Dermatology

In a cross-sectional study of malpractice and medical liability claims for cutaneous energy-based device procedures, the most litigated health professionals were plastic surgeons, and the most commonly affected anatomical sites were the face, head, and/or neck.

“The utilization of laser and energy-based devices (LEBD) has grown substantially,” corresponding author Scott Stratman, MD, MPH, and coauthors wrote in their study, which was published online in the Journal of the American Academy of Dermatology. “This has led to a rise in practitioners, both physicians and nonphysicians, who may lack the requisite training in LEBD procedures. Subsequently, procedures performed by these untrained practitioners have resulted in more lawsuits related to patient complications. As the demand for LEBD procedures and the number of practitioners performing these procedures increase, it remains paramount to characterize the trends of malpractice cases involving these procedures.”

Dr. Stratman, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, and colleagues queried the LexisNexis database from 1985 to Sept. 30, 2023, for all state, federal, and appellate cases that included the terms “negligence” or “malpractice” and “skin” and “laser.” After they removed duplicate cases and excluded cases that did not report dermatologic complications or cutaneous energy-based procedures, the final analysis included 75 cases.

Most of the appellants/plaintiffs (66; 88%) were women, a greater number of cases were in the Northeast (26; 34.7%) and the South (23; 30.7%), and the fewest cases were in the Midwest (12 [16%]). The most common anatomical sites were the face, head, and/or neck, and 43 of the cases (57.3%) were decided in favor of the appellee/defendant or the party defending against the appeal, while 29 (38.7%) were in favor of the appellant/plaintiff or the party appealing, and three cases (4%) did not report a verdict.

[embed:render:related:node:268907]

In other findings, plastic surgeons were the most litigated healthcare professionals (18; 24%), while 39 of the overall cases (52%) involved nonphysician operators (NPOs), 32 (42.7%) involved a physician operator, and 4 cases (5.3%) did not name a device operator. The most common procedure performed in the included cases was laser hair removal (33; 44%). Complications from energy-based devices included burns, scarring, and pigmentation changes. Statistically significant associations were neither found between verdict outcome and appellee/defendant type nor found between energy-device operator or anatomical site.

The authors acknowledged certain limitations of the study, including the fact that the LexisNexis database does not contain cases handled in out-of-court settlements and cases that underwent third-party arbitration.

“Physicians must recognize their responsibility when delegating procedures to NPOs and their role in supervision of these procedures,” they concluded. “Comprehensive training for physicians and their agents is necessary to diminish adverse outcomes and legal risks. Moreover, all practitioners should be held to the same standard of care. Familiarity with malpractice trends not only strengthens the patient-provider relationship but also equips providers with effective strategies to minimize the risk of legal repercussions.”

Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, who was asked to comment on the study, said that it “reaffirms previous studies which show that laser hair removal continues to be the most litigated procedure in laser surgery, and that nonphysician operators are most commonly litigated against. It further reiterates the importance of close supervision and expert training of procedures delegated by physicians.”

Neither the authors nor Dr. Avram reported having relevant financial disclosures.

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

In a cross-sectional study of malpractice and medical liability claims for cutaneous energy-based device procedures, the most litigated health professionals were plastic surgeons, and the most commonly affected anatomical sites were the face, head, and/or neck.

“The utilization of laser and energy-based devices (LEBD) has grown substantially,” corresponding author Scott Stratman, MD, MPH, and coauthors wrote in their study, which was published online in the Journal of the American Academy of Dermatology. “This has led to a rise in practitioners, both physicians and nonphysicians, who may lack the requisite training in LEBD procedures. Subsequently, procedures performed by these untrained practitioners have resulted in more lawsuits related to patient complications. As the demand for LEBD procedures and the number of practitioners performing these procedures increase, it remains paramount to characterize the trends of malpractice cases involving these procedures.”

Dr. Stratman, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, and colleagues queried the LexisNexis database from 1985 to Sept. 30, 2023, for all state, federal, and appellate cases that included the terms “negligence” or “malpractice” and “skin” and “laser.” After they removed duplicate cases and excluded cases that did not report dermatologic complications or cutaneous energy-based procedures, the final analysis included 75 cases.

Most of the appellants/plaintiffs (66; 88%) were women, a greater number of cases were in the Northeast (26; 34.7%) and the South (23; 30.7%), and the fewest cases were in the Midwest (12 [16%]). The most common anatomical sites were the face, head, and/or neck, and 43 of the cases (57.3%) were decided in favor of the appellee/defendant or the party defending against the appeal, while 29 (38.7%) were in favor of the appellant/plaintiff or the party appealing, and three cases (4%) did not report a verdict.

[embed:render:related:node:268907]

In other findings, plastic surgeons were the most litigated healthcare professionals (18; 24%), while 39 of the overall cases (52%) involved nonphysician operators (NPOs), 32 (42.7%) involved a physician operator, and 4 cases (5.3%) did not name a device operator. The most common procedure performed in the included cases was laser hair removal (33; 44%). Complications from energy-based devices included burns, scarring, and pigmentation changes. Statistically significant associations were neither found between verdict outcome and appellee/defendant type nor found between energy-device operator or anatomical site.

The authors acknowledged certain limitations of the study, including the fact that the LexisNexis database does not contain cases handled in out-of-court settlements and cases that underwent third-party arbitration.

“Physicians must recognize their responsibility when delegating procedures to NPOs and their role in supervision of these procedures,” they concluded. “Comprehensive training for physicians and their agents is necessary to diminish adverse outcomes and legal risks. Moreover, all practitioners should be held to the same standard of care. Familiarity with malpractice trends not only strengthens the patient-provider relationship but also equips providers with effective strategies to minimize the risk of legal repercussions.”

Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, who was asked to comment on the study, said that it “reaffirms previous studies which show that laser hair removal continues to be the most litigated procedure in laser surgery, and that nonphysician operators are most commonly litigated against. It further reiterates the importance of close supervision and expert training of procedures delegated by physicians.”

Neither the authors nor Dr. Avram reported having relevant financial disclosures.

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

In a cross-sectional study of malpractice and medical liability claims for cutaneous energy-based device procedures, the most litigated health professionals were plastic surgeons, and the most commonly affected anatomical sites were the face, head, and/or neck.

“The utilization of laser and energy-based devices (LEBD) has grown substantially,” corresponding author Scott Stratman, MD, MPH, and coauthors wrote in their study, which was published online in the Journal of the American Academy of Dermatology. “This has led to a rise in practitioners, both physicians and nonphysicians, who may lack the requisite training in LEBD procedures. Subsequently, procedures performed by these untrained practitioners have resulted in more lawsuits related to patient complications. As the demand for LEBD procedures and the number of practitioners performing these procedures increase, it remains paramount to characterize the trends of malpractice cases involving these procedures.”

Dr. Stratman, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, and colleagues queried the LexisNexis database from 1985 to Sept. 30, 2023, for all state, federal, and appellate cases that included the terms “negligence” or “malpractice” and “skin” and “laser.” After they removed duplicate cases and excluded cases that did not report dermatologic complications or cutaneous energy-based procedures, the final analysis included 75 cases.

Most of the appellants/plaintiffs (66; 88%) were women, a greater number of cases were in the Northeast (26; 34.7%) and the South (23; 30.7%), and the fewest cases were in the Midwest (12 [16%]). The most common anatomical sites were the face, head, and/or neck, and 43 of the cases (57.3%) were decided in favor of the appellee/defendant or the party defending against the appeal, while 29 (38.7%) were in favor of the appellant/plaintiff or the party appealing, and three cases (4%) did not report a verdict.

[embed:render:related:node:268907]

In other findings, plastic surgeons were the most litigated healthcare professionals (18; 24%), while 39 of the overall cases (52%) involved nonphysician operators (NPOs), 32 (42.7%) involved a physician operator, and 4 cases (5.3%) did not name a device operator. The most common procedure performed in the included cases was laser hair removal (33; 44%). Complications from energy-based devices included burns, scarring, and pigmentation changes. Statistically significant associations were neither found between verdict outcome and appellee/defendant type nor found between energy-device operator or anatomical site.

The authors acknowledged certain limitations of the study, including the fact that the LexisNexis database does not contain cases handled in out-of-court settlements and cases that underwent third-party arbitration.

“Physicians must recognize their responsibility when delegating procedures to NPOs and their role in supervision of these procedures,” they concluded. “Comprehensive training for physicians and their agents is necessary to diminish adverse outcomes and legal risks. Moreover, all practitioners should be held to the same standard of care. Familiarity with malpractice trends not only strengthens the patient-provider relationship but also equips providers with effective strategies to minimize the risk of legal repercussions.”

Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, who was asked to comment on the study, said that it “reaffirms previous studies which show that laser hair removal continues to be the most litigated procedure in laser surgery, and that nonphysician operators are most commonly litigated against. It further reiterates the importance of close supervision and expert training of procedures delegated by physicians.”

Neither the authors nor Dr. Avram reported having relevant financial disclosures.

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

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

The Food and Drug Administration has approved a topical anticholinergic, sofpironium topical gel, 12.45%, for the treatment of primary axillary hyperhidrosis in adults and children aged ≥ 9 years.

[embed:render:related:node:263559]

According to a press release from Botanix Pharmaceuticals, which developed the product and will market it under the brand name Sofdra, approval was based on results from two phase 3 studies that enrolled 710 patients with primary axillary hyperhidrosis. In the trials, patients treated with sofpironium topical gel, 12.45%, experienced “clinically and statistically meaningful changes” from baseline in the Gravimetric Sweat Production and the Hyperhidrosis Disease Severity Measure–Axillary seven-item score, according to the company.

Botanix plans to enable qualified patients to gain early access to the product in the third quarter of 2024, with commercial sales expected in the fourth quarter of 2024.
 

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

The Food and Drug Administration has approved a topical anticholinergic, sofpironium topical gel, 12.45%, for the treatment of primary axillary hyperhidrosis in adults and children aged ≥ 9 years.

[embed:render:related:node:263559]

According to a press release from Botanix Pharmaceuticals, which developed the product and will market it under the brand name Sofdra, approval was based on results from two phase 3 studies that enrolled 710 patients with primary axillary hyperhidrosis. In the trials, patients treated with sofpironium topical gel, 12.45%, experienced “clinically and statistically meaningful changes” from baseline in the Gravimetric Sweat Production and the Hyperhidrosis Disease Severity Measure–Axillary seven-item score, according to the company.

Botanix plans to enable qualified patients to gain early access to the product in the third quarter of 2024, with commercial sales expected in the fourth quarter of 2024.
 

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

The Food and Drug Administration has approved a topical anticholinergic, sofpironium topical gel, 12.45%, for the treatment of primary axillary hyperhidrosis in adults and children aged ≥ 9 years.

[embed:render:related:node:263559]

According to a press release from Botanix Pharmaceuticals, which developed the product and will market it under the brand name Sofdra, approval was based on results from two phase 3 studies that enrolled 710 patients with primary axillary hyperhidrosis. In the trials, patients treated with sofpironium topical gel, 12.45%, experienced “clinically and statistically meaningful changes” from baseline in the Gravimetric Sweat Production and the Hyperhidrosis Disease Severity Measure–Axillary seven-item score, according to the company.

Botanix plans to enable qualified patients to gain early access to the product in the third quarter of 2024, with commercial sales expected in the fourth quarter of 2024.
 

