Medical Dermatology

AMSTERDAM — Following the report of results from a randomized trial in which a topically applied Janus kinase (JAK) inhibitor was highly active in patients with mild to moderate hidradenitis suppurativa (HS), an open-label extension showed that 16 more weeks of treatment on as-needed basis provided complete or near complete clearance of lesions in up to 38.5% of patients.

“Ruxolitinib cream may be a novel approach to address an unmet medical need in the treatment of milder HS for which there are no currently approved treatments,” reported Martina L. Porter, MD, assistant professor of dermatology, Harvard Medical School, and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts.

In the earlier 16-week, double-blind, randomized period of this phase 2b study, 69 adults with mild to moderate HS were randomized to 1.5% ruxolitinib cream or vehicle, applied twice daily for 16 weeks. The new results are from the open-label extension period, where those on the vehicle were crossed over to topical ruxolitinib and treatment was continued for another 16 weeks.
 

Over 80% Meet Primary Endpoint at 32 Weeks

Entry criteria for the study included Hurley stage I or II HS with no draining tunnels. Hurley stage III patients were not eligible. Patients had to have an abscess or inflammatory nodule (AN) count of 3 lesions concentrated in a single anatomic area or up to 10 lesions if disseminated. The median AN count of those enrolled was 5.4. 

In the randomized portion of the study and in the open-label extension, the recommendation for application was to apply the medication to nodules and a 1-cm area of surrounding skin. As-needed treatment was only recommended in the extension portion of the study and rescue medication was not allowed.

The goal of the open-label extension was to evaluate how long the improvements were sustained, according to Dr. Porter, who presented the results at the 2024 European Academy of Dermatology and Venereology (EADV) meeting.

The primary endpoints of AN50, signaling at least a 50% reduction in AN count from baseline, among those initially randomized to ruxolitinib cream climbed slightly from 79.2% at the end of 16 weeks to 81.0% at the end of 32 weeks.

This shows that the benefits recorded in the randomized phase of the trial were sustained during the open-label extension, Dr. Porter said. 

For those randomized to vehicle, there was a substantial response of 56.3% for AN50 during the randomized portion of the study, but catchup in the vehicle group to those on active therapy occurred rapidly over the open-label extension. By the end of 32 weeks, the score among the crossover patients slightly exceeded that of those on continuous therapy (88.5% vs 81.0%).

AN75 responses at week 32 were 66.7% and 61.5% in the continuous arm and crossover arm, respectively. The proportion of patients reaching an AN90 or AN100 response, meaning clear or almost clear, were 19% and 38.5%, in continuous treatment and crossover arms, respectively.

One of the secondary endpoints was the HS Clinical Response 50, indicating at least a 50% reduction in the AN count with no increase in abscesses or draining fistulae. At 32 weeks, the proportions of patients who met this endpoint were 81.0% and 88.5% in the continuous treatment and crossover arms, respectively. 

The mean reduction in International HS Severity Scoring System scores from baseline were 4.1 and 4.5 in the continuous treatment and crossover arms, respectively. 
 

Patients in the Study Mostly Women, 42% Black Individuals

Most (94%) of the participants were women; about 45% and 42% were White and Black individuals, respectively. Most of the remaining patients were Asian individuals. The median age at entry was 29 years, and the mean body mass index was approximately 34 kg/m². A substantial proportion of patients had systemic comorbidities, according to Dr. Porter, who noted that about 25% had anxiety, depression, or both.

“This phenotype — a high proportion of women with nodules but no draining tunnels and a substantial number of comorbidities — is one we often see in patients with mild HS,” Dr. Porter said.

The safety and tolerability profile of ruxolitinib cream was quite good, according to Dr. Porter, who noted that there were fewer treatment-related adverse events in the open-label extension. Overall, the number of treatment-related adverse events (3.6%), including application site reactions leading to discontinuation (1.8%) was low. 

Although there is a growing list of therapies now approved for HS, Dr. Porter emphasized that all have been developed for moderate to severe disease. She suggested that there is a sizable group of patients with mild disease for whom such therapies as biologics might not be warranted even if symptom relief is needed.

Given this unmet need, she said phase 3 trials are warranted to confirm the benefits and the safety of a topical therapy that can be used as needed to control intermittent HS flares.

Asked to comment, the lead author of a recently published review article on the “evolving treatment landscape” of HS, James G. Krueger, MD, professor in clinical investigation at Rockefeller University, New York City, agreed that there is an unmet need for effective and safe therapies in milder HS.

“I agree with the premise,” said Dr. Krueger, indicating that phase 3 data will be essential to confirm the promise of this approach. Dr. Krueger, who did not hear the results presented at the EADV meeting, listed several JAK inhibitors in his review that have shown promising efficacy as oral agents and support JAK signaling as a target of HS treatment. 

Topical ruxolitinib (Opzelura) is currently approved in the United States for treating nonsegmental vitiligo in patients aged ≥ 12 years and for mild to moderate atopic dermatitis in patients aged ≥ 12 years. In Europe, it is approved for treatment of nonsegmental vitiligo with facial involvement in patients aged ≥ 12 years. 

Dr. Porter reported no potential conflicts of interest. Dr. Krueger reported financial relationships with more than 25 pharmaceutical companies not including Incyte, which is developing ruxolitinib cream.

A version of this article appeared on Medscape.com.

AMSTERDAM — Following the report of results from a randomized trial in which a topically applied Janus kinase (JAK) inhibitor was highly active in patients with mild to moderate hidradenitis suppurativa (HS), an open-label extension showed that 16 more weeks of treatment on as-needed basis provided complete or near complete clearance of lesions in up to 38.5% of patients.

“Ruxolitinib cream may be a novel approach to address an unmet medical need in the treatment of milder HS for which there are no currently approved treatments,” reported Martina L. Porter, MD, assistant professor of dermatology, Harvard Medical School, and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts.

In the earlier 16-week, double-blind, randomized period of this phase 2b study, 69 adults with mild to moderate HS were randomized to 1.5% ruxolitinib cream or vehicle, applied twice daily for 16 weeks. The new results are from the open-label extension period, where those on the vehicle were crossed over to topical ruxolitinib and treatment was continued for another 16 weeks.
 

Over 80% Meet Primary Endpoint at 32 Weeks

Entry criteria for the study included Hurley stage I or II HS with no draining tunnels. Hurley stage III patients were not eligible. Patients had to have an abscess or inflammatory nodule (AN) count of 3 lesions concentrated in a single anatomic area or up to 10 lesions if disseminated. The median AN count of those enrolled was 5.4. 

In the randomized portion of the study and in the open-label extension, the recommendation for application was to apply the medication to nodules and a 1-cm area of surrounding skin. As-needed treatment was only recommended in the extension portion of the study and rescue medication was not allowed.

The goal of the open-label extension was to evaluate how long the improvements were sustained, according to Dr. Porter, who presented the results at the 2024 European Academy of Dermatology and Venereology (EADV) meeting.

The primary endpoints of AN50, signaling at least a 50% reduction in AN count from baseline, among those initially randomized to ruxolitinib cream climbed slightly from 79.2% at the end of 16 weeks to 81.0% at the end of 32 weeks.

This shows that the benefits recorded in the randomized phase of the trial were sustained during the open-label extension, Dr. Porter said. 

For those randomized to vehicle, there was a substantial response of 56.3% for AN50 during the randomized portion of the study, but catchup in the vehicle group to those on active therapy occurred rapidly over the open-label extension. By the end of 32 weeks, the score among the crossover patients slightly exceeded that of those on continuous therapy (88.5% vs 81.0%).

AN75 responses at week 32 were 66.7% and 61.5% in the continuous arm and crossover arm, respectively. The proportion of patients reaching an AN90 or AN100 response, meaning clear or almost clear, were 19% and 38.5%, in continuous treatment and crossover arms, respectively.

One of the secondary endpoints was the HS Clinical Response 50, indicating at least a 50% reduction in the AN count with no increase in abscesses or draining fistulae. At 32 weeks, the proportions of patients who met this endpoint were 81.0% and 88.5% in the continuous treatment and crossover arms, respectively. 

The mean reduction in International HS Severity Scoring System scores from baseline were 4.1 and 4.5 in the continuous treatment and crossover arms, respectively. 
 

Patients in the Study Mostly Women, 42% Black Individuals

Most (94%) of the participants were women; about 45% and 42% were White and Black individuals, respectively. Most of the remaining patients were Asian individuals. The median age at entry was 29 years, and the mean body mass index was approximately 34 kg/m². A substantial proportion of patients had systemic comorbidities, according to Dr. Porter, who noted that about 25% had anxiety, depression, or both.

“This phenotype — a high proportion of women with nodules but no draining tunnels and a substantial number of comorbidities — is one we often see in patients with mild HS,” Dr. Porter said.

The safety and tolerability profile of ruxolitinib cream was quite good, according to Dr. Porter, who noted that there were fewer treatment-related adverse events in the open-label extension. Overall, the number of treatment-related adverse events (3.6%), including application site reactions leading to discontinuation (1.8%) was low. 

Although there is a growing list of therapies now approved for HS, Dr. Porter emphasized that all have been developed for moderate to severe disease. She suggested that there is a sizable group of patients with mild disease for whom such therapies as biologics might not be warranted even if symptom relief is needed.

Given this unmet need, she said phase 3 trials are warranted to confirm the benefits and the safety of a topical therapy that can be used as needed to control intermittent HS flares.

Asked to comment, the lead author of a recently published review article on the “evolving treatment landscape” of HS, James G. Krueger, MD, professor in clinical investigation at Rockefeller University, New York City, agreed that there is an unmet need for effective and safe therapies in milder HS.

“I agree with the premise,” said Dr. Krueger, indicating that phase 3 data will be essential to confirm the promise of this approach. Dr. Krueger, who did not hear the results presented at the EADV meeting, listed several JAK inhibitors in his review that have shown promising efficacy as oral agents and support JAK signaling as a target of HS treatment. 

Topical ruxolitinib (Opzelura) is currently approved in the United States for treating nonsegmental vitiligo in patients aged ≥ 12 years and for mild to moderate atopic dermatitis in patients aged ≥ 12 years. In Europe, it is approved for treatment of nonsegmental vitiligo with facial involvement in patients aged ≥ 12 years. 

Dr. Porter reported no potential conflicts of interest. Dr. Krueger reported financial relationships with more than 25 pharmaceutical companies not including Incyte, which is developing ruxolitinib cream.

A version of this article appeared on Medscape.com.

AMSTERDAM — Following the report of results from a randomized trial in which a topically applied Janus kinase (JAK) inhibitor was highly active in patients with mild to moderate hidradenitis suppurativa (HS), an open-label extension showed that 16 more weeks of treatment on as-needed basis provided complete or near complete clearance of lesions in up to 38.5% of patients.

“Ruxolitinib cream may be a novel approach to address an unmet medical need in the treatment of milder HS for which there are no currently approved treatments,” reported Martina L. Porter, MD, assistant professor of dermatology, Harvard Medical School, and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts.

In the earlier 16-week, double-blind, randomized period of this phase 2b study, 69 adults with mild to moderate HS were randomized to 1.5% ruxolitinib cream or vehicle, applied twice daily for 16 weeks. The new results are from the open-label extension period, where those on the vehicle were crossed over to topical ruxolitinib and treatment was continued for another 16 weeks.
 

Over 80% Meet Primary Endpoint at 32 Weeks

Entry criteria for the study included Hurley stage I or II HS with no draining tunnels. Hurley stage III patients were not eligible. Patients had to have an abscess or inflammatory nodule (AN) count of 3 lesions concentrated in a single anatomic area or up to 10 lesions if disseminated. The median AN count of those enrolled was 5.4. 

In the randomized portion of the study and in the open-label extension, the recommendation for application was to apply the medication to nodules and a 1-cm area of surrounding skin. As-needed treatment was only recommended in the extension portion of the study and rescue medication was not allowed.

