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Study: Lifetime Cost of Vyjuvek Gene Therapy for DEB Could Be $15-$22 Million
according to the authors of a new study.
The US Food and Drug Administration (FDA) approved Vyjuvek (Krystal Biotech) in May 2023 for the treatment of wounds in patients ages 6 months and older with dystrophic epidermolysis bullosa (DEB), which includes two types, the most severe form (autosomal recessive, or RDEB) and the autosomal dominant form of DEB (DDEB), which tends to be milder.
Treatment with Vyjuvek “represents an important advance in the treatment of RDEB,” wrote Adam J.N. Raymakers, PhD, and colleagues at the Program on Regulation, Therapeutics, and Law; the Department of Dermatology; and the Division of Pulmonary and Critical Care Medicine at Brigham & Women’s Hospital in Boston, Massachusetts, in their paper, published in JAMA Dermatology. But the price “will be high, potentially limiting patients’ access to it,” they added. Evidence to support it in DDEB “is less conclusive,” they wrote, noting that the pivotal phase 3 study that led to approval included one patient with DDEB.
“The wider indication granted by the FDA may lead to friction between payers on the one hand and patients and physicians on the other,” they wrote, noting a potential minimum price of $300,000 per patient a year, which was based on Krystal’s regulatory filings.
There is no cure for DEB. Vyjuvek, applied as a gel on an ongoing basis, uses a nonreplicating herpes simplex virus type 1 vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure.
The authors estimated that in the United States, 894 individuals – largely children – with both forms of the disease would be eligible for Vyjuvek treatment in the first year. Based on the $300,000 price, spending on gene therapy could range from $179 million to $357 million for those 894 patients, they reported in the study.
Over the first 3 years, spending could range as high as $1 billion, the authors estimated. Even if patients with only the most severe disease (RDEB) — an estimated 442 patients — received treatment, spending could be $132 million and up to $400 million or more over the first 3 years, they wrote.
Some media outlets have reported that Vyjuvek could cost as much as $600,000, said Dr. Raymakers, a research fellow. That price “would double all of our estimates,” he told this news organization.
The study assumed that patients with RDEB would only live to age 50, which led to a lifetime cost estimate of $15 million. But that is likely a conservative estimate, he and his coauthors wrote, noting that many patients with RDEB die from squamous cell carcinoma, but that Vyjuvek could, by attenuating skin damage, also potentially prevent skin cancer.
Dr. Raymakers said he and his colleagues began their study when Vyjuvek was approved, and thus they did not have any real-world data on the price or payer responses. Their estimates also did not include differing dosing regimens, which also could change their spending figures.
Krystal Biotech recently reported that in its third quarter of 2023 – representing just 1 month of Vyjuvek availability – it received requests to begin treatment for 284 patients from 136 unique clinicians. Twenty percent of the start requests were for patients with the milder form (DDEB), and a third of all the requests were for patients 10 years of age or younger. The company also said that it had “received positive coverage determinations from all major commercial national health plans” and that it was on track to receive approval from most state Medicaid plans.
In 1 month, Krystal reported net Vyjuvek revenues of $8.6 million.
The authors suggested that one way to evaluate Vyjuvek’s value — especially for those with DDEB — would be through a cost-effectiveness study. While important, a cost-effectiveness study would not get at the impact on a payer, said Dr. Raymakers. “Something can be cost-effective but unaffordable to the system,” he said.
“When there’s one of these very expensive therapies, that’s one thing,” he said. “But when there’s more and more coming to market, you wonder how much can be tolerated,” said Dr. Raymakers.
CMS Launching Gene Therapy Program
The Biden administration recently announced that it was launching a program aimed at increasing access, curbing costs, and ensuring value of gene therapies, starting with sickle cell disease. The program will begin in early 2025. Among other aspects, the federal government will negotiate the price of the product with the manufacturer.
“The goal of the Cell and Gene Therapy Access Model is to increase access to innovative cell and gene therapies for people with Medicaid by making it easier for states to pay for these therapies,” said Liz Fowler, CMS Deputy Administrator and Director of the CMS Innovation Center, in a statement announcing the program.
Whether the new program takes a look at Vyjuvek – and when – is not clear.
But the authors of the study noted that the lifetime costs of treating a patient with Vyjuvek “exceed the costs of all other one-time gene therapies for other diseases.” And they wrote, even at the most conservative estimates, Vyjuvek “will be the most expensive gene therapy currently marketed in the US.”
The study was funded by a grant from Arnold Ventures, grants from the Kaiser Permanente Institute for Health Policy, the Commonwealth Fund, and the National Heart, Lung, and Blood Institute. Dr. Raymakers and co-authors reported no financial relationships relevant to the work.
according to the authors of a new study.
The US Food and Drug Administration (FDA) approved Vyjuvek (Krystal Biotech) in May 2023 for the treatment of wounds in patients ages 6 months and older with dystrophic epidermolysis bullosa (DEB), which includes two types, the most severe form (autosomal recessive, or RDEB) and the autosomal dominant form of DEB (DDEB), which tends to be milder.
Treatment with Vyjuvek “represents an important advance in the treatment of RDEB,” wrote Adam J.N. Raymakers, PhD, and colleagues at the Program on Regulation, Therapeutics, and Law; the Department of Dermatology; and the Division of Pulmonary and Critical Care Medicine at Brigham & Women’s Hospital in Boston, Massachusetts, in their paper, published in JAMA Dermatology. But the price “will be high, potentially limiting patients’ access to it,” they added. Evidence to support it in DDEB “is less conclusive,” they wrote, noting that the pivotal phase 3 study that led to approval included one patient with DDEB.
“The wider indication granted by the FDA may lead to friction between payers on the one hand and patients and physicians on the other,” they wrote, noting a potential minimum price of $300,000 per patient a year, which was based on Krystal’s regulatory filings.
There is no cure for DEB. Vyjuvek, applied as a gel on an ongoing basis, uses a nonreplicating herpes simplex virus type 1 vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure.
The authors estimated that in the United States, 894 individuals – largely children – with both forms of the disease would be eligible for Vyjuvek treatment in the first year. Based on the $300,000 price, spending on gene therapy could range from $179 million to $357 million for those 894 patients, they reported in the study.
Over the first 3 years, spending could range as high as $1 billion, the authors estimated. Even if patients with only the most severe disease (RDEB) — an estimated 442 patients — received treatment, spending could be $132 million and up to $400 million or more over the first 3 years, they wrote.
Some media outlets have reported that Vyjuvek could cost as much as $600,000, said Dr. Raymakers, a research fellow. That price “would double all of our estimates,” he told this news organization.
The study assumed that patients with RDEB would only live to age 50, which led to a lifetime cost estimate of $15 million. But that is likely a conservative estimate, he and his coauthors wrote, noting that many patients with RDEB die from squamous cell carcinoma, but that Vyjuvek could, by attenuating skin damage, also potentially prevent skin cancer.
Dr. Raymakers said he and his colleagues began their study when Vyjuvek was approved, and thus they did not have any real-world data on the price or payer responses. Their estimates also did not include differing dosing regimens, which also could change their spending figures.
Krystal Biotech recently reported that in its third quarter of 2023 – representing just 1 month of Vyjuvek availability – it received requests to begin treatment for 284 patients from 136 unique clinicians. Twenty percent of the start requests were for patients with the milder form (DDEB), and a third of all the requests were for patients 10 years of age or younger. The company also said that it had “received positive coverage determinations from all major commercial national health plans” and that it was on track to receive approval from most state Medicaid plans.
In 1 month, Krystal reported net Vyjuvek revenues of $8.6 million.
The authors suggested that one way to evaluate Vyjuvek’s value — especially for those with DDEB — would be through a cost-effectiveness study. While important, a cost-effectiveness study would not get at the impact on a payer, said Dr. Raymakers. “Something can be cost-effective but unaffordable to the system,” he said.
“When there’s one of these very expensive therapies, that’s one thing,” he said. “But when there’s more and more coming to market, you wonder how much can be tolerated,” said Dr. Raymakers.
CMS Launching Gene Therapy Program
The Biden administration recently announced that it was launching a program aimed at increasing access, curbing costs, and ensuring value of gene therapies, starting with sickle cell disease. The program will begin in early 2025. Among other aspects, the federal government will negotiate the price of the product with the manufacturer.
“The goal of the Cell and Gene Therapy Access Model is to increase access to innovative cell and gene therapies for people with Medicaid by making it easier for states to pay for these therapies,” said Liz Fowler, CMS Deputy Administrator and Director of the CMS Innovation Center, in a statement announcing the program.
Whether the new program takes a look at Vyjuvek – and when – is not clear.
But the authors of the study noted that the lifetime costs of treating a patient with Vyjuvek “exceed the costs of all other one-time gene therapies for other diseases.” And they wrote, even at the most conservative estimates, Vyjuvek “will be the most expensive gene therapy currently marketed in the US.”
The study was funded by a grant from Arnold Ventures, grants from the Kaiser Permanente Institute for Health Policy, the Commonwealth Fund, and the National Heart, Lung, and Blood Institute. Dr. Raymakers and co-authors reported no financial relationships relevant to the work.
according to the authors of a new study.
The US Food and Drug Administration (FDA) approved Vyjuvek (Krystal Biotech) in May 2023 for the treatment of wounds in patients ages 6 months and older with dystrophic epidermolysis bullosa (DEB), which includes two types, the most severe form (autosomal recessive, or RDEB) and the autosomal dominant form of DEB (DDEB), which tends to be milder.
Treatment with Vyjuvek “represents an important advance in the treatment of RDEB,” wrote Adam J.N. Raymakers, PhD, and colleagues at the Program on Regulation, Therapeutics, and Law; the Department of Dermatology; and the Division of Pulmonary and Critical Care Medicine at Brigham & Women’s Hospital in Boston, Massachusetts, in their paper, published in JAMA Dermatology. But the price “will be high, potentially limiting patients’ access to it,” they added. Evidence to support it in DDEB “is less conclusive,” they wrote, noting that the pivotal phase 3 study that led to approval included one patient with DDEB.
“The wider indication granted by the FDA may lead to friction between payers on the one hand and patients and physicians on the other,” they wrote, noting a potential minimum price of $300,000 per patient a year, which was based on Krystal’s regulatory filings.
There is no cure for DEB. Vyjuvek, applied as a gel on an ongoing basis, uses a nonreplicating herpes simplex virus type 1 vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure.
The authors estimated that in the United States, 894 individuals – largely children – with both forms of the disease would be eligible for Vyjuvek treatment in the first year. Based on the $300,000 price, spending on gene therapy could range from $179 million to $357 million for those 894 patients, they reported in the study.
Over the first 3 years, spending could range as high as $1 billion, the authors estimated. Even if patients with only the most severe disease (RDEB) — an estimated 442 patients — received treatment, spending could be $132 million and up to $400 million or more over the first 3 years, they wrote.
Some media outlets have reported that Vyjuvek could cost as much as $600,000, said Dr. Raymakers, a research fellow. That price “would double all of our estimates,” he told this news organization.
The study assumed that patients with RDEB would only live to age 50, which led to a lifetime cost estimate of $15 million. But that is likely a conservative estimate, he and his coauthors wrote, noting that many patients with RDEB die from squamous cell carcinoma, but that Vyjuvek could, by attenuating skin damage, also potentially prevent skin cancer.
Dr. Raymakers said he and his colleagues began their study when Vyjuvek was approved, and thus they did not have any real-world data on the price or payer responses. Their estimates also did not include differing dosing regimens, which also could change their spending figures.
Krystal Biotech recently reported that in its third quarter of 2023 – representing just 1 month of Vyjuvek availability – it received requests to begin treatment for 284 patients from 136 unique clinicians. Twenty percent of the start requests were for patients with the milder form (DDEB), and a third of all the requests were for patients 10 years of age or younger. The company also said that it had “received positive coverage determinations from all major commercial national health plans” and that it was on track to receive approval from most state Medicaid plans.
In 1 month, Krystal reported net Vyjuvek revenues of $8.6 million.