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

Patients with atopic dermatitis (AD) had a lower risk for major adverse cardiovascular events (MACE) than the general population, and this risk was significantly lower than that of patients with rheumatoid arthritis (RA), according to an analysis of national claims data.

The results of the analysis were presented during a poster session at the Revolutionizing Atopic Dermatitis conference in Chicago. “While it is known that atopic dermatitis is associated with some comorbidities, the specific risk of major adverse cardiovascular events in patients with AD, especially those with moderate to severe AD within the US population, is unclear,” the study’s first author Christopher G. Bunick, MD, PhD, said in an interview following the conference.

Bunick_Christopher_CONN_web.jpg

To characterize the risk for MACE in patients with AD vs matched controls without AD (non-AD) and patients with RA, Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut, and colleagues retrospectively evaluated US claims data from Optum’s Clinformatics Data Mart. The study population consisted of 381,221 patients aged 18 years and older who were diagnosed with AD from March 2017 to March 2023. Comparator groups included 381,221 non-AD controls matched by age, sex, and cohort entry, and 97,445 patients diagnosed with RA based on at least two claims for RA ≥ 7 days apart.

Patients were classified as having moderate to severe disease if they received dupilumab for AD or advanced systemic therapy for RA at any time during the follow-up period. The matched moderate to severe AD and non-AD cohorts were composed of 7134 patients each. The incidence of MACE was defined as inpatient hospitalization with myocardial infarction or stroke. The researchers used multivariable Cox proportional hazard models adjusted for baseline demographics, comorbidities, and medications to calculate the relative risk for MACE.
 

MACE Incidence, Relative Risk

The mean age of the AD cohort and non-AD matched controls was 58 years, and the mean age of the RA cohort was 67 years. The incidence of MACE per 100 patient-years was 1.78 among patients with AD, 1.83 among non-AD matched controls, and 2.12 among patients with RA. Patients with moderate to severe AD had a MACE incidence of 1.18 per 100 patient-years, which was lower than that of non-AD matched controls (1.52) and patients with moderate to severe RA (1.67).

In other findings, the relative risk for MACE in patients with AD was lower vs non-AD controls (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.89-0.93; P < .001) and patients with RA (aHR, 0.83; 95% CI, 0.80-0.85; P < .001). Among patients with moderate to severe AD, MACE risk was similar to that of non-AD matched controls (aHR, 0.92; 95% CI, 0.73-1.14) and lower vs those with moderate to severe RA (aHR, 0.83; 95% CI, 0.73-0.94; P < .01).

MACE risk associated with AD was greater in patients who were older (per year, aHR, 1.05; 95% CI, 1.05-1.05), male (aHR, 0.81; 95% CI, 0.79-0.84), and Black vs White (aHR, 1.16; 95% CI, 1.11-1.21), and among those who received systemic corticosteroids in the 3 months before diagnosis (aHR, 1.10; 95% CI, 1.06-1.14), were hospitalized in the year before diagnosis (aHR, 1.35; 95% CI, 1.30-1.41), and had a history of smoking (aHR, 1.20; 95% CI, 1.16-1.24) and drug abuse (aHR, 1.34; 95% CI, 1.25-1.43).
 

Unexpected Results

“One surprising finding was that the incidence of MACE in patients with moderate to severe AD was actually lower than that in non-AD matched controls and significantly lower compared to patients with moderate to severe RA,” Dr. Bunick said. “This contrasts with the expectation that increased systemic inflammation in moderate to severe AD would correspond with a higher incidence of MACE.”

Another unexpected result, he said, was that, among patients with moderate to severe AD, the risk for MACE was not significantly different from that of non-AD matched controls, suggesting that the inflammatory burden in AD might not translate to as high a cardiovascular risk as previously assumed.

Dr. Bunick noted that advanced treatments for AD such as Janus kinase (JAK) inhibitors (upadacitinib and abrocitinib) have a class boxed warning for MACE based on a study of another JAK inhibitor (tofacitinib) in patients with RA, but “this may not apply to AD because patients with AD have a lower risk for MACE.”

[embed:render:related:node:267679]

In his opinion, he said, the study “underscores the importance of understanding the specific risks associated with different inflammatory conditions.” Moreover, “it emphasizes the potential benefits of newer systemic therapies in potentially mitigating cardiovascular risks in patients with moderate to severe AD.”

Dr. Bunick acknowledged certain limitations of the study, including its retrospective design and reliance on administrative claims data, which “may introduce coding errors and misclassification,” and the generalizability of the results, which may be limited to the US population.

AbbVie funded the study, and three of the coauthors are employees of the company. Dr. Bunick disclosed that he has served as an investigator and/or a consultant for AbbVie, Almirall, Apogee, Arcutis Biotherapeutics, Connect Biopharma, Daiichi Sankyo, EPI Health/Novan, LEO, Lilly, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer, Sanofi Regeneron, Sun, Takeda, Timber, and UCB.

A version of this article appeared on Medscape.com.

Patients with atopic dermatitis (AD) had a lower risk for major adverse cardiovascular events (MACE) than the general population, and this risk was significantly lower than that of patients with rheumatoid arthritis (RA), according to an analysis of national claims data.

The results of the analysis were presented during a poster session at the Revolutionizing Atopic Dermatitis conference in Chicago. “While it is known that atopic dermatitis is associated with some comorbidities, the specific risk of major adverse cardiovascular events in patients with AD, especially those with moderate to severe AD within the US population, is unclear,” the study’s first author Christopher G. Bunick, MD, PhD, said in an interview following the conference.

Bunick_Christopher_CONN_web.jpg

To characterize the risk for MACE in patients with AD vs matched controls without AD (non-AD) and patients with RA, Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut, and colleagues retrospectively evaluated US claims data from Optum’s Clinformatics Data Mart. The study population consisted of 381,221 patients aged 18 years and older who were diagnosed with AD from March 2017 to March 2023. Comparator groups included 381,221 non-AD controls matched by age, sex, and cohort entry, and 97,445 patients diagnosed with RA based on at least two claims for RA ≥ 7 days apart.

Patients were classified as having moderate to severe disease if they received dupilumab for AD or advanced systemic therapy for RA at any time during the follow-up period. The matched moderate to severe AD and non-AD cohorts were composed of 7134 patients each. The incidence of MACE was defined as inpatient hospitalization with myocardial infarction or stroke. The researchers used multivariable Cox proportional hazard models adjusted for baseline demographics, comorbidities, and medications to calculate the relative risk for MACE.
 

MACE Incidence, Relative Risk

The mean age of the AD cohort and non-AD matched controls was 58 years, and the mean age of the RA cohort was 67 years. The incidence of MACE per 100 patient-years was 1.78 among patients with AD, 1.83 among non-AD matched controls, and 2.12 among patients with RA. Patients with moderate to severe AD had a MACE incidence of 1.18 per 100 patient-years, which was lower than that of non-AD matched controls (1.52) and patients with moderate to severe RA (1.67).

In other findings, the relative risk for MACE in patients with AD was lower vs non-AD controls (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.89-0.93; P < .001) and patients with RA (aHR, 0.83; 95% CI, 0.80-0.85; P < .001). Among patients with moderate to severe AD, MACE risk was similar to that of non-AD matched controls (aHR, 0.92; 95% CI, 0.73-1.14) and lower vs those with moderate to severe RA (aHR, 0.83; 95% CI, 0.73-0.94; P < .01).

MACE risk associated with AD was greater in patients who were older (per year, aHR, 1.05; 95% CI, 1.05-1.05), male (aHR, 0.81; 95% CI, 0.79-0.84), and Black vs White (aHR, 1.16; 95% CI, 1.11-1.21), and among those who received systemic corticosteroids in the 3 months before diagnosis (aHR, 1.10; 95% CI, 1.06-1.14), were hospitalized in the year before diagnosis (aHR, 1.35; 95% CI, 1.30-1.41), and had a history of smoking (aHR, 1.20; 95% CI, 1.16-1.24) and drug abuse (aHR, 1.34; 95% CI, 1.25-1.43).
 

Unexpected Results

“One surprising finding was that the incidence of MACE in patients with moderate to severe AD was actually lower than that in non-AD matched controls and significantly lower compared to patients with moderate to severe RA,” Dr. Bunick said. “This contrasts with the expectation that increased systemic inflammation in moderate to severe AD would correspond with a higher incidence of MACE.”

Another unexpected result, he said, was that, among patients with moderate to severe AD, the risk for MACE was not significantly different from that of non-AD matched controls, suggesting that the inflammatory burden in AD might not translate to as high a cardiovascular risk as previously assumed.

Dr. Bunick noted that advanced treatments for AD such as Janus kinase (JAK) inhibitors (upadacitinib and abrocitinib) have a class boxed warning for MACE based on a study of another JAK inhibitor (tofacitinib) in patients with RA, but “this may not apply to AD because patients with AD have a lower risk for MACE.”

[embed:render:related:node:267679]

In his opinion, he said, the study “underscores the importance of understanding the specific risks associated with different inflammatory conditions.” Moreover, “it emphasizes the potential benefits of newer systemic therapies in potentially mitigating cardiovascular risks in patients with moderate to severe AD.”

Dr. Bunick acknowledged certain limitations of the study, including its retrospective design and reliance on administrative claims data, which “may introduce coding errors and misclassification,” and the generalizability of the results, which may be limited to the US population.

AbbVie funded the study, and three of the coauthors are employees of the company. Dr. Bunick disclosed that he has served as an investigator and/or a consultant for AbbVie, Almirall, Apogee, Arcutis Biotherapeutics, Connect Biopharma, Daiichi Sankyo, EPI Health/Novan, LEO, Lilly, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer, Sanofi Regeneron, Sun, Takeda, Timber, and UCB.

A version of this article appeared on Medscape.com.

Patients with atopic dermatitis (AD) had a lower risk for major adverse cardiovascular events (MACE) than the general population, and this risk was significantly lower than that of patients with rheumatoid arthritis (RA), according to an analysis of national claims data.

The results of the analysis were presented during a poster session at the Revolutionizing Atopic Dermatitis conference in Chicago. “While it is known that atopic dermatitis is associated with some comorbidities, the specific risk of major adverse cardiovascular events in patients with AD, especially those with moderate to severe AD within the US population, is unclear,” the study’s first author Christopher G. Bunick, MD, PhD, said in an interview following the conference.

Bunick_Christopher_CONN_web.jpg

To characterize the risk for MACE in patients with AD vs matched controls without AD (non-AD) and patients with RA, Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut, and colleagues retrospectively evaluated US claims data from Optum’s Clinformatics Data Mart. The study population consisted of 381,221 patients aged 18 years and older who were diagnosed with AD from March 2017 to March 2023. Comparator groups included 381,221 non-AD controls matched by age, sex, and cohort entry, and 97,445 patients diagnosed with RA based on at least two claims for RA ≥ 7 days apart.

Patients were classified as having moderate to severe disease if they received dupilumab for AD or advanced systemic therapy for RA at any time during the follow-up period. The matched moderate to severe AD and non-AD cohorts were composed of 7134 patients each. The incidence of MACE was defined as inpatient hospitalization with myocardial infarction or stroke. The researchers used multivariable Cox proportional hazard models adjusted for baseline demographics, comorbidities, and medications to calculate the relative risk for MACE.
 