The goal of the open-label extension was to evaluate how long the improvements were sustained, according to Dr. Porter, who presented the results at the 2024 European Academy of Dermatology and Venereology (EADV) meeting.

The primary endpoints of AN50, signaling at least a 50% reduction in AN count from baseline, among those initially randomized to ruxolitinib cream climbed slightly from 79.2% at the end of 16 weeks to 81.0% at the end of 32 weeks.

This shows that the benefits recorded in the randomized phase of the trial were sustained during the open-label extension, Dr. Porter said. 

For those randomized to vehicle, there was a substantial response of 56.3% for AN50 during the randomized portion of the study, but catchup in the vehicle group to those on active therapy occurred rapidly over the open-label extension. By the end of 32 weeks, the score among the crossover patients slightly exceeded that of those on continuous therapy (88.5% vs 81.0%).

AN75 responses at week 32 were 66.7% and 61.5% in the continuous arm and crossover arm, respectively. The proportion of patients reaching an AN90 or AN100 response, meaning clear or almost clear, were 19% and 38.5%, in continuous treatment and crossover arms, respectively.

One of the secondary endpoints was the HS Clinical Response 50, indicating at least a 50% reduction in the AN count with no increase in abscesses or draining fistulae. At 32 weeks, the proportions of patients who met this endpoint were 81.0% and 88.5% in the continuous treatment and crossover arms, respectively. 

The mean reduction in International HS Severity Scoring System scores from baseline were 4.1 and 4.5 in the continuous treatment and crossover arms, respectively. 
 

Patients in the Study Mostly Women, 42% Black Individuals

Most (94%) of the participants were women; about 45% and 42% were White and Black individuals, respectively. Most of the remaining patients were Asian individuals. The median age at entry was 29 years, and the mean body mass index was approximately 34 kg/m². A substantial proportion of patients had systemic comorbidities, according to Dr. Porter, who noted that about 25% had anxiety, depression, or both.

“This phenotype — a high proportion of women with nodules but no draining tunnels and a substantial number of comorbidities — is one we often see in patients with mild HS,” Dr. Porter said.

The safety and tolerability profile of ruxolitinib cream was quite good, according to Dr. Porter, who noted that there were fewer treatment-related adverse events in the open-label extension. Overall, the number of treatment-related adverse events (3.6%), including application site reactions leading to discontinuation (1.8%) was low. 

Although there is a growing list of therapies now approved for HS, Dr. Porter emphasized that all have been developed for moderate to severe disease. She suggested that there is a sizable group of patients with mild disease for whom such therapies as biologics might not be warranted even if symptom relief is needed.

Given this unmet need, she said phase 3 trials are warranted to confirm the benefits and the safety of a topical therapy that can be used as needed to control intermittent HS flares.

Asked to comment, the lead author of a recently published review article on the “evolving treatment landscape” of HS, James G. Krueger, MD, professor in clinical investigation at Rockefeller University, New York City, agreed that there is an unmet need for effective and safe therapies in milder HS.

“I agree with the premise,” said Dr. Krueger, indicating that phase 3 data will be essential to confirm the promise of this approach. Dr. Krueger, who did not hear the results presented at the EADV meeting, listed several JAK inhibitors in his review that have shown promising efficacy as oral agents and support JAK signaling as a target of HS treatment. 

Topical ruxolitinib (Opzelura) is currently approved in the United States for treating nonsegmental vitiligo in patients aged ≥ 12 years and for mild to moderate atopic dermatitis in patients aged ≥ 12 years. In Europe, it is approved for treatment of nonsegmental vitiligo with facial involvement in patients aged ≥ 12 years. 

Dr. Porter reported no potential conflicts of interest. Dr. Krueger reported financial relationships with more than 25 pharmaceutical companies not including Incyte, which is developing ruxolitinib cream.

A version of this article appeared on Medscape.com.

TOPLINE:

A study has found that less than half of US veterans on chronic immunosuppressive medications, and a much lower percentage of those younger than 50 years, received at least one dose of the recombinant zoster vaccine (RZV) by mid-2023; the low rate of herpes zoster vaccination in this immunocompromised group, especially among younger individuals, is concerning.

METHODOLOGY:

• In 2021, the Food and Drug Administration authorized the use of RZV for adults aged 18 years or older on chronic immunosuppressive medications because of their high risk for herpes zoster and its related complications, followed by updated guidance from the Centers for Disease Control and Prevention and American College of Rheumatology in 2021 and 2022, respectively.
• This study aimed to assess the receipt of RZV among veterans receiving immunosuppressive medications within the Veterans Health Administration (VHA) healthcare system before and after the expanded indications in February 2022.
• It included 190,162 veterans who were prescribed one or more immunosuppressive medications for at least 90 days at 130 medical facilities between January 1, 2018, and June 30, 2023.
• A total of 23,295 veterans (12.3%) were younger than 50 years by the end of the study period.
• The outcome measured was the percentage of veterans with one or more doses of RZV documented during the study period.

TAKEAWAY:

• Among veterans aged 50 years or older, 36.2% and 49.8% received an RZV before the expanded indication and by mid-2023, respectively. Even though the rate of vaccination is higher than that observed in the 2021 National Health Interview Survey, significant room for improvement remains.
• Among veterans younger than 50 years, very few (2.8%) received an RZV before the expanded indication, and only 13.4% received it by mid-2023.
• Demographic factors associated with lower odds of vaccination included male sex, African American or unknown race, and nonurban residence (P ≤ .004 for all).
• Those who received targeted synthetic disease-modifying antirheumatic drugs (DMARDs) alone or in combination with other drugs or those who received other vaccines were more likely to receive RZV than those who received conventional synthetic DMARD monotherapy (P < .001 for both).

IN PRACTICE:

“Future work to improve RZV vaccination in patients at high risk should focus on creating informatics tools to identify individuals at high risk and standardizing vaccination guidelines across subspecialties,” the authors wrote.

SOURCE:

This study was led by Sharon Abada, MD, University of California, San Francisco. It was published online on October 11, 2024, in JAMA Network Open.

LIMITATIONS:

This study may not be generalizable to nonveteran populations or countries outside the United States. Limitations also included difficulty with capturing vaccinations not administered within the VHA system, which may have resulted in an underestimation of the percentage of patients vaccinated.

DISCLOSURES:

This work was funded by grants from the VA Quality Enhancement Research Initiative and the Agency for Healthcare Research and Quality. Some authors reported receiving grants from institutions and pharmaceutical companies.

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 first appeared on Medscape.com.

TOPLINE:

A study has found that less than half of US veterans on chronic immunosuppressive medications, and a much lower percentage of those younger than 50 years, received at least one dose of the recombinant zoster vaccine (RZV) by mid-2023; the low rate of herpes zoster vaccination in this immunocompromised group, especially among younger individuals, is concerning.

METHODOLOGY:

• In 2021, the Food and Drug Administration authorized the use of RZV for adults aged 18 years or older on chronic immunosuppressive medications because of their high risk for herpes zoster and its related complications, followed by updated guidance from the Centers for Disease Control and Prevention and American College of Rheumatology in 2021 and 2022, respectively.
• This study aimed to assess the receipt of RZV among veterans receiving immunosuppressive medications within the Veterans Health Administration (VHA) healthcare system before and after the expanded indications in February 2022.
• It included 190,162 veterans who were prescribed one or more immunosuppressive medications for at least 90 days at 130 medical facilities between January 1, 2018, and June 30, 2023.
• A total of 23,295 veterans (12.3%) were younger than 50 years by the end of the study period.
• The outcome measured was the percentage of veterans with one or more doses of RZV documented during the study period.

TAKEAWAY:

• Among veterans aged 50 years or older, 36.2% and 49.8% received an RZV before the expanded indication and by mid-2023, respectively. Even though the rate of vaccination is higher than that observed in the 2021 National Health Interview Survey, significant room for improvement remains.
• Among veterans younger than 50 years, very few (2.8%) received an RZV before the expanded indication, and only 13.4% received it by mid-2023.
• Demographic factors associated with lower odds of vaccination included male sex, African American or unknown race, and nonurban residence (P ≤ .004 for all).
• Those who received targeted synthetic disease-modifying antirheumatic drugs (DMARDs) alone or in combination with other drugs or those who received other vaccines were more likely to receive RZV than those who received conventional synthetic DMARD monotherapy (P < .001 for both).

IN PRACTICE:

“Future work to improve RZV vaccination in patients at high risk should focus on creating informatics tools to identify individuals at high risk and standardizing vaccination guidelines across subspecialties,” the authors wrote.

SOURCE:

This study was led by Sharon Abada, MD, University of California, San Francisco. It was published online on October 11, 2024, in JAMA Network Open.

LIMITATIONS:

This study may not be generalizable to nonveteran populations or countries outside the United States. Limitations also included difficulty with capturing vaccinations not administered within the VHA system, which may have resulted in an underestimation of the percentage of patients vaccinated.

DISCLOSURES:

This work was funded by grants from the VA Quality Enhancement Research Initiative and the Agency for Healthcare Research and Quality. Some authors reported receiving grants from institutions and pharmaceutical companies.

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 first appeared on Medscape.com.

TOPLINE:

A study has found that less than half of US veterans on chronic immunosuppressive medications, and a much lower percentage of those younger than 50 years, received at least one dose of the recombinant zoster vaccine (RZV) by mid-2023; the low rate of herpes zoster vaccination in this immunocompromised group, especially among younger individuals, is concerning.

METHODOLOGY:

• In 2021, the Food and Drug Administration authorized the use of RZV for adults aged 18 years or older on chronic immunosuppressive medications because of their high risk for herpes zoster and its related complications, followed by updated guidance from the Centers for Disease Control and Prevention and American College of Rheumatology in 2021 and 2022, respectively.
• This study aimed to assess the receipt of RZV among veterans receiving immunosuppressive medications within the Veterans Health Administration (VHA) healthcare system before and after the expanded indications in February 2022.
• It included 190,162 veterans who were prescribed one or more immunosuppressive medications for at least 90 days at 130 medical facilities between January 1, 2018, and June 30, 2023.
• A total of 23,295 veterans (12.3%) were younger than 50 years by the end of the study period.
• The outcome measured was the percentage of veterans with one or more doses of RZV documented during the study period.

TAKEAWAY:

• Among veterans aged 50 years or older, 36.2% and 49.8% received an RZV before the expanded indication and by mid-2023, respectively. Even though the rate of vaccination is higher than that observed in the 2021 National Health Interview Survey, significant room for improvement remains.
• Among veterans younger than 50 years, very few (2.8%) received an RZV before the expanded indication, and only 13.4% received it by mid-2023.
• Demographic factors associated with lower odds of vaccination included male sex, African American or unknown race, and nonurban residence (P ≤ .004 for all).
• Those who received targeted synthetic disease-modifying antirheumatic drugs (DMARDs) alone or in combination with other drugs or those who received other vaccines were more likely to receive RZV than those who received conventional synthetic DMARD monotherapy (P < .001 for both).

IN PRACTICE:

“Future work to improve RZV vaccination in patients at high risk should focus on creating informatics tools to identify individuals at high risk and standardizing vaccination guidelines across subspecialties,” the authors wrote.

SOURCE:

This study was led by Sharon Abada, MD, University of California, San Francisco. It was published online on October 11, 2024, in JAMA Network Open.

LIMITATIONS:

This study may not be generalizable to nonveteran populations or countries outside the United States. Limitations also included difficulty with capturing vaccinations not administered within the VHA system, which may have resulted in an underestimation of the percentage of patients vaccinated.

DISCLOSURES:

This work was funded by grants from the VA Quality Enhancement Research Initiative and the Agency for Healthcare Research and Quality. Some authors reported receiving grants from institutions and pharmaceutical companies.

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 first appeared on Medscape.com.

HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.