The authors suggested that one way to evaluate Vyjuvek’s value — especially for those with DDEB — would be through a cost-effectiveness study. While important, a cost-effectiveness study would not get at the impact on a payer, said Dr. Raymakers. “Something can be cost-effective but unaffordable to the system,” he said.
“When there’s one of these very expensive therapies, that’s one thing,” he said. “But when there’s more and more coming to market, you wonder how much can be tolerated,” said Dr. Raymakers.
CMS Launching Gene Therapy Program
The Biden administration recently announced that it was launching a program aimed at increasing access, curbing costs, and ensuring value of gene therapies, starting with sickle cell disease. The program will begin in early 2025. Among other aspects, the federal government will negotiate the price of the product with the manufacturer.
“The goal of the Cell and Gene Therapy Access Model is to increase access to innovative cell and gene therapies for people with Medicaid by making it easier for states to pay for these therapies,” said Liz Fowler, CMS Deputy Administrator and Director of the CMS Innovation Center, in a statement announcing the program.
Whether the new program takes a look at Vyjuvek – and when – is not clear.
But the authors of the study noted that the lifetime costs of treating a patient with Vyjuvek “exceed the costs of all other one-time gene therapies for other diseases.” And they wrote, even at the most conservative estimates, Vyjuvek “will be the most expensive gene therapy currently marketed in the US.”
The study was funded by a grant from Arnold Ventures, grants from the Kaiser Permanente Institute for Health Policy, the Commonwealth Fund, and the National Heart, Lung, and Blood Institute. Dr. Raymakers and co-authors reported no financial relationships relevant to the work.
FROM JAMA DERMATOLOGY
Dupilumab Improves AD Affecting the Hands, Feet
TOPLINE:
compared with placebo.
METHODOLOGY:
- The multinational phase 3 LIBERTY-AD-HAFT trial of adults and adolescents with moderate to severe chronic atopic dermatitis (AD) of the hands, feet, or both included 67 participants at 48 sites randomized to dupilumab monotherapy and 66 to placebo.
- The primary endpoint was the proportion of patients scoring 0 or 1 on Hand and Foot Investigator’s Global Assessment (HF-IGA) at week 16.
- Secondary endpoints were severity and extent of signs, symptom intensity (itch and pain), sleep, and quality of life.
TAKEAWAY:
- At week 16, 27 patients receiving dupilumab vs 11 receiving placebo achieved an HF-IGA score of 0 or 1 (40.3% vs 16.7%; P = .003).
- At week 16, 35 participants receiving dupilumab vs nine receiving placebo improved at least four points in the weekly average of daily HF-Peak Pruritus Numeric Rating Scale (52.2% vs 13.6%; P < .0001).
- At week 16, Quality of Life Hand Eczema Questionnaire results improved in the dupilumab group compared with controls (P < .0001), and weekly average of daily Sleep Numeric Rating Scale results improved in the dupilumab group compared with controls (P < .05).
- The safety profile was similar to the known profile in adults and adolescents with moderate to severe AD.
IN PRACTICE:
The results of the study “support dupilumab” as an “efficacious systemic therapy for moderate to severe H/F AD,” the authors wrote.
SOURCE:
The study, led by Eric L. Simpson, MD, MCR, professor of dermatology at the Oregon Health & Science University in Portland, was published on January 29, 2024, in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The short duration of the study and the large proportion of patients with positive patch tests (31 of 133) suggested that some participants may have had concurrent AD and allergic contact dermatitis, so the effect of dupilumab on those patients needs further evaluation.
DISCLOSURES:
The study was sponsored by Sanofi and Regeneron. All but one author had financial relationships with Sanofi, Regeneron, or both. Several authors were employees of, and may hold stocks or stock options in, Sanofi or Regeneron.
TOPLINE:
compared with placebo.
METHODOLOGY:
- The multinational phase 3 LIBERTY-AD-HAFT trial of adults and adolescents with moderate to severe chronic atopic dermatitis (AD) of the hands, feet, or both included 67 participants at 48 sites randomized to dupilumab monotherapy and 66 to placebo.
- The primary endpoint was the proportion of patients scoring 0 or 1 on Hand and Foot Investigator’s Global Assessment (HF-IGA) at week 16.
- Secondary endpoints were severity and extent of signs, symptom intensity (itch and pain), sleep, and quality of life.
TAKEAWAY:
- At week 16, 27 patients receiving dupilumab vs 11 receiving placebo achieved an HF-IGA score of 0 or 1 (40.3% vs 16.7%; P = .003).
- At week 16, 35 participants receiving dupilumab vs nine receiving placebo improved at least four points in the weekly average of daily HF-Peak Pruritus Numeric Rating Scale (52.2% vs 13.6%; P < .0001).
- At week 16, Quality of Life Hand Eczema Questionnaire results improved in the dupilumab group compared with controls (P < .0001), and weekly average of daily Sleep Numeric Rating Scale results improved in the dupilumab group compared with controls (P < .05).
- The safety profile was similar to the known profile in adults and adolescents with moderate to severe AD.
IN PRACTICE:
The results of the study “support dupilumab” as an “efficacious systemic therapy for moderate to severe H/F AD,” the authors wrote.
SOURCE:
The study, led by Eric L. Simpson, MD, MCR, professor of dermatology at the Oregon Health & Science University in Portland, was published on January 29, 2024, in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The short duration of the study and the large proportion of patients with positive patch tests (31 of 133) suggested that some participants may have had concurrent AD and allergic contact dermatitis, so the effect of dupilumab on those patients needs further evaluation.
DISCLOSURES:
The study was sponsored by Sanofi and Regeneron. All but one author had financial relationships with Sanofi, Regeneron, or both. Several authors were employees of, and may hold stocks or stock options in, Sanofi or Regeneron.
TOPLINE:
compared with placebo.
METHODOLOGY:
- The multinational phase 3 LIBERTY-AD-HAFT trial of adults and adolescents with moderate to severe chronic atopic dermatitis (AD) of the hands, feet, or both included 67 participants at 48 sites randomized to dupilumab monotherapy and 66 to placebo.
- The primary endpoint was the proportion of patients scoring 0 or 1 on Hand and Foot Investigator’s Global Assessment (HF-IGA) at week 16.
- Secondary endpoints were severity and extent of signs, symptom intensity (itch and pain), sleep, and quality of life.
TAKEAWAY:
- At week 16, 27 patients receiving dupilumab vs 11 receiving placebo achieved an HF-IGA score of 0 or 1 (40.3% vs 16.7%; P = .003).
- At week 16, 35 participants receiving dupilumab vs nine receiving placebo improved at least four points in the weekly average of daily HF-Peak Pruritus Numeric Rating Scale (52.2% vs 13.6%; P < .0001).
- At week 16, Quality of Life Hand Eczema Questionnaire results improved in the dupilumab group compared with controls (P < .0001), and weekly average of daily Sleep Numeric Rating Scale results improved in the dupilumab group compared with controls (P < .05).
- The safety profile was similar to the known profile in adults and adolescents with moderate to severe AD.
IN PRACTICE:
The results of the study “support dupilumab” as an “efficacious systemic therapy for moderate to severe H/F AD,” the authors wrote.
SOURCE:
The study, led by Eric L. Simpson, MD, MCR, professor of dermatology at the Oregon Health & Science University in Portland, was published on January 29, 2024, in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The short duration of the study and the large proportion of patients with positive patch tests (31 of 133) suggested that some participants may have had concurrent AD and allergic contact dermatitis, so the effect of dupilumab on those patients needs further evaluation.
DISCLOSURES:
The study was sponsored by Sanofi and Regeneron. All but one author had financial relationships with Sanofi, Regeneron, or both. Several authors were employees of, and may hold stocks or stock options in, Sanofi or Regeneron.
Survey: Dermatology Residents Shortchanged on Sensitive Skin Education
Although sensitive skin affects an estimated 40%-70% of the population, knowledge of the pathophysiology of sensitive skin is incomplete, and consensus is lacking as to the best diagnosis and treatment strategies, and the inclusion of sensitive skin education in dermatology curricula has not been examined, according to Erika T. McCormick, BS, and Adam Friedman, MD, of George Washington University, Washington, DC.
For the study, published in the Journal of Drugs in Dermatology, they developed a 26-question survey for dermatology residents that asked about sensitive skin in dermatology residency training. Participants came from the Orlando Dermatology, Aesthetic, and Surgical Conference email list.
Survey respondents included 214 residents at various levels of training at programs across the United States; 67.1% were female, 92.1% were aged 25-34 years, and 85.5% were in academic or university programs.
Overall, 99% of respondents believed that sensitive skin issues should be part of their residency training to some extent, and 84% reported experiences with patients for whom the chief presenting complaint was sensitive skin.
However, fewer than half (48%) of the residents reported specific resident education in sensitive skin, while 51% reported nonspecific education about sensitive skin education in the context of other skin diseases, and 1% reported no education about sensitive skin.
Less than one-quarter of the respondents who received any sensitive skin education reported feeling comfortable in their ability to diagnose, evaluate, and manage sensitive skin, while those with sensitive skin–specific education were significantly more likely to describe themselves as “very knowledgeable.”
As for treatment approaches, residents with specific sensitive skin education were more likely than were those without sensitive skin–specific training to ask patients about allergies and past reactions to skin products, and to counsel them about environmental triggers.
Notably, 96% of the respondents were not familiar with the Sensitive Skin (SS) Scale–10, a validated measure of sensitive skin severity.
The most common challenges in care of patients with sensitive skin were assessing improvement over time, reported by 25% of respondents, recommending products (23%), and prescribing/medical management (22%). The topics residents expressed most interest in learning about were product recommendations (78%), patient counseling (77%), reviewing research on sensitive skin (70%), diagnosing sensitive skin (67%), using the SS-10 (48%), and clinical research updates (40%).
The findings were limited by several factors including the reliance on self-reports, the researchers noted. However, the results highlight the lack of consensus in treatment of sensitive skin and the need to address this knowledge gap at the residency level, they said.
Improving Tools for Practice
“Many practice patterns and approaches are forged in the fires of training,” corresponding author Dr. Friedman, professor and chair of dermatology and residency program director at George Washington University, said in an interview. “Identifying gaps, especially for heavily prevalent issues, questions, and concerns such as sensitive skin that residents will encounter in practice is important to ensure an educated workforce,” he said.
Education on sensitive skin is lacking because, until recently, research and clinical guidance have been lacking, Dr. Friedman said. The root of the problem is that sensitive skin is mainly considered a symptom, rather than an independent condition, he explained. “Depending on the study, the prevalence of sensitive skin has been reported as high as 70%, with roughly 40% of these patients having no primary skin condition,” he said. This means sensitive skin can be both a symptom and a condition, which causes confusion for clinicians and patients, he added.
“Therefore, in order to overcome this gap, the condition itself at a minimum needs a standard definition and a way to diagnosis, which we fortunately have in the validated research tool known as the SS-10,” said Dr. Friedman.
Almost all residents surveyed in the current study had never heard of the SS-10, but more than half found it to be useful after learning of it through the study survey, he noted.
Looking ahead, greater elucidation of the pathophysiology of sensitive skin is needed to effectively pursue studies of products and treatments for these patients, but the SS-10 can be used to define and monitor the condition to evaluate improvement, he added.
The study was funded by an independent fellowship grant from Galderma. Ms. McCormick is supported by an unrestricted fellowship grant funded by Galderma. Dr. Friedman has served as a consultant for Galderma.
Although sensitive skin affects an estimated 40%-70% of the population, knowledge of the pathophysiology of sensitive skin is incomplete, and consensus is lacking as to the best diagnosis and treatment strategies, and the inclusion of sensitive skin education in dermatology curricula has not been examined, according to Erika T. McCormick, BS, and Adam Friedman, MD, of George Washington University, Washington, DC.
For the study, published in the Journal of Drugs in Dermatology, they developed a 26-question survey for dermatology residents that asked about sensitive skin in dermatology residency training. Participants came from the Orlando Dermatology, Aesthetic, and Surgical Conference email list.