MACE Incidence, Relative Risk

The mean age of the AD cohort and non-AD matched controls was 58 years, and the mean age of the RA cohort was 67 years. The incidence of MACE per 100 patient-years was 1.78 among patients with AD, 1.83 among non-AD matched controls, and 2.12 among patients with RA. Patients with moderate to severe AD had a MACE incidence of 1.18 per 100 patient-years, which was lower than that of non-AD matched controls (1.52) and patients with moderate to severe RA (1.67).

In other findings, the relative risk for MACE in patients with AD was lower vs non-AD controls (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.89-0.93; P < .001) and patients with RA (aHR, 0.83; 95% CI, 0.80-0.85; P < .001). Among patients with moderate to severe AD, MACE risk was similar to that of non-AD matched controls (aHR, 0.92; 95% CI, 0.73-1.14) and lower vs those with moderate to severe RA (aHR, 0.83; 95% CI, 0.73-0.94; P < .01).

MACE risk associated with AD was greater in patients who were older (per year, aHR, 1.05; 95% CI, 1.05-1.05), male (aHR, 0.81; 95% CI, 0.79-0.84), and Black vs White (aHR, 1.16; 95% CI, 1.11-1.21), and among those who received systemic corticosteroids in the 3 months before diagnosis (aHR, 1.10; 95% CI, 1.06-1.14), were hospitalized in the year before diagnosis (aHR, 1.35; 95% CI, 1.30-1.41), and had a history of smoking (aHR, 1.20; 95% CI, 1.16-1.24) and drug abuse (aHR, 1.34; 95% CI, 1.25-1.43).
 

Unexpected Results

“One surprising finding was that the incidence of MACE in patients with moderate to severe AD was actually lower than that in non-AD matched controls and significantly lower compared to patients with moderate to severe RA,” Dr. Bunick said. “This contrasts with the expectation that increased systemic inflammation in moderate to severe AD would correspond with a higher incidence of MACE.”

Another unexpected result, he said, was that, among patients with moderate to severe AD, the risk for MACE was not significantly different from that of non-AD matched controls, suggesting that the inflammatory burden in AD might not translate to as high a cardiovascular risk as previously assumed.

Dr. Bunick noted that advanced treatments for AD such as Janus kinase (JAK) inhibitors (upadacitinib and abrocitinib) have a class boxed warning for MACE based on a study of another JAK inhibitor (tofacitinib) in patients with RA, but “this may not apply to AD because patients with AD have a lower risk for MACE.”

[embed:render:related:node:267679]

In his opinion, he said, the study “underscores the importance of understanding the specific risks associated with different inflammatory conditions.” Moreover, “it emphasizes the potential benefits of newer systemic therapies in potentially mitigating cardiovascular risks in patients with moderate to severe AD.”

Dr. Bunick acknowledged certain limitations of the study, including its retrospective design and reliance on administrative claims data, which “may introduce coding errors and misclassification,” and the generalizability of the results, which may be limited to the US population.

AbbVie funded the study, and three of the coauthors are employees of the company. Dr. Bunick disclosed that he has served as an investigator and/or a consultant for AbbVie, Almirall, Apogee, Arcutis Biotherapeutics, Connect Biopharma, Daiichi Sankyo, EPI Health/Novan, LEO, Lilly, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer, Sanofi Regeneron, Sun, Takeda, Timber, and UCB.

A version of this article appeared on Medscape.com.

In the United States, the prevalence of patient-reported atopic dermatitis (AD) is higher in children and adult women, while Hispanic adults have a lower prevalence of AD than adults from other ethnic backgrounds.

Those are among the key findings from an analysis of nationally representative cross-sectional data that were presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis conference in Chicago.

“In the past few years, there has been a much-needed focus on better understanding disparities in atopic dermatitis,” one of the study authors, Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University, North Chicago, told this news organization after the conference.

Chovatiya_Ray_ILL_web.jpg

“Epidemiology is one of the key ways in which we can query differences in AD at a population level.”

Drawing from the 2021 National Health Interview Survey, the researchers identified 3103 respondents who reported being diagnosed with AD or eczema. They estimated the prevalence rates of AD for the overall population and each subgroup by dividing US frequency estimates by their corresponding US population totals and used multivariable logistic regression to assess the odds of having AD.

More than half of the respondents (1643) were aged between 18 and 64 years, 522 were aged 65 years and older, and 922 were children younger than 18 years. Overall, the prevalence of AD was 7.6% in adults aged 18-64 years and 6.1% in adults aged 65 years and older, for a weighted US estimate of 15.3 and 3.2 million, respectively. The prevalence of AD varied by race/ethnicity and was highest for those from “other single and multiple races” group (12.4%), followed by Black/African American (8.5%), White (7.7%), Asian (6.5%), American Indian/Alaskan Native (4.9%), and Hispanic (4.8%) populations.

In children, race/ethnicity prevalence were highest for those from other single and multiple races (15.2.%), followed by Black/African American (14.2%), American Indian/Alaskan Native (12%), White (10.2%), Hispanic (9.5%), and Asian (9%) populations.

When the researchers combined all age groups, they observed higher prevalence rates of AD among females than among males. However, in an analysis limited to children, the prevalence rates were similar between girls and boys (10.8% vs 10.7%, respectively), for a weighted US estimate of 7.8 million children with AD.

[embed:render:related:node:269284]

On multiple regression, the odds of having AD were greater among women than among men (odds ratio [OR], 1.4), among adults aged 18-64 years than among those aged 65 years and older (OR, 1.4), among those younger than 18 years than among those aged 65 years and older (OR, 2.0), and among Black/African American individuals than among White individuals (OR, 1.2). Hispanic adults had a lower risk for AD than non-Hispanic White adults (OR, 0.69) as did Asian adults than White adults (OR, 0.82).

“We found AD prevalence rates were higher in children and adult females, Hispanic adults had a lower prevalence of AD than all other adult groups, and there were numerical differences in AD prevalence across racial groups,” Dr. Chovatiya said in the interview. “While there are of course limitations to the use of any nationally representative cross-sectional dataset that requires weighting to project results from a smaller sample to reflect a larger more heterogeneous group, these results are important for us to consider targeted strategies to address AD burden.”

Jonathan I. Silverberg, MD, PhD, professor of dermatology at The George Washington University, Washington, who was asked to comment on the study, said that while the prevalence of AD in children has been well documented in prior research, “this study fills an important gap by showing us that the prevalence does remain high in adults.”

In addition, “it has not shown any evidence of AD decreasing over time; if anything, it might be slightly increasing,” he said. “We’re also seeing differences [in AD] by race and ethnicity. We have seen that demonstrated in children but [has been] less clearly demonstrated in adults.”

Eli Lilly and Company funded the analysis. Dr. Chovatiya and Dr. Silverberg disclosed ties to several pharmaceutical companies, including Eli Lilly.

A version of this article appeared on Medscape.com .

In the United States, the prevalence of patient-reported atopic dermatitis (AD) is higher in children and adult women, while Hispanic adults have a lower prevalence of AD than adults from other ethnic backgrounds.

Those are among the key findings from an analysis of nationally representative cross-sectional data that were presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis conference in Chicago.

“In the past few years, there has been a much-needed focus on better understanding disparities in atopic dermatitis,” one of the study authors, Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University, North Chicago, told this news organization after the conference.

Chovatiya_Ray_ILL_web.jpg

“Epidemiology is one of the key ways in which we can query differences in AD at a population level.”

Drawing from the 2021 National Health Interview Survey, the researchers identified 3103 respondents who reported being diagnosed with AD or eczema. They estimated the prevalence rates of AD for the overall population and each subgroup by dividing US frequency estimates by their corresponding US population totals and used multivariable logistic regression to assess the odds of having AD.

More than half of the respondents (1643) were aged between 18 and 64 years, 522 were aged 65 years and older, and 922 were children younger than 18 years. Overall, the prevalence of AD was 7.6% in adults aged 18-64 years and 6.1% in adults aged 65 years and older, for a weighted US estimate of 15.3 and 3.2 million, respectively. The prevalence of AD varied by race/ethnicity and was highest for those from “other single and multiple races” group (12.4%), followed by Black/African American (8.5%), White (7.7%), Asian (6.5%), American Indian/Alaskan Native (4.9%), and Hispanic (4.8%) populations.

In children, race/ethnicity prevalence were highest for those from other single and multiple races (15.2.%), followed by Black/African American (14.2%), American Indian/Alaskan Native (12%), White (10.2%), Hispanic (9.5%), and Asian (9%) populations.

When the researchers combined all age groups, they observed higher prevalence rates of AD among females than among males. However, in an analysis limited to children, the prevalence rates were similar between girls and boys (10.8% vs 10.7%, respectively), for a weighted US estimate of 7.8 million children with AD.

[embed:render:related:node:269284]

On multiple regression, the odds of having AD were greater among women than among men (odds ratio [OR], 1.4), among adults aged 18-64 years than among those aged 65 years and older (OR, 1.4), among those younger than 18 years than among those aged 65 years and older (OR, 2.0), and among Black/African American individuals than among White individuals (OR, 1.2). Hispanic adults had a lower risk for AD than non-Hispanic White adults (OR, 0.69) as did Asian adults than White adults (OR, 0.82).

“We found AD prevalence rates were higher in children and adult females, Hispanic adults had a lower prevalence of AD than all other adult groups, and there were numerical differences in AD prevalence across racial groups,” Dr. Chovatiya said in the interview. “While there are of course limitations to the use of any nationally representative cross-sectional dataset that requires weighting to project results from a smaller sample to reflect a larger more heterogeneous group, these results are important for us to consider targeted strategies to address AD burden.”

Jonathan I. Silverberg, MD, PhD, professor of dermatology at The George Washington University, Washington, who was asked to comment on the study, said that while the prevalence of AD in children has been well documented in prior research, “this study fills an important gap by showing us that the prevalence does remain high in adults.”

In addition, “it has not shown any evidence of AD decreasing over time; if anything, it might be slightly increasing,” he said. “We’re also seeing differences [in AD] by race and ethnicity. We have seen that demonstrated in children but [has been] less clearly demonstrated in adults.”

Eli Lilly and Company funded the analysis. Dr. Chovatiya and Dr. Silverberg disclosed ties to several pharmaceutical companies, including Eli Lilly.

A version of this article appeared on Medscape.com .

In the United States, the prevalence of patient-reported atopic dermatitis (AD) is higher in children and adult women, while Hispanic adults have a lower prevalence of AD than adults from other ethnic backgrounds.

Those are among the key findings from an analysis of nationally representative cross-sectional data that were presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis conference in Chicago.

“In the past few years, there has been a much-needed focus on better understanding disparities in atopic dermatitis,” one of the study authors, Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University, North Chicago, told this news organization after the conference.

Chovatiya_Ray_ILL_web.jpg

“Epidemiology is one of the key ways in which we can query differences in AD at a population level.”

Drawing from the 2021 National Health Interview Survey, the researchers identified 3103 respondents who reported being diagnosed with AD or eczema. They estimated the prevalence rates of AD for the overall population and each subgroup by dividing US frequency estimates by their corresponding US population totals and used multivariable logistic regression to assess the odds of having AD.

More than half of the respondents (1643) were aged between 18 and 64 years, 522 were aged 65 years and older, and 922 were children younger than 18 years. Overall, the prevalence of AD was 7.6% in adults aged 18-64 years and 6.1% in adults aged 65 years and older, for a weighted US estimate of 15.3 and 3.2 million, respectively. The prevalence of AD varied by race/ethnicity and was highest for those from “other single and multiple races” group (12.4%), followed by Black/African American (8.5%), White (7.7%), Asian (6.5%), American Indian/Alaskan Native (4.9%), and Hispanic (4.8%) populations.

