MDedge Dermatology

To the Editor:

Immune checkpoint inhibitors have revolutionized the treatment of advanced-stage melanoma, with remarkably improved progression-free survival.¹ Anti–programmed death receptor 1 (anti–PD-1) therapies, such as nivolumab and pembrolizumab, are a class of checkpoint inhibitors that have been approved by the US Food and Drug Administration for unresectable metastatic melanoma. Anti–PD-1 agents block the interaction of programmed death-ligand 1 (PD-L1) found on tumor cells with the PD-1 receptor on T cells, facilitating a positive immune response.²

Although these therapies have demonstrated notable antitumor efficacy, they also give rise to numerous immune-related adverse events (irAEs). As many as 70% of patients treated with PD-1/PD-L1 inhibitors experience some type of organ system irAE, of which 30% to 40% are cutaneous.^3-6 Dermatologic adverse events are the most common irAEs, specifically spongiotic dermatitis, lichenoid dermatitis, pruritus, and vitiligo.⁷ Bullous pemphigoid (BP), an autoimmune bullous skin disorder caused by autoantibodies to basement membrane zone antigens, is a rare but potentially serious cutaneous irAE.⁸ Systemic corticosteroids commonly are used to treat immune checkpoint inhibitor–induced BP; other options include tetracyclines for maintenance therapy and rituximab for corticosteroid-refractory BP associated with anti-PD-1.⁹ We present a case of recalcitrant BP secondary to nivolumab therapy in a patient with metastatic melanoma who had near-complete resolution of BP following 2 months of cyclosporine.

A 41-year-old man presented with a generalized papular skin eruption of 1 month’s duration. He had a history of stage IIIC malignant melanoma of the lower right leg with positive sentinel lymph node biopsy. The largest lymph node deposit was 0.03 mm without extracapsular extension. Whole-body positron emission tomography–computed tomography showed no evidence of distant disease. The patient was treated with wide local excision with clear surgical margins plus 12 cycles of nivolumab, which was discontinued due to colitis. Four months after the final cycle of nivolumab, the patient developed widespread erythematous papules with hemorrhagic yellow crusting and no mucosal involvement. He was referred to dermatology by his primary oncologist for further evaluation.

A punch biopsy from the abdomen showed para­keratosis with leukocytoclasis and a superficial dermal infiltrate of neutrophils and eosinophils (Figure 1). Direct immunofluorescence revealed linear basement membrane deposits of IgG and C3, consistent with subepidermal blistering disease. Indirect immunofluorescence demonstrated trace IgG and IgG4 antibodies localized to the epidermal roof of salt-split skin and was negative for IgA antibodies. An enzyme-linked immunoassay was positive for BP antigen 2 (BP180) antibodies (98.4 U/mL [positive, ≥9 U/mL]) and negative for BP antigen 1 (BP230) antibodies (4.3 U/mL [positive, ≥9 U/mL]). Overall, these findings were consistent with a diagnosis of BP.

The patient was treated with prednisone 60 mg daily with initial response; however, there was disease recurrence with tapering. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily were added as steroid-sparing agents, as prednisone was discontinued due to mood changes. Three months after the prednisone taper, the patient continued to develop new blisters. He completed treatment with doxycycline and nicotinamide. Rituximab 375 mg weekly was then initiated for 4 weeks.

At 2-week follow-up after completing the rituximab course, the patient reported worsening symptoms and presented with new bullae on the abdomen and upper extremities (Figure 2). Because of the recent history of mood changes while taking prednisone, a trial of cyclosporine 100 mg twice daily (1.37 mg/kg/d) was initiated, with notable improvement within 2 weeks of treatment. After 2 months of cyclosporine, approximately 90% of the rash had resolved with a few tense bullae remaining on the left frontal scalp but no new flares (Figure 3). One month after treatment ended, the patient remained clear of lesions without relapse.