“In most cases, mycosis fungoides will not shorten one’s life, but it can cause significant symptoms,” Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”

courtesy Dr. Aaron Mangold

Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
 

When Close Follow-Up Is Advised

According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)

According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”

Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”

Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
 

UVB Phototherapy Effective

For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”

Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.

For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.

Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.

Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
 

Radiation An Option in Some Cases

Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”

Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.

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

HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.

“In most cases, mycosis fungoides will not shorten one’s life, but it can cause significant symptoms,” Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”

courtesy Dr. Aaron Mangold

Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
 

When Close Follow-Up Is Advised

According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)

According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”

Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”

Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
 

UVB Phototherapy Effective

For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”

Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.

For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.

Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.

Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
 

Radiation An Option in Some Cases

Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”

Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.

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

HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.

“In most cases, mycosis fungoides will not shorten one’s life, but it can cause significant symptoms,” Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”

courtesy Dr. Aaron Mangold

Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
 

When Close Follow-Up Is Advised

According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)

According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”

Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”

Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
 

UVB Phototherapy Effective

For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”

Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.

For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.

Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.

Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
 

Radiation An Option in Some Cases

Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”

Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.

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

The patient had been diagnosed with pemphigus vulgaris (PV) 1 year prior to presentation with erosions on the axilla. Biopsy at that time revealed intraepithelial acantholytic blistering with areas of suprabasilar and subcorneal clefting. Direct immunofluorescence was positive for linear/granular IgG deposition throughout the epithelial cell surfaces, as well as linear/granular C3 deposits of the lower two thirds of the epithelial strata, consistent for pemphigus vulgaris.

PV is a rare autoimmune bullous disease in which antibodies are directed against desmoglein 1 and 3 and less commonly, plakoglobin. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.

Clinically, PV presents with flaccid blistering lesions that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions can involve the lips, esophagus, conjunctiva, and genitals.

Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.

There are numerous reports in the literature of PV occurring in previous surgical scars, and areas of friction or trauma. This so-called Koebner’s phenomenon is seen more commonly in several dermatologic conditions, such as psoriasis, lichen planus, verruca vulgaris, and vitiligo.

Treatment for PV is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid sparing agent such as mycophenolate mofetil. Other steroid sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Cerottini JP et al. Eur J Dermatol. 2000 Oct-Nov;10(7):546-7.

Reichert-Penetrat S et al. Eur J Dermatol. 1998 Jan-Feb;8(1):60-2.

Saini P et al. Skinmed. 2020 Aug 1;18(4):252-253.

The patient had been diagnosed with pemphigus vulgaris (PV) 1 year prior to presentation with erosions on the axilla. Biopsy at that time revealed intraepithelial acantholytic blistering with areas of suprabasilar and subcorneal clefting. Direct immunofluorescence was positive for linear/granular IgG deposition throughout the epithelial cell surfaces, as well as linear/granular C3 deposits of the lower two thirds of the epithelial strata, consistent for pemphigus vulgaris.

PV is a rare autoimmune bullous disease in which antibodies are directed against desmoglein 1 and 3 and less commonly, plakoglobin. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.

Clinically, PV presents with flaccid blistering lesions that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions can involve the lips, esophagus, conjunctiva, and genitals.

Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.

There are numerous reports in the literature of PV occurring in previous surgical scars, and areas of friction or trauma. This so-called Koebner’s phenomenon is seen more commonly in several dermatologic conditions, such as psoriasis, lichen planus, verruca vulgaris, and vitiligo.

Treatment for PV is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid sparing agent such as mycophenolate mofetil. Other steroid sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Cerottini JP et al. Eur J Dermatol. 2000 Oct-Nov;10(7):546-7.

Reichert-Penetrat S et al. Eur J Dermatol. 1998 Jan-Feb;8(1):60-2.

Saini P et al. Skinmed. 2020 Aug 1;18(4):252-253.

The patient had been diagnosed with pemphigus vulgaris (PV) 1 year prior to presentation with erosions on the axilla. Biopsy at that time revealed intraepithelial acantholytic blistering with areas of suprabasilar and subcorneal clefting. Direct immunofluorescence was positive for linear/granular IgG deposition throughout the epithelial cell surfaces, as well as linear/granular C3 deposits of the lower two thirds of the epithelial strata, consistent for pemphigus vulgaris.

PV is a rare autoimmune bullous disease in which antibodies are directed against desmoglein 1 and 3 and less commonly, plakoglobin. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.

Clinically, PV presents with flaccid blistering lesions that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions can involve the lips, esophagus, conjunctiva, and genitals.

Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.

There are numerous reports in the literature of PV occurring in previous surgical scars, and areas of friction or trauma. This so-called Koebner’s phenomenon is seen more commonly in several dermatologic conditions, such as psoriasis, lichen planus, verruca vulgaris, and vitiligo.

Treatment for PV is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid sparing agent such as mycophenolate mofetil. Other steroid sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Cerottini JP et al. Eur J Dermatol. 2000 Oct-Nov;10(7):546-7.

Reichert-Penetrat S et al. Eur J Dermatol. 1998 Jan-Feb;8(1):60-2.

Saini P et al. Skinmed. 2020 Aug 1;18(4):252-253.

TOPLINE:

Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.

METHODOLOGY:

• Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
• They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
• Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
• Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.

TAKEAWAY:

• Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
• Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
• The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
• Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.

IN PRACTICE:

“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.

SOURCE:

The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.

DISCLOSURES:

The study did not have a funding source. The authors declared 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:

Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.

METHODOLOGY:

• Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
• They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
• Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
• Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.

TAKEAWAY:

• Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
• Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
• The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
• Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.

IN PRACTICE:

“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.

SOURCE:

The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.

DISCLOSURES:

The study did not have a funding source. The authors declared 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:

Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.

METHODOLOGY:

• Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
• They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
• Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
• Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.

TAKEAWAY:

• Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
• Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
• The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
• Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.

IN PRACTICE:

“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.

SOURCE:

The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.

DISCLOSURES:

The study did not have a funding source. The authors declared 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.

NEW YORK — Seborrheic dermatitis (SD) is a common and shared disorder across populations, but it is the third most common dermatologic complaint that Black individuals bring to the dermatologist and deserves more attention not only in this group but also overall, now that there is an approved therapy with an array of alternatives and adjunctive medications, according to Shawn Kwatra, MD.

The list of therapies effective against SD, often employed in combination, is lengthy, but topical 0.3% roflumilast foam (Zoryve), approved by the Food and Drug Administration (FDA) late last year for treating SD, has a high rate of efficacy and should now be considered a first-line treatment option, according to Dr. Kwatra, professor and chair of the Department of Dermatology, University of Maryland School of Medicine, Baltimore.
 

New Approved Therapy Draws Attention to SD

Emphasizing that topical roflumilast does not necessarily replace the use of over-the-counter shampoos and emollients or a list of prescription drugs used off-label to control this condition, he said it is also important for another reason.

Dr. Kwatra

“It shines a light on this disease,” said Dr. Kwatra, speaking at the 2024 Skin of Color Update. While his comments were focused primarily on individuals with darker skin, his major take home messages were broadly relevant across skin types.

He acknowledged that for years he “had not given seborrheic dermatitis the respect that it deserves” even though this condition comes after only acne and eczema as chief complaints among Black individuals seeing a dermatologist. The estimated global incidence is 5%, according to Dr. Kwatra, but he considers this estimate of an often “forgotten disease” too low.

One reason is that many individuals self-treat with over-the-counter solutions and never bring the complaint to a clinician. Dr. Kwatra said that he now looks for it routinely and points it out to patients who have come to him for another reason.

In patients with darker skin, the signs of SD can differ. While scalp involvement is generally easy to identify across skin types, the inflammation and erythema, sebum production, scaling and itch, and Malassezia that accompanies and drives SD might be missed in a patient with darker skin without specifically looking for these signs.
 

Skin and Gut Microbiome Involvement Suspected

The underlying causes of SD are understood as an inflammatory process involving keratinocyte disruption and proliferation that ultimately impairs skin barrier function, causes water loss, and produces scale stemming from stratum corneum, but Dr. Kwatra said that there is increasing evidence of a major role for both the skin and gut microbiome.

In regard to the skin microbiome, Malassezia has long been recognized as linked to SD and is a target of treatment, but evidence that the gut microbiome might be participating is relatively new. One clue comes from the fact that oral antifungal therapies, such as itraconazole, are known to reduce risk for SD relapse, an effect that might be a function of their ability to modulate the gut microbiome, according to Dr. Kwatra.

Topical roflumilast, a phosphodiesterase-4 inhibitor, was effective for SD in a vehicle-controlled phase 3 trial published in 2023. He characterized the adverse event profile as “pretty clean,” but he emphasized that a role for many other strategies remains. This is particularly true for challenging forms of SD. For example, topical tacrolimus provided meaningful protection against relapse over a period of more than 6 months in a 2021 trial that enrolled patients with severe facial SD.

The topical Janus kinase inhibitor ruxolitinib, 1.5%, (approved for atopic dermatitis and vitiligo) has also been reported to be effective for refractory facial SD. It is being evaluated in a phase 2 study of SD, according to Dr. Kwatra. A topical PDE4 inhibitor is also being evaluated for SD in a phase 2 study, he said.

Given the heterogeneity of the presentation of SD and the value of combining different mechanisms of action, Dr. Kwatra does not think any drug by itself will be a cure for SD. However, the chances of success with current drug combinations are high.

It is for this reason that Dr. Kwatra encourages clinicians to look for this disease routinely, including among patients who have a different presenting complaint. “Patients do not always bring it up, so bring it up,” he said.

This is good advice, according to Andrew F. Alexis, MD, MPH, professor of clinical dermatology and Vice-chair for Diversity and Inclusion of the Department of Dermatology, Weill Cornell Medicine, New York City. He agreed that the recent introduction of a therapy approved by the FDA is an impetus to look for SD and to talk with patients about treatment options.

In addition, while he also considers roflumilast foam to be a first-line drug, he agreed that combination therapies might be needed to increase the likely of rapid control of scalp and skin involvement. “SD is probably underestimated as a clinical problem, and we do have good treatments to offer for the patients who are affected,” he said at the meeting.

Dr. Kwatra reported no relevant disclosures. Dr. Alexis reported financial relationships with more than 25 pharmaceutical companies.

A version of this article appeared on Medscape.com.

NEW YORK — Seborrheic dermatitis (SD) is a common and shared disorder across populations, but it is the third most common dermatologic complaint that Black individuals bring to the dermatologist and deserves more attention not only in this group but also overall, now that there is an approved therapy with an array of alternatives and adjunctive medications, according to Shawn Kwatra, MD.

The list of therapies effective against SD, often employed in combination, is lengthy, but topical 0.3% roflumilast foam (Zoryve), approved by the Food and Drug Administration (FDA) late last year for treating SD, has a high rate of efficacy and should now be considered a first-line treatment option, according to Dr. Kwatra, professor and chair of the Department of Dermatology, University of Maryland School of Medicine, Baltimore.
 

New Approved Therapy Draws Attention to SD

Emphasizing that topical roflumilast does not necessarily replace the use of over-the-counter shampoos and emollients or a list of prescription drugs used off-label to control this condition, he said it is also important for another reason.

Dr. Kwatra

“It shines a light on this disease,” said Dr. Kwatra, speaking at the 2024 Skin of Color Update. While his comments were focused primarily on individuals with darker skin, his major take home messages were broadly relevant across skin types.

He acknowledged that for years he “had not given seborrheic dermatitis the respect that it deserves” even though this condition comes after only acne and eczema as chief complaints among Black individuals seeing a dermatologist. The estimated global incidence is 5%, according to Dr. Kwatra, but he considers this estimate of an often “forgotten disease” too low.

One reason is that many individuals self-treat with over-the-counter solutions and never bring the complaint to a clinician. Dr. Kwatra said that he now looks for it routinely and points it out to patients who have come to him for another reason.

In patients with darker skin, the signs of SD can differ. While scalp involvement is generally easy to identify across skin types, the inflammation and erythema, sebum production, scaling and itch, and Malassezia that accompanies and drives SD might be missed in a patient with darker skin without specifically looking for these signs.
 