In children, race/ethnicity prevalence were highest for those from other single and multiple races (15.2.%), followed by Black/African American (14.2%), American Indian/Alaskan Native (12%), White (10.2%), Hispanic (9.5%), and Asian (9%) populations.

When the researchers combined all age groups, they observed higher prevalence rates of AD among females than among males. However, in an analysis limited to children, the prevalence rates were similar between girls and boys (10.8% vs 10.7%, respectively), for a weighted US estimate of 7.8 million children with AD.

[embed:render:related:node:269284]

On multiple regression, the odds of having AD were greater among women than among men (odds ratio [OR], 1.4), among adults aged 18-64 years than among those aged 65 years and older (OR, 1.4), among those younger than 18 years than among those aged 65 years and older (OR, 2.0), and among Black/African American individuals than among White individuals (OR, 1.2). Hispanic adults had a lower risk for AD than non-Hispanic White adults (OR, 0.69) as did Asian adults than White adults (OR, 0.82).

“We found AD prevalence rates were higher in children and adult females, Hispanic adults had a lower prevalence of AD than all other adult groups, and there were numerical differences in AD prevalence across racial groups,” Dr. Chovatiya said in the interview. “While there are of course limitations to the use of any nationally representative cross-sectional dataset that requires weighting to project results from a smaller sample to reflect a larger more heterogeneous group, these results are important for us to consider targeted strategies to address AD burden.”

Jonathan I. Silverberg, MD, PhD, professor of dermatology at The George Washington University, Washington, who was asked to comment on the study, said that while the prevalence of AD in children has been well documented in prior research, “this study fills an important gap by showing us that the prevalence does remain high in adults.”

In addition, “it has not shown any evidence of AD decreasing over time; if anything, it might be slightly increasing,” he said. “We’re also seeing differences [in AD] by race and ethnicity. We have seen that demonstrated in children but [has been] less clearly demonstrated in adults.”

Eli Lilly and Company funded the analysis. Dr. Chovatiya and Dr. Silverberg disclosed ties to several pharmaceutical companies, including Eli Lilly.

A version of this article appeared on Medscape.com .

Treatment with topical ruxolitinib cream 1.5% showed good tolerability and was effective over the course of 52 weeks in children aged 2-11 years with atopic dermatitis (AD) affecting ≥ 35% or more of their body surface area (BSA), results from a small open-label maximum-use trial showed.

When approved for this age group, ruxolitinib cream will provide a topical nonsteroidal option for patients aged 2-11, which will “simplify the treatment regimen,” one of the study investigators, Linda Stein Gold, MD, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit, said in an interview after the Revolutionizing Atopic Dermatitis conference, where the study was presented during a late-breaking abstract session.

clucradashouasiclotaseselecepugashosheduuebicredracrivefruwraslahucluninowujawrolostoswewusteparikaswejuhicaspodosososhotewroslerishochujucudrokulaueslewaclospamiceprechubraniclebrowrojocluhiphid

A topical formulation of the selective Janus kinase (JAK) 1/JAK2 inhibitor, ruxolitinib cream 1.5% is currently approved by the Food and Drug Administration for the short-term and noncontinuous chronic treatment of mild to moderate AD in non-immunocompromised adult and pediatric patients aged 12 years and older, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

In previous reports of this trial in children aged 2-11 years with ≥ 35% affected BSA, ruxolitinib cream 1.5% was generally well tolerated, with rapid anti-inflammatory and antipruritic effects and improvements in patient-reported outcomes observed with ≤ 4 weeks of continuous treatment and maintained with as-needed treatment from 4 to 8 weeks.

For the current trial, investigators evaluated data on tolerability, safety, systemic exposure, and clinical and patient-reported outcomes through 52 weeks to determine whether clinical benefits and tolerability observed through 8 weeks were sustained.

Dr. Stein Gold and colleagues reported results from 29 children who received ruxolitinib cream 1.5% from baseline through week 8. Of these, 22 continued into the long-term safety period from week 8 through 52. From baseline through week 8, patients applied a mean of 6.5 g per day of ruxolitinib cream; this dropped to a mean of 3.2 g per day from weeks 8 through 52. The mean steady-state plasma concentration of ruxolitinib throughout the study was 98.2 nM, which is “well below half-maximal concentration of JAK-mediated myelosuppression in adults (281 nM),” the researchers stated in their abstract.

[embed:render:related:node:266259]

No treatment-related interruptions, discontinuations, or serious adverse events were observed between baseline and week 52. One patient (3.4%) had two treatment-related application site reactions (paresthesia and folliculitis). At weeks 4 and 52, 53.8% of patients achieved treatment success, which was defined as an Investigator Global Assessment of 0/1 with a ≥ 2-grade improvement from baseline. The mean affected BSA decreased from 58.0% at baseline to 11.4% at week 4 and continued to decrease to 2.2% through week 52. “I was surprised that patients could maintain control over the long-term using the medication as needed,” Dr. Stein Gold told this news organization. “I was also pleased to see that there was low systemic exposure even when used on large body surface areas.”

In other findings, the mean total Patient Oriented Eczema Measure score dropped from a baseline of 19.4 to a mean of 4.5 at week 8 and 3.6 at week 52 and the mean total Children’s Dermatology Life Quality Index score fell from a baseline of 15.4 to a mean of 5.3 at week 8 and a mean of 2.1 at week 52. Meanwhile, the mean total Infants’ Dermatology Quality of Life Index score fell from a mean of 12.3 at baseline to a mean of 2.8 at week 8 and a mean of 0.7 at week 52.

Dr. Stein Gold noted certain limitations of the study, including the fact that it did not study children aged younger than 2 years.

The study was funded by Incyte, which markets ruxolitinib cream 1.5% as Opzelura. Dr. Stein Gold disclosed that she has served as an investigator, advisor, and/or speaker for several pharmaceutical companies, including Incyte.

A version of this article appeared on Medscape.com.

Treatment with topical ruxolitinib cream 1.5% showed good tolerability and was effective over the course of 52 weeks in children aged 2-11 years with atopic dermatitis (AD) affecting ≥ 35% or more of their body surface area (BSA), results from a small open-label maximum-use trial showed.

When approved for this age group, ruxolitinib cream will provide a topical nonsteroidal option for patients aged 2-11, which will “simplify the treatment regimen,” one of the study investigators, Linda Stein Gold, MD, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit, said in an interview after the Revolutionizing Atopic Dermatitis conference, where the study was presented during a late-breaking abstract session.

clucradashouasiclotaseselecepugashosheduuebicredracrivefruwraslahucluninowujawrolostoswewusteparikaswejuhicaspodosososhotewroslerishochujucudrokulaueslewaclospamiceprechubraniclebrowrojocluhiphid

A topical formulation of the selective Janus kinase (JAK) 1/JAK2 inhibitor, ruxolitinib cream 1.5% is currently approved by the Food and Drug Administration for the short-term and noncontinuous chronic treatment of mild to moderate AD in non-immunocompromised adult and pediatric patients aged 12 years and older, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

In previous reports of this trial in children aged 2-11 years with ≥ 35% affected BSA, ruxolitinib cream 1.5% was generally well tolerated, with rapid anti-inflammatory and antipruritic effects and improvements in patient-reported outcomes observed with ≤ 4 weeks of continuous treatment and maintained with as-needed treatment from 4 to 8 weeks.

For the current trial, investigators evaluated data on tolerability, safety, systemic exposure, and clinical and patient-reported outcomes through 52 weeks to determine whether clinical benefits and tolerability observed through 8 weeks were sustained.

Dr. Stein Gold and colleagues reported results from 29 children who received ruxolitinib cream 1.5% from baseline through week 8. Of these, 22 continued into the long-term safety period from week 8 through 52. From baseline through week 8, patients applied a mean of 6.5 g per day of ruxolitinib cream; this dropped to a mean of 3.2 g per day from weeks 8 through 52. The mean steady-state plasma concentration of ruxolitinib throughout the study was 98.2 nM, which is “well below half-maximal concentration of JAK-mediated myelosuppression in adults (281 nM),” the researchers stated in their abstract.

[embed:render:related:node:266259]

No treatment-related interruptions, discontinuations, or serious adverse events were observed between baseline and week 52. One patient (3.4%) had two treatment-related application site reactions (paresthesia and folliculitis). At weeks 4 and 52, 53.8% of patients achieved treatment success, which was defined as an Investigator Global Assessment of 0/1 with a ≥ 2-grade improvement from baseline. The mean affected BSA decreased from 58.0% at baseline to 11.4% at week 4 and continued to decrease to 2.2% through week 52. “I was surprised that patients could maintain control over the long-term using the medication as needed,” Dr. Stein Gold told this news organization. “I was also pleased to see that there was low systemic exposure even when used on large body surface areas.”

In other findings, the mean total Patient Oriented Eczema Measure score dropped from a baseline of 19.4 to a mean of 4.5 at week 8 and 3.6 at week 52 and the mean total Children’s Dermatology Life Quality Index score fell from a baseline of 15.4 to a mean of 5.3 at week 8 and a mean of 2.1 at week 52. Meanwhile, the mean total Infants’ Dermatology Quality of Life Index score fell from a mean of 12.3 at baseline to a mean of 2.8 at week 8 and a mean of 0.7 at week 52.

Dr. Stein Gold noted certain limitations of the study, including the fact that it did not study children aged younger than 2 years.

The study was funded by Incyte, which markets ruxolitinib cream 1.5% as Opzelura. Dr. Stein Gold disclosed that she has served as an investigator, advisor, and/or speaker for several pharmaceutical companies, including Incyte.

A version of this article appeared on Medscape.com.

Treatment with topical ruxolitinib cream 1.5% showed good tolerability and was effective over the course of 52 weeks in children aged 2-11 years with atopic dermatitis (AD) affecting ≥ 35% or more of their body surface area (BSA), results from a small open-label maximum-use trial showed.

When approved for this age group, ruxolitinib cream will provide a topical nonsteroidal option for patients aged 2-11, which will “simplify the treatment regimen,” one of the study investigators, Linda Stein Gold, MD, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit, said in an interview after the Revolutionizing Atopic Dermatitis conference, where the study was presented during a late-breaking abstract session.

clucradashouasiclotaseselecepugashosheduuebicredracrivefruwraslahucluninowujawrolostoswewusteparikaswejuhicaspodosososhotewroslerishochujucudrokulaueslewaclospamiceprechubraniclebrowrojocluhiphid

A topical formulation of the selective Janus kinase (JAK) 1/JAK2 inhibitor, ruxolitinib cream 1.5% is currently approved by the Food and Drug Administration for the short-term and noncontinuous chronic treatment of mild to moderate AD in non-immunocompromised adult and pediatric patients aged 12 years and older, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

In previous reports of this trial in children aged 2-11 years with ≥ 35% affected BSA, ruxolitinib cream 1.5% was generally well tolerated, with rapid anti-inflammatory and antipruritic effects and improvements in patient-reported outcomes observed with ≤ 4 weeks of continuous treatment and maintained with as-needed treatment from 4 to 8 weeks.