Programmed death receptor 1 inhibitors have shown dramatic efficacy for a growing number of solid and hematologic malignancies, especially malignant melanoma. However, their use is accompanied by nonspecific activation of the immune system, resulting in a variety of adverse events, many manifesting on the skin. Several cases of BP in patients treated with PD-1/PD-L1 inhibitors have been reported.⁹ Cutaneous irAEs usually manifest within 3 weeks of initiation of PD-1 inhibitor therapy; however, the onset of BP typically occurs later at approximately 21 weeks.^4,9 Our patient developed cutaneous manifestations 4 months after cessation of nivolumab.

To the Editor:

Immune checkpoint inhibitors have revolutionized the treatment of advanced-stage melanoma, with remarkably improved progression-free survival.¹ Anti–programmed death receptor 1 (anti–PD-1) therapies, such as nivolumab and pembrolizumab, are a class of checkpoint inhibitors that have been approved by the US Food and Drug Administration for unresectable metastatic melanoma. Anti–PD-1 agents block the interaction of programmed death-ligand 1 (PD-L1) found on tumor cells with the PD-1 receptor on T cells, facilitating a positive immune response.²

Although these therapies have demonstrated notable antitumor efficacy, they also give rise to numerous immune-related adverse events (irAEs). As many as 70% of patients treated with PD-1/PD-L1 inhibitors experience some type of organ system irAE, of which 30% to 40% are cutaneous.^3-6 Dermatologic adverse events are the most common irAEs, specifically spongiotic dermatitis, lichenoid dermatitis, pruritus, and vitiligo.⁷ Bullous pemphigoid (BP), an autoimmune bullous skin disorder caused by autoantibodies to basement membrane zone antigens, is a rare but potentially serious cutaneous irAE.⁸ Systemic corticosteroids commonly are used to treat immune checkpoint inhibitor–induced BP; other options include tetracyclines for maintenance therapy and rituximab for corticosteroid-refractory BP associated with anti-PD-1.⁹ We present a case of recalcitrant BP secondary to nivolumab therapy in a patient with metastatic melanoma who had near-complete resolution of BP following 2 months of cyclosporine.

A 41-year-old man presented with a generalized papular skin eruption of 1 month’s duration. He had a history of stage IIIC malignant melanoma of the lower right leg with positive sentinel lymph node biopsy. The largest lymph node deposit was 0.03 mm without extracapsular extension. Whole-body positron emission tomography–computed tomography showed no evidence of distant disease. The patient was treated with wide local excision with clear surgical margins plus 12 cycles of nivolumab, which was discontinued due to colitis. Four months after the final cycle of nivolumab, the patient developed widespread erythematous papules with hemorrhagic yellow crusting and no mucosal involvement. He was referred to dermatology by his primary oncologist for further evaluation.

A punch biopsy from the abdomen showed para­keratosis with leukocytoclasis and a superficial dermal infiltrate of neutrophils and eosinophils (Figure 1). Direct immunofluorescence revealed linear basement membrane deposits of IgG and C3, consistent with subepidermal blistering disease. Indirect immunofluorescence demonstrated trace IgG and IgG4 antibodies localized to the epidermal roof of salt-split skin and was negative for IgA antibodies. An enzyme-linked immunoassay was positive for BP antigen 2 (BP180) antibodies (98.4 U/mL [positive, ≥9 U/mL]) and negative for BP antigen 1 (BP230) antibodies (4.3 U/mL [positive, ≥9 U/mL]). Overall, these findings were consistent with a diagnosis of BP.

The patient was treated with prednisone 60 mg daily with initial response; however, there was disease recurrence with tapering. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily were added as steroid-sparing agents, as prednisone was discontinued due to mood changes. Three months after the prednisone taper, the patient continued to develop new blisters. He completed treatment with doxycycline and nicotinamide. Rituximab 375 mg weekly was then initiated for 4 weeks.

At 2-week follow-up after completing the rituximab course, the patient reported worsening symptoms and presented with new bullae on the abdomen and upper extremities (Figure 2). Because of the recent history of mood changes while taking prednisone, a trial of cyclosporine 100 mg twice daily (1.37 mg/kg/d) was initiated, with notable improvement within 2 weeks of treatment. After 2 months of cyclosporine, approximately 90% of the rash had resolved with a few tense bullae remaining on the left frontal scalp but no new flares (Figure 3). One month after treatment ended, the patient remained clear of lesions without relapse.