Skin and Gut Microbiome Involvement Suspected

The underlying causes of SD are understood as an inflammatory process involving keratinocyte disruption and proliferation that ultimately impairs skin barrier function, causes water loss, and produces scale stemming from stratum corneum, but Dr. Kwatra said that there is increasing evidence of a major role for both the skin and gut microbiome.

In regard to the skin microbiome, Malassezia has long been recognized as linked to SD and is a target of treatment, but evidence that the gut microbiome might be participating is relatively new. One clue comes from the fact that oral antifungal therapies, such as itraconazole, are known to reduce risk for SD relapse, an effect that might be a function of their ability to modulate the gut microbiome, according to Dr. Kwatra.

Topical roflumilast, a phosphodiesterase-4 inhibitor, was effective for SD in a vehicle-controlled phase 3 trial published in 2023. He characterized the adverse event profile as “pretty clean,” but he emphasized that a role for many other strategies remains. This is particularly true for challenging forms of SD. For example, topical tacrolimus provided meaningful protection against relapse over a period of more than 6 months in a 2021 trial that enrolled patients with severe facial SD.

The topical Janus kinase inhibitor ruxolitinib, 1.5%, (approved for atopic dermatitis and vitiligo) has also been reported to be effective for refractory facial SD. It is being evaluated in a phase 2 study of SD, according to Dr. Kwatra. A topical PDE4 inhibitor is also being evaluated for SD in a phase 2 study, he said.

Given the heterogeneity of the presentation of SD and the value of combining different mechanisms of action, Dr. Kwatra does not think any drug by itself will be a cure for SD. However, the chances of success with current drug combinations are high.

It is for this reason that Dr. Kwatra encourages clinicians to look for this disease routinely, including among patients who have a different presenting complaint. “Patients do not always bring it up, so bring it up,” he said.

This is good advice, according to Andrew F. Alexis, MD, MPH, professor of clinical dermatology and Vice-chair for Diversity and Inclusion of the Department of Dermatology, Weill Cornell Medicine, New York City. He agreed that the recent introduction of a therapy approved by the FDA is an impetus to look for SD and to talk with patients about treatment options.

In addition, while he also considers roflumilast foam to be a first-line drug, he agreed that combination therapies might be needed to increase the likely of rapid control of scalp and skin involvement. “SD is probably underestimated as a clinical problem, and we do have good treatments to offer for the patients who are affected,” he said at the meeting.

Dr. Kwatra reported no relevant disclosures. Dr. Alexis reported financial relationships with more than 25 pharmaceutical companies.

A version of this article appeared on Medscape.com.

NEW YORK — Seborrheic dermatitis (SD) is a common and shared disorder across populations, but it is the third most common dermatologic complaint that Black individuals bring to the dermatologist and deserves more attention not only in this group but also overall, now that there is an approved therapy with an array of alternatives and adjunctive medications, according to Shawn Kwatra, MD.

The list of therapies effective against SD, often employed in combination, is lengthy, but topical 0.3% roflumilast foam (Zoryve), approved by the Food and Drug Administration (FDA) late last year for treating SD, has a high rate of efficacy and should now be considered a first-line treatment option, according to Dr. Kwatra, professor and chair of the Department of Dermatology, University of Maryland School of Medicine, Baltimore.
 

New Approved Therapy Draws Attention to SD

Emphasizing that topical roflumilast does not necessarily replace the use of over-the-counter shampoos and emollients or a list of prescription drugs used off-label to control this condition, he said it is also important for another reason.

Dr. Kwatra

“It shines a light on this disease,” said Dr. Kwatra, speaking at the 2024 Skin of Color Update. While his comments were focused primarily on individuals with darker skin, his major take home messages were broadly relevant across skin types.

He acknowledged that for years he “had not given seborrheic dermatitis the respect that it deserves” even though this condition comes after only acne and eczema as chief complaints among Black individuals seeing a dermatologist. The estimated global incidence is 5%, according to Dr. Kwatra, but he considers this estimate of an often “forgotten disease” too low.

One reason is that many individuals self-treat with over-the-counter solutions and never bring the complaint to a clinician. Dr. Kwatra said that he now looks for it routinely and points it out to patients who have come to him for another reason.

In patients with darker skin, the signs of SD can differ. While scalp involvement is generally easy to identify across skin types, the inflammation and erythema, sebum production, scaling and itch, and Malassezia that accompanies and drives SD might be missed in a patient with darker skin without specifically looking for these signs.
 

Skin and Gut Microbiome Involvement Suspected

The underlying causes of SD are understood as an inflammatory process involving keratinocyte disruption and proliferation that ultimately impairs skin barrier function, causes water loss, and produces scale stemming from stratum corneum, but Dr. Kwatra said that there is increasing evidence of a major role for both the skin and gut microbiome.

In regard to the skin microbiome, Malassezia has long been recognized as linked to SD and is a target of treatment, but evidence that the gut microbiome might be participating is relatively new. One clue comes from the fact that oral antifungal therapies, such as itraconazole, are known to reduce risk for SD relapse, an effect that might be a function of their ability to modulate the gut microbiome, according to Dr. Kwatra.

Topical roflumilast, a phosphodiesterase-4 inhibitor, was effective for SD in a vehicle-controlled phase 3 trial published in 2023. He characterized the adverse event profile as “pretty clean,” but he emphasized that a role for many other strategies remains. This is particularly true for challenging forms of SD. For example, topical tacrolimus provided meaningful protection against relapse over a period of more than 6 months in a 2021 trial that enrolled patients with severe facial SD.

The topical Janus kinase inhibitor ruxolitinib, 1.5%, (approved for atopic dermatitis and vitiligo) has also been reported to be effective for refractory facial SD. It is being evaluated in a phase 2 study of SD, according to Dr. Kwatra. A topical PDE4 inhibitor is also being evaluated for SD in a phase 2 study, he said.

Given the heterogeneity of the presentation of SD and the value of combining different mechanisms of action, Dr. Kwatra does not think any drug by itself will be a cure for SD. However, the chances of success with current drug combinations are high.

It is for this reason that Dr. Kwatra encourages clinicians to look for this disease routinely, including among patients who have a different presenting complaint. “Patients do not always bring it up, so bring it up,” he said.

This is good advice, according to Andrew F. Alexis, MD, MPH, professor of clinical dermatology and Vice-chair for Diversity and Inclusion of the Department of Dermatology, Weill Cornell Medicine, New York City. He agreed that the recent introduction of a therapy approved by the FDA is an impetus to look for SD and to talk with patients about treatment options.

In addition, while he also considers roflumilast foam to be a first-line drug, he agreed that combination therapies might be needed to increase the likely of rapid control of scalp and skin involvement. “SD is probably underestimated as a clinical problem, and we do have good treatments to offer for the patients who are affected,” he said at the meeting.

Dr. Kwatra reported no relevant disclosures. Dr. Alexis reported financial relationships with more than 25 pharmaceutical companies.

A version of this article appeared on Medscape.com.

NEW YORK — Because of their heterogeneity in appearance, drug-induced skin rashes are a common diagnostic challenge, but eruptions in skin of color, particularly those with a delayed onset, require a high index of suspicion to speed the diagnosis.

This risk for a delayed or missed diagnosis in patients with darker skin is shared across skin rashes, but drug-induced hypersensitivity syndrome (DIHS) is a telling example, according to Joanna Harp, MD, director of the Inpatient Dermatology Consult Service, NewYork–Presbyterian Hospital, New York City.

DIHS, also known as a drug reaction with eosinophilia and systemic symptoms, is a type IV hypersensitivity reaction, Dr. Harp explained. While the fact that this disorder does not always include eosinophilia prompted the DIHS acronym, the maculopapular rash often serves as a critical clue of the underlying etiology.

Signs of AGEP Can Be Subtle in Black Patients

Some of the same principles for diagnosing drug-induced rash in darker skin can also be applied to acute generalized exanthematous pustulosis (AGEP), another type IV hypersensitivity reaction. Like all drug-induced rashes, the earlier AGEP is recognized and treated, the better the outcome, but in Black patients, the signs can be subtle.

“The onset is usually fast and occurs in 1-2 days after [the causative drug] exposure,” said Dr. Harp, adding that antibiotics, such as cephalosporins or penicillin, and calcium channel blockers are among the prominent causes of AGEP.

One of the hallmark signs of early-onset AGEP are tiny erythematous pustules in flexural areas, such as the neck or the armpits. The issue of detecting erythema in darker skin is also relevant to this area, but there is an additional problem, according to Dr. Harp. The pustules often dry up quickly, leaving a neutrophilic scale that further complicates the effort to see the characteristic erythema.

“If you see a lot of scale, look for erythema underneath. Think of inflammation,” Dr. Harp said, explaining that the clinical appearance evolves quickly. “If you do not see the pustules, it does not mean they were not there; you just missed them.”

In addition to the flexural areas, “AGEP loves the ears, the face, and the geographic tongue,” she said, offering several pearls to help with the diagnosis. These include side lighting to make papules easier to see, pressing on the skin to highlight the difference between erythematous skin and blanched skin, and checking less pigmented skin, such as on the hands and feet, which makes erythema easier to see.

Steroids are often the first-line treatment for drug-induced skin rashes, but Dr. Harp moves to etanercept or cyclosporine for the most serious drug reactions, such as SJS and toxic epidermal necrolysis.

Etanercept is typically her first choice because patients with systemic hypersensitivity reactions with major organ involvement are often quite ill, making cyclosporine harder to use. In her experience, etanercept has been well tolerated.

Conversely, she cautioned against the use of intravenous immunoglobulin (IVIG). Although this has been used traditionally for severe drug hypersensitivity reactions, “the data are not there,” she said. The data are stronger for a combination of high-dose steroids and IVIG, but she thinks even these data are inconsistent and not as strong as the data supporting etanercept or cyclosporine. She encouraged centers still using IVIG to consider alternatives.

After drug sensitivity reactions are controlled, follow-up care is particularly important for Black patients who face greater risks for sequelae, such as hypopigmentation, hyperpigmentation, or keloids. She recommended aggressive use of emollients and sunscreens for an extended period after lesions resolve to lessen these risks.

Differences in the manifestations of drug-induced skin rashes by race and ethnicity are important and perhaps underappreciated, agreed Shawn Kwatra, MD, professor and chairman of the Department of Dermatology, University of Maryland, Baltimore.

Asked to comment at the meeting, Dr. Kwatra said that he appreciated Dr. Harp’s effort to translate published data and her experience into an overview that increases awareness of the risk for missed or delayed diagnoses of drug-induced rashes in skin of color. He noted that the strategies to identify erythema and pustules, such as increased suspicion in skin of color and the extra steps to rule them out, such as the use of side lighting in the case of pustules for AGEP, are simple and practical.

Dr. Harp and Dr. Kwatra had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

NEW YORK — Because of their heterogeneity in appearance, drug-induced skin rashes are a common diagnostic challenge, but eruptions in skin of color, particularly those with a delayed onset, require a high index of suspicion to speed the diagnosis.

This risk for a delayed or missed diagnosis in patients with darker skin is shared across skin rashes, but drug-induced hypersensitivity syndrome (DIHS) is a telling example, according to Joanna Harp, MD, director of the Inpatient Dermatology Consult Service, NewYork–Presbyterian Hospital, New York City.

DIHS, also known as a drug reaction with eosinophilia and systemic symptoms, is a type IV hypersensitivity reaction, Dr. Harp explained. While the fact that this disorder does not always include eosinophilia prompted the DIHS acronym, the maculopapular rash often serves as a critical clue of the underlying etiology.

Signs of AGEP Can Be Subtle in Black Patients

Some of the same principles for diagnosing drug-induced rash in darker skin can also be applied to acute generalized exanthematous pustulosis (AGEP), another type IV hypersensitivity reaction. Like all drug-induced rashes, the earlier AGEP is recognized and treated, the better the outcome, but in Black patients, the signs can be subtle.