Survey respondents included 214 residents at various levels of training at programs across the United States; 67.1% were female, 92.1% were aged 25-34 years, and 85.5% were in academic or university programs.
Overall, 99% of respondents believed that sensitive skin issues should be part of their residency training to some extent, and 84% reported experiences with patients for whom the chief presenting complaint was sensitive skin.
However, fewer than half (48%) of the residents reported specific resident education in sensitive skin, while 51% reported nonspecific education about sensitive skin education in the context of other skin diseases, and 1% reported no education about sensitive skin.
Less than one-quarter of the respondents who received any sensitive skin education reported feeling comfortable in their ability to diagnose, evaluate, and manage sensitive skin, while those with sensitive skin–specific education were significantly more likely to describe themselves as “very knowledgeable.”
As for treatment approaches, residents with specific sensitive skin education were more likely than were those without sensitive skin–specific training to ask patients about allergies and past reactions to skin products, and to counsel them about environmental triggers.
Notably, 96% of the respondents were not familiar with the Sensitive Skin (SS) Scale–10, a validated measure of sensitive skin severity.
The most common challenges in care of patients with sensitive skin were assessing improvement over time, reported by 25% of respondents, recommending products (23%), and prescribing/medical management (22%). The topics residents expressed most interest in learning about were product recommendations (78%), patient counseling (77%), reviewing research on sensitive skin (70%), diagnosing sensitive skin (67%), using the SS-10 (48%), and clinical research updates (40%).
The findings were limited by several factors including the reliance on self-reports, the researchers noted. However, the results highlight the lack of consensus in treatment of sensitive skin and the need to address this knowledge gap at the residency level, they said.
Improving Tools for Practice
“Many practice patterns and approaches are forged in the fires of training,” corresponding author Dr. Friedman, professor and chair of dermatology and residency program director at George Washington University, said in an interview. “Identifying gaps, especially for heavily prevalent issues, questions, and concerns such as sensitive skin that residents will encounter in practice is important to ensure an educated workforce,” he said.
Education on sensitive skin is lacking because, until recently, research and clinical guidance have been lacking, Dr. Friedman said. The root of the problem is that sensitive skin is mainly considered a symptom, rather than an independent condition, he explained. “Depending on the study, the prevalence of sensitive skin has been reported as high as 70%, with roughly 40% of these patients having no primary skin condition,” he said. This means sensitive skin can be both a symptom and a condition, which causes confusion for clinicians and patients, he added.
“Therefore, in order to overcome this gap, the condition itself at a minimum needs a standard definition and a way to diagnosis, which we fortunately have in the validated research tool known as the SS-10,” said Dr. Friedman.
Almost all residents surveyed in the current study had never heard of the SS-10, but more than half found it to be useful after learning of it through the study survey, he noted.
Looking ahead, greater elucidation of the pathophysiology of sensitive skin is needed to effectively pursue studies of products and treatments for these patients, but the SS-10 can be used to define and monitor the condition to evaluate improvement, he added.
The study was funded by an independent fellowship grant from Galderma. Ms. McCormick is supported by an unrestricted fellowship grant funded by Galderma. Dr. Friedman has served as a consultant for Galderma.
Although sensitive skin affects an estimated 40%-70% of the population, knowledge of the pathophysiology of sensitive skin is incomplete, and consensus is lacking as to the best diagnosis and treatment strategies, and the inclusion of sensitive skin education in dermatology curricula has not been examined, according to Erika T. McCormick, BS, and Adam Friedman, MD, of George Washington University, Washington, DC.
For the study, published in the Journal of Drugs in Dermatology, they developed a 26-question survey for dermatology residents that asked about sensitive skin in dermatology residency training. Participants came from the Orlando Dermatology, Aesthetic, and Surgical Conference email list.
Survey respondents included 214 residents at various levels of training at programs across the United States; 67.1% were female, 92.1% were aged 25-34 years, and 85.5% were in academic or university programs.
Overall, 99% of respondents believed that sensitive skin issues should be part of their residency training to some extent, and 84% reported experiences with patients for whom the chief presenting complaint was sensitive skin.
However, fewer than half (48%) of the residents reported specific resident education in sensitive skin, while 51% reported nonspecific education about sensitive skin education in the context of other skin diseases, and 1% reported no education about sensitive skin.
Less than one-quarter of the respondents who received any sensitive skin education reported feeling comfortable in their ability to diagnose, evaluate, and manage sensitive skin, while those with sensitive skin–specific education were significantly more likely to describe themselves as “very knowledgeable.”
As for treatment approaches, residents with specific sensitive skin education were more likely than were those without sensitive skin–specific training to ask patients about allergies and past reactions to skin products, and to counsel them about environmental triggers.
Notably, 96% of the respondents were not familiar with the Sensitive Skin (SS) Scale–10, a validated measure of sensitive skin severity.
The most common challenges in care of patients with sensitive skin were assessing improvement over time, reported by 25% of respondents, recommending products (23%), and prescribing/medical management (22%). The topics residents expressed most interest in learning about were product recommendations (78%), patient counseling (77%), reviewing research on sensitive skin (70%), diagnosing sensitive skin (67%), using the SS-10 (48%), and clinical research updates (40%).
The findings were limited by several factors including the reliance on self-reports, the researchers noted. However, the results highlight the lack of consensus in treatment of sensitive skin and the need to address this knowledge gap at the residency level, they said.
Improving Tools for Practice
“Many practice patterns and approaches are forged in the fires of training,” corresponding author Dr. Friedman, professor and chair of dermatology and residency program director at George Washington University, said in an interview. “Identifying gaps, especially for heavily prevalent issues, questions, and concerns such as sensitive skin that residents will encounter in practice is important to ensure an educated workforce,” he said.
Education on sensitive skin is lacking because, until recently, research and clinical guidance have been lacking, Dr. Friedman said. The root of the problem is that sensitive skin is mainly considered a symptom, rather than an independent condition, he explained. “Depending on the study, the prevalence of sensitive skin has been reported as high as 70%, with roughly 40% of these patients having no primary skin condition,” he said. This means sensitive skin can be both a symptom and a condition, which causes confusion for clinicians and patients, he added.
“Therefore, in order to overcome this gap, the condition itself at a minimum needs a standard definition and a way to diagnosis, which we fortunately have in the validated research tool known as the SS-10,” said Dr. Friedman.
Almost all residents surveyed in the current study had never heard of the SS-10, but more than half found it to be useful after learning of it through the study survey, he noted.
Looking ahead, greater elucidation of the pathophysiology of sensitive skin is needed to effectively pursue studies of products and treatments for these patients, but the SS-10 can be used to define and monitor the condition to evaluate improvement, he added.
The study was funded by an independent fellowship grant from Galderma. Ms. McCormick is supported by an unrestricted fellowship grant funded by Galderma. Dr. Friedman has served as a consultant for Galderma.
FROM THE JOURNAL OF DRUGS IN DERMATOLOGY
Despite An AI Assist, Imaging Study Shows Disparities in Diagnosing Different Skin Tones
When clinicians in a large-scale study viewed a series of digital images that showed skin diseases across skin tones and were asked to make a diagnosis, the accuracy was 38% among dermatologists and 19% among primary care physicians (PCPs). But when decision support from a deep learning system (DLS) was introduced, diagnostic accuracy increased by 33% among dermatologists and 69% among PCPs, results from a multicenter study showed.
However, the researchers found that across all images, diseases in dark skin (Fitzpatrick skin types 5 and 6) were diagnosed less accurately than diseases in light skin (Fitzpatrick skin types 1-4).
“,” researchers led by Matthew Groh, PhD, of Northwestern University’s Kellogg School of Management, wrote in their study, published online in Nature Medicine.
For the study, 389 board-certified dermatologists and 450 PCPs in 39 countries were presented with 364 images to view spanning 46 skin diseases and asked to submit up to four differential diagnoses. Nearly 80% of the images were of 8 diseases: atopic dermatitis, cutaneous T-cell lymphoma (CTCL), dermatomyositis, lichen planus, Lyme disease, pityriasis rosea, pityriasis rubra pilaris, and secondary syphilis.
Dermatologists and PCPs achieved a diagnostic accuracy of 38% and 19%, respectively, but both groups of clinicians were 4 percentage points less accurate for diagnosis of images of dark skin as compared with light skin. With assistance from DLS decision support, diagnostic accuracy increased by 33% among dermatologists and 69% among primary care physicians. Among dermatologists, DLS support generally increased diagnostic accuracy evenly across skin tones. However, among PCPs, DLS support increased their diagnostic accuracy more in light skin tones than in dark ones.
In the survey component of the study, when the participants were asked, “Do you feel you received sufficient training for diagnosing skin diseases in patients with skin of color (non-white patients)?” 67% of all PCPs and 33% of all dermatologists responded no. “Furthermore, we have found differences in how often BCDs [board-certified dermatologists] and PCPs refer patients with light and dark skin for biopsy,” the authors wrote. “Specifically, for CTCL (a life-threatening disease), we found that both BCDs and PCPs report that they would refer patients for biopsy significantly more often in light skin than dark skin. Moreover, for the common skin diseases atopic dermatitis and pityriasis rosea, we found that BCDs report they would refer patients for biopsy more often in dark skin than light skin, which creates an unnecessary overburden on patients with dark skin.”
In a press release about the study, Dr. Groh emphasized that he and other scientists who investigate human-computer interaction “have to find a way to incorporate underrepresented demographics in our research. That way we will be ready to accurately implement these models in the real world and build AI systems that serve as tools that are designed to avoid the kind of systematic errors we know humans and machines are prone to. Then you can update curricula, you can change norms in different fields and hopefully everyone gets better.”
Ronald Moy, MD, a dermatologist who practices in Beverly Hills, Calif., who was asked to comment on the work, said that the study contributes insights into physician-AI interaction and highlights the need for further training on diagnosing skin diseases in people with darker skin tones. “The strengths of this study include its large sample size of dermatologists and primary care physicians, use of quality-controlled images across skin tones, and thorough evaluation of diagnostic accuracy with and without AI assistance,” said Dr. Moy, who is a past president of the American Academy of Dermatology, the American Society for Dermatologic Surgery, and the American Board of Facial Cosmetic Surgery.
“The study is limited to diagnosis and skin tone estimation based purely on a single image, which does not fully represent a clinical evaluation,” he added. However, “it does provide important benchmark data on diagnostic accuracy disparities across skin tones, but also demonstrates that while AI assistance can improve overall diagnostic accuracy, it may exacerbate disparities for non-specialists.”
Funding for the study was provided by MIT Media Lab consortium members and the Harold Horowitz Student Research Fund. One of the study authors, P. Murali Doraiswamy, MBBS, disclosed that he has received grants, advisory fees, and/or stock from several biotechnology companies outside the scope of this work and that he is a co-inventor on several patents through Duke University. The remaining authors reported having no disclosures. Dr. Moy reported having no disclosures.
When clinicians in a large-scale study viewed a series of digital images that showed skin diseases across skin tones and were asked to make a diagnosis, the accuracy was 38% among dermatologists and 19% among primary care physicians (PCPs). But when decision support from a deep learning system (DLS) was introduced, diagnostic accuracy increased by 33% among dermatologists and 69% among PCPs, results from a multicenter study showed.
However, the researchers found that across all images, diseases in dark skin (Fitzpatrick skin types 5 and 6) were diagnosed less accurately than diseases in light skin (Fitzpatrick skin types 1-4).
“,” researchers led by Matthew Groh, PhD, of Northwestern University’s Kellogg School of Management, wrote in their study, published online in Nature Medicine.
For the study, 389 board-certified dermatologists and 450 PCPs in 39 countries were presented with 364 images to view spanning 46 skin diseases and asked to submit up to four differential diagnoses. Nearly 80% of the images were of 8 diseases: atopic dermatitis, cutaneous T-cell lymphoma (CTCL), dermatomyositis, lichen planus, Lyme disease, pityriasis rosea, pityriasis rubra pilaris, and secondary syphilis.