Programmed death receptor 1 inhibitors have shown dramatic efficacy for a growing number of solid and hematologic malignancies, especially malignant melanoma. However, their use is accompanied by nonspecific activation of the immune system, resulting in a variety of adverse events, many manifesting on the skin. Several cases of BP in patients treated with PD-1/PD-L1 inhibitors have been reported.⁹ Cutaneous irAEs usually manifest within 3 weeks of initiation of PD-1 inhibitor therapy; however, the onset of BP typically occurs later at approximately 21 weeks.^4,9 Our patient developed cutaneous manifestations 4 months after cessation of nivolumab.

To the Editor:

Immune checkpoint inhibitors have revolutionized the treatment of advanced-stage melanoma, with remarkably improved progression-free survival.¹ Anti–programmed death receptor 1 (anti–PD-1) therapies, such as nivolumab and pembrolizumab, are a class of checkpoint inhibitors that have been approved by the US Food and Drug Administration for unresectable metastatic melanoma. Anti–PD-1 agents block the interaction of programmed death-ligand 1 (PD-L1) found on tumor cells with the PD-1 receptor on T cells, facilitating a positive immune response.²

Although these therapies have demonstrated notable antitumor efficacy, they also give rise to numerous immune-related adverse events (irAEs). As many as 70% of patients treated with PD-1/PD-L1 inhibitors experience some type of organ system irAE, of which 30% to 40% are cutaneous.^3-6 Dermatologic adverse events are the most common irAEs, specifically spongiotic dermatitis, lichenoid dermatitis, pruritus, and vitiligo.⁷ Bullous pemphigoid (BP), an autoimmune bullous skin disorder caused by autoantibodies to basement membrane zone antigens, is a rare but potentially serious cutaneous irAE.⁸ Systemic corticosteroids commonly are used to treat immune checkpoint inhibitor–induced BP; other options include tetracyclines for maintenance therapy and rituximab for corticosteroid-refractory BP associated with anti-PD-1.⁹ We present a case of recalcitrant BP secondary to nivolumab therapy in a patient with metastatic melanoma who had near-complete resolution of BP following 2 months of cyclosporine.

A 41-year-old man presented with a generalized papular skin eruption of 1 month’s duration. He had a history of stage IIIC malignant melanoma of the lower right leg with positive sentinel lymph node biopsy. The largest lymph node deposit was 0.03 mm without extracapsular extension. Whole-body positron emission tomography–computed tomography showed no evidence of distant disease. The patient was treated with wide local excision with clear surgical margins plus 12 cycles of nivolumab, which was discontinued due to colitis. Four months after the final cycle of nivolumab, the patient developed widespread erythematous papules with hemorrhagic yellow crusting and no mucosal involvement. He was referred to dermatology by his primary oncologist for further evaluation.

A punch biopsy from the abdomen showed para­keratosis with leukocytoclasis and a superficial dermal infiltrate of neutrophils and eosinophils (Figure 1). Direct immunofluorescence revealed linear basement membrane deposits of IgG and C3, consistent with subepidermal blistering disease. Indirect immunofluorescence demonstrated trace IgG and IgG4 antibodies localized to the epidermal roof of salt-split skin and was negative for IgA antibodies. An enzyme-linked immunoassay was positive for BP antigen 2 (BP180) antibodies (98.4 U/mL [positive, ≥9 U/mL]) and negative for BP antigen 1 (BP230) antibodies (4.3 U/mL [positive, ≥9 U/mL]). Overall, these findings were consistent with a diagnosis of BP.

The patient was treated with prednisone 60 mg daily with initial response; however, there was disease recurrence with tapering. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily were added as steroid-sparing agents, as prednisone was discontinued due to mood changes. Three months after the prednisone taper, the patient continued to develop new blisters. He completed treatment with doxycycline and nicotinamide. Rituximab 375 mg weekly was then initiated for 4 weeks.