“The onset is usually fast and occurs in 1-2 days after [the causative drug] exposure,” said Dr. Harp, adding that antibiotics, such as cephalosporins or penicillin, and calcium channel blockers are among the prominent causes of AGEP.

One of the hallmark signs of early-onset AGEP are tiny erythematous pustules in flexural areas, such as the neck or the armpits. The issue of detecting erythema in darker skin is also relevant to this area, but there is an additional problem, according to Dr. Harp. The pustules often dry up quickly, leaving a neutrophilic scale that further complicates the effort to see the characteristic erythema.

“If you see a lot of scale, look for erythema underneath. Think of inflammation,” Dr. Harp said, explaining that the clinical appearance evolves quickly. “If you do not see the pustules, it does not mean they were not there; you just missed them.”

In addition to the flexural areas, “AGEP loves the ears, the face, and the geographic tongue,” she said, offering several pearls to help with the diagnosis. These include side lighting to make papules easier to see, pressing on the skin to highlight the difference between erythematous skin and blanched skin, and checking less pigmented skin, such as on the hands and feet, which makes erythema easier to see.

Steroids are often the first-line treatment for drug-induced skin rashes, but Dr. Harp moves to etanercept or cyclosporine for the most serious drug reactions, such as SJS and toxic epidermal necrolysis.

Etanercept is typically her first choice because patients with systemic hypersensitivity reactions with major organ involvement are often quite ill, making cyclosporine harder to use. In her experience, etanercept has been well tolerated.

Conversely, she cautioned against the use of intravenous immunoglobulin (IVIG). Although this has been used traditionally for severe drug hypersensitivity reactions, “the data are not there,” she said. The data are stronger for a combination of high-dose steroids and IVIG, but she thinks even these data are inconsistent and not as strong as the data supporting etanercept or cyclosporine. She encouraged centers still using IVIG to consider alternatives.

After drug sensitivity reactions are controlled, follow-up care is particularly important for Black patients who face greater risks for sequelae, such as hypopigmentation, hyperpigmentation, or keloids. She recommended aggressive use of emollients and sunscreens for an extended period after lesions resolve to lessen these risks.

Differences in the manifestations of drug-induced skin rashes by race and ethnicity are important and perhaps underappreciated, agreed Shawn Kwatra, MD, professor and chairman of the Department of Dermatology, University of Maryland, Baltimore.

Asked to comment at the meeting, Dr. Kwatra said that he appreciated Dr. Harp’s effort to translate published data and her experience into an overview that increases awareness of the risk for missed or delayed diagnoses of drug-induced rashes in skin of color. He noted that the strategies to identify erythema and pustules, such as increased suspicion in skin of color and the extra steps to rule them out, such as the use of side lighting in the case of pustules for AGEP, are simple and practical.

Dr. Harp and Dr. Kwatra had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

NEW YORK — Because of their heterogeneity in appearance, drug-induced skin rashes are a common diagnostic challenge, but eruptions in skin of color, particularly those with a delayed onset, require a high index of suspicion to speed the diagnosis.

This risk for a delayed or missed diagnosis in patients with darker skin is shared across skin rashes, but drug-induced hypersensitivity syndrome (DIHS) is a telling example, according to Joanna Harp, MD, director of the Inpatient Dermatology Consult Service, NewYork–Presbyterian Hospital, New York City.

DIHS, also known as a drug reaction with eosinophilia and systemic symptoms, is a type IV hypersensitivity reaction, Dr. Harp explained. While the fact that this disorder does not always include eosinophilia prompted the DIHS acronym, the maculopapular rash often serves as a critical clue of the underlying etiology.

Signs of AGEP Can Be Subtle in Black Patients

Some of the same principles for diagnosing drug-induced rash in darker skin can also be applied to acute generalized exanthematous pustulosis (AGEP), another type IV hypersensitivity reaction. Like all drug-induced rashes, the earlier AGEP is recognized and treated, the better the outcome, but in Black patients, the signs can be subtle.

“The onset is usually fast and occurs in 1-2 days after [the causative drug] exposure,” said Dr. Harp, adding that antibiotics, such as cephalosporins or penicillin, and calcium channel blockers are among the prominent causes of AGEP.

One of the hallmark signs of early-onset AGEP are tiny erythematous pustules in flexural areas, such as the neck or the armpits. The issue of detecting erythema in darker skin is also relevant to this area, but there is an additional problem, according to Dr. Harp. The pustules often dry up quickly, leaving a neutrophilic scale that further complicates the effort to see the characteristic erythema.

“If you see a lot of scale, look for erythema underneath. Think of inflammation,” Dr. Harp said, explaining that the clinical appearance evolves quickly. “If you do not see the pustules, it does not mean they were not there; you just missed them.”

In addition to the flexural areas, “AGEP loves the ears, the face, and the geographic tongue,” she said, offering several pearls to help with the diagnosis. These include side lighting to make papules easier to see, pressing on the skin to highlight the difference between erythematous skin and blanched skin, and checking less pigmented skin, such as on the hands and feet, which makes erythema easier to see.

Steroids are often the first-line treatment for drug-induced skin rashes, but Dr. Harp moves to etanercept or cyclosporine for the most serious drug reactions, such as SJS and toxic epidermal necrolysis.

Etanercept is typically her first choice because patients with systemic hypersensitivity reactions with major organ involvement are often quite ill, making cyclosporine harder to use. In her experience, etanercept has been well tolerated.

Conversely, she cautioned against the use of intravenous immunoglobulin (IVIG). Although this has been used traditionally for severe drug hypersensitivity reactions, “the data are not there,” she said. The data are stronger for a combination of high-dose steroids and IVIG, but she thinks even these data are inconsistent and not as strong as the data supporting etanercept or cyclosporine. She encouraged centers still using IVIG to consider alternatives.

After drug sensitivity reactions are controlled, follow-up care is particularly important for Black patients who face greater risks for sequelae, such as hypopigmentation, hyperpigmentation, or keloids. She recommended aggressive use of emollients and sunscreens for an extended period after lesions resolve to lessen these risks.

Differences in the manifestations of drug-induced skin rashes by race and ethnicity are important and perhaps underappreciated, agreed Shawn Kwatra, MD, professor and chairman of the Department of Dermatology, University of Maryland, Baltimore.

Asked to comment at the meeting, Dr. Kwatra said that he appreciated Dr. Harp’s effort to translate published data and her experience into an overview that increases awareness of the risk for missed or delayed diagnoses of drug-induced rashes in skin of color. He noted that the strategies to identify erythema and pustules, such as increased suspicion in skin of color and the extra steps to rule them out, such as the use of side lighting in the case of pustules for AGEP, are simple and practical.

Dr. Harp and Dr. Kwatra had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

NEW YORK — Underrepresentation by gender and race in major clinical trials has been a cause for complaint for decades, but the Food and Drug Administration (FDA) has drafted a regulatory solution to this issue expected to be implemented sometime in 2025.

This initiative, known as the FDA’s Diversity Action Plan (DAP), will require plans for all pivotal and phase 3 trials to provide details in their design of how diversity will be achieved or, if there are no plans for diversity, the reason why, according to Valerie M. Harvey, MD, MPH, associate clinical professor, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia. These rules will be codified, she said at the 2024 Skin of Color Update.

Once the DAP is enacted, “the sponsor must specify the rationale and goals for study enrollment by age, ethnicity, sex, and race,” she said. Furthermore, the submission to the FDA must “describe the methods to meet the diversity benchmarks.”
 

Lack of Trial Diversity Is Common Across Medicine

Although she focused on the relevance of this initiative to dermatology, Dr. Harvey said the lack of diversity in clinical trials is pervasive throughout medicine. In one survey of randomized controlled trials, less than 60% of trials even specified the race and ethnicity of the participants. In recent psoriasis trials, only 30% met a diversity definition of ≥ 20% of patients identifying as minority (Black, Hispanic, Asian, or other non-White group), said Dr. Harvey, who practices dermatology in Newport News, Virginia.

The FDA draft guidance for the DAP was released in June 2024 and is now available for submitting comments (until September 26). The plan is expected to be published in June 2025, according to Dr. Harvey. It will pertain to all pivotal and phase 3 trials enrolling 180 days after the publication date and will be relevant to all drugs and biologics as well as certain devices.

This initiative could be a critical step toward ensuring diversity in major clinical trials after years of stagnation, Dr. Harvey said, noting that despite repeated calls for more diversity in clinical trials, the literature suggests “little progress.”

However, she said that increasing diversity in clinical trials is just one step toward gathering data about the generalizability of efficacy and safety across racial and ethnic groups. A much more complex issue involves how race and ethnicity are defined in order to understand differences, if any, for efficacy and risk.

“Race is a dynamic social construct and a poor measure for biologic variation and skin color,” Dr. Harvey said. This means that work is needed to address the more complex issue of race and ethnicity stratification that will help clinicians understand the relative benefits and risks for the drugs in these trials.

Rather than differences based on genetic or other sources of biologic differences, she said, outcomes by race alone are often suspected of reflecting disparities in access to healthcare rather than a difference in therapeutic response.
 

Skin Color Is Inadequate to Define Race

When stratifying patients by race or ethnicity, Dr. Harvey said that “we have to be very, very careful in considering the study purpose and what the study question is.” A study attempting to compare benefits and risks among subgroups by race or ethnicity will require descriptors beyond skin color.

The recognized limitations of measuring skin tone as a surrogate of race are one reason for widespread interest in moving away from the Fitzpatrick skin type (FST) rating that has been widely considered a standard, according to Dr. Harvey. Several alternatives have been proposed, including the Monk Skin Tone Scale, the Individual Typology Angle, and the Eumelanin Human Skin Color Scale, but she cautioned that these are less well validated and generally have the limitations of the FST.

If skin color was ever useful for grouping individuals on the basis of shared physiology, growing rates of intermarriage and immigration have made skin color increasingly irrelevant to racial identity. If the goal is to evaluate the safety and efficacy of drugs across racial groups and ethnicities, the characterization of populations will almost certainly require multiple descriptors and biomarkers, she said.

“It is very important to have many tools for characterizing patients by skin type,” Susan Taylor, MD, professor of dermatology and vice chair for diversity, equity, and inclusion for the Department of Dermatology, University of Pennsylvania, Philadelphia, said in an interview at the meeting.

The reason is “there are limitations to all of them,” she said, noting also that the questions being asked about how and if skin color and race are relevant to therapeutic options differ by the question, such as innate response or access to care.

Dr. Taylor is part of a workshop that she said is evaluating a combination of instruments for characterizing skin color and race in ways relevant to the specific question being asked.

The solutions might differ. While simple clinical assessments involving skin color might be made with methods captured on a smartphone app, Dr. Taylor acknowledged that far more complex tools might be required to document the effect of racial or ethnic differences in drug efficacy and safety in a research setting.

Outside of a research setting, any tools that might be useful for assessing race as a variable must be practical, according to Dr. Harvey. She suggested that these must be time efficient, of reasonable cost, and most importantly, reliable.

Tools meeting these criteria do not currently exist, but Dr. Harvey said the work is underway. She expects a “top-down” collaborative approach to validate alternatives to the FST. If such tools can be developed with buy-in from the FDA, they might be particularly useful for translating trial data to patient care, she added.

Dr. Harvey reported financial relationships with AbbVie, Bristol-Myers Squibb, Janssen, Johnson & Johnson, L’Oréal, and SkinCeuticals. Dr. Taylor, president-elect of the American Academy of Dermatology, reported financial relationships with more than 25 pharmaceutical and cosmetic companies.

A version of this article appeared on Medscape.com.

NEW YORK — Underrepresentation by gender and race in major clinical trials has been a cause for complaint for decades, but the Food and Drug Administration (FDA) has drafted a regulatory solution to this issue expected to be implemented sometime in 2025.