Dermatologists and PCPs achieved a diagnostic accuracy of 38% and 19%, respectively, but both groups of clinicians were 4 percentage points less accurate for diagnosis of images of dark skin as compared with light skin. With assistance from DLS decision support, diagnostic accuracy increased by 33% among dermatologists and 69% among primary care physicians. Among dermatologists, DLS support generally increased diagnostic accuracy evenly across skin tones. However, among PCPs, DLS support increased their diagnostic accuracy more in light skin tones than in dark ones.
In the survey component of the study, when the participants were asked, “Do you feel you received sufficient training for diagnosing skin diseases in patients with skin of color (non-white patients)?” 67% of all PCPs and 33% of all dermatologists responded no. “Furthermore, we have found differences in how often BCDs [board-certified dermatologists] and PCPs refer patients with light and dark skin for biopsy,” the authors wrote. “Specifically, for CTCL (a life-threatening disease), we found that both BCDs and PCPs report that they would refer patients for biopsy significantly more often in light skin than dark skin. Moreover, for the common skin diseases atopic dermatitis and pityriasis rosea, we found that BCDs report they would refer patients for biopsy more often in dark skin than light skin, which creates an unnecessary overburden on patients with dark skin.”
In a press release about the study, Dr. Groh emphasized that he and other scientists who investigate human-computer interaction “have to find a way to incorporate underrepresented demographics in our research. That way we will be ready to accurately implement these models in the real world and build AI systems that serve as tools that are designed to avoid the kind of systematic errors we know humans and machines are prone to. Then you can update curricula, you can change norms in different fields and hopefully everyone gets better.”
Ronald Moy, MD, a dermatologist who practices in Beverly Hills, Calif., who was asked to comment on the work, said that the study contributes insights into physician-AI interaction and highlights the need for further training on diagnosing skin diseases in people with darker skin tones. “The strengths of this study include its large sample size of dermatologists and primary care physicians, use of quality-controlled images across skin tones, and thorough evaluation of diagnostic accuracy with and without AI assistance,” said Dr. Moy, who is a past president of the American Academy of Dermatology, the American Society for Dermatologic Surgery, and the American Board of Facial Cosmetic Surgery.
“The study is limited to diagnosis and skin tone estimation based purely on a single image, which does not fully represent a clinical evaluation,” he added. However, “it does provide important benchmark data on diagnostic accuracy disparities across skin tones, but also demonstrates that while AI assistance can improve overall diagnostic accuracy, it may exacerbate disparities for non-specialists.”
Funding for the study was provided by MIT Media Lab consortium members and the Harold Horowitz Student Research Fund. One of the study authors, P. Murali Doraiswamy, MBBS, disclosed that he has received grants, advisory fees, and/or stock from several biotechnology companies outside the scope of this work and that he is a co-inventor on several patents through Duke University. The remaining authors reported having no disclosures. Dr. Moy reported having no disclosures.
When clinicians in a large-scale study viewed a series of digital images that showed skin diseases across skin tones and were asked to make a diagnosis, the accuracy was 38% among dermatologists and 19% among primary care physicians (PCPs). But when decision support from a deep learning system (DLS) was introduced, diagnostic accuracy increased by 33% among dermatologists and 69% among PCPs, results from a multicenter study showed.
However, the researchers found that across all images, diseases in dark skin (Fitzpatrick skin types 5 and 6) were diagnosed less accurately than diseases in light skin (Fitzpatrick skin types 1-4).
“,” researchers led by Matthew Groh, PhD, of Northwestern University’s Kellogg School of Management, wrote in their study, published online in Nature Medicine.
For the study, 389 board-certified dermatologists and 450 PCPs in 39 countries were presented with 364 images to view spanning 46 skin diseases and asked to submit up to four differential diagnoses. Nearly 80% of the images were of 8 diseases: atopic dermatitis, cutaneous T-cell lymphoma (CTCL), dermatomyositis, lichen planus, Lyme disease, pityriasis rosea, pityriasis rubra pilaris, and secondary syphilis.
Dermatologists and PCPs achieved a diagnostic accuracy of 38% and 19%, respectively, but both groups of clinicians were 4 percentage points less accurate for diagnosis of images of dark skin as compared with light skin. With assistance from DLS decision support, diagnostic accuracy increased by 33% among dermatologists and 69% among primary care physicians. Among dermatologists, DLS support generally increased diagnostic accuracy evenly across skin tones. However, among PCPs, DLS support increased their diagnostic accuracy more in light skin tones than in dark ones.
In the survey component of the study, when the participants were asked, “Do you feel you received sufficient training for diagnosing skin diseases in patients with skin of color (non-white patients)?” 67% of all PCPs and 33% of all dermatologists responded no. “Furthermore, we have found differences in how often BCDs [board-certified dermatologists] and PCPs refer patients with light and dark skin for biopsy,” the authors wrote. “Specifically, for CTCL (a life-threatening disease), we found that both BCDs and PCPs report that they would refer patients for biopsy significantly more often in light skin than dark skin. Moreover, for the common skin diseases atopic dermatitis and pityriasis rosea, we found that BCDs report they would refer patients for biopsy more often in dark skin than light skin, which creates an unnecessary overburden on patients with dark skin.”
In a press release about the study, Dr. Groh emphasized that he and other scientists who investigate human-computer interaction “have to find a way to incorporate underrepresented demographics in our research. That way we will be ready to accurately implement these models in the real world and build AI systems that serve as tools that are designed to avoid the kind of systematic errors we know humans and machines are prone to. Then you can update curricula, you can change norms in different fields and hopefully everyone gets better.”
Ronald Moy, MD, a dermatologist who practices in Beverly Hills, Calif., who was asked to comment on the work, said that the study contributes insights into physician-AI interaction and highlights the need for further training on diagnosing skin diseases in people with darker skin tones. “The strengths of this study include its large sample size of dermatologists and primary care physicians, use of quality-controlled images across skin tones, and thorough evaluation of diagnostic accuracy with and without AI assistance,” said Dr. Moy, who is a past president of the American Academy of Dermatology, the American Society for Dermatologic Surgery, and the American Board of Facial Cosmetic Surgery.
“The study is limited to diagnosis and skin tone estimation based purely on a single image, which does not fully represent a clinical evaluation,” he added. However, “it does provide important benchmark data on diagnostic accuracy disparities across skin tones, but also demonstrates that while AI assistance can improve overall diagnostic accuracy, it may exacerbate disparities for non-specialists.”
Funding for the study was provided by MIT Media Lab consortium members and the Harold Horowitz Student Research Fund. One of the study authors, P. Murali Doraiswamy, MBBS, disclosed that he has received grants, advisory fees, and/or stock from several biotechnology companies outside the scope of this work and that he is a co-inventor on several patents through Duke University. The remaining authors reported having no disclosures. Dr. Moy reported having no disclosures.
FROM NATURE MEDICINE
Comorbidities and Disease Type Weigh Heavily in Pregnancy Outcomes of Immune-Mediated Inflammatory Diseases
Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).
In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.
The study was published online on February 1 in eClinicalMedicine.
While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
Pregnancy Outcome Risks Varied Between IMIDs
To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.
Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.
In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.
After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.
But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.
“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.
Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.
Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.
“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
A Large Study, But How Representative Is It?
Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”
She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.
“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.
“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”
Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.
The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.
However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.
“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.
Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.
“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.
The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.
A version of this article first appeared on Medscape.com.
Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).
In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.
The study was published online on February 1 in eClinicalMedicine.
While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
Pregnancy Outcome Risks Varied Between IMIDs
To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.
Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.
In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.
After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.
But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.
“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.
Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.
Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.
“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
A Large Study, But How Representative Is It?
Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”
She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.
“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.
“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”
Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.
The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.
However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.
“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.
Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.
“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.
The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.
A version of this article first appeared on Medscape.com.
Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).
In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.
The study was published online on February 1 in eClinicalMedicine.
While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
Pregnancy Outcome Risks Varied Between IMIDs
To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.
Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.
In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.
After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.
But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.
“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.
Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.
Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.
“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
A Large Study, But How Representative Is It?
Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”
She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.
“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.
“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”
Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.
The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.
However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.
“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.
Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.
“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.
The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.
A version of this article first appeared on Medscape.com.
FROM ECLINICALMEDICINE
While Rare, Periocular Melanoma May Be Slightly Increasing
SAN DIEGO — Every year, about 4000 patients in the United States are diagnosed with periocular melanoma, according to Geva Mannor, MD, MPH.
“Though rare, the incidence is thought to be slightly increasing, while the onset tends to occur in patients over age 40 years,” Dr. Mannor, an oculofacial plastic surgeon in the division of ophthalmology at Scripps Clinic, San Diego, said at the annual Cutaneous Malignancy Update. “It may be more common in males and welding is a risk factor. Pain and vision loss are late symptoms, and there are amelanotic variants. Gene expression profiling and other genetic testing can predict metastasis, especially expression of BRCA1-associated protein 1 (BAP1).”
. Extrapolating from the best available data, Dr. Mannor said that the annual incidence of choroidal melanoma in the United States is less than 2500, the annual incidence of eyelid melanoma is less than 750, and the annual incidence of conjunctival melanoma is less than 250 — much lower than for cutaneous melanomas. Put another way, the ratio between cutaneous and choroid melanoma is 80:1, the ratio between cutaneous and eyelid melanoma is 266:1, and the ratio between cutaneous and conjunctival melanoma is 800:1.
According to an article published in 2021 on the topic, risk factors for periocular melanoma include light eye color (blue/gray; relative risk, 1.75), fair skin (RR, 1.80), and inability to tan (RR, 1.64), but not blonde hair. A review of 210 patients with melanoma of the eyelid from 11 studies showed that 57% were located on the lower lid, 13% were on the upper lid (“I think because the brow protects sun exposure to the upper lid,” Dr. Mannor said), 12% were on the brow, 10% were on the lateral canthus, and 2% were on the medial canthus. In addition, 35% of the eyelid melanomas were superficial spreading cases, 31% were lentigo maligna, and 19% were nodular. The mean Breslow depth was 1.36 mm and the mortality rate was 4.9%.
Dr. Mannor said that cheek and brow melanomas can extend to the inside of the eyelid and conjunctiva. “Therefore, you want to examine the inside of upper and lower eyelids,” he said at the meeting, which was hosted by the Scripps Cancer Center. “Margin-control excision of lid melanoma is the standard treatment.”
On a related note, he said that glaucoma eye drops that contain prostaglandin F2alpha induce cutaneous and iris pigmentation with varying rates depending on the specific type of prostaglandin. “There have been case reports of these eye drops causing periocular pigmentation that masquerades as suspicious, melanoma-like skin cancer, often necessitating a skin biopsy,” he said.
Dr. Mannor reported having no disclosures.
SAN DIEGO — Every year, about 4000 patients in the United States are diagnosed with periocular melanoma, according to Geva Mannor, MD, MPH.
“Though rare, the incidence is thought to be slightly increasing, while the onset tends to occur in patients over age 40 years,” Dr. Mannor, an oculofacial plastic surgeon in the division of ophthalmology at Scripps Clinic, San Diego, said at the annual Cutaneous Malignancy Update. “It may be more common in males and welding is a risk factor. Pain and vision loss are late symptoms, and there are amelanotic variants. Gene expression profiling and other genetic testing can predict metastasis, especially expression of BRCA1-associated protein 1 (BAP1).”
. Extrapolating from the best available data, Dr. Mannor said that the annual incidence of choroidal melanoma in the United States is less than 2500, the annual incidence of eyelid melanoma is less than 750, and the annual incidence of conjunctival melanoma is less than 250 — much lower than for cutaneous melanomas. Put another way, the ratio between cutaneous and choroid melanoma is 80:1, the ratio between cutaneous and eyelid melanoma is 266:1, and the ratio between cutaneous and conjunctival melanoma is 800:1.