At 2-week follow-up after completing the rituximab course, the patient reported worsening symptoms and presented with new bullae on the abdomen and upper extremities (Figure 2). Because of the recent history of mood changes while taking prednisone, a trial of cyclosporine 100 mg twice daily (1.37 mg/kg/d) was initiated, with notable improvement within 2 weeks of treatment. After 2 months of cyclosporine, approximately 90% of the rash had resolved with a few tense bullae remaining on the left frontal scalp but no new flares (Figure 3). One month after treatment ended, the patient remained clear of lesions without relapse.

Programmed death receptor 1 inhibitors have shown dramatic efficacy for a growing number of solid and hematologic malignancies, especially malignant melanoma. However, their use is accompanied by nonspecific activation of the immune system, resulting in a variety of adverse events, many manifesting on the skin. Several cases of BP in patients treated with PD-1/PD-L1 inhibitors have been reported.⁹ Cutaneous irAEs usually manifest within 3 weeks of initiation of PD-1 inhibitor therapy; however, the onset of BP typically occurs later at approximately 21 weeks.^4,9 Our patient developed cutaneous manifestations 4 months after cessation of nivolumab.

Lifetime skin cancer prevalence in sexual minority (SM) Americans varied by race, ethnicity, and individual sexual identity, compared with that in heterosexual peers, according to a large cross-sectional study. Addressing dynamics of each SM subgroup will require increasingly tailored prevention, screening, and research efforts, the study authors said.

“We identified specific subgroups within the sexual minority community who are at higher risk for skin cancer, specifically White gay males and Hispanic and non-Hispanic Black SM men and women — particularly individuals who identify as bisexual,” senior author Matthew Mansh, MD, said in an interview. He is an assistant professor of dermatology at the University of California, San Francisco. The study was published online in JAMA Dermatology.

Using data of adults in the US general population from the Behavioral Risk Factor Surveillance System from January 2014 to December 2021, investigators included more than 1.5 million respondents. The proportions of SM women and men (who self-identified as bisexual, lesbian, gay, “something else,” or other) were 2.6% and 2.0%, respectively.

Lifetime skin cancer prevalence was higher among SM men than among heterosexual men (7.4% vs 6.8%; adjusted odds ratio [aOR], 1.16). In analyses stratified by racial and ethnic group, AORs for non-Hispanic Black and Hispanic SM men vs their heterosexual counterparts were 2.18 and 3.81, respectively. The corresponding figures for non-Hispanic Black and Hispanic SM women were 2.33 and 2.46, respectively.

When investigators combined all minority respondents along gender lines, lifetime skin cancer prevalence was higher in bisexual men (aOR, 3.94), bisexual women (aOR, 1.51), and women identifying as something else or other (aOR, 2.70) than in their heterosexual peers.

“I wasn’t expecting that Hispanic or non-Hispanic Black SMs would be at higher risk for skin cancer,” Dr. Mansh said. Even if these groups have more behavioral risk factors for UV radiation (UVR) exposure, he explained, UVR exposure is less strongly linked with skin cancer in darker skin than in lighter skin. Reasons for the counterintuitive finding could include different screening habits among SM people of different racial and ethnic groups, he said, and analyzing such factors will require further research.

Although some effect sizes were modest, the authors wrote, their findings may have important implications for population-based research and public health efforts aimed at early skin cancer detection and prevention. Presently, the United States lacks established guidelines for skin cancer screening. In a 2023 statement published in JAMA, the US Preventive Services Task Force said that there is insufficient evidence to determine the benefit-harm balance of skin cancer screening in asymptomatic people.

“So there has been a lot of recent talk and a need to identify which subset groups of patients might be higher risk for skin cancer and might benefit from more screening,” Dr. Mansh said in an interview. “Understanding more about the high-risk demographic and clinical features that predispose someone to skin cancer helps identify these high-risk populations that could be used to develop better screening guidelines.”

Identifying groups at a higher risk for skin cancer also allows experts to design more targeted counseling or public health interventions focused on these groups, Dr. Mansh added. Absent screening guidelines, experts emphasize changing modifiable risk factors such as UVR exposure, smoking, and alcohol use. “And we know that the message that might change behaviors in a cisgender heterosexual man might be different than in a gay White male or a Hispanic bisexual male.”