This initiative, known as the FDA’s Diversity Action Plan (DAP), will require plans for all pivotal and phase 3 trials to provide details in their design of how diversity will be achieved or, if there are no plans for diversity, the reason why, according to Valerie M. Harvey, MD, MPH, associate clinical professor, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia. These rules will be codified, she said at the 2024 Skin of Color Update.

Once the DAP is enacted, “the sponsor must specify the rationale and goals for study enrollment by age, ethnicity, sex, and race,” she said. Furthermore, the submission to the FDA must “describe the methods to meet the diversity benchmarks.”
 

Lack of Trial Diversity Is Common Across Medicine

Although she focused on the relevance of this initiative to dermatology, Dr. Harvey said the lack of diversity in clinical trials is pervasive throughout medicine. In one survey of randomized controlled trials, less than 60% of trials even specified the race and ethnicity of the participants. In recent psoriasis trials, only 30% met a diversity definition of ≥ 20% of patients identifying as minority (Black, Hispanic, Asian, or other non-White group), said Dr. Harvey, who practices dermatology in Newport News, Virginia.

The FDA draft guidance for the DAP was released in June 2024 and is now available for submitting comments (until September 26). The plan is expected to be published in June 2025, according to Dr. Harvey. It will pertain to all pivotal and phase 3 trials enrolling 180 days after the publication date and will be relevant to all drugs and biologics as well as certain devices.

This initiative could be a critical step toward ensuring diversity in major clinical trials after years of stagnation, Dr. Harvey said, noting that despite repeated calls for more diversity in clinical trials, the literature suggests “little progress.”

However, she said that increasing diversity in clinical trials is just one step toward gathering data about the generalizability of efficacy and safety across racial and ethnic groups. A much more complex issue involves how race and ethnicity are defined in order to understand differences, if any, for efficacy and risk.

“Race is a dynamic social construct and a poor measure for biologic variation and skin color,” Dr. Harvey said. This means that work is needed to address the more complex issue of race and ethnicity stratification that will help clinicians understand the relative benefits and risks for the drugs in these trials.

Rather than differences based on genetic or other sources of biologic differences, she said, outcomes by race alone are often suspected of reflecting disparities in access to healthcare rather than a difference in therapeutic response.
 

Skin Color Is Inadequate to Define Race

When stratifying patients by race or ethnicity, Dr. Harvey said that “we have to be very, very careful in considering the study purpose and what the study question is.” A study attempting to compare benefits and risks among subgroups by race or ethnicity will require descriptors beyond skin color.

The recognized limitations of measuring skin tone as a surrogate of race are one reason for widespread interest in moving away from the Fitzpatrick skin type (FST) rating that has been widely considered a standard, according to Dr. Harvey. Several alternatives have been proposed, including the Monk Skin Tone Scale, the Individual Typology Angle, and the Eumelanin Human Skin Color Scale, but she cautioned that these are less well validated and generally have the limitations of the FST.

If skin color was ever useful for grouping individuals on the basis of shared physiology, growing rates of intermarriage and immigration have made skin color increasingly irrelevant to racial identity. If the goal is to evaluate the safety and efficacy of drugs across racial groups and ethnicities, the characterization of populations will almost certainly require multiple descriptors and biomarkers, she said.

“It is very important to have many tools for characterizing patients by skin type,” Susan Taylor, MD, professor of dermatology and vice chair for diversity, equity, and inclusion for the Department of Dermatology, University of Pennsylvania, Philadelphia, said in an interview at the meeting.

The reason is “there are limitations to all of them,” she said, noting also that the questions being asked about how and if skin color and race are relevant to therapeutic options differ by the question, such as innate response or access to care.

Dr. Taylor is part of a workshop that she said is evaluating a combination of instruments for characterizing skin color and race in ways relevant to the specific question being asked.

The solutions might differ. While simple clinical assessments involving skin color might be made with methods captured on a smartphone app, Dr. Taylor acknowledged that far more complex tools might be required to document the effect of racial or ethnic differences in drug efficacy and safety in a research setting.

Outside of a research setting, any tools that might be useful for assessing race as a variable must be practical, according to Dr. Harvey. She suggested that these must be time efficient, of reasonable cost, and most importantly, reliable.

Tools meeting these criteria do not currently exist, but Dr. Harvey said the work is underway. She expects a “top-down” collaborative approach to validate alternatives to the FST. If such tools can be developed with buy-in from the FDA, they might be particularly useful for translating trial data to patient care, she added.

Dr. Harvey reported financial relationships with AbbVie, Bristol-Myers Squibb, Janssen, Johnson & Johnson, L’Oréal, and SkinCeuticals. Dr. Taylor, president-elect of the American Academy of Dermatology, reported financial relationships with more than 25 pharmaceutical and cosmetic companies.

A version of this article appeared on Medscape.com.

NEW YORK — Underrepresentation by gender and race in major clinical trials has been a cause for complaint for decades, but the Food and Drug Administration (FDA) has drafted a regulatory solution to this issue expected to be implemented sometime in 2025.

This initiative, known as the FDA’s Diversity Action Plan (DAP), will require plans for all pivotal and phase 3 trials to provide details in their design of how diversity will be achieved or, if there are no plans for diversity, the reason why, according to Valerie M. Harvey, MD, MPH, associate clinical professor, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia. These rules will be codified, she said at the 2024 Skin of Color Update.

Once the DAP is enacted, “the sponsor must specify the rationale and goals for study enrollment by age, ethnicity, sex, and race,” she said. Furthermore, the submission to the FDA must “describe the methods to meet the diversity benchmarks.”
 

Lack of Trial Diversity Is Common Across Medicine

Although she focused on the relevance of this initiative to dermatology, Dr. Harvey said the lack of diversity in clinical trials is pervasive throughout medicine. In one survey of randomized controlled trials, less than 60% of trials even specified the race and ethnicity of the participants. In recent psoriasis trials, only 30% met a diversity definition of ≥ 20% of patients identifying as minority (Black, Hispanic, Asian, or other non-White group), said Dr. Harvey, who practices dermatology in Newport News, Virginia.

The FDA draft guidance for the DAP was released in June 2024 and is now available for submitting comments (until September 26). The plan is expected to be published in June 2025, according to Dr. Harvey. It will pertain to all pivotal and phase 3 trials enrolling 180 days after the publication date and will be relevant to all drugs and biologics as well as certain devices.

This initiative could be a critical step toward ensuring diversity in major clinical trials after years of stagnation, Dr. Harvey said, noting that despite repeated calls for more diversity in clinical trials, the literature suggests “little progress.”

However, she said that increasing diversity in clinical trials is just one step toward gathering data about the generalizability of efficacy and safety across racial and ethnic groups. A much more complex issue involves how race and ethnicity are defined in order to understand differences, if any, for efficacy and risk.

“Race is a dynamic social construct and a poor measure for biologic variation and skin color,” Dr. Harvey said. This means that work is needed to address the more complex issue of race and ethnicity stratification that will help clinicians understand the relative benefits and risks for the drugs in these trials.

Rather than differences based on genetic or other sources of biologic differences, she said, outcomes by race alone are often suspected of reflecting disparities in access to healthcare rather than a difference in therapeutic response.
 

Skin Color Is Inadequate to Define Race

When stratifying patients by race or ethnicity, Dr. Harvey said that “we have to be very, very careful in considering the study purpose and what the study question is.” A study attempting to compare benefits and risks among subgroups by race or ethnicity will require descriptors beyond skin color.

The recognized limitations of measuring skin tone as a surrogate of race are one reason for widespread interest in moving away from the Fitzpatrick skin type (FST) rating that has been widely considered a standard, according to Dr. Harvey. Several alternatives have been proposed, including the Monk Skin Tone Scale, the Individual Typology Angle, and the Eumelanin Human Skin Color Scale, but she cautioned that these are less well validated and generally have the limitations of the FST.

If skin color was ever useful for grouping individuals on the basis of shared physiology, growing rates of intermarriage and immigration have made skin color increasingly irrelevant to racial identity. If the goal is to evaluate the safety and efficacy of drugs across racial groups and ethnicities, the characterization of populations will almost certainly require multiple descriptors and biomarkers, she said.

“It is very important to have many tools for characterizing patients by skin type,” Susan Taylor, MD, professor of dermatology and vice chair for diversity, equity, and inclusion for the Department of Dermatology, University of Pennsylvania, Philadelphia, said in an interview at the meeting.

The reason is “there are limitations to all of them,” she said, noting also that the questions being asked about how and if skin color and race are relevant to therapeutic options differ by the question, such as innate response or access to care.

Dr. Taylor is part of a workshop that she said is evaluating a combination of instruments for characterizing skin color and race in ways relevant to the specific question being asked.

The solutions might differ. While simple clinical assessments involving skin color might be made with methods captured on a smartphone app, Dr. Taylor acknowledged that far more complex tools might be required to document the effect of racial or ethnic differences in drug efficacy and safety in a research setting.

Outside of a research setting, any tools that might be useful for assessing race as a variable must be practical, according to Dr. Harvey. She suggested that these must be time efficient, of reasonable cost, and most importantly, reliable.

Tools meeting these criteria do not currently exist, but Dr. Harvey said the work is underway. She expects a “top-down” collaborative approach to validate alternatives to the FST. If such tools can be developed with buy-in from the FDA, they might be particularly useful for translating trial data to patient care, she added.

Dr. Harvey reported financial relationships with AbbVie, Bristol-Myers Squibb, Janssen, Johnson & Johnson, L’Oréal, and SkinCeuticals. Dr. Taylor, president-elect of the American Academy of Dermatology, reported financial relationships with more than 25 pharmaceutical and cosmetic companies.

A version of this article appeared on Medscape.com.

HUNTINGTON BEACH, CALIF. — When Roxana Daneshjou, MD, PhD, began reviewing responses to an exploratory survey she and her colleagues created on dermatologists’ use of large language models (LLMs) such as ChatGPT in clinical practice, she was both surprised and alarmed.

Of the 134 respondents who completed the survey, 87 (65%) reported using LLMs in a clinical setting. Of those 87 respondents, 17 (20%) used LMMs daily, 28 (32%) weekly, 5 (6%) monthly, and 37 (43%) rarely. That represents “pretty significant usage,” Dr. Daneshjou, assistant professor of biomedical data science and dermatology at Stanford University, Palo Alto, California, said at the annual meeting of the Pacific Dermatologic Association.

courtesy Dr. Roxana Daneshjou

Most of the respondents reported using LLMs for patient care (79%), followed by administrative tasks (74%), medical records (43%), and education (18%), “which can be problematic,” she said. “These models are not appropriate to use for patient care.”

When asked about their thoughts on the accuracy of LLMs, 58% of respondents deemed them to be “somewhat accurate” and 7% viewed them as “extremely accurate.”

The overall survey responses raise concern because LLMs “are not trained for accuracy; they are trained initially as a next-word predictor on large bodies of tech data,” Dr. Daneshjou said. “LLMs are already being implemented but have the potential to cause harm and bias, and I believe they will if we implement them the way things are rolling out right now. I don’t understand why we’re implementing something without any clinical trial or showing that it improves care before we throw untested technology into our healthcare system.”

Meanwhile, Epic and Microsoft are collaborating to bring AI technology to electronic health records, she said, and Epic is building more than 100 new AI features for physicians and patients. “I think it’s important for every physician and trainee to understand what is going on in the realm of AI,” said Dr. Daneshjou, who is an associate editor for the monthly journal NEJM AI. “Be involved in the conversation because we are the clinical experts, and a lot of people making decisions and building tools do not have the clinical expertise.”

To further illustrate her concerns, Dr. Daneshjou referenced a red teaming event she and her colleagues held with computer scientists, biomedical data scientists, engineers, and physicians across multiple specialties to identify issues related to safety, bias, factual errors, and/or security issues in GPT-3.5, GPT-4, and GPT-4 with internet. The goal was to mimic clinical health scenarios, ask the LLM to respond, and have the team members review the accuracy of LLM responses.