According to an article published in 2021 on the topic, risk factors for periocular melanoma include light eye color (blue/gray; relative risk, 1.75), fair skin (RR, 1.80), and inability to tan (RR, 1.64), but not blonde hair. A review of 210 patients with melanoma of the eyelid from 11 studies showed that 57% were located on the lower lid, 13% were on the upper lid (“I think because the brow protects sun exposure to the upper lid,” Dr. Mannor said), 12% were on the brow, 10% were on the lateral canthus, and 2% were on the medial canthus. In addition, 35% of the eyelid melanomas were superficial spreading cases, 31% were lentigo maligna, and 19% were nodular. The mean Breslow depth was 1.36 mm and the mortality rate was 4.9%.
Dr. Mannor said that cheek and brow melanomas can extend to the inside of the eyelid and conjunctiva. “Therefore, you want to examine the inside of upper and lower eyelids,” he said at the meeting, which was hosted by the Scripps Cancer Center. “Margin-control excision of lid melanoma is the standard treatment.”
On a related note, he said that glaucoma eye drops that contain prostaglandin F2alpha induce cutaneous and iris pigmentation with varying rates depending on the specific type of prostaglandin. “There have been case reports of these eye drops causing periocular pigmentation that masquerades as suspicious, melanoma-like skin cancer, often necessitating a skin biopsy,” he said.
Dr. Mannor reported having no disclosures.
SAN DIEGO — Every year, about 4000 patients in the United States are diagnosed with periocular melanoma, according to Geva Mannor, MD, MPH.
“Though rare, the incidence is thought to be slightly increasing, while the onset tends to occur in patients over age 40 years,” Dr. Mannor, an oculofacial plastic surgeon in the division of ophthalmology at Scripps Clinic, San Diego, said at the annual Cutaneous Malignancy Update. “It may be more common in males and welding is a risk factor. Pain and vision loss are late symptoms, and there are amelanotic variants. Gene expression profiling and other genetic testing can predict metastasis, especially expression of BRCA1-associated protein 1 (BAP1).”
. Extrapolating from the best available data, Dr. Mannor said that the annual incidence of choroidal melanoma in the United States is less than 2500, the annual incidence of eyelid melanoma is less than 750, and the annual incidence of conjunctival melanoma is less than 250 — much lower than for cutaneous melanomas. Put another way, the ratio between cutaneous and choroid melanoma is 80:1, the ratio between cutaneous and eyelid melanoma is 266:1, and the ratio between cutaneous and conjunctival melanoma is 800:1.
According to an article published in 2021 on the topic, risk factors for periocular melanoma include light eye color (blue/gray; relative risk, 1.75), fair skin (RR, 1.80), and inability to tan (RR, 1.64), but not blonde hair. A review of 210 patients with melanoma of the eyelid from 11 studies showed that 57% were located on the lower lid, 13% were on the upper lid (“I think because the brow protects sun exposure to the upper lid,” Dr. Mannor said), 12% were on the brow, 10% were on the lateral canthus, and 2% were on the medial canthus. In addition, 35% of the eyelid melanomas were superficial spreading cases, 31% were lentigo maligna, and 19% were nodular. The mean Breslow depth was 1.36 mm and the mortality rate was 4.9%.
Dr. Mannor said that cheek and brow melanomas can extend to the inside of the eyelid and conjunctiva. “Therefore, you want to examine the inside of upper and lower eyelids,” he said at the meeting, which was hosted by the Scripps Cancer Center. “Margin-control excision of lid melanoma is the standard treatment.”
On a related note, he said that glaucoma eye drops that contain prostaglandin F2alpha induce cutaneous and iris pigmentation with varying rates depending on the specific type of prostaglandin. “There have been case reports of these eye drops causing periocular pigmentation that masquerades as suspicious, melanoma-like skin cancer, often necessitating a skin biopsy,” he said.
Dr. Mannor reported having no disclosures.
FROM MELANOMA 2024
A Neurotoxin, an Antidepressant, and More Emerging Options for Treating Rosacea
ORLANDO, FLORIDA — At the same time, there is new recognition that systemic inflammation can occur with rosacea, and targeting treatment to the phenotype continues to gain steam as a way to help people with this difficult-to-manage condition.
“Anyone here think they’ve got rosacea under control? No, I wish — not yet,” Diane Dr. Thiboutot, MD, said at the annual ODAC Dermatology, Aesthetic & Surgical Conference.
Botulinum Toxin Benefits
With that in mind, Dr. Thiboutot highlighted emerging therapies for treating rosacea. “Last year, there were a couple of reports … looking at the use of botulinum toxin injections for patients with rosacea,” said Dr. Thiboutot, professor of dermatology and vice chair for research in the Department of Dermatology at Penn State College of Medicine, Hershey, Pennsylvania.
One report describes the case of a woman with rosacea who had severe recurrent episodes of erythema and flushing. She also experienced occasional papules and pustules and had been recalcitrant to multiple treatments for rosacea, according to the report published in the Journal of Drugs in Dermatology in June 2023. The patient was treated with a total of 150-180 units of botulinum toxin administered as 3-6 units spaced 1 cm apart every 2-4 months. She was “eventually maintained every 6 months with excellent improvement,” Dr. Thiboutot said.
In another case, a man with refractory vascular and papulopustular rosacea was treated with half of a unit of botulinum toxin spaced every 0.5 cm. Images taken at baseline, 1 month, and 3 months after treatment demonstrated improvements, as reported in June 2023.
Regarding botulinum toxin for rosacea, Dr. Thiboutot said, “it’s a very interesting thing to think about.”
Susan Weinkle, MD, ODAC conference cochair, session moderator, and collaborative associate professor of dermatology at the University of South Florida, Tampa, Florida, agreed. “I do think it holds some interesting potential,” she said. “How good are your hands? Because administering 0.5-unit injections evenly is a little bit challenging.”
However, one approach that might help is “if we could be a little more innovative like they are in Europe.” Physicians in Europe can use a metered syringe, one where they dial in the exact amount per injection, which allows them to be consistent, she added.
With rosacea erythema, Dr. Thiboutot noted, a spotted effect can result if injections are not administered uniformly.
Potential Role for Paroxetine
The antidepressant paroxetine, a potent selective serotonin reuptake inhibitor, could be an effective treatment for refractory erythema of rosacea, Dr. Thiboutot said. It is approved for treating depression, obsessive-compulsive disorder, and social phobia. The agent has also shown effectiveness in alleviating hot flashes associated with vascular dysregulation in menopause.
Uptake in serotonin and changes in receptors are closely related to vascular dilation and constriction, Dr. Thiboutot added, so paroxetine “may be beneficial in treating vascular dysfunction” including in people with rosacea. Evidence to support this potential approach comes from the primary results of a randomized controlled trial published in June 2023. Based on the results, the researchers concluded that paroxetine “appears to be an efficacious and well-tolerated treatment for refractory erythema in rosacea.”
In the trial, almost 43% of people treated with paroxetine met the primary endpoint for improving recalcitrant erythema at week 12 compared with almost 21% who took a placebo, a statistically significant difference.
Heparan Sulfate Analog in a Cream
Evidence suggests that a low-molecular-weight heparan sulfate analog is another agent that holds potential for treating rosacea. For example, a 2023 randomized controlled trial evaluated the immune response in rosacea, focusing on a specific cathelicidin peptide called LL-37 that activates an inflammasome in rosacea. Low-molecular-weight heparan sulfate holds the potential to inhibit LL-37 activity, as LL-37 is inhibited by binding to heparan sulfate, a cell surface glycosaminoglycan.
The study of 16 people assessed the ability of the analog to modulate this response; they were also treated with the pulsed dye laser. Participants who applied a dermal repair cream that contained this ingredient experienced a one-grade reduction in erythema at weeks 4 and 8 compared with a control group applying a moisturizer.
A Growing Case for Systemic Inflammation
In the meantime, treating rosacea with more traditional therapies remains challenging.
But there’s hope. Success has been reported in the few years since an expert panel recommended treating based on phenotype — a treat-what-you-see approach, Dr. Thiboutot said.
“We don’t have a single treatment that is one-size-fits-all. We have to individualize our treatment [based] more on what we are seeing and what the patient is experiencing.”
Eventually, therapies to treat systemic inflammation could provide benefits as well. As with hidradenitis suppurativa and psoriasis, “there’s evidence of systemic inflammation in some of our rosacea patients,” Dr. Thiboutot said.
For example, researchers compared blood taken from people with and without rosacea and found increased levels of some inflammatory markers among participants with the condition.
The retrospective study published in June 2023 in Scientific Reports included 100 patients with rosacea and 58 controls. The investigators found significantly higher elevations in the SII index, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels in the patients with rosacea.
“There was no significant link between the severity of rosacea and the ESR, CRP, or SII index values, Dr. Thiboutot added. “This study suggests inflammation beyond the skin in rosacea patients.”
For more guidance on treating rosacea through standard management options, including how to tailor therapy to each individual, she recommended the 2019 Update by the National Rosacea Society Expert Committee. “It’s a nice quick way to see, based on expert opinion, the most effective treatments and what the evidence base is,” said Dr. Thiboutot, lead author of the paper, published in the Journal of the American Academy of Dermatology in February 2020.
Dr. Thiboutot reported no relevant financial relationships.
ORLANDO, FLORIDA — At the same time, there is new recognition that systemic inflammation can occur with rosacea, and targeting treatment to the phenotype continues to gain steam as a way to help people with this difficult-to-manage condition.
“Anyone here think they’ve got rosacea under control? No, I wish — not yet,” Diane Dr. Thiboutot, MD, said at the annual ODAC Dermatology, Aesthetic & Surgical Conference.
Botulinum Toxin Benefits
With that in mind, Dr. Thiboutot highlighted emerging therapies for treating rosacea. “Last year, there were a couple of reports … looking at the use of botulinum toxin injections for patients with rosacea,” said Dr. Thiboutot, professor of dermatology and vice chair for research in the Department of Dermatology at Penn State College of Medicine, Hershey, Pennsylvania.
One report describes the case of a woman with rosacea who had severe recurrent episodes of erythema and flushing. She also experienced occasional papules and pustules and had been recalcitrant to multiple treatments for rosacea, according to the report published in the Journal of Drugs in Dermatology in June 2023. The patient was treated with a total of 150-180 units of botulinum toxin administered as 3-6 units spaced 1 cm apart every 2-4 months. She was “eventually maintained every 6 months with excellent improvement,” Dr. Thiboutot said.
In another case, a man with refractory vascular and papulopustular rosacea was treated with half of a unit of botulinum toxin spaced every 0.5 cm. Images taken at baseline, 1 month, and 3 months after treatment demonstrated improvements, as reported in June 2023.
Regarding botulinum toxin for rosacea, Dr. Thiboutot said, “it’s a very interesting thing to think about.”
Susan Weinkle, MD, ODAC conference cochair, session moderator, and collaborative associate professor of dermatology at the University of South Florida, Tampa, Florida, agreed. “I do think it holds some interesting potential,” she said. “How good are your hands? Because administering 0.5-unit injections evenly is a little bit challenging.”
However, one approach that might help is “if we could be a little more innovative like they are in Europe.” Physicians in Europe can use a metered syringe, one where they dial in the exact amount per injection, which allows them to be consistent, she added.
With rosacea erythema, Dr. Thiboutot noted, a spotted effect can result if injections are not administered uniformly.
Potential Role for Paroxetine
The antidepressant paroxetine, a potent selective serotonin reuptake inhibitor, could be an effective treatment for refractory erythema of rosacea, Dr. Thiboutot said. It is approved for treating depression, obsessive-compulsive disorder, and social phobia. The agent has also shown effectiveness in alleviating hot flashes associated with vascular dysregulation in menopause.
Uptake in serotonin and changes in receptors are closely related to vascular dilation and constriction, Dr. Thiboutot added, so paroxetine “may be beneficial in treating vascular dysfunction” including in people with rosacea. Evidence to support this potential approach comes from the primary results of a randomized controlled trial published in June 2023. Based on the results, the researchers concluded that paroxetine “appears to be an efficacious and well-tolerated treatment for refractory erythema in rosacea.”
In the trial, almost 43% of people treated with paroxetine met the primary endpoint for improving recalcitrant erythema at week 12 compared with almost 21% who took a placebo, a statistically significant difference.
