions, like that one our patient had in the back, have also been described. Resistant diaper dermatitis and cradle cap should prompt the clinician to think about LCH. Lesions can be so varied that can present with hypopigmentation (vitiligo like), hyperpigmentation, varicella-like papulo-pustules, and red blue nodules within others. Oral mucosa and nail involvement can also occur.
Bone involvement can present as soft-tissue mass with swelling and pain as it occur in our patient.
Endocrinopathies have been described in patients with LCH including diabetes insipidus, growth hormone deficiency, and less likely thyroid disease.
Multidisciplinary care
The diagnosis of LCH in infants necessitates a combination of clinical, radiological, and histopathologic findings. In infants, cutaneous involvement is a frequent initial presentation, with characteristic lesions that are often misdiagnosed as other dermatologic conditions. Timely recognition of these lesions and appropriate skin biopsies for histological examination are essential steps in achieving an accurate diagnosis.
Radiological imaging, including x-rays, CT, and MRI, plays a crucial role in assessing the extent of involvement.
The management of LCH in infants requires a well-coordinated multidisciplinary approach involving pediatric oncologists, dermatologists, radiologists, orthopedic surgeons, and other relevant specialists. Treatment strategies vary depending on the extent of disease involvement and the presence of risk factors. In localized cases, observation with close monitoring may be considered, as some cases of LCH in infants may undergo spontaneous regression. However, cases with severe symptoms, extensive organ involvement, or high-risk features may require systemic therapies.
Chemotherapy agents, including vinblastine and prednisone have been utilized in the treatment of infantile LCH with varying success. The selection of treatment regimens should be tailored to each individual case, considering disease severity, potential toxicities, and long-term effects. In cases of bone lesions causing significant deformities or functional impairment, surgical intervention may be necessary. Skin only disease can be treated with topical corticosteroids.
Prognosis
Survival rates in patients with single-organ involvement without risk-organ involvement is close to 100% and with risk-organ involvement of 98% at 5 years.
Long-term follow-up is essential for infants diagnosed with LCH, as recurrence and late effects can occur even after successful treatment. Continued monitoring allows for the timely detection of relapses or the development of secondary complications.
Infants thought to have common skin conditions like eczema, seborrheic dermatitis, or diaper dermatitis not responding to treatment should be referred to pediatric dermatology for evaluation to rule out the possibility of LCH.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1035-44.
Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1047-56.
Leung AKC et al. World J Pediatr. 2019 Dec;15(6):536-45.
At the week follow-up, the lesions were unchanged and the swelling on the left lateral eyebrow was worsening. A biopsy of the yellow lesion on the back and one of the scaly papules on the abdomen was performed. A fungal and bacterial cultures were also ordered.
He was referred to ophthalmology for evaluation of the eyelid swelling and an ultrasound was requested.
The skin biopsy showed a clonal proliferation of reniform histiocytes with eosinophils within the dermis. The cells were positive for S100, CD207 (langerin), and CD1a and negative for pancytokeratin and Melan-A, supportive of the diagnosis of Langerhans cell histiocytosis (LCH).
Diagnosis
The patient was admitted to the hospital, where a skeletal survey was performed, which showed an asymmetric lucency involving the left frontal calvarium extending to the superior lateral orbital rim. The brain MRI demonstrated a destructive avidly enhancing soft-tissue process which involved the superior left orbital rim likely with some degree of intracranial extension. This lesion exerts mass effect upon surrounding structures to the left ocular globe. With the skin and skeletal findings, the patient was diagnosed with LCH. His blood count was significant for thrombocytopenia. His liver and kidney function were normal. His electrolytes were also with in normal range. He was started on chemotherapy with vinblastine and systemic corticosteroids with resolution of the rash and decrease on the size of the lesion on the orbit within a few weeks.
Infantile LCH is a rare neoplastic disorder of hematopoietic myeloid precursor cells caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway, particularly BRAF-V600E mutation. White male children are mostly affected, with a peak incidence of 1-3 years of age. Nine out of 10 children with cutaneous involvement also have multisystemic disease, such as the case of our patient. LCH is classified as single or multisystem organ disease. Two-thirds of the cases present with single system involvement. Organs most commonly affected include the bone (the skull being the most commonly affected), skin, and high-risk organs like the liver, spleen, and bone marrow, and less commonly the lungs, lymph nodes, and central nervous system. Some patients can present with fever, lethargy, and weight loss. None were noted in our patient.