For the current trial, investigators evaluated data on tolerability, safety, systemic exposure, and clinical and patient-reported outcomes through 52 weeks to determine whether clinical benefits and tolerability observed through 8 weeks were sustained.

Dr. Stein Gold and colleagues reported results from 29 children who received ruxolitinib cream 1.5% from baseline through week 8. Of these, 22 continued into the long-term safety period from week 8 through 52. From baseline through week 8, patients applied a mean of 6.5 g per day of ruxolitinib cream; this dropped to a mean of 3.2 g per day from weeks 8 through 52. The mean steady-state plasma concentration of ruxolitinib throughout the study was 98.2 nM, which is “well below half-maximal concentration of JAK-mediated myelosuppression in adults (281 nM),” the researchers stated in their abstract.

[embed:render:related:node:266259]

No treatment-related interruptions, discontinuations, or serious adverse events were observed between baseline and week 52. One patient (3.4%) had two treatment-related application site reactions (paresthesia and folliculitis). At weeks 4 and 52, 53.8% of patients achieved treatment success, which was defined as an Investigator Global Assessment of 0/1 with a ≥ 2-grade improvement from baseline. The mean affected BSA decreased from 58.0% at baseline to 11.4% at week 4 and continued to decrease to 2.2% through week 52. “I was surprised that patients could maintain control over the long-term using the medication as needed,” Dr. Stein Gold told this news organization. “I was also pleased to see that there was low systemic exposure even when used on large body surface areas.”

In other findings, the mean total Patient Oriented Eczema Measure score dropped from a baseline of 19.4 to a mean of 4.5 at week 8 and 3.6 at week 52 and the mean total Children’s Dermatology Life Quality Index score fell from a baseline of 15.4 to a mean of 5.3 at week 8 and a mean of 2.1 at week 52. Meanwhile, the mean total Infants’ Dermatology Quality of Life Index score fell from a mean of 12.3 at baseline to a mean of 2.8 at week 8 and a mean of 0.7 at week 52.

Dr. Stein Gold noted certain limitations of the study, including the fact that it did not study children aged younger than 2 years.

The study was funded by Incyte, which markets ruxolitinib cream 1.5% as Opzelura. Dr. Stein Gold disclosed that she has served as an investigator, advisor, and/or speaker for several pharmaceutical companies, including Incyte.

A version of this article appeared on Medscape.com.

TOPLINE:

Pediatric patients with atopic dermatitis (AD) who are prescribed dupilumab may be at a reduced risk for atopic march progression, defined as the development of asthma or allergic rhinitis.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the US Collaborative Network, focusing on pediatric patients aged 18 years and younger with two AD diagnoses at least 30 days apart.
• Patients were divided into two cohorts: Those treated with dupilumab (n = 2192) and those who received conventional therapies (n = 2192), including systemic corticosteroids or conventional immunomodulators. They were stratified into three age groups: Preschoolers (< 6 years), school-aged children (6 to < 12 years), and adolescents (12-18 years).
• Both cohorts underwent 1:1 propensity score matching based on current age, age at index (first prescription of dupilumab or conventional therapy), sex, race, comorbidities, laboratory measurements, and prior medications. The primary outcome was atopic march progression, defined by incident asthma or allergic rhinitis.

TAKEAWAY:

• Over 3 years, the dupilumab-treated cohort had a significantly lower cumulative incidence of atopic march progression (20.09% vs 27.22%; P < .001), asthma (9.43% vs 14.64%; P = .001), and allergic rhinitis (13.57% vs 20.52%; P = .003) than the conventional therapy cohort.
• The risk for atopic march progression, asthma, and allergic rhinitis was also significantly reduced by 32%, 40%, and 31%, respectively, in the dupilumab vs conventional therapy cohort.
• Age-specific analyses found that the protective effect of dupilumab against allergic rhinitis was the most pronounced in adolescents (hazard ratio [HR], 0.503; 95% CI, 0.322-0.784), followed by school-aged children (HR, 0.577; 95% CI, 0.399-0.834), and preschoolers (HR, 0.623; 95% CI, 0.412-0.942).
• However, dupilumab was associated with reduced risk for asthma only in preschoolers (HR, 0.427; 95% CI, 0.247-0.738) and not in school-aged children or adolescents.

IN PRACTICE:

“Dupilumab in AD not only treats the disease but may influence atopic march mechanisms, suggesting its role as a disease-modifying atopic march drug,” the authors wrote, adding that more research “with extended follow-up and proof-of-concept is warranted.”

SOURCE:

The study was led by Teng-Li Lin, MD, Department of Dermatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan, and was published online on June 13, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The observational nature of the study limited the ability to infer direct causality between dupilumab use and reduced atopic march risk. Lack of detailed information on AD severity, total dosage, and duration of medication treatment may affect the interpretation of the study’s findings. The demographic data suggest that the dupilumab cohort had more severe AD, so the observed risk reduction may be greater than that reported in this study.

DISCLOSURES:

The study was supported in part by the National Science and Technology Council, Taiwan, and Taichung Veterans General Hospital. The authors had no relevant conflicts of interest.

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

A version of this article appeared on Medscape.com .

TOPLINE:

Pediatric patients with atopic dermatitis (AD) who are prescribed dupilumab may be at a reduced risk for atopic march progression, defined as the development of asthma or allergic rhinitis.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the US Collaborative Network, focusing on pediatric patients aged 18 years and younger with two AD diagnoses at least 30 days apart.
• Patients were divided into two cohorts: Those treated with dupilumab (n = 2192) and those who received conventional therapies (n = 2192), including systemic corticosteroids or conventional immunomodulators. They were stratified into three age groups: Preschoolers (< 6 years), school-aged children (6 to < 12 years), and adolescents (12-18 years).
• Both cohorts underwent 1:1 propensity score matching based on current age, age at index (first prescription of dupilumab or conventional therapy), sex, race, comorbidities, laboratory measurements, and prior medications. The primary outcome was atopic march progression, defined by incident asthma or allergic rhinitis.

TAKEAWAY:

• Over 3 years, the dupilumab-treated cohort had a significantly lower cumulative incidence of atopic march progression (20.09% vs 27.22%; P < .001), asthma (9.43% vs 14.64%; P = .001), and allergic rhinitis (13.57% vs 20.52%; P = .003) than the conventional therapy cohort.
• The risk for atopic march progression, asthma, and allergic rhinitis was also significantly reduced by 32%, 40%, and 31%, respectively, in the dupilumab vs conventional therapy cohort.
• Age-specific analyses found that the protective effect of dupilumab against allergic rhinitis was the most pronounced in adolescents (hazard ratio [HR], 0.503; 95% CI, 0.322-0.784), followed by school-aged children (HR, 0.577; 95% CI, 0.399-0.834), and preschoolers (HR, 0.623; 95% CI, 0.412-0.942).
• However, dupilumab was associated with reduced risk for asthma only in preschoolers (HR, 0.427; 95% CI, 0.247-0.738) and not in school-aged children or adolescents.

IN PRACTICE:

“Dupilumab in AD not only treats the disease but may influence atopic march mechanisms, suggesting its role as a disease-modifying atopic march drug,” the authors wrote, adding that more research “with extended follow-up and proof-of-concept is warranted.”

SOURCE:

The study was led by Teng-Li Lin, MD, Department of Dermatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan, and was published online on June 13, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The observational nature of the study limited the ability to infer direct causality between dupilumab use and reduced atopic march risk. Lack of detailed information on AD severity, total dosage, and duration of medication treatment may affect the interpretation of the study’s findings. The demographic data suggest that the dupilumab cohort had more severe AD, so the observed risk reduction may be greater than that reported in this study.

DISCLOSURES:

The study was supported in part by the National Science and Technology Council, Taiwan, and Taichung Veterans General Hospital. The authors had no relevant conflicts of interest.

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

A version of this article appeared on Medscape.com .

TOPLINE:

Pediatric patients with atopic dermatitis (AD) who are prescribed dupilumab may be at a reduced risk for atopic march progression, defined as the development of asthma or allergic rhinitis.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the US Collaborative Network, focusing on pediatric patients aged 18 years and younger with two AD diagnoses at least 30 days apart.
• Patients were divided into two cohorts: Those treated with dupilumab (n = 2192) and those who received conventional therapies (n = 2192), including systemic corticosteroids or conventional immunomodulators. They were stratified into three age groups: Preschoolers (< 6 years), school-aged children (6 to < 12 years), and adolescents (12-18 years).
• Both cohorts underwent 1:1 propensity score matching based on current age, age at index (first prescription of dupilumab or conventional therapy), sex, race, comorbidities, laboratory measurements, and prior medications. The primary outcome was atopic march progression, defined by incident asthma or allergic rhinitis.

TAKEAWAY:

• Over 3 years, the dupilumab-treated cohort had a significantly lower cumulative incidence of atopic march progression (20.09% vs 27.22%; P < .001), asthma (9.43% vs 14.64%; P = .001), and allergic rhinitis (13.57% vs 20.52%; P = .003) than the conventional therapy cohort.
• The risk for atopic march progression, asthma, and allergic rhinitis was also significantly reduced by 32%, 40%, and 31%, respectively, in the dupilumab vs conventional therapy cohort.
• Age-specific analyses found that the protective effect of dupilumab against allergic rhinitis was the most pronounced in adolescents (hazard ratio [HR], 0.503; 95% CI, 0.322-0.784), followed by school-aged children (HR, 0.577; 95% CI, 0.399-0.834), and preschoolers (HR, 0.623; 95% CI, 0.412-0.942).
• However, dupilumab was associated with reduced risk for asthma only in preschoolers (HR, 0.427; 95% CI, 0.247-0.738) and not in school-aged children or adolescents.

IN PRACTICE:

“Dupilumab in AD not only treats the disease but may influence atopic march mechanisms, suggesting its role as a disease-modifying atopic march drug,” the authors wrote, adding that more research “with extended follow-up and proof-of-concept is warranted.”

SOURCE:

The study was led by Teng-Li Lin, MD, Department of Dermatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan, and was published online on June 13, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The observational nature of the study limited the ability to infer direct causality between dupilumab use and reduced atopic march risk. Lack of detailed information on AD severity, total dosage, and duration of medication treatment may affect the interpretation of the study’s findings. The demographic data suggest that the dupilumab cohort had more severe AD, so the observed risk reduction may be greater than that reported in this study.

DISCLOSURES:

The study was supported in part by the National Science and Technology Council, Taiwan, and Taichung Veterans General Hospital. The authors had no relevant conflicts of interest.

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

A version of this article appeared on Medscape.com .

TOPLINE:

A meta-analysis showed that the use of oral tranexamic acid along with the standard triple combination cream (TCC) reduces melasma severity and recurrence in patients with melasma, without increasing toxicity.

METHODOLOGY:

• Current treatments for melasma focus on inducing remission and preventing relapse. Tranexamic acid, an antifibrinolytic drug, has shown promise in recent studies, but its optimal use, either alone or as an adjunct to TCC, remains unclear.
• Researchers conducted a meta-analysis of four randomized controlled trials patients that compared oral tranexamic acid plus TCC (hydroquinone, retinoic acid, and hydrocortisone) and TCC alone in 480 patients with melasma, divided almost evenly into the two treatment groups.
• The main outcome was the change in the Melasma Severity Area Index (MASI) score and recurrence rate from baseline.