Heparan Sulfate Analog in a Cream
Evidence suggests that a low-molecular-weight heparan sulfate analog is another agent that holds potential for treating rosacea. For example, a 2023 randomized controlled trial evaluated the immune response in rosacea, focusing on a specific cathelicidin peptide called LL-37 that activates an inflammasome in rosacea. Low-molecular-weight heparan sulfate holds the potential to inhibit LL-37 activity, as LL-37 is inhibited by binding to heparan sulfate, a cell surface glycosaminoglycan.
The study of 16 people assessed the ability of the analog to modulate this response; they were also treated with the pulsed dye laser. Participants who applied a dermal repair cream that contained this ingredient experienced a one-grade reduction in erythema at weeks 4 and 8 compared with a control group applying a moisturizer.
A Growing Case for Systemic Inflammation
In the meantime, treating rosacea with more traditional therapies remains challenging.
But there’s hope. Success has been reported in the few years since an expert panel recommended treating based on phenotype — a treat-what-you-see approach, Dr. Thiboutot said.
“We don’t have a single treatment that is one-size-fits-all. We have to individualize our treatment [based] more on what we are seeing and what the patient is experiencing.”
Eventually, therapies to treat systemic inflammation could provide benefits as well. As with hidradenitis suppurativa and psoriasis, “there’s evidence of systemic inflammation in some of our rosacea patients,” Dr. Thiboutot said.
For example, researchers compared blood taken from people with and without rosacea and found increased levels of some inflammatory markers among participants with the condition.
The retrospective study published in June 2023 in Scientific Reports included 100 patients with rosacea and 58 controls. The investigators found significantly higher elevations in the SII index, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels in the patients with rosacea.
“There was no significant link between the severity of rosacea and the ESR, CRP, or SII index values, Dr. Thiboutot added. “This study suggests inflammation beyond the skin in rosacea patients.”
For more guidance on treating rosacea through standard management options, including how to tailor therapy to each individual, she recommended the 2019 Update by the National Rosacea Society Expert Committee. “It’s a nice quick way to see, based on expert opinion, the most effective treatments and what the evidence base is,” said Dr. Thiboutot, lead author of the paper, published in the Journal of the American Academy of Dermatology in February 2020.
Dr. Thiboutot reported no relevant financial relationships.
ORLANDO, FLORIDA — At the same time, there is new recognition that systemic inflammation can occur with rosacea, and targeting treatment to the phenotype continues to gain steam as a way to help people with this difficult-to-manage condition.
“Anyone here think they’ve got rosacea under control? No, I wish — not yet,” Diane Dr. Thiboutot, MD, said at the annual ODAC Dermatology, Aesthetic & Surgical Conference.
Botulinum Toxin Benefits
With that in mind, Dr. Thiboutot highlighted emerging therapies for treating rosacea. “Last year, there were a couple of reports … looking at the use of botulinum toxin injections for patients with rosacea,” said Dr. Thiboutot, professor of dermatology and vice chair for research in the Department of Dermatology at Penn State College of Medicine, Hershey, Pennsylvania.
One report describes the case of a woman with rosacea who had severe recurrent episodes of erythema and flushing. She also experienced occasional papules and pustules and had been recalcitrant to multiple treatments for rosacea, according to the report published in the Journal of Drugs in Dermatology in June 2023. The patient was treated with a total of 150-180 units of botulinum toxin administered as 3-6 units spaced 1 cm apart every 2-4 months. She was “eventually maintained every 6 months with excellent improvement,” Dr. Thiboutot said.
In another case, a man with refractory vascular and papulopustular rosacea was treated with half of a unit of botulinum toxin spaced every 0.5 cm. Images taken at baseline, 1 month, and 3 months after treatment demonstrated improvements, as reported in June 2023.
Regarding botulinum toxin for rosacea, Dr. Thiboutot said, “it’s a very interesting thing to think about.”
Susan Weinkle, MD, ODAC conference cochair, session moderator, and collaborative associate professor of dermatology at the University of South Florida, Tampa, Florida, agreed. “I do think it holds some interesting potential,” she said. “How good are your hands? Because administering 0.5-unit injections evenly is a little bit challenging.”
However, one approach that might help is “if we could be a little more innovative like they are in Europe.” Physicians in Europe can use a metered syringe, one where they dial in the exact amount per injection, which allows them to be consistent, she added.
With rosacea erythema, Dr. Thiboutot noted, a spotted effect can result if injections are not administered uniformly.
Potential Role for Paroxetine
The antidepressant paroxetine, a potent selective serotonin reuptake inhibitor, could be an effective treatment for refractory erythema of rosacea, Dr. Thiboutot said. It is approved for treating depression, obsessive-compulsive disorder, and social phobia. The agent has also shown effectiveness in alleviating hot flashes associated with vascular dysregulation in menopause.
Uptake in serotonin and changes in receptors are closely related to vascular dilation and constriction, Dr. Thiboutot added, so paroxetine “may be beneficial in treating vascular dysfunction” including in people with rosacea. Evidence to support this potential approach comes from the primary results of a randomized controlled trial published in June 2023. Based on the results, the researchers concluded that paroxetine “appears to be an efficacious and well-tolerated treatment for refractory erythema in rosacea.”
In the trial, almost 43% of people treated with paroxetine met the primary endpoint for improving recalcitrant erythema at week 12 compared with almost 21% who took a placebo, a statistically significant difference.
Heparan Sulfate Analog in a Cream
Evidence suggests that a low-molecular-weight heparan sulfate analog is another agent that holds potential for treating rosacea. For example, a 2023 randomized controlled trial evaluated the immune response in rosacea, focusing on a specific cathelicidin peptide called LL-37 that activates an inflammasome in rosacea. Low-molecular-weight heparan sulfate holds the potential to inhibit LL-37 activity, as LL-37 is inhibited by binding to heparan sulfate, a cell surface glycosaminoglycan.
The study of 16 people assessed the ability of the analog to modulate this response; they were also treated with the pulsed dye laser. Participants who applied a dermal repair cream that contained this ingredient experienced a one-grade reduction in erythema at weeks 4 and 8 compared with a control group applying a moisturizer.
A Growing Case for Systemic Inflammation
In the meantime, treating rosacea with more traditional therapies remains challenging.
But there’s hope. Success has been reported in the few years since an expert panel recommended treating based on phenotype — a treat-what-you-see approach, Dr. Thiboutot said.
“We don’t have a single treatment that is one-size-fits-all. We have to individualize our treatment [based] more on what we are seeing and what the patient is experiencing.”
Eventually, therapies to treat systemic inflammation could provide benefits as well. As with hidradenitis suppurativa and psoriasis, “there’s evidence of systemic inflammation in some of our rosacea patients,” Dr. Thiboutot said.
For example, researchers compared blood taken from people with and without rosacea and found increased levels of some inflammatory markers among participants with the condition.
The retrospective study published in June 2023 in Scientific Reports included 100 patients with rosacea and 58 controls. The investigators found significantly higher elevations in the SII index, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels in the patients with rosacea.
“There was no significant link between the severity of rosacea and the ESR, CRP, or SII index values, Dr. Thiboutot added. “This study suggests inflammation beyond the skin in rosacea patients.”
For more guidance on treating rosacea through standard management options, including how to tailor therapy to each individual, she recommended the 2019 Update by the National Rosacea Society Expert Committee. “It’s a nice quick way to see, based on expert opinion, the most effective treatments and what the evidence base is,” said Dr. Thiboutot, lead author of the paper, published in the Journal of the American Academy of Dermatology in February 2020.
Dr. Thiboutot reported no relevant financial relationships.
FROM ODAC 2024
Expert Shares Tips for Diagnosing, Managing Spitz Nevi
SAN DIEGO —
“For a pigmented Spitz nevus, we were taught to look for a starburst pattern, a central area of homogeneous pigment, and peripheral symmetrical streaks or pseudopods,” Dr. Piggott, an adult and pediatric dermatologist at Scripps Clinic, San Diego, said at the annual Cutaneous Malignancy Update. “For Spitz nevi without pigment, we were taught to look for symmetric dotted vessels.”
However, results from a retrospective study published in 2015 gave her pause in relying on dermoscopy alone for assessing Spitz nevi. Researchers from Italy, Japan, and Brazil studied excision specimens of 384 Spitzoid-looking lesions in patients 12 years and older. On histology, 86.7% were diagnosed as benign Spitz nevi and 13.3% were diagnosed as melanoma.
When the researchers looked at the dermoscopic images, many cases of atypical Spitz nevi were indistinguishable from the benign Spitz nevi. Now, Dr. Piggott said, “I respect the dermoscopy criteria, but I don’t rely solely on it.”
If a child presents with Spitzoid-looking lesion, biopsy is generally preferred to observation. “The traditional belief was that punch biopsy was preferable, followed by shave biopsy,” she said. “This is always on a case-by-case basis.”
However, results from a retrospective study of the records of 123 cases of biopsy-proven Spitz nevi with incomplete removal on biopsy suggests that the method of biopsy matters. The researchers found that the presence of residual lesion in the re-excision specimen was significantly higher when the initial biopsy was done by punch biopsy (90.9%) when compared with shave biopsy (48.9%) and formal excision (62.5%; P < .05).
“This suggests that shave may better than punch for the initial biopsy, but the study was limited by its retrospective design,” Dr. Piggott said at the meeting, which was hosted by Scripps Cancer Center. “Even today it remains controversial whether you should do a shave or punch biopsy.”
Parameters for diagnosing Spitzoid tumors that pathologists look for under the microscope are asymmetry, Clark’s level IV/V, lack of maturation, solid growth, nuclear pleomorphism, high nuclear-cytoplasmic ratio, and mitoses that are atypical, deep, or that exceed 6 mm2 in size.
In terms of treatment recommendations for children with biopsy-proven Spitz nevi, Dr. Piggott said that there is no consensus among pediatric dermatologists. If the biopsy comes back as a benign Spitz nevus, the most reasonable approach is observation, “especially if there is no clinical residue — no pigment on exam, no papule left over in the scar,” she said. “You also want to educate the family about the rare potential for transformation down the line. Monitor for recurrence and consider re-excision if recurrence occurs.”
If the initial Spitz nevus biopsy reveals any degree of atypia, excision is preferred. “In young children, you have to weigh the risks of anesthesia for removal,” she said. “If you’re unable to excise the lesion, close observation is recommended at 6 months or 1 year.”
Treatment for borderline atypical Spitz tumor is excision, she continued, but no outcomes data exist that document a survival benefit with sentinel lymph node (SLN) biopsy. “The decision on whether to do a SLN biopsy is usually made on a case-by-case basis,” Dr. Piggott said. “Nodal metastases from atypical Spitzoid tumors are not uncommon, but death from widespread disease is rare. If the SLN biopsy is positive, complete lymphadenectomy is associated with increased risk of morbidity and no evidence of increased survival. If lymph node disease is found, we in pediatric dermatology would consider referral to a pediatric oncologist for consideration of systemic therapy such as interferon or a newer immunotherapy.”
Dr. Piggott reported having no relevant disclosures.
SAN DIEGO —
“For a pigmented Spitz nevus, we were taught to look for a starburst pattern, a central area of homogeneous pigment, and peripheral symmetrical streaks or pseudopods,” Dr. Piggott, an adult and pediatric dermatologist at Scripps Clinic, San Diego, said at the annual Cutaneous Malignancy Update. “For Spitz nevi without pigment, we were taught to look for symmetric dotted vessels.”
However, results from a retrospective study published in 2015 gave her pause in relying on dermoscopy alone for assessing Spitz nevi. Researchers from Italy, Japan, and Brazil studied excision specimens of 384 Spitzoid-looking lesions in patients 12 years and older. On histology, 86.7% were diagnosed as benign Spitz nevi and 13.3% were diagnosed as melanoma.
When the researchers looked at the dermoscopic images, many cases of atypical Spitz nevi were indistinguishable from the benign Spitz nevi. Now, Dr. Piggott said, “I respect the dermoscopy criteria, but I don’t rely solely on it.”