Skin findings of LCH can have multiple morphologies and presentations and often described as a big mimicker. In young infants like our patient, the seborrheic dermatitis–mimicking type is often seen. In other cases, the skin lesions can appear eczematous, petechial, with scabbing, crusting, or purpura. Xanthoma-like lesions, like that one our patient had in the back, have also been described. Resistant diaper dermatitis and cradle cap should prompt the clinician to think about LCH. Lesions can be so varied that can present with hypopigmentation (vitiligo like), hyperpigmentation, varicella-like papulo-pustules, and red blue nodules within others. Oral mucosa and nail involvement can also occur.
Bone involvement can present as soft-tissue mass with swelling and pain as it occur in our patient.
Endocrinopathies have been described in patients with LCH including diabetes insipidus, growth hormone deficiency, and less likely thyroid disease.
Multidisciplinary care
The diagnosis of LCH in infants necessitates a combination of clinical, radiological, and histopathologic findings. In infants, cutaneous involvement is a frequent initial presentation, with characteristic lesions that are often misdiagnosed as other dermatologic conditions. Timely recognition of these lesions and appropriate skin biopsies for histological examination are essential steps in achieving an accurate diagnosis.
Radiological imaging, including x-rays, CT, and MRI, plays a crucial role in assessing the extent of involvement.
The management of LCH in infants requires a well-coordinated multidisciplinary approach involving pediatric oncologists, dermatologists, radiologists, orthopedic surgeons, and other relevant specialists. Treatment strategies vary depending on the extent of disease involvement and the presence of risk factors. In localized cases, observation with close monitoring may be considered, as some cases of LCH in infants may undergo spontaneous regression. However, cases with severe symptoms, extensive organ involvement, or high-risk features may require systemic therapies.
Chemotherapy agents, including vinblastine and prednisone have been utilized in the treatment of infantile LCH with varying success. The selection of treatment regimens should be tailored to each individual case, considering disease severity, potential toxicities, and long-term effects. In cases of bone lesions causing significant deformities or functional impairment, surgical intervention may be necessary. Skin only disease can be treated with topical corticosteroids.
Prognosis
Survival rates in patients with single-organ involvement without risk-organ involvement is close to 100% and with risk-organ involvement of 98% at 5 years.
Long-term follow-up is essential for infants diagnosed with LCH, as recurrence and late effects can occur even after successful treatment. Continued monitoring allows for the timely detection of relapses or the development of secondary complications.
Infants thought to have common skin conditions like eczema, seborrheic dermatitis, or diaper dermatitis not responding to treatment should be referred to pediatric dermatology for evaluation to rule out the possibility of LCH.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1035-44.
Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1047-56.
Leung AKC et al. World J Pediatr. 2019 Dec;15(6):536-45.
At the week follow-up, the lesions were unchanged and the swelling on the left lateral eyebrow was worsening. A biopsy of the yellow lesion on the back and one of the scaly papules on the abdomen was performed. A fungal and bacterial cultures were also ordered.
He was referred to ophthalmology for evaluation of the eyelid swelling and an ultrasound was requested.
The skin biopsy showed a clonal proliferation of reniform histiocytes with eosinophils within the dermis. The cells were positive for S100, CD207 (langerin), and CD1a and negative for pancytokeratin and Melan-A, supportive of the diagnosis of Langerhans cell histiocytosis (LCH).
Diagnosis
The patient was admitted to the hospital, where a skeletal survey was performed, which showed an asymmetric lucency involving the left frontal calvarium extending to the superior lateral orbital rim. The brain MRI demonstrated a destructive avidly enhancing soft-tissue process which involved the superior left orbital rim likely with some degree of intracranial extension. This lesion exerts mass effect upon surrounding structures to the left ocular globe. With the skin and skeletal findings, the patient was diagnosed with LCH. His blood count was significant for thrombocytopenia. His liver and kidney function were normal. His electrolytes were also with in normal range. He was started on chemotherapy with vinblastine and systemic corticosteroids with resolution of the rash and decrease on the size of the lesion on the orbit within a few weeks.