The participants found that nearly 20% of LLM responses were inappropriate. For example, in one task, an LLM was asked to calculate a RegiSCAR score for Drug Reaction With Eosinophilia and Systemic Symptoms for a patient, but the response included an incorrect score for eosinophilia. “That’s why these tools can be so dangerous because you’re reading along and everything seems right, but there might be something so minor that can impact patient care and you might miss it,” Dr. Daneshjou said.

On a related note, she advised against dermatologists uploading images into GPT-4 Vision, an LLM that can analyze images and provide textual responses to questions about them, and she recommends not using GPT-4 Vision for any diagnostic support. At this time, “GPT-4 Vision overcalls malignancies, and the specificity and sensitivity are not very good,” she explained.

Dr. Daneshjou disclosed that she has served as an adviser to MDalgorithms and Revea and has received consulting fees from Pfizer, L’Oréal, Frazier Healthcare Partners, and DWA and research funding from UCB.

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

HUNTINGTON BEACH, CALIF. — When Roxana Daneshjou, MD, PhD, began reviewing responses to an exploratory survey she and her colleagues created on dermatologists’ use of large language models (LLMs) such as ChatGPT in clinical practice, she was both surprised and alarmed.

Of the 134 respondents who completed the survey, 87 (65%) reported using LLMs in a clinical setting. Of those 87 respondents, 17 (20%) used LMMs daily, 28 (32%) weekly, 5 (6%) monthly, and 37 (43%) rarely. That represents “pretty significant usage,” Dr. Daneshjou, assistant professor of biomedical data science and dermatology at Stanford University, Palo Alto, California, said at the annual meeting of the Pacific Dermatologic Association.

courtesy Dr. Roxana Daneshjou

Most of the respondents reported using LLMs for patient care (79%), followed by administrative tasks (74%), medical records (43%), and education (18%), “which can be problematic,” she said. “These models are not appropriate to use for patient care.”

When asked about their thoughts on the accuracy of LLMs, 58% of respondents deemed them to be “somewhat accurate” and 7% viewed them as “extremely accurate.”

The overall survey responses raise concern because LLMs “are not trained for accuracy; they are trained initially as a next-word predictor on large bodies of tech data,” Dr. Daneshjou said. “LLMs are already being implemented but have the potential to cause harm and bias, and I believe they will if we implement them the way things are rolling out right now. I don’t understand why we’re implementing something without any clinical trial or showing that it improves care before we throw untested technology into our healthcare system.”

Meanwhile, Epic and Microsoft are collaborating to bring AI technology to electronic health records, she said, and Epic is building more than 100 new AI features for physicians and patients. “I think it’s important for every physician and trainee to understand what is going on in the realm of AI,” said Dr. Daneshjou, who is an associate editor for the monthly journal NEJM AI. “Be involved in the conversation because we are the clinical experts, and a lot of people making decisions and building tools do not have the clinical expertise.”

To further illustrate her concerns, Dr. Daneshjou referenced a red teaming event she and her colleagues held with computer scientists, biomedical data scientists, engineers, and physicians across multiple specialties to identify issues related to safety, bias, factual errors, and/or security issues in GPT-3.5, GPT-4, and GPT-4 with internet. The goal was to mimic clinical health scenarios, ask the LLM to respond, and have the team members review the accuracy of LLM responses.

The participants found that nearly 20% of LLM responses were inappropriate. For example, in one task, an LLM was asked to calculate a RegiSCAR score for Drug Reaction With Eosinophilia and Systemic Symptoms for a patient, but the response included an incorrect score for eosinophilia. “That’s why these tools can be so dangerous because you’re reading along and everything seems right, but there might be something so minor that can impact patient care and you might miss it,” Dr. Daneshjou said.

On a related note, she advised against dermatologists uploading images into GPT-4 Vision, an LLM that can analyze images and provide textual responses to questions about them, and she recommends not using GPT-4 Vision for any diagnostic support. At this time, “GPT-4 Vision overcalls malignancies, and the specificity and sensitivity are not very good,” she explained.

Dr. Daneshjou disclosed that she has served as an adviser to MDalgorithms and Revea and has received consulting fees from Pfizer, L’Oréal, Frazier Healthcare Partners, and DWA and research funding from UCB.

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

HUNTINGTON BEACH, CALIF. — When Roxana Daneshjou, MD, PhD, began reviewing responses to an exploratory survey she and her colleagues created on dermatologists’ use of large language models (LLMs) such as ChatGPT in clinical practice, she was both surprised and alarmed.

Of the 134 respondents who completed the survey, 87 (65%) reported using LLMs in a clinical setting. Of those 87 respondents, 17 (20%) used LMMs daily, 28 (32%) weekly, 5 (6%) monthly, and 37 (43%) rarely. That represents “pretty significant usage,” Dr. Daneshjou, assistant professor of biomedical data science and dermatology at Stanford University, Palo Alto, California, said at the annual meeting of the Pacific Dermatologic Association.

courtesy Dr. Roxana Daneshjou

Most of the respondents reported using LLMs for patient care (79%), followed by administrative tasks (74%), medical records (43%), and education (18%), “which can be problematic,” she said. “These models are not appropriate to use for patient care.”

When asked about their thoughts on the accuracy of LLMs, 58% of respondents deemed them to be “somewhat accurate” and 7% viewed them as “extremely accurate.”

The overall survey responses raise concern because LLMs “are not trained for accuracy; they are trained initially as a next-word predictor on large bodies of tech data,” Dr. Daneshjou said. “LLMs are already being implemented but have the potential to cause harm and bias, and I believe they will if we implement them the way things are rolling out right now. I don’t understand why we’re implementing something without any clinical trial or showing that it improves care before we throw untested technology into our healthcare system.”

Meanwhile, Epic and Microsoft are collaborating to bring AI technology to electronic health records, she said, and Epic is building more than 100 new AI features for physicians and patients. “I think it’s important for every physician and trainee to understand what is going on in the realm of AI,” said Dr. Daneshjou, who is an associate editor for the monthly journal NEJM AI. “Be involved in the conversation because we are the clinical experts, and a lot of people making decisions and building tools do not have the clinical expertise.”

To further illustrate her concerns, Dr. Daneshjou referenced a red teaming event she and her colleagues held with computer scientists, biomedical data scientists, engineers, and physicians across multiple specialties to identify issues related to safety, bias, factual errors, and/or security issues in GPT-3.5, GPT-4, and GPT-4 with internet. The goal was to mimic clinical health scenarios, ask the LLM to respond, and have the team members review the accuracy of LLM responses.

The participants found that nearly 20% of LLM responses were inappropriate. For example, in one task, an LLM was asked to calculate a RegiSCAR score for Drug Reaction With Eosinophilia and Systemic Symptoms for a patient, but the response included an incorrect score for eosinophilia. “That’s why these tools can be so dangerous because you’re reading along and everything seems right, but there might be something so minor that can impact patient care and you might miss it,” Dr. Daneshjou said.

On a related note, she advised against dermatologists uploading images into GPT-4 Vision, an LLM that can analyze images and provide textual responses to questions about them, and she recommends not using GPT-4 Vision for any diagnostic support. At this time, “GPT-4 Vision overcalls malignancies, and the specificity and sensitivity are not very good,” she explained.

Dr. Daneshjou disclosed that she has served as an adviser to MDalgorithms and Revea and has received consulting fees from Pfizer, L’Oréal, Frazier Healthcare Partners, and DWA and research funding from UCB.

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

CHICAGO — Use of CO₂ lasers and similar “energy-based” treatments result in little to no benefit for genitourinary syndrome of menopause (GSM) symptoms, according to research presented at the The Menopause Society 2024 Annual Meeting in Chicago on September 12.

“There was a concern that menopausal women are being targeted for treatments that may not have a lot of benefit and might have significant harms,” Elisheva Danan, MD, MPH, a physician at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, told this news organization. While she was not surprised to find little evidence of benefit, “we were a little bit surprised that we also didn’t find significant evidence of harms.”

The study was unable to evaluate the potential for financial harms, but Dr. Danan noted that these therapies are often expensive and not typically covered by insurance. The treatments appear to be used primarily in private practice, she said, while “most academic clinicians were not familiar with these and do not use these lasers.”

The American Urological Association had requested the review, Dr. Danan said, “to inform clinical guidelines that they could put out for practitioners about treating genital urinary syndrome from menopause.” Yet the evidence available remains slim. “There’s a lot of outcomes that were not looked at by most of these [trials], or they were looked at in a way that we couldn’t separate out,” she said.

Kamalini Das, MD, a professor of ob.gyn. at the University of Minnesota who was not involved in the research, was surprised by the findings because studies to date have been variable, “but since this looks at multiple studies and they find no benefits, I would take these results as more significant than any of the small studies,” she told this news organization.

Dr. Das said she has patients who ask about using these therapies and have had them done. “So far, I’ve told them the jury is out on whether it will help or not, that there are some studies that say they’re beneficial and some studies that they’re not,” Dr. Das said.

But this new review changes what she will tell patients going forward, she said. “This is a good study because it consolidates lots of little studies, so I think I would use this to say, looking at all the studies together, this treatment is not beneficial.”

GSM occurs due to the body’s reduced production of estrogen and affects anywhere from 27% to 84% of postmenopausal women. It can involve a constellation of symptoms ranging from vaginal discomfort and irritation to painful urination or intercourse. Typical recommended treatments for GSM include systemic hormone therapy, localized hormonal treatments such as vaginal estrogen or dehydroepiandrosterone, nonhormonal creams and moisturizers, and the prescription drug ospemifene.

Most of these have been found effective, according to a recent systematic review  Dr. Danan published in the Annals of Internal Medicine that this news organization covered. But recent years have also seen a rapid increase in interest and the availability of energy-based treatments for GSM, such as CO₂ laser and radiofrequency interventions, particularly for those who cannot or do not want to use hormonal treatments. The idea behind these newer therapies is that they “heat tissue to cause a denaturation of collagen fibers and induce a wound-healing response,” with the aim of “enhancement of vaginal elasticity, restoration of premenopausal epithelial function, and symptom improvement,” the authors wrote.

Evidence has been scant and uneven for the safety and effectiveness of these treatments, and they have not been evaluated by the US Food and Drug Administration. The agency issued a warning in 2018 with remarks from then Commissioner Scott Gottlieb that the “products have serious risks and don’t have adequate evidence to support their use for these purposes.”

Much of the evidence has focused on CO₂ lasers instead of other energy-based treatments, however, and a raft of new studies have been published on these interventions in the past 2 years. Dr. Danan and colleagues, therefore, assessed the most current state of the research with a systematic review of randomized controlled trials (RCTs) and prospective observational studies with control groups published through December 11, 2023.

Included studies needed to evaluate an energy-based treatment for at least 8 weeks in a minimum of 40 postmenopausal women (20 in each group) who had one or more GSM symptoms. The authors also included nonrandomized and uncontrolled studies with a follow-up of a year or more to assess possible adverse events. The studies also needed to assess at least one of eight core outcomes: Dyspareunia; vulvovaginal dryness; vulvovaginal discomfort/irritation; dysuria; change in most bothersome symptom; treatment satisfaction; adverse events; and distress, bother, or interference associated with genitourinary symptoms.

The authors identified 32 studies, including 16 RCTs, one quasi-RCT, and 15 nonrandomized studies. The researchers extracted and analyzed data from the 10 RCTs and one quasi-RCT that were rated as having low to moderate risk for bias.

Most of these studies assessed CO₂ lasers alone, while three assessed erbium:yttrium-aluminum-garnet (Er:YAG) laser, and one looked at CO₂ lasers vs radiofrequency treatments.

The average age of participants ranged from 56 to 64 years, and most trials were in the United States. Results showed that CO₂ lasers led to little or no difference in dysuria, dyspareunia, or quality of life when compared with sham lasers. The CO₂ laser therapy also showed little to no difference compared with vaginal estrogen creams for dyspareunia, dryness, discomfort/irritation, dysuria, or quality of life.