TAKEAWAY:

• Patients treated with oral tranexamic acid plus TCC showed a greater reduction in MASI scores compared with those who received TCC alone (mean difference, −3.10; P = .03).
• The recurrence rate of melasma was significantly lower in the tranexamic acid plus TCC group (risk ratio [RR], 0.28; P < .001).
• There was no significant difference in the incidences of erythema (RR, 0.63; P = .147) and burning (RR, 0.59; P = .131).

IN PRACTICE:

“Evidence indicates that oral tranexamic acid confers clinical benefits, contributing to the enhancement of treatment outcomes in melasma when used in conjunction with TCC therapy,” and results are promising with regards to minimizing recurrence, the authors concluded.

SOURCE:

The study was led by Ocílio Ribeiro Gonçalves, MS, of the Federal University of Piauí, Teresina, Brazil, and was published online on June 8, 2024, in Clinical and Experimental Dermatology.

LIMITATIONS:

There was heterogeneity across studies, including different methods of administration, treatment protocols (including dosage), and timing of treatment.

DISCLOSURES:

The study reported receiving no funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A meta-analysis showed that the use of oral tranexamic acid along with the standard triple combination cream (TCC) reduces melasma severity and recurrence in patients with melasma, without increasing toxicity.

METHODOLOGY:

• Current treatments for melasma focus on inducing remission and preventing relapse. Tranexamic acid, an antifibrinolytic drug, has shown promise in recent studies, but its optimal use, either alone or as an adjunct to TCC, remains unclear.
• Researchers conducted a meta-analysis of four randomized controlled trials patients that compared oral tranexamic acid plus TCC (hydroquinone, retinoic acid, and hydrocortisone) and TCC alone in 480 patients with melasma, divided almost evenly into the two treatment groups.
• The main outcome was the change in the Melasma Severity Area Index (MASI) score and recurrence rate from baseline.

TAKEAWAY:

• Patients treated with oral tranexamic acid plus TCC showed a greater reduction in MASI scores compared with those who received TCC alone (mean difference, −3.10; P = .03).
• The recurrence rate of melasma was significantly lower in the tranexamic acid plus TCC group (risk ratio [RR], 0.28; P < .001).
• There was no significant difference in the incidences of erythema (RR, 0.63; P = .147) and burning (RR, 0.59; P = .131).

IN PRACTICE:

“Evidence indicates that oral tranexamic acid confers clinical benefits, contributing to the enhancement of treatment outcomes in melasma when used in conjunction with TCC therapy,” and results are promising with regards to minimizing recurrence, the authors concluded.

SOURCE:

The study was led by Ocílio Ribeiro Gonçalves, MS, of the Federal University of Piauí, Teresina, Brazil, and was published online on June 8, 2024, in Clinical and Experimental Dermatology.

LIMITATIONS:

There was heterogeneity across studies, including different methods of administration, treatment protocols (including dosage), and timing of treatment.

DISCLOSURES:

The study reported receiving no funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A meta-analysis showed that the use of oral tranexamic acid along with the standard triple combination cream (TCC) reduces melasma severity and recurrence in patients with melasma, without increasing toxicity.

METHODOLOGY:

• Current treatments for melasma focus on inducing remission and preventing relapse. Tranexamic acid, an antifibrinolytic drug, has shown promise in recent studies, but its optimal use, either alone or as an adjunct to TCC, remains unclear.
• Researchers conducted a meta-analysis of four randomized controlled trials patients that compared oral tranexamic acid plus TCC (hydroquinone, retinoic acid, and hydrocortisone) and TCC alone in 480 patients with melasma, divided almost evenly into the two treatment groups.
• The main outcome was the change in the Melasma Severity Area Index (MASI) score and recurrence rate from baseline.

TAKEAWAY:

• Patients treated with oral tranexamic acid plus TCC showed a greater reduction in MASI scores compared with those who received TCC alone (mean difference, −3.10; P = .03).
• The recurrence rate of melasma was significantly lower in the tranexamic acid plus TCC group (risk ratio [RR], 0.28; P < .001).
• There was no significant difference in the incidences of erythema (RR, 0.63; P = .147) and burning (RR, 0.59; P = .131).

IN PRACTICE:

“Evidence indicates that oral tranexamic acid confers clinical benefits, contributing to the enhancement of treatment outcomes in melasma when used in conjunction with TCC therapy,” and results are promising with regards to minimizing recurrence, the authors concluded.

SOURCE:

The study was led by Ocílio Ribeiro Gonçalves, MS, of the Federal University of Piauí, Teresina, Brazil, and was published online on June 8, 2024, in Clinical and Experimental Dermatology.

LIMITATIONS:

There was heterogeneity across studies, including different methods of administration, treatment protocols (including dosage), and timing of treatment.

DISCLOSURES:

The study reported receiving no funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

CHICAGO —The use of kratom, an opioid-like supplement widely available over the counter at convenience stores, smoke shops, and online, is resulting in emerging cases of hyperpigmentation, most often on the face and hands.

“This is something we will see more and more,” Heather Woolery-Lloyd, MD, director of the Skin of Color Division at the University of Miami Department of Dermatology, said at the Pigmentary Disorders Exchange Symposium. The key marker of this hyperpigmentation, she said, is that “it’s strongly photoaccentuated,” affecting areas exposed to the sun — but it also tends to spare the knuckles on patients’ hands.
 

Used Like an Opioid, But It’s Not Regulated

Kratom is a plant common in southeast Asia and is used as an analgesic. It’s marketed as a “legal opioid” or “legal high” and is sold in 2- or 3-ounce containers of extract or sold as a powder, Dr. Woolery-Lloyd said. The leaves may be boiled into a tea, smoked, chewed, or put into capsules, according to a case report published in February in the Journal of Integrative Dermatology. It is used worldwide and is not regulated in the United States.

“Many of our patients think kratom is a safe, herbal supplement” but often don’t know it can have several side effects and can be addictive, Dr. Woolery-Lloyd said. Its popularity is increasing as reflected by the number of posts related to kratom on social media platforms.

In the February case report, Shaina Patel, BA, and Nathaniel Phelan, MD, from Kansas City University, Kansas City, Missouri, wrote that side effects of kratom include drowsiness, tachycardia, vomiting, respiratory depression, and cardiac arrest, in addition to confusion and hallucinations.

Kratom also has many different effects on the psyche, Dr. Woolery-Lloyd said at the meeting. At low doses, it blocks the reuptake of norepinephrine, serotonin, and dopamine, producing a motivational effect, and at high doses, it creates an analgesic, calming effect. And people who chronically consume high doses of kratom may be susceptible to hyperpigmentation.

Kratom-associated hyperpigmentation should be considered as a diagnosis when evaluating patients for other drug-associated pigmentary disorders, “especially if pigment is photodistributed,” she said. “If you see new-onset hyperpigmentation or onset over several months and it’s very photoaccentuated, definitely ask about use of kratom.”
 

Case Reports Show Patterns of Presentation

A 2022 report from Landon R. Powell, BS, with the department of biology, Whitworth University in Spokane, Washington, and coauthors, published in JAAD Case Reports, noted that kratom use in the United States has increased dramatically. “As measured by call reports to the United States National Poison Data System, in 2011, there were 11 reported kratom exposures, and in the first 7 months of 2018, there were 357 reported exposures,” they wrote.

An estimated 1.7 million Americans aged ≥ 12 years said they had used kratom in the previous year, according to the Substance Abuse and Mental Health Services Administration 2021 National Survey on Drug Use and Health.

In the case report, Mr. Powell and coauthors described a 54-year-old White male patient who had been using kratom for the previous four to five years to reduce opioid use. During this period, he consumed kratom powder mixed with orange juice three to four times a day. He presented with “diffuse hyperpigmented patches on his arms and face in a photodistributed manner, with notable sparing of the knuckles on both hands.”
 

Dark Gray-Blue Skin

In the more recent case report, Ms. Patel and Dr. Phelan described a 30-year-old White male patient who presented with dark gray-blue skin coloring on his cheeks, back of his neck, and the backs of his hands and forearms. He had no other medical conditions and did not take any medications or supplements that cause hyperpigmentation while using kratom.

The patient had been taking kratom for years in the wake of an opioid addiction following medications for a high school injury. He developed an opioid use disorder and tried to replace his pain medications with kratom.

“The patient stopped using kratom in May 2022, but the discoloration remains. It has not regressed in the following 16 months after discontinuing kratom use,” the authors wrote, noting that “whether or not the hyperpigmentation is able to regress is unknown.”

Dr. Woolery-Lloyd is a consultant for AbbVie, Incyte, Johnson & Johnson Consumer, LivDerm, and L’Oreal; a speaker for Eli Lilly, Incyte, L’Oreal, and Ortho Dermatologics; and a researcher/investigator for AbbVie, Allergan, Eirion Therapeutics, Galderma, Pfizer, Sanofi, and Vyne Therapeutics.
 

According to an information page on kratom on the Food and Drug Administration website, health care professionals and consumers can report adverse reactions associated with kratom to the FDA’s MedWatch program.

A version of this article appeared on Medscape.com.

CHICAGO —The use of kratom, an opioid-like supplement widely available over the counter at convenience stores, smoke shops, and online, is resulting in emerging cases of hyperpigmentation, most often on the face and hands.

“This is something we will see more and more,” Heather Woolery-Lloyd, MD, director of the Skin of Color Division at the University of Miami Department of Dermatology, said at the Pigmentary Disorders Exchange Symposium. The key marker of this hyperpigmentation, she said, is that “it’s strongly photoaccentuated,” affecting areas exposed to the sun — but it also tends to spare the knuckles on patients’ hands.
 

Used Like an Opioid, But It’s Not Regulated

Kratom is a plant common in southeast Asia and is used as an analgesic. It’s marketed as a “legal opioid” or “legal high” and is sold in 2- or 3-ounce containers of extract or sold as a powder, Dr. Woolery-Lloyd said. The leaves may be boiled into a tea, smoked, chewed, or put into capsules, according to a case report published in February in the Journal of Integrative Dermatology. It is used worldwide and is not regulated in the United States.

“Many of our patients think kratom is a safe, herbal supplement” but often don’t know it can have several side effects and can be addictive, Dr. Woolery-Lloyd said. Its popularity is increasing as reflected by the number of posts related to kratom on social media platforms.

In the February case report, Shaina Patel, BA, and Nathaniel Phelan, MD, from Kansas City University, Kansas City, Missouri, wrote that side effects of kratom include drowsiness, tachycardia, vomiting, respiratory depression, and cardiac arrest, in addition to confusion and hallucinations.

Kratom also has many different effects on the psyche, Dr. Woolery-Lloyd said at the meeting. At low doses, it blocks the reuptake of norepinephrine, serotonin, and dopamine, producing a motivational effect, and at high doses, it creates an analgesic, calming effect. And people who chronically consume high doses of kratom may be susceptible to hyperpigmentation.

Kratom-associated hyperpigmentation should be considered as a diagnosis when evaluating patients for other drug-associated pigmentary disorders, “especially if pigment is photodistributed,” she said. “If you see new-onset hyperpigmentation or onset over several months and it’s very photoaccentuated, definitely ask about use of kratom.”
 

Case Reports Show Patterns of Presentation

A 2022 report from Landon R. Powell, BS, with the department of biology, Whitworth University in Spokane, Washington, and coauthors, published in JAAD Case Reports, noted that kratom use in the United States has increased dramatically. “As measured by call reports to the United States National Poison Data System, in 2011, there were 11 reported kratom exposures, and in the first 7 months of 2018, there were 357 reported exposures,” they wrote.