A 2017 review showed that interventions to reduce behaviors involving UVR exposure, such as indoor tanning, among young cisgender women focused largely on aging and appearance-based concerns. A 2019 study showed that messages focused on avoiding skin cancer may help motivate SM men to reduce tanning behaviors.

Furthermore, said Dr. Mansh, all electronic health record products available in the United States must provide data fields for sexual orientation. “I don’t believe many dermatologists, depending on the setting, collect that information routinely. Integrating sexual orientation and/or gender identity data into patient intake forms so that it can be integrated into the electronic health record is probably very helpful, not only for your clinical practice but also for future research studies.”

Asked to comment on the results, Rebecca I. Hartman, MD, MPH, who was not involved with the study, said that its impact on clinical practice will be challenging to ascertain. She is chief of dermatology with the VA Boston Healthcare System, assistant professor of dermatology at Harvard Medical School, and director of melanoma epidemiology at Brigham and Women’s Hospital, all in Boston, Massachusetts.

“The study found significant adjusted odds ratios,” Dr. Hartman explained, “but for some of the different populations, the overall lifetime rate of skin cancer is still quite low.” For example, 1.0% for SM non-Hispanic Black men or a difference of 2.1% vs 1.8% in SM Hispanic women. “Thus, I am not sure specific screening recommendations are warranted, although some populations, such as Hispanic sexual minority males, seemed to have a much higher risk (3.8-fold on adjusted analysis) that warrants further investigation.”

For now, she advised assessing patients’ risks for skin cancer based on well-established risk factors such as sun exposure/indoor tanning, skin phototype, immunosuppression, and age.

Dr. Mansh reported no relevant conflicts or funding sources for the study. Dr. Hartman reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Lifetime skin cancer prevalence in sexual minority (SM) Americans varied by race, ethnicity, and individual sexual identity, compared with that in heterosexual peers, according to a large cross-sectional study. Addressing dynamics of each SM subgroup will require increasingly tailored prevention, screening, and research efforts, the study authors said.

“We identified specific subgroups within the sexual minority community who are at higher risk for skin cancer, specifically White gay males and Hispanic and non-Hispanic Black SM men and women — particularly individuals who identify as bisexual,” senior author Matthew Mansh, MD, said in an interview. He is an assistant professor of dermatology at the University of California, San Francisco. The study was published online in JAMA Dermatology.

Using data of adults in the US general population from the Behavioral Risk Factor Surveillance System from January 2014 to December 2021, investigators included more than 1.5 million respondents. The proportions of SM women and men (who self-identified as bisexual, lesbian, gay, “something else,” or other) were 2.6% and 2.0%, respectively.

Lifetime skin cancer prevalence was higher among SM men than among heterosexual men (7.4% vs 6.8%; adjusted odds ratio [aOR], 1.16). In analyses stratified by racial and ethnic group, AORs for non-Hispanic Black and Hispanic SM men vs their heterosexual counterparts were 2.18 and 3.81, respectively. The corresponding figures for non-Hispanic Black and Hispanic SM women were 2.33 and 2.46, respectively.

When investigators combined all minority respondents along gender lines, lifetime skin cancer prevalence was higher in bisexual men (aOR, 3.94), bisexual women (aOR, 1.51), and women identifying as something else or other (aOR, 2.70) than in their heterosexual peers.

“I wasn’t expecting that Hispanic or non-Hispanic Black SMs would be at higher risk for skin cancer,” Dr. Mansh said. Even if these groups have more behavioral risk factors for UV radiation (UVR) exposure, he explained, UVR exposure is less strongly linked with skin cancer in darker skin than in lighter skin. Reasons for the counterintuitive finding could include different screening habits among SM people of different racial and ethnic groups, he said, and analyzing such factors will require further research.

Although some effect sizes were modest, the authors wrote, their findings may have important implications for population-based research and public health efforts aimed at early skin cancer detection and prevention. Presently, the United States lacks established guidelines for skin cancer screening. In a 2023 statement published in JAMA, the US Preventive Services Task Force said that there is insufficient evidence to determine the benefit-harm balance of skin cancer screening in asymptomatic people.