If a child presents with Spitzoid-looking lesion, biopsy is generally preferred to observation. “The traditional belief was that punch biopsy was preferable, followed by shave biopsy,” she said. “This is always on a case-by-case basis.”
However, results from a retrospective study of the records of 123 cases of biopsy-proven Spitz nevi with incomplete removal on biopsy suggests that the method of biopsy matters. The researchers found that the presence of residual lesion in the re-excision specimen was significantly higher when the initial biopsy was done by punch biopsy (90.9%) when compared with shave biopsy (48.9%) and formal excision (62.5%; P < .05).
“This suggests that shave may better than punch for the initial biopsy, but the study was limited by its retrospective design,” Dr. Piggott said at the meeting, which was hosted by Scripps Cancer Center. “Even today it remains controversial whether you should do a shave or punch biopsy.”
Parameters for diagnosing Spitzoid tumors that pathologists look for under the microscope are asymmetry, Clark’s level IV/V, lack of maturation, solid growth, nuclear pleomorphism, high nuclear-cytoplasmic ratio, and mitoses that are atypical, deep, or that exceed 6 mm2 in size.
In terms of treatment recommendations for children with biopsy-proven Spitz nevi, Dr. Piggott said that there is no consensus among pediatric dermatologists. If the biopsy comes back as a benign Spitz nevus, the most reasonable approach is observation, “especially if there is no clinical residue — no pigment on exam, no papule left over in the scar,” she said. “You also want to educate the family about the rare potential for transformation down the line. Monitor for recurrence and consider re-excision if recurrence occurs.”
If the initial Spitz nevus biopsy reveals any degree of atypia, excision is preferred. “In young children, you have to weigh the risks of anesthesia for removal,” she said. “If you’re unable to excise the lesion, close observation is recommended at 6 months or 1 year.”
Treatment for borderline atypical Spitz tumor is excision, she continued, but no outcomes data exist that document a survival benefit with sentinel lymph node (SLN) biopsy. “The decision on whether to do a SLN biopsy is usually made on a case-by-case basis,” Dr. Piggott said. “Nodal metastases from atypical Spitzoid tumors are not uncommon, but death from widespread disease is rare. If the SLN biopsy is positive, complete lymphadenectomy is associated with increased risk of morbidity and no evidence of increased survival. If lymph node disease is found, we in pediatric dermatology would consider referral to a pediatric oncologist for consideration of systemic therapy such as interferon or a newer immunotherapy.”
Dr. Piggott reported having no relevant disclosures.
SAN DIEGO —
“For a pigmented Spitz nevus, we were taught to look for a starburst pattern, a central area of homogeneous pigment, and peripheral symmetrical streaks or pseudopods,” Dr. Piggott, an adult and pediatric dermatologist at Scripps Clinic, San Diego, said at the annual Cutaneous Malignancy Update. “For Spitz nevi without pigment, we were taught to look for symmetric dotted vessels.”
However, results from a retrospective study published in 2015 gave her pause in relying on dermoscopy alone for assessing Spitz nevi. Researchers from Italy, Japan, and Brazil studied excision specimens of 384 Spitzoid-looking lesions in patients 12 years and older. On histology, 86.7% were diagnosed as benign Spitz nevi and 13.3% were diagnosed as melanoma.
When the researchers looked at the dermoscopic images, many cases of atypical Spitz nevi were indistinguishable from the benign Spitz nevi. Now, Dr. Piggott said, “I respect the dermoscopy criteria, but I don’t rely solely on it.”
If a child presents with Spitzoid-looking lesion, biopsy is generally preferred to observation. “The traditional belief was that punch biopsy was preferable, followed by shave biopsy,” she said. “This is always on a case-by-case basis.”
However, results from a retrospective study of the records of 123 cases of biopsy-proven Spitz nevi with incomplete removal on biopsy suggests that the method of biopsy matters. The researchers found that the presence of residual lesion in the re-excision specimen was significantly higher when the initial biopsy was done by punch biopsy (90.9%) when compared with shave biopsy (48.9%) and formal excision (62.5%; P < .05).
“This suggests that shave may better than punch for the initial biopsy, but the study was limited by its retrospective design,” Dr. Piggott said at the meeting, which was hosted by Scripps Cancer Center. “Even today it remains controversial whether you should do a shave or punch biopsy.”
Parameters for diagnosing Spitzoid tumors that pathologists look for under the microscope are asymmetry, Clark’s level IV/V, lack of maturation, solid growth, nuclear pleomorphism, high nuclear-cytoplasmic ratio, and mitoses that are atypical, deep, or that exceed 6 mm2 in size.
In terms of treatment recommendations for children with biopsy-proven Spitz nevi, Dr. Piggott said that there is no consensus among pediatric dermatologists. If the biopsy comes back as a benign Spitz nevus, the most reasonable approach is observation, “especially if there is no clinical residue — no pigment on exam, no papule left over in the scar,” she said. “You also want to educate the family about the rare potential for transformation down the line. Monitor for recurrence and consider re-excision if recurrence occurs.”
If the initial Spitz nevus biopsy reveals any degree of atypia, excision is preferred. “In young children, you have to weigh the risks of anesthesia for removal,” she said. “If you’re unable to excise the lesion, close observation is recommended at 6 months or 1 year.”
Treatment for borderline atypical Spitz tumor is excision, she continued, but no outcomes data exist that document a survival benefit with sentinel lymph node (SLN) biopsy. “The decision on whether to do a SLN biopsy is usually made on a case-by-case basis,” Dr. Piggott said. “Nodal metastases from atypical Spitzoid tumors are not uncommon, but death from widespread disease is rare. If the SLN biopsy is positive, complete lymphadenectomy is associated with increased risk of morbidity and no evidence of increased survival. If lymph node disease is found, we in pediatric dermatology would consider referral to a pediatric oncologist for consideration of systemic therapy such as interferon or a newer immunotherapy.”
Dr. Piggott reported having no relevant disclosures.
FROM MELANOMA 2024
AAD Updates Guidelines for Managing Acne
. The guidelines also conditionally recommend the use of topical clascoterone, salicylic acid, azelaic acid, oral minocycline, sarecycline, combined oral contraceptives, and spironolactone.
The development updates the AAD’s 2016 guidelines for managing acne. “Since there have been several important new treatments introduced since the prior guidelines, it was determined that there was a need to update these guidelines,” John S. Barbieri, MD, MBA, who cochaired a 16-member multidisciplinary work group that assembled the guidelines, told this news organization.
For the new guidelines, which were published online January 30, 2023, in the Journal of the American Academy of Dermatology, Dr. Barbieri, a dermatologist who directs the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, guidelines cochair Rachel V. Reynolds, MD, a dermatologist at Beth Israel Deaconess Medical Center, Boston, and colleagues conducted a systematic review of evidence regarding the management of acne. Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
In all, the work group made 18 recommendations and 5 good practice statements. They ranked 7 of the recommendations as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of benzoyl peroxide, the use of topical retinoids, the use of topical antibiotics, a fixed dose of a combination topical antibiotic with benzoyl peroxide, a fixed dose of a combination topical retinoid with topical antibiotic, a fixed dose combination of a topical retinoid with benzoyl peroxide, and the use of doxycycline.
“Conditional” recommendations include those for the use of clascoterone, salicylic acid, azelaic acid, minocycline, sarecycline, doxycycline over azithromycin; combined oral contraceptive pills, spironolactone, and, for patients with severe acne, traditional daily dosing of isotretinoin over intermittent dosing of isotretinoin.
Meanwhile, good clinical practice statements contained in the document include using topical therapies combining multiple mechanisms of action, limiting systemic antibiotic use, combining topical and systemic antibiotics with benzoyl peroxide and other topical therapies, and adjuvant intralesional corticosteroid injections.
In Dr. Barbieri’s opinion, the recommendations regarding clascoterone and sarecycline represent important developments. “Clascoterone is the first FDA-approved treatment that can address hormonal causes of acne in both men and women,” he told this news organization. “Sarecycline is a narrow-spectrum tetracycline that might have some advantages over other tetracyclines such as doxycycline and minocycline. It will be important to payers to provide coverage to ensure that patients have access to these valuable new treatments.”
Dr. Barbieri added that while no evidence exists to suggest that minocycline is more effective than doxycycline, minocycline can be associated with rare but serious side effects, such as vestibular dysfunction, autoimmune hepatitis, drug-induced lupus, and drug reaction with eosinophilia and systemic symptoms (DRESS). “We should consider whether reducing use of minocycline might be beneficial to our overall care of patients with acne,” he said. “In addition, we discuss that use of trimethoprim-sulfamethoxazole should be limited due to risk of severe adverse reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute respiratory failure.”
Another highlight of the guidelines, he continued, are specific recommendations for young, healthy patients on isotretinoin or spironolactone, which “can help clinicians and patients who are interested in less frequent monitoring feel more comfortable with these approaches,” he said.
Many discussions among work group members dealt with how to best implement the GRADE approach to the project “while ensuring the guidelines were as clinically relevant and actionable as possible,” according to Dr. Barbieri. “I think an important issue going forward will be to consider how to update and modify the GRADE approach to fit the unique needs of creating evidence-based guidelines for the management of skin disease.”
The work group acknowledged limitations of the guidelines, including identification of “important evidence gaps on the use of microbiology and endocrinology testing in acne, the use of systemic antibiotics beyond tetracycline-class antibiotics, physical modalities, complementary and alternative therapies, dietary interventions for the treatment of acne, and cost-effectiveness of acne treatments,” they wrote. “RCTs with long-term follow-up and comparative effectiveness research are necessary to examine and compare patient-centered acne treatment outcomes.”
The AAD funded the project. Dr. Barbieri disclosed that he serves as investigator for the National Institutes of Health and the National Psoriasis Foundation. Many coauthors reported being a speaker for and/or a consultant and advisory board member to many pharmaceutical companies.
. The guidelines also conditionally recommend the use of topical clascoterone, salicylic acid, azelaic acid, oral minocycline, sarecycline, combined oral contraceptives, and spironolactone.
The development updates the AAD’s 2016 guidelines for managing acne. “Since there have been several important new treatments introduced since the prior guidelines, it was determined that there was a need to update these guidelines,” John S. Barbieri, MD, MBA, who cochaired a 16-member multidisciplinary work group that assembled the guidelines, told this news organization.
For the new guidelines, which were published online January 30, 2023, in the Journal of the American Academy of Dermatology, Dr. Barbieri, a dermatologist who directs the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, guidelines cochair Rachel V. Reynolds, MD, a dermatologist at Beth Israel Deaconess Medical Center, Boston, and colleagues conducted a systematic review of evidence regarding the management of acne. Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
In all, the work group made 18 recommendations and 5 good practice statements. They ranked 7 of the recommendations as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of benzoyl peroxide, the use of topical retinoids, the use of topical antibiotics, a fixed dose of a combination topical antibiotic with benzoyl peroxide, a fixed dose of a combination topical retinoid with topical antibiotic, a fixed dose combination of a topical retinoid with benzoyl peroxide, and the use of doxycycline.
“Conditional” recommendations include those for the use of clascoterone, salicylic acid, azelaic acid, minocycline, sarecycline, doxycycline over azithromycin; combined oral contraceptive pills, spironolactone, and, for patients with severe acne, traditional daily dosing of isotretinoin over intermittent dosing of isotretinoin.
Meanwhile, good clinical practice statements contained in the document include using topical therapies combining multiple mechanisms of action, limiting systemic antibiotic use, combining topical and systemic antibiotics with benzoyl peroxide and other topical therapies, and adjuvant intralesional corticosteroid injections.
In Dr. Barbieri’s opinion, the recommendations regarding clascoterone and sarecycline represent important developments. “Clascoterone is the first FDA-approved treatment that can address hormonal causes of acne in both men and women,” he told this news organization. “Sarecycline is a narrow-spectrum tetracycline that might have some advantages over other tetracyclines such as doxycycline and minocycline. It will be important to payers to provide coverage to ensure that patients have access to these valuable new treatments.”