Most CO₂ laser studies reported on most outcomes, but the Er:YAG studies tended to report only on quality of life and/or one or two other outcomes. The radiofrequency study only assessed dyspareunia and quality of life.

“Treatment effects on other outcomes and effects of Er:YAG laser or radiofrequency on any outcomes are very uncertain,” the authors reported. Few adverse events and no serious adverse events were reported based on 15 studies, including the additional non-RCTs that had follow-up for at least a year.

“There are case reports and other types of studies that have shown some bad outcomes using laser therapies, and we really wanted to be expansive and include anything, especially because this is such a new treatment and all these trials were in the last couple of years,” Dr. Danan said. 

The review was limited by inconsistent or nonvalidated outcome reporting in the studies as well as small populations and short follow-up, typically less than 3 months.

The research was funded by the Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. Dr. Danan and Dr. Das had no disclosures.
 

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

CHICAGO — Use of CO₂ lasers and similar “energy-based” treatments result in little to no benefit for genitourinary syndrome of menopause (GSM) symptoms, according to research presented at the The Menopause Society 2024 Annual Meeting in Chicago on September 12.

“There was a concern that menopausal women are being targeted for treatments that may not have a lot of benefit and might have significant harms,” Elisheva Danan, MD, MPH, a physician at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, told this news organization. While she was not surprised to find little evidence of benefit, “we were a little bit surprised that we also didn’t find significant evidence of harms.”

The study was unable to evaluate the potential for financial harms, but Dr. Danan noted that these therapies are often expensive and not typically covered by insurance. The treatments appear to be used primarily in private practice, she said, while “most academic clinicians were not familiar with these and do not use these lasers.”

The American Urological Association had requested the review, Dr. Danan said, “to inform clinical guidelines that they could put out for practitioners about treating genital urinary syndrome from menopause.” Yet the evidence available remains slim. “There’s a lot of outcomes that were not looked at by most of these [trials], or they were looked at in a way that we couldn’t separate out,” she said.

Kamalini Das, MD, a professor of ob.gyn. at the University of Minnesota who was not involved in the research, was surprised by the findings because studies to date have been variable, “but since this looks at multiple studies and they find no benefits, I would take these results as more significant than any of the small studies,” she told this news organization.

Dr. Das said she has patients who ask about using these therapies and have had them done. “So far, I’ve told them the jury is out on whether it will help or not, that there are some studies that say they’re beneficial and some studies that they’re not,” Dr. Das said.

But this new review changes what she will tell patients going forward, she said. “This is a good study because it consolidates lots of little studies, so I think I would use this to say, looking at all the studies together, this treatment is not beneficial.”

GSM occurs due to the body’s reduced production of estrogen and affects anywhere from 27% to 84% of postmenopausal women. It can involve a constellation of symptoms ranging from vaginal discomfort and irritation to painful urination or intercourse. Typical recommended treatments for GSM include systemic hormone therapy, localized hormonal treatments such as vaginal estrogen or dehydroepiandrosterone, nonhormonal creams and moisturizers, and the prescription drug ospemifene.

Most of these have been found effective, according to a recent systematic review  Dr. Danan published in the Annals of Internal Medicine that this news organization covered. But recent years have also seen a rapid increase in interest and the availability of energy-based treatments for GSM, such as CO₂ laser and radiofrequency interventions, particularly for those who cannot or do not want to use hormonal treatments. The idea behind these newer therapies is that they “heat tissue to cause a denaturation of collagen fibers and induce a wound-healing response,” with the aim of “enhancement of vaginal elasticity, restoration of premenopausal epithelial function, and symptom improvement,” the authors wrote.

Evidence has been scant and uneven for the safety and effectiveness of these treatments, and they have not been evaluated by the US Food and Drug Administration. The agency issued a warning in 2018 with remarks from then Commissioner Scott Gottlieb that the “products have serious risks and don’t have adequate evidence to support their use for these purposes.”

Much of the evidence has focused on CO₂ lasers instead of other energy-based treatments, however, and a raft of new studies have been published on these interventions in the past 2 years. Dr. Danan and colleagues, therefore, assessed the most current state of the research with a systematic review of randomized controlled trials (RCTs) and prospective observational studies with control groups published through December 11, 2023.

Included studies needed to evaluate an energy-based treatment for at least 8 weeks in a minimum of 40 postmenopausal women (20 in each group) who had one or more GSM symptoms. The authors also included nonrandomized and uncontrolled studies with a follow-up of a year or more to assess possible adverse events. The studies also needed to assess at least one of eight core outcomes: Dyspareunia; vulvovaginal dryness; vulvovaginal discomfort/irritation; dysuria; change in most bothersome symptom; treatment satisfaction; adverse events; and distress, bother, or interference associated with genitourinary symptoms.

The authors identified 32 studies, including 16 RCTs, one quasi-RCT, and 15 nonrandomized studies. The researchers extracted and analyzed data from the 10 RCTs and one quasi-RCT that were rated as having low to moderate risk for bias.

Most of these studies assessed CO₂ lasers alone, while three assessed erbium:yttrium-aluminum-garnet (Er:YAG) laser, and one looked at CO₂ lasers vs radiofrequency treatments.

The average age of participants ranged from 56 to 64 years, and most trials were in the United States. Results showed that CO₂ lasers led to little or no difference in dysuria, dyspareunia, or quality of life when compared with sham lasers. The CO₂ laser therapy also showed little to no difference compared with vaginal estrogen creams for dyspareunia, dryness, discomfort/irritation, dysuria, or quality of life.

Most CO₂ laser studies reported on most outcomes, but the Er:YAG studies tended to report only on quality of life and/or one or two other outcomes. The radiofrequency study only assessed dyspareunia and quality of life.

“Treatment effects on other outcomes and effects of Er:YAG laser or radiofrequency on any outcomes are very uncertain,” the authors reported. Few adverse events and no serious adverse events were reported based on 15 studies, including the additional non-RCTs that had follow-up for at least a year.

“There are case reports and other types of studies that have shown some bad outcomes using laser therapies, and we really wanted to be expansive and include anything, especially because this is such a new treatment and all these trials were in the last couple of years,” Dr. Danan said. 

The review was limited by inconsistent or nonvalidated outcome reporting in the studies as well as small populations and short follow-up, typically less than 3 months.

The research was funded by the Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. Dr. Danan and Dr. Das had no disclosures.
 

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

CHICAGO — Use of CO₂ lasers and similar “energy-based” treatments result in little to no benefit for genitourinary syndrome of menopause (GSM) symptoms, according to research presented at the The Menopause Society 2024 Annual Meeting in Chicago on September 12.

“There was a concern that menopausal women are being targeted for treatments that may not have a lot of benefit and might have significant harms,” Elisheva Danan, MD, MPH, a physician at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, told this news organization. While she was not surprised to find little evidence of benefit, “we were a little bit surprised that we also didn’t find significant evidence of harms.”

The study was unable to evaluate the potential for financial harms, but Dr. Danan noted that these therapies are often expensive and not typically covered by insurance. The treatments appear to be used primarily in private practice, she said, while “most academic clinicians were not familiar with these and do not use these lasers.”

The American Urological Association had requested the review, Dr. Danan said, “to inform clinical guidelines that they could put out for practitioners about treating genital urinary syndrome from menopause.” Yet the evidence available remains slim. “There’s a lot of outcomes that were not looked at by most of these [trials], or they were looked at in a way that we couldn’t separate out,” she said.

Kamalini Das, MD, a professor of ob.gyn. at the University of Minnesota who was not involved in the research, was surprised by the findings because studies to date have been variable, “but since this looks at multiple studies and they find no benefits, I would take these results as more significant than any of the small studies,” she told this news organization.

Dr. Das said she has patients who ask about using these therapies and have had them done. “So far, I’ve told them the jury is out on whether it will help or not, that there are some studies that say they’re beneficial and some studies that they’re not,” Dr. Das said.

But this new review changes what she will tell patients going forward, she said. “This is a good study because it consolidates lots of little studies, so I think I would use this to say, looking at all the studies together, this treatment is not beneficial.”

GSM occurs due to the body’s reduced production of estrogen and affects anywhere from 27% to 84% of postmenopausal women. It can involve a constellation of symptoms ranging from vaginal discomfort and irritation to painful urination or intercourse. Typical recommended treatments for GSM include systemic hormone therapy, localized hormonal treatments such as vaginal estrogen or dehydroepiandrosterone, nonhormonal creams and moisturizers, and the prescription drug ospemifene.

Most of these have been found effective, according to a recent systematic review  Dr. Danan published in the Annals of Internal Medicine that this news organization covered. But recent years have also seen a rapid increase in interest and the availability of energy-based treatments for GSM, such as CO₂ laser and radiofrequency interventions, particularly for those who cannot or do not want to use hormonal treatments. The idea behind these newer therapies is that they “heat tissue to cause a denaturation of collagen fibers and induce a wound-healing response,” with the aim of “enhancement of vaginal elasticity, restoration of premenopausal epithelial function, and symptom improvement,” the authors wrote.

Evidence has been scant and uneven for the safety and effectiveness of these treatments, and they have not been evaluated by the US Food and Drug Administration. The agency issued a warning in 2018 with remarks from then Commissioner Scott Gottlieb that the “products have serious risks and don’t have adequate evidence to support their use for these purposes.”

Much of the evidence has focused on CO₂ lasers instead of other energy-based treatments, however, and a raft of new studies have been published on these interventions in the past 2 years. Dr. Danan and colleagues, therefore, assessed the most current state of the research with a systematic review of randomized controlled trials (RCTs) and prospective observational studies with control groups published through December 11, 2023.

Included studies needed to evaluate an energy-based treatment for at least 8 weeks in a minimum of 40 postmenopausal women (20 in each group) who had one or more GSM symptoms. The authors also included nonrandomized and uncontrolled studies with a follow-up of a year or more to assess possible adverse events. The studies also needed to assess at least one of eight core outcomes: Dyspareunia; vulvovaginal dryness; vulvovaginal discomfort/irritation; dysuria; change in most bothersome symptom; treatment satisfaction; adverse events; and distress, bother, or interference associated with genitourinary symptoms.

The authors identified 32 studies, including 16 RCTs, one quasi-RCT, and 15 nonrandomized studies. The researchers extracted and analyzed data from the 10 RCTs and one quasi-RCT that were rated as having low to moderate risk for bias.

Most of these studies assessed CO₂ lasers alone, while three assessed erbium:yttrium-aluminum-garnet (Er:YAG) laser, and one looked at CO₂ lasers vs radiofrequency treatments.

The average age of participants ranged from 56 to 64 years, and most trials were in the United States. Results showed that CO₂ lasers led to little or no difference in dysuria, dyspareunia, or quality of life when compared with sham lasers. The CO₂ laser therapy also showed little to no difference compared with vaginal estrogen creams for dyspareunia, dryness, discomfort/irritation, dysuria, or quality of life.

Most CO₂ laser studies reported on most outcomes, but the Er:YAG studies tended to report only on quality of life and/or one or two other outcomes. The radiofrequency study only assessed dyspareunia and quality of life.

“Treatment effects on other outcomes and effects of Er:YAG laser or radiofrequency on any outcomes are very uncertain,” the authors reported. Few adverse events and no serious adverse events were reported based on 15 studies, including the additional non-RCTs that had follow-up for at least a year.

“There are case reports and other types of studies that have shown some bad outcomes using laser therapies, and we really wanted to be expansive and include anything, especially because this is such a new treatment and all these trials were in the last couple of years,” Dr. Danan said. 

The review was limited by inconsistent or nonvalidated outcome reporting in the studies as well as small populations and short follow-up, typically less than 3 months.

The research was funded by the Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. Dr. Danan and Dr. Das had no disclosures.
 

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