Infantile LCH is a rare neoplastic disorder of hematopoietic myeloid precursor cells caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway, particularly BRAF-V600E mutation. White male children are mostly affected, with a peak incidence of 1-3 years of age. Nine out of 10 children with cutaneous involvement also have multisystemic disease, such as the case of our patient. LCH is classified as single or multisystem organ disease. Two-thirds of the cases present with single system involvement. Organs most commonly affected include the bone (the skull being the most commonly affected), skin, and high-risk organs like the liver, spleen, and bone marrow, and less commonly the lungs, lymph nodes, and central nervous system. Some patients can present with fever, lethargy, and weight loss. None were noted in our patient.
Skin findings of LCH can have multiple morphologies and presentations and often described as a big mimicker. In young infants like our patient, the seborrheic dermatitis–mimicking type is often seen. In other cases, the skin lesions can appear eczematous, petechial, with scabbing, crusting, or purpura. Xanthoma-like lesions, like that one our patient had in the back, have also been described. Resistant diaper dermatitis and cradle cap should prompt the clinician to think about LCH. Lesions can be so varied that can present with hypopigmentation (vitiligo like), hyperpigmentation, varicella-like papulo-pustules, and red blue nodules within others. Oral mucosa and nail involvement can also occur.
Bone involvement can present as soft-tissue mass with swelling and pain as it occur in our patient.
Endocrinopathies have been described in patients with LCH including diabetes insipidus, growth hormone deficiency, and less likely thyroid disease.
Multidisciplinary care
The diagnosis of LCH in infants necessitates a combination of clinical, radiological, and histopathologic findings. In infants, cutaneous involvement is a frequent initial presentation, with characteristic lesions that are often misdiagnosed as other dermatologic conditions. Timely recognition of these lesions and appropriate skin biopsies for histological examination are essential steps in achieving an accurate diagnosis.
Radiological imaging, including x-rays, CT, and MRI, plays a crucial role in assessing the extent of involvement.
The management of LCH in infants requires a well-coordinated multidisciplinary approach involving pediatric oncologists, dermatologists, radiologists, orthopedic surgeons, and other relevant specialists. Treatment strategies vary depending on the extent of disease involvement and the presence of risk factors. In localized cases, observation with close monitoring may be considered, as some cases of LCH in infants may undergo spontaneous regression. However, cases with severe symptoms, extensive organ involvement, or high-risk features may require systemic therapies.
Chemotherapy agents, including vinblastine and prednisone have been utilized in the treatment of infantile LCH with varying success. The selection of treatment regimens should be tailored to each individual case, considering disease severity, potential toxicities, and long-term effects. In cases of bone lesions causing significant deformities or functional impairment, surgical intervention may be necessary. Skin only disease can be treated with topical corticosteroids.
Prognosis
Survival rates in patients with single-organ involvement without risk-organ involvement is close to 100% and with risk-organ involvement of 98% at 5 years.
Long-term follow-up is essential for infants diagnosed with LCH, as recurrence and late effects can occur even after successful treatment. Continued monitoring allows for the timely detection of relapses or the development of secondary complications.
Infants thought to have common skin conditions like eczema, seborrheic dermatitis, or diaper dermatitis not responding to treatment should be referred to pediatric dermatology for evaluation to rule out the possibility of LCH.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1035-44.
Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1047-56.
Leung AKC et al. World J Pediatr. 2019 Dec;15(6):536-45.
A 4-month male was referred to the pediatric dermatology clinic for a rash on the scalp, torso, and the diaper area since he was 2 months of age. He has been treated with nystatin, clotrimazole, and zinc oxide paste with partial improvement. After 2 months of partial improvement the rash worsened again, and he was referred to pediatric dermatology. The mother also reported asymptomatic left upper lateral eyebrow swelling noted a few weeks prior.
On the torso and diaper area, he had multiple scaly pink papules. On the groin he had eroded pink scaly plaques (Picture 2).
On his back he had a 3-mm yellow papule (Picture 3).