An estimated 1.7 million Americans aged ≥ 12 years said they had used kratom in the previous year, according to the Substance Abuse and Mental Health Services Administration 2021 National Survey on Drug Use and Health.

In the case report, Mr. Powell and coauthors described a 54-year-old White male patient who had been using kratom for the previous four to five years to reduce opioid use. During this period, he consumed kratom powder mixed with orange juice three to four times a day. He presented with “diffuse hyperpigmented patches on his arms and face in a photodistributed manner, with notable sparing of the knuckles on both hands.”
 

Dark Gray-Blue Skin

In the more recent case report, Ms. Patel and Dr. Phelan described a 30-year-old White male patient who presented with dark gray-blue skin coloring on his cheeks, back of his neck, and the backs of his hands and forearms. He had no other medical conditions and did not take any medications or supplements that cause hyperpigmentation while using kratom.

The patient had been taking kratom for years in the wake of an opioid addiction following medications for a high school injury. He developed an opioid use disorder and tried to replace his pain medications with kratom.

“The patient stopped using kratom in May 2022, but the discoloration remains. It has not regressed in the following 16 months after discontinuing kratom use,” the authors wrote, noting that “whether or not the hyperpigmentation is able to regress is unknown.”

Dr. Woolery-Lloyd is a consultant for AbbVie, Incyte, Johnson & Johnson Consumer, LivDerm, and L’Oreal; a speaker for Eli Lilly, Incyte, L’Oreal, and Ortho Dermatologics; and a researcher/investigator for AbbVie, Allergan, Eirion Therapeutics, Galderma, Pfizer, Sanofi, and Vyne Therapeutics.
 

According to an information page on kratom on the Food and Drug Administration website, health care professionals and consumers can report adverse reactions associated with kratom to the FDA’s MedWatch program.

A version of this article appeared on Medscape.com.

CHICAGO —The use of kratom, an opioid-like supplement widely available over the counter at convenience stores, smoke shops, and online, is resulting in emerging cases of hyperpigmentation, most often on the face and hands.

“This is something we will see more and more,” Heather Woolery-Lloyd, MD, director of the Skin of Color Division at the University of Miami Department of Dermatology, said at the Pigmentary Disorders Exchange Symposium. The key marker of this hyperpigmentation, she said, is that “it’s strongly photoaccentuated,” affecting areas exposed to the sun — but it also tends to spare the knuckles on patients’ hands.
 

Used Like an Opioid, But It’s Not Regulated

Kratom is a plant common in southeast Asia and is used as an analgesic. It’s marketed as a “legal opioid” or “legal high” and is sold in 2- or 3-ounce containers of extract or sold as a powder, Dr. Woolery-Lloyd said. The leaves may be boiled into a tea, smoked, chewed, or put into capsules, according to a case report published in February in the Journal of Integrative Dermatology. It is used worldwide and is not regulated in the United States.

“Many of our patients think kratom is a safe, herbal supplement” but often don’t know it can have several side effects and can be addictive, Dr. Woolery-Lloyd said. Its popularity is increasing as reflected by the number of posts related to kratom on social media platforms.

In the February case report, Shaina Patel, BA, and Nathaniel Phelan, MD, from Kansas City University, Kansas City, Missouri, wrote that side effects of kratom include drowsiness, tachycardia, vomiting, respiratory depression, and cardiac arrest, in addition to confusion and hallucinations.

Kratom also has many different effects on the psyche, Dr. Woolery-Lloyd said at the meeting. At low doses, it blocks the reuptake of norepinephrine, serotonin, and dopamine, producing a motivational effect, and at high doses, it creates an analgesic, calming effect. And people who chronically consume high doses of kratom may be susceptible to hyperpigmentation.

Kratom-associated hyperpigmentation should be considered as a diagnosis when evaluating patients for other drug-associated pigmentary disorders, “especially if pigment is photodistributed,” she said. “If you see new-onset hyperpigmentation or onset over several months and it’s very photoaccentuated, definitely ask about use of kratom.”
 

Case Reports Show Patterns of Presentation

A 2022 report from Landon R. Powell, BS, with the department of biology, Whitworth University in Spokane, Washington, and coauthors, published in JAAD Case Reports, noted that kratom use in the United States has increased dramatically. “As measured by call reports to the United States National Poison Data System, in 2011, there were 11 reported kratom exposures, and in the first 7 months of 2018, there were 357 reported exposures,” they wrote.

An estimated 1.7 million Americans aged ≥ 12 years said they had used kratom in the previous year, according to the Substance Abuse and Mental Health Services Administration 2021 National Survey on Drug Use and Health.

In the case report, Mr. Powell and coauthors described a 54-year-old White male patient who had been using kratom for the previous four to five years to reduce opioid use. During this period, he consumed kratom powder mixed with orange juice three to four times a day. He presented with “diffuse hyperpigmented patches on his arms and face in a photodistributed manner, with notable sparing of the knuckles on both hands.”
 

Dark Gray-Blue Skin

In the more recent case report, Ms. Patel and Dr. Phelan described a 30-year-old White male patient who presented with dark gray-blue skin coloring on his cheeks, back of his neck, and the backs of his hands and forearms. He had no other medical conditions and did not take any medications or supplements that cause hyperpigmentation while using kratom.

The patient had been taking kratom for years in the wake of an opioid addiction following medications for a high school injury. He developed an opioid use disorder and tried to replace his pain medications with kratom.

“The patient stopped using kratom in May 2022, but the discoloration remains. It has not regressed in the following 16 months after discontinuing kratom use,” the authors wrote, noting that “whether or not the hyperpigmentation is able to regress is unknown.”

Dr. Woolery-Lloyd is a consultant for AbbVie, Incyte, Johnson & Johnson Consumer, LivDerm, and L’Oreal; a speaker for Eli Lilly, Incyte, L’Oreal, and Ortho Dermatologics; and a researcher/investigator for AbbVie, Allergan, Eirion Therapeutics, Galderma, Pfizer, Sanofi, and Vyne Therapeutics.
 

According to an information page on kratom on the Food and Drug Administration website, health care professionals and consumers can report adverse reactions associated with kratom to the FDA’s MedWatch program.

A version of this article appeared on Medscape.com.

Skin manifestations are common in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome and present early in the disease course. Additionally, the most common histologic findings include leukocytoclastic vasculitis, neutrophilic dermatosis, and perivascular dermatitis; different variants in the UBA1 gene are associated with specific skin manifestations.

Those are key findings from a cohort study of 112 patients with VEXAS published online in JAMA Dermatology. The study, conducted by researchers at the National Institutes of Health (NIH) and several other institutions, aimed to define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histologic, and other clinical findings.

vutipragesahuledustukumuroceuuwefracawonauowragoslurajosadrethodrejuwraswocradawrocrapobebithagirespodrowapawrugiuochobaprustoverecewrepabribromebutiphiclislupanacrasuslishumitislojethoclepabajegibacrolo

First described in 2020, VEXAS syndrome is an adult-onset multisystem disease that can pose a diagnostic challenge to clinicians, the study’s corresponding author, Edward W. Cowen, MD, MHSc, of the dermatology branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), said in an interview. The disease is caused by pathogenic variants in the UBA1 gene, located on the X chromosome. Affected individuals exhibit a wide range of manifestations, including cytopenia/myelodysplasia, multiorgan systemic inflammation, and cutaneous involvement.

“Patients may present to a variety of disease specialists depending on their symptoms and providers may not immediately consider a genetic etiology in an older individual,” Dr. Cowen said in an interview. “Although skin involvement occurs in more than 80% of patients, it is pleomorphic and may resemble a variety of other conditions such as vasculitis and Sweet syndrome.”

To better understand the cutaneous manifestations of VEXAS syndrome, the researchers evaluated data from 112 patients with VEXAS-defining genetic variants in the UBA1 gene between 2019 and 2023. Of the 112 patients, 73 underwent medical record review only, and 39 were prospectively evaluated at NIH. All but one of the patients were men, 94% were White individuals, and their mean age was 64 years. Skin involvement occurred in 83% of cases and was the most common presenting feature of VEXAS in 61% of cases.

Of the 64 histopathologic reports available from 60 patients, the main skin histopathologic findings were leukocytoclastic vasculitis in 23 patients (36%), neutrophilic dermatosis in 22 patients (34%), and perivascular dermatitis in 19 patients (30%). According to Dr. Cowen, one key histologic finding was a distinct pattern of “histiocytoid” dermal neutrophilic inflammation, which was present in 13 of 15 specimens (86%) that underwent central re-review. “This pattern can occasionally also be seen in patients with Sweet syndrome, unrelated to VEXAS, but was a hallmark feature found in the majority of skin biopsies of patients with VEXAS,” he said.

chetrabibrocrinutipishoprouodawubochushetibreshororuvustuphatrodadrofrepesheneclimothosilispucewriclamabisanibisiberiwowru

“Together with another pathologic finding, leukocytoclasia, these features can be useful clues to alert the pathologist to a potential diagnosis of VEXAS. This myeloid predominant pattern of skin inflammation was also most strongly associated with the leucine pathogenic variant of the UBA1 gene.” In contrast, cutaneous vasculitis was most strongly associated with the valine pathogenic variant of UBA1. “This is important because the valine variant has been previously independently linked to decreased survival,” he said.

In findings related to pathogenic genetic variants, the researchers observed that the p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates in 14 of 17 patients (82%) with this variant and often resembled histiocytoid Sweet syndrome. In addition, the p.Met41Val variant was associated with vasculitic lesions in 11 of 20 patients (55%) with this variant and with a mixed leukocytic infiltrate in 17 of these 20 patients (85%).
 

Treatment Outcomes

In the realm of therapies, skin manifestations improved in 67 of 73 patients (92%) treated with oral prednisone, while treatment with the interleukin-1 receptor antagonist anakinra improved cutaneous disease in 9 of the 16 (56%) who received it. However, 12 (75%) of those who received anakinra developed severe injection-site reactions, including ulceration in two patients and abscess formation in one patient.

Dr. Cowen noted that VEXAS is associated with high mortality (22% in this cohort), and a high degree of suspicion is required to diagnose patients with VEXAS before significant end organ damage has occurred. “This diagnosis should be considered in all older male patients who present with neutrophilic dermatosis — particularly histiocytoid Sweet syndrome, vasculitis, or leukocytoclasia without vasculitis. Patients who appear to have isolated skin involvement may have cytopenias and acute phase reactants. Therefore, complete blood count with differential and ESR and CRP should be considered to investigate for macrocytosis, cytopenias, and systemic inflammation.”

He acknowledged certain limitations of the study, including the fact that many patients were first evaluated at the NIH after having disease symptoms for many months or years. “It is possible that patients with VEXAS referred to the NIH, either for genetic testing or in person evaluation, represent a population with more aggressive disease.”

[embed:render:related:node:238910]

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the study, emphasized the importance of the UBA1 mutation in the diagnosis of this complex syndrome. “Dermatologists should be aware of VEXAS syndrome as the majority of patients present with skin lesions, which can range from urticarial to Sweet syndrome–like to palpable purpura,” Dr. Ko said.

“Chondritis and periorbital edema, sometimes unilateral, are also associated. Histopathologic clues include a predominantly histiocytoid infiltrate,” she noted. In addition, “the prominent myxoid stroma around blood vessels and adnexal structures as a clue to VEXAS syndrome surprised me; I had not read that before.”