“So there has been a lot of recent talk and a need to identify which subset groups of patients might be higher risk for skin cancer and might benefit from more screening,” Dr. Mansh said in an interview. “Understanding more about the high-risk demographic and clinical features that predispose someone to skin cancer helps identify these high-risk populations that could be used to develop better screening guidelines.”

Identifying groups at a higher risk for skin cancer also allows experts to design more targeted counseling or public health interventions focused on these groups, Dr. Mansh added. Absent screening guidelines, experts emphasize changing modifiable risk factors such as UVR exposure, smoking, and alcohol use. “And we know that the message that might change behaviors in a cisgender heterosexual man might be different than in a gay White male or a Hispanic bisexual male.”

A 2017 review showed that interventions to reduce behaviors involving UVR exposure, such as indoor tanning, among young cisgender women focused largely on aging and appearance-based concerns. A 2019 study showed that messages focused on avoiding skin cancer may help motivate SM men to reduce tanning behaviors.

Furthermore, said Dr. Mansh, all electronic health record products available in the United States must provide data fields for sexual orientation. “I don’t believe many dermatologists, depending on the setting, collect that information routinely. Integrating sexual orientation and/or gender identity data into patient intake forms so that it can be integrated into the electronic health record is probably very helpful, not only for your clinical practice but also for future research studies.”

Asked to comment on the results, Rebecca I. Hartman, MD, MPH, who was not involved with the study, said that its impact on clinical practice will be challenging to ascertain. She is chief of dermatology with the VA Boston Healthcare System, assistant professor of dermatology at Harvard Medical School, and director of melanoma epidemiology at Brigham and Women’s Hospital, all in Boston, Massachusetts.

“The study found significant adjusted odds ratios,” Dr. Hartman explained, “but for some of the different populations, the overall lifetime rate of skin cancer is still quite low.” For example, 1.0% for SM non-Hispanic Black men or a difference of 2.1% vs 1.8% in SM Hispanic women. “Thus, I am not sure specific screening recommendations are warranted, although some populations, such as Hispanic sexual minority males, seemed to have a much higher risk (3.8-fold on adjusted analysis) that warrants further investigation.”

For now, she advised assessing patients’ risks for skin cancer based on well-established risk factors such as sun exposure/indoor tanning, skin phototype, immunosuppression, and age.

Dr. Mansh reported no relevant conflicts or funding sources for the study. Dr. Hartman reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Lifetime skin cancer prevalence in sexual minority (SM) Americans varied by race, ethnicity, and individual sexual identity, compared with that in heterosexual peers, according to a large cross-sectional study. Addressing dynamics of each SM subgroup will require increasingly tailored prevention, screening, and research efforts, the study authors said.

“We identified specific subgroups within the sexual minority community who are at higher risk for skin cancer, specifically White gay males and Hispanic and non-Hispanic Black SM men and women — particularly individuals who identify as bisexual,” senior author Matthew Mansh, MD, said in an interview. He is an assistant professor of dermatology at the University of California, San Francisco. The study was published online in JAMA Dermatology.

Using data of adults in the US general population from the Behavioral Risk Factor Surveillance System from January 2014 to December 2021, investigators included more than 1.5 million respondents. The proportions of SM women and men (who self-identified as bisexual, lesbian, gay, “something else,” or other) were 2.6% and 2.0%, respectively.

Lifetime skin cancer prevalence was higher among SM men than among heterosexual men (7.4% vs 6.8%; adjusted odds ratio [aOR], 1.16). In analyses stratified by racial and ethnic group, AORs for non-Hispanic Black and Hispanic SM men vs their heterosexual counterparts were 2.18 and 3.81, respectively. The corresponding figures for non-Hispanic Black and Hispanic SM women were 2.33 and 2.46, respectively.

When investigators combined all minority respondents along gender lines, lifetime skin cancer prevalence was higher in bisexual men (aOR, 3.94), bisexual women (aOR, 1.51), and women identifying as something else or other (aOR, 2.70) than in their heterosexual peers.

“I wasn’t expecting that Hispanic or non-Hispanic Black SMs would be at higher risk for skin cancer,” Dr. Mansh said. Even if these groups have more behavioral risk factors for UV radiation (UVR) exposure, he explained, UVR exposure is less strongly linked with skin cancer in darker skin than in lighter skin. Reasons for the counterintuitive finding could include different screening habits among SM people of different racial and ethnic groups, he said, and analyzing such factors will require further research.