Dr. Barbieri added that while no evidence exists to suggest that minocycline is more effective than doxycycline, minocycline can be associated with rare but serious side effects, such as vestibular dysfunction, autoimmune hepatitis, drug-induced lupus, and drug reaction with eosinophilia and systemic symptoms (DRESS). “We should consider whether reducing use of minocycline might be beneficial to our overall care of patients with acne,” he said. “In addition, we discuss that use of trimethoprim-sulfamethoxazole should be limited due to risk of severe adverse reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute respiratory failure.”
Another highlight of the guidelines, he continued, are specific recommendations for young, healthy patients on isotretinoin or spironolactone, which “can help clinicians and patients who are interested in less frequent monitoring feel more comfortable with these approaches,” he said.
Many discussions among work group members dealt with how to best implement the GRADE approach to the project “while ensuring the guidelines were as clinically relevant and actionable as possible,” according to Dr. Barbieri. “I think an important issue going forward will be to consider how to update and modify the GRADE approach to fit the unique needs of creating evidence-based guidelines for the management of skin disease.”
The work group acknowledged limitations of the guidelines, including identification of “important evidence gaps on the use of microbiology and endocrinology testing in acne, the use of systemic antibiotics beyond tetracycline-class antibiotics, physical modalities, complementary and alternative therapies, dietary interventions for the treatment of acne, and cost-effectiveness of acne treatments,” they wrote. “RCTs with long-term follow-up and comparative effectiveness research are necessary to examine and compare patient-centered acne treatment outcomes.”
The AAD funded the project. Dr. Barbieri disclosed that he serves as investigator for the National Institutes of Health and the National Psoriasis Foundation. Many coauthors reported being a speaker for and/or a consultant and advisory board member to many pharmaceutical companies.
. The guidelines also conditionally recommend the use of topical clascoterone, salicylic acid, azelaic acid, oral minocycline, sarecycline, combined oral contraceptives, and spironolactone.
The development updates the AAD’s 2016 guidelines for managing acne. “Since there have been several important new treatments introduced since the prior guidelines, it was determined that there was a need to update these guidelines,” John S. Barbieri, MD, MBA, who cochaired a 16-member multidisciplinary work group that assembled the guidelines, told this news organization.
For the new guidelines, which were published online January 30, 2023, in the Journal of the American Academy of Dermatology, Dr. Barbieri, a dermatologist who directs the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, guidelines cochair Rachel V. Reynolds, MD, a dermatologist at Beth Israel Deaconess Medical Center, Boston, and colleagues conducted a systematic review of evidence regarding the management of acne. Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
In all, the work group made 18 recommendations and 5 good practice statements. They ranked 7 of the recommendations as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of benzoyl peroxide, the use of topical retinoids, the use of topical antibiotics, a fixed dose of a combination topical antibiotic with benzoyl peroxide, a fixed dose of a combination topical retinoid with topical antibiotic, a fixed dose combination of a topical retinoid with benzoyl peroxide, and the use of doxycycline.
“Conditional” recommendations include those for the use of clascoterone, salicylic acid, azelaic acid, minocycline, sarecycline, doxycycline over azithromycin; combined oral contraceptive pills, spironolactone, and, for patients with severe acne, traditional daily dosing of isotretinoin over intermittent dosing of isotretinoin.
Meanwhile, good clinical practice statements contained in the document include using topical therapies combining multiple mechanisms of action, limiting systemic antibiotic use, combining topical and systemic antibiotics with benzoyl peroxide and other topical therapies, and adjuvant intralesional corticosteroid injections.
In Dr. Barbieri’s opinion, the recommendations regarding clascoterone and sarecycline represent important developments. “Clascoterone is the first FDA-approved treatment that can address hormonal causes of acne in both men and women,” he told this news organization. “Sarecycline is a narrow-spectrum tetracycline that might have some advantages over other tetracyclines such as doxycycline and minocycline. It will be important to payers to provide coverage to ensure that patients have access to these valuable new treatments.”
Dr. Barbieri added that while no evidence exists to suggest that minocycline is more effective than doxycycline, minocycline can be associated with rare but serious side effects, such as vestibular dysfunction, autoimmune hepatitis, drug-induced lupus, and drug reaction with eosinophilia and systemic symptoms (DRESS). “We should consider whether reducing use of minocycline might be beneficial to our overall care of patients with acne,” he said. “In addition, we discuss that use of trimethoprim-sulfamethoxazole should be limited due to risk of severe adverse reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute respiratory failure.”
Another highlight of the guidelines, he continued, are specific recommendations for young, healthy patients on isotretinoin or spironolactone, which “can help clinicians and patients who are interested in less frequent monitoring feel more comfortable with these approaches,” he said.
Many discussions among work group members dealt with how to best implement the GRADE approach to the project “while ensuring the guidelines were as clinically relevant and actionable as possible,” according to Dr. Barbieri. “I think an important issue going forward will be to consider how to update and modify the GRADE approach to fit the unique needs of creating evidence-based guidelines for the management of skin disease.”
The work group acknowledged limitations of the guidelines, including identification of “important evidence gaps on the use of microbiology and endocrinology testing in acne, the use of systemic antibiotics beyond tetracycline-class antibiotics, physical modalities, complementary and alternative therapies, dietary interventions for the treatment of acne, and cost-effectiveness of acne treatments,” they wrote. “RCTs with long-term follow-up and comparative effectiveness research are necessary to examine and compare patient-centered acne treatment outcomes.”
The AAD funded the project. Dr. Barbieri disclosed that he serves as investigator for the National Institutes of Health and the National Psoriasis Foundation. Many coauthors reported being a speaker for and/or a consultant and advisory board member to many pharmaceutical companies.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
More Than 100K New Cutaneous Melanoma Diagnoses Expected in 2024
SAN DIEGO — According to data from the
“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist at Skin Care Physicians of Georgia, Macon, said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”
In 2024, the ACS estimates that about 100,640 new melanomas will be diagnosed in the United States (59,170 in men and 41,470 in women), and about 8,290 people are expected to die of melanoma (5,430 men and 2,860 women). Meanwhile, the lifetime risk of melanoma is about 3% (1 in 33) for Whites, 0.1% (1 in 1,000) for Blacks, and 0.5% (1 in 200) for Hispanics. In 2019, there were an estimated 1.4 million people in the United States living with cutaneous melanoma, and the overall 5-year survival is 93.7%.
Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due to sun exposure, changes in recreational behaviors, and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3%-7% per year, “which means that the rate is doubling every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.
While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color, according to a 2023 paper. Black individuals present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.
Risk Factors
Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1 and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.
Dr. Kent said that genetic testing for melanoma is warranted for individuals who meet criteria for the “rule of 3s.” He defined this as three primary melanomas in an individual, or three cases of melanoma in first- or second-degree relatives, or two cases of melanoma and one pancreatic cancer or astrocytoma in first or second-degree relatives, or one case of melanoma and two of pancreatic cancer/astrocytoma in first- or second-degree relatives.
The main environmental risk factor for melanoma is exposure to ultraviolet radiation. Individuals can track their UV exposure with a variety of wearable devices and apps, including SunSense One Digital UV Tracker, the SunSense App, the UV Index Widget, the SunSmart Global UV App, the SunKnown UV light photometer, and the EPA’s UV Index Mobile App. Other environment-related risk factors include having a high socioeconomic status (SES), being immunosuppressed, as well as exposure to heavy metals, insecticides, or hormones; and ones distance from the equator.
In a study published in 2023, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than first melanomas. In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio, 6.36 vs 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03). Second melanomas were also more strongly associated with a history of multiple skin cancer excisions (HR, 2.63 vs 1.86; P = .05).
Dr. Kent noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey in 2014 found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits — even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said at the meeting, which was hosted by the Scripps Cancer Center. “We as dermatologists have work to do to help educate them.”
Dr. Kent reported having no relevant disclosures.
SAN DIEGO — According to data from the
“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist at Skin Care Physicians of Georgia, Macon, said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”
In 2024, the ACS estimates that about 100,640 new melanomas will be diagnosed in the United States (59,170 in men and 41,470 in women), and about 8,290 people are expected to die of melanoma (5,430 men and 2,860 women). Meanwhile, the lifetime risk of melanoma is about 3% (1 in 33) for Whites, 0.1% (1 in 1,000) for Blacks, and 0.5% (1 in 200) for Hispanics. In 2019, there were an estimated 1.4 million people in the United States living with cutaneous melanoma, and the overall 5-year survival is 93.7%.
Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due to sun exposure, changes in recreational behaviors, and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3%-7% per year, “which means that the rate is doubling every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.
While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color, according to a 2023 paper. Black individuals present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.
Risk Factors
Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1 and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.
Dr. Kent said that genetic testing for melanoma is warranted for individuals who meet criteria for the “rule of 3s.” He defined this as three primary melanomas in an individual, or three cases of melanoma in first- or second-degree relatives, or two cases of melanoma and one pancreatic cancer or astrocytoma in first or second-degree relatives, or one case of melanoma and two of pancreatic cancer/astrocytoma in first- or second-degree relatives.
The main environmental risk factor for melanoma is exposure to ultraviolet radiation. Individuals can track their UV exposure with a variety of wearable devices and apps, including SunSense One Digital UV Tracker, the SunSense App, the UV Index Widget, the SunSmart Global UV App, the SunKnown UV light photometer, and the EPA’s UV Index Mobile App. Other environment-related risk factors include having a high socioeconomic status (SES), being immunosuppressed, as well as exposure to heavy metals, insecticides, or hormones; and ones distance from the equator.
In a study published in 2023, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than first melanomas. In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio, 6.36 vs 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03). Second melanomas were also more strongly associated with a history of multiple skin cancer excisions (HR, 2.63 vs 1.86; P = .05).
Dr. Kent noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey in 2014 found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits — even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said at the meeting, which was hosted by the Scripps Cancer Center. “We as dermatologists have work to do to help educate them.”
Dr. Kent reported having no relevant disclosures.
SAN DIEGO — According to data from the
“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist at Skin Care Physicians of Georgia, Macon, said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”
In 2024, the ACS estimates that about 100,640 new melanomas will be diagnosed in the United States (59,170 in men and 41,470 in women), and about 8,290 people are expected to die of melanoma (5,430 men and 2,860 women). Meanwhile, the lifetime risk of melanoma is about 3% (1 in 33) for Whites, 0.1% (1 in 1,000) for Blacks, and 0.5% (1 in 200) for Hispanics. In 2019, there were an estimated 1.4 million people in the United States living with cutaneous melanoma, and the overall 5-year survival is 93.7%.
Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due to sun exposure, changes in recreational behaviors, and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3%-7% per year, “which means that the rate is doubling every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.
While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color, according to a 2023 paper. Black individuals present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.
Risk Factors
Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1 and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.
Dr. Kent said that genetic testing for melanoma is warranted for individuals who meet criteria for the “rule of 3s.” He defined this as three primary melanomas in an individual, or three cases of melanoma in first- or second-degree relatives, or two cases of melanoma and one pancreatic cancer or astrocytoma in first or second-degree relatives, or one case of melanoma and two of pancreatic cancer/astrocytoma in first- or second-degree relatives.
The main environmental risk factor for melanoma is exposure to ultraviolet radiation. Individuals can track their UV exposure with a variety of wearable devices and apps, including SunSense One Digital UV Tracker, the SunSense App, the UV Index Widget, the SunSmart Global UV App, the SunKnown UV light photometer, and the EPA’s UV Index Mobile App. Other environment-related risk factors include having a high socioeconomic status (SES), being immunosuppressed, as well as exposure to heavy metals, insecticides, or hormones; and ones distance from the equator.
In a study published in 2023, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than first melanomas. In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio, 6.36 vs 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03). Second melanomas were also more strongly associated with a history of multiple skin cancer excisions (HR, 2.63 vs 1.86; P = .05).
Dr. Kent noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey in 2014 found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits — even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said at the meeting, which was hosted by the Scripps Cancer Center. “We as dermatologists have work to do to help educate them.”
Dr. Kent reported having no relevant disclosures.
FROM MELANOMA 2024