The study was supported by the Intramural Research Program of NIAMS. One of the study authors reported personal fees from Alexion, Novartis, and Sobi outside of the submitted work. No other disclosures were reported. Dr. Ko reported having no disclosures.

A version of this article appeared on Medscape.com .

Skin manifestations are common in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome and present early in the disease course. Additionally, the most common histologic findings include leukocytoclastic vasculitis, neutrophilic dermatosis, and perivascular dermatitis; different variants in the UBA1 gene are associated with specific skin manifestations.

Those are key findings from a cohort study of 112 patients with VEXAS published online in JAMA Dermatology. The study, conducted by researchers at the National Institutes of Health (NIH) and several other institutions, aimed to define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histologic, and other clinical findings.

vutipragesahuledustukumuroceuuwefracawonauowragoslurajosadrethodrejuwraswocradawrocrapobebithagirespodrowapawrugiuochobaprustoverecewrepabribromebutiphiclislupanacrasuslishumitislojethoclepabajegibacrolo

First described in 2020, VEXAS syndrome is an adult-onset multisystem disease that can pose a diagnostic challenge to clinicians, the study’s corresponding author, Edward W. Cowen, MD, MHSc, of the dermatology branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), said in an interview. The disease is caused by pathogenic variants in the UBA1 gene, located on the X chromosome. Affected individuals exhibit a wide range of manifestations, including cytopenia/myelodysplasia, multiorgan systemic inflammation, and cutaneous involvement.

“Patients may present to a variety of disease specialists depending on their symptoms and providers may not immediately consider a genetic etiology in an older individual,” Dr. Cowen said in an interview. “Although skin involvement occurs in more than 80% of patients, it is pleomorphic and may resemble a variety of other conditions such as vasculitis and Sweet syndrome.”

To better understand the cutaneous manifestations of VEXAS syndrome, the researchers evaluated data from 112 patients with VEXAS-defining genetic variants in the UBA1 gene between 2019 and 2023. Of the 112 patients, 73 underwent medical record review only, and 39 were prospectively evaluated at NIH. All but one of the patients were men, 94% were White individuals, and their mean age was 64 years. Skin involvement occurred in 83% of cases and was the most common presenting feature of VEXAS in 61% of cases.

Of the 64 histopathologic reports available from 60 patients, the main skin histopathologic findings were leukocytoclastic vasculitis in 23 patients (36%), neutrophilic dermatosis in 22 patients (34%), and perivascular dermatitis in 19 patients (30%). According to Dr. Cowen, one key histologic finding was a distinct pattern of “histiocytoid” dermal neutrophilic inflammation, which was present in 13 of 15 specimens (86%) that underwent central re-review. “This pattern can occasionally also be seen in patients with Sweet syndrome, unrelated to VEXAS, but was a hallmark feature found in the majority of skin biopsies of patients with VEXAS,” he said.

chetrabibrocrinutipishoprouodawubochushetibreshororuvustuphatrodadrofrepesheneclimothosilispucewriclamabisanibisiberiwowru

“Together with another pathologic finding, leukocytoclasia, these features can be useful clues to alert the pathologist to a potential diagnosis of VEXAS. This myeloid predominant pattern of skin inflammation was also most strongly associated with the leucine pathogenic variant of the UBA1 gene.” In contrast, cutaneous vasculitis was most strongly associated with the valine pathogenic variant of UBA1. “This is important because the valine variant has been previously independently linked to decreased survival,” he said.

In findings related to pathogenic genetic variants, the researchers observed that the p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates in 14 of 17 patients (82%) with this variant and often resembled histiocytoid Sweet syndrome. In addition, the p.Met41Val variant was associated with vasculitic lesions in 11 of 20 patients (55%) with this variant and with a mixed leukocytic infiltrate in 17 of these 20 patients (85%).
 

Treatment Outcomes

In the realm of therapies, skin manifestations improved in 67 of 73 patients (92%) treated with oral prednisone, while treatment with the interleukin-1 receptor antagonist anakinra improved cutaneous disease in 9 of the 16 (56%) who received it. However, 12 (75%) of those who received anakinra developed severe injection-site reactions, including ulceration in two patients and abscess formation in one patient.

Dr. Cowen noted that VEXAS is associated with high mortality (22% in this cohort), and a high degree of suspicion is required to diagnose patients with VEXAS before significant end organ damage has occurred. “This diagnosis should be considered in all older male patients who present with neutrophilic dermatosis — particularly histiocytoid Sweet syndrome, vasculitis, or leukocytoclasia without vasculitis. Patients who appear to have isolated skin involvement may have cytopenias and acute phase reactants. Therefore, complete blood count with differential and ESR and CRP should be considered to investigate for macrocytosis, cytopenias, and systemic inflammation.”

He acknowledged certain limitations of the study, including the fact that many patients were first evaluated at the NIH after having disease symptoms for many months or years. “It is possible that patients with VEXAS referred to the NIH, either for genetic testing or in person evaluation, represent a population with more aggressive disease.”

[embed:render:related:node:238910]

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the study, emphasized the importance of the UBA1 mutation in the diagnosis of this complex syndrome. “Dermatologists should be aware of VEXAS syndrome as the majority of patients present with skin lesions, which can range from urticarial to Sweet syndrome–like to palpable purpura,” Dr. Ko said.

“Chondritis and periorbital edema, sometimes unilateral, are also associated. Histopathologic clues include a predominantly histiocytoid infiltrate,” she noted. In addition, “the prominent myxoid stroma around blood vessels and adnexal structures as a clue to VEXAS syndrome surprised me; I had not read that before.”

The study was supported by the Intramural Research Program of NIAMS. One of the study authors reported personal fees from Alexion, Novartis, and Sobi outside of the submitted work. No other disclosures were reported. Dr. Ko reported having no disclosures.

A version of this article appeared on Medscape.com .

Skin manifestations are common in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome and present early in the disease course. Additionally, the most common histologic findings include leukocytoclastic vasculitis, neutrophilic dermatosis, and perivascular dermatitis; different variants in the UBA1 gene are associated with specific skin manifestations.

Those are key findings from a cohort study of 112 patients with VEXAS published online in JAMA Dermatology. The study, conducted by researchers at the National Institutes of Health (NIH) and several other institutions, aimed to define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histologic, and other clinical findings.

vutipragesahuledustukumuroceuuwefracawonauowragoslurajosadrethodrejuwraswocradawrocrapobebithagirespodrowapawrugiuochobaprustoverecewrepabribromebutiphiclislupanacrasuslishumitislojethoclepabajegibacrolo

First described in 2020, VEXAS syndrome is an adult-onset multisystem disease that can pose a diagnostic challenge to clinicians, the study’s corresponding author, Edward W. Cowen, MD, MHSc, of the dermatology branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), said in an interview. The disease is caused by pathogenic variants in the UBA1 gene, located on the X chromosome. Affected individuals exhibit a wide range of manifestations, including cytopenia/myelodysplasia, multiorgan systemic inflammation, and cutaneous involvement.

“Patients may present to a variety of disease specialists depending on their symptoms and providers may not immediately consider a genetic etiology in an older individual,” Dr. Cowen said in an interview. “Although skin involvement occurs in more than 80% of patients, it is pleomorphic and may resemble a variety of other conditions such as vasculitis and Sweet syndrome.”

To better understand the cutaneous manifestations of VEXAS syndrome, the researchers evaluated data from 112 patients with VEXAS-defining genetic variants in the UBA1 gene between 2019 and 2023. Of the 112 patients, 73 underwent medical record review only, and 39 were prospectively evaluated at NIH. All but one of the patients were men, 94% were White individuals, and their mean age was 64 years. Skin involvement occurred in 83% of cases and was the most common presenting feature of VEXAS in 61% of cases.

Of the 64 histopathologic reports available from 60 patients, the main skin histopathologic findings were leukocytoclastic vasculitis in 23 patients (36%), neutrophilic dermatosis in 22 patients (34%), and perivascular dermatitis in 19 patients (30%). According to Dr. Cowen, one key histologic finding was a distinct pattern of “histiocytoid” dermal neutrophilic inflammation, which was present in 13 of 15 specimens (86%) that underwent central re-review. “This pattern can occasionally also be seen in patients with Sweet syndrome, unrelated to VEXAS, but was a hallmark feature found in the majority of skin biopsies of patients with VEXAS,” he said.

chetrabibrocrinutipishoprouodawubochushetibreshororuvustuphatrodadrofrepesheneclimothosilispucewriclamabisanibisiberiwowru

“Together with another pathologic finding, leukocytoclasia, these features can be useful clues to alert the pathologist to a potential diagnosis of VEXAS. This myeloid predominant pattern of skin inflammation was also most strongly associated with the leucine pathogenic variant of the UBA1 gene.” In contrast, cutaneous vasculitis was most strongly associated with the valine pathogenic variant of UBA1. “This is important because the valine variant has been previously independently linked to decreased survival,” he said.

In findings related to pathogenic genetic variants, the researchers observed that the p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates in 14 of 17 patients (82%) with this variant and often resembled histiocytoid Sweet syndrome. In addition, the p.Met41Val variant was associated with vasculitic lesions in 11 of 20 patients (55%) with this variant and with a mixed leukocytic infiltrate in 17 of these 20 patients (85%).
 

Treatment Outcomes

In the realm of therapies, skin manifestations improved in 67 of 73 patients (92%) treated with oral prednisone, while treatment with the interleukin-1 receptor antagonist anakinra improved cutaneous disease in 9 of the 16 (56%) who received it. However, 12 (75%) of those who received anakinra developed severe injection-site reactions, including ulceration in two patients and abscess formation in one patient.

Dr. Cowen noted that VEXAS is associated with high mortality (22% in this cohort), and a high degree of suspicion is required to diagnose patients with VEXAS before significant end organ damage has occurred. “This diagnosis should be considered in all older male patients who present with neutrophilic dermatosis — particularly histiocytoid Sweet syndrome, vasculitis, or leukocytoclasia without vasculitis. Patients who appear to have isolated skin involvement may have cytopenias and acute phase reactants. Therefore, complete blood count with differential and ESR and CRP should be considered to investigate for macrocytosis, cytopenias, and systemic inflammation.”

He acknowledged certain limitations of the study, including the fact that many patients were first evaluated at the NIH after having disease symptoms for many months or years. “It is possible that patients with VEXAS referred to the NIH, either for genetic testing or in person evaluation, represent a population with more aggressive disease.”

[embed:render:related:node:238910]

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the study, emphasized the importance of the UBA1 mutation in the diagnosis of this complex syndrome. “Dermatologists should be aware of VEXAS syndrome as the majority of patients present with skin lesions, which can range from urticarial to Sweet syndrome–like to palpable purpura,” Dr. Ko said.

“Chondritis and periorbital edema, sometimes unilateral, are also associated. Histopathologic clues include a predominantly histiocytoid infiltrate,” she noted. In addition, “the prominent myxoid stroma around blood vessels and adnexal structures as a clue to VEXAS syndrome surprised me; I had not read that before.”

The study was supported by the Intramural Research Program of NIAMS. One of the study authors reported personal fees from Alexion, Novartis, and Sobi outside of the submitted work. No other disclosures were reported. Dr. Ko reported having no disclosures.

A version of this article appeared on Medscape.com .