Although some effect sizes were modest, the authors wrote, their findings may have important implications for population-based research and public health efforts aimed at early skin cancer detection and prevention. Presently, the United States lacks established guidelines for skin cancer screening. In a 2023 statement published in JAMA, the US Preventive Services Task Force said that there is insufficient evidence to determine the benefit-harm balance of skin cancer screening in asymptomatic people.

“So there has been a lot of recent talk and a need to identify which subset groups of patients might be higher risk for skin cancer and might benefit from more screening,” Dr. Mansh said in an interview. “Understanding more about the high-risk demographic and clinical features that predispose someone to skin cancer helps identify these high-risk populations that could be used to develop better screening guidelines.”

Identifying groups at a higher risk for skin cancer also allows experts to design more targeted counseling or public health interventions focused on these groups, Dr. Mansh added. Absent screening guidelines, experts emphasize changing modifiable risk factors such as UVR exposure, smoking, and alcohol use. “And we know that the message that might change behaviors in a cisgender heterosexual man might be different than in a gay White male or a Hispanic bisexual male.”

A 2017 review showed that interventions to reduce behaviors involving UVR exposure, such as indoor tanning, among young cisgender women focused largely on aging and appearance-based concerns. A 2019 study showed that messages focused on avoiding skin cancer may help motivate SM men to reduce tanning behaviors.

Furthermore, said Dr. Mansh, all electronic health record products available in the United States must provide data fields for sexual orientation. “I don’t believe many dermatologists, depending on the setting, collect that information routinely. Integrating sexual orientation and/or gender identity data into patient intake forms so that it can be integrated into the electronic health record is probably very helpful, not only for your clinical practice but also for future research studies.”

Asked to comment on the results, Rebecca I. Hartman, MD, MPH, who was not involved with the study, said that its impact on clinical practice will be challenging to ascertain. She is chief of dermatology with the VA Boston Healthcare System, assistant professor of dermatology at Harvard Medical School, and director of melanoma epidemiology at Brigham and Women’s Hospital, all in Boston, Massachusetts.

“The study found significant adjusted odds ratios,” Dr. Hartman explained, “but for some of the different populations, the overall lifetime rate of skin cancer is still quite low.” For example, 1.0% for SM non-Hispanic Black men or a difference of 2.1% vs 1.8% in SM Hispanic women. “Thus, I am not sure specific screening recommendations are warranted, although some populations, such as Hispanic sexual minority males, seemed to have a much higher risk (3.8-fold on adjusted analysis) that warrants further investigation.”

For now, she advised assessing patients’ risks for skin cancer based on well-established risk factors such as sun exposure/indoor tanning, skin phototype, immunosuppression, and age.

Dr. Mansh reported no relevant conflicts or funding sources for the study. Dr. Hartman reported no relevant conflicts.

A version of this article appeared on Medscape.com.

TOPLINE:

Intercurrent infections are associated with an increased risk for systemic lupus erythematosus (SLE) flares within 3 months, with major infections associated with a 7.4 times higher risk for major flares.

METHODOLOGY:

• The researchers prospectively examined the association between intercurrent infections and subsequent SLE flares in 203 patients (median age, 40 years; 91% women) with SLE from the Amsterdam SLE cohort study.
• SLE flares were defined as an increase in disease activity combined with an intensification of immunosuppressive therapy. They were categorized into minor and major flares according to the severity and required treatment.
• Major infections were defined as those requiring hospital admission or intravenous antibiotic therapy, while minor infections did not require hospital admission.
• The risk interval for the occurrence of a disease flare was defined as 3 months from the index date of an infection.
• Patients were followed for a median duration of 6 years.

TAKEAWAY:

• The incidence of major and minor infections was 5.3 (95% CI, 4.1-6.9) and 63.9 per 100 patient-years (95% CI, 59.3-69.0), respectively.
• Intercurrent infections were associated with a 1.9 times higher risk for SLE flares within 3 months (95% CI, 1.3-2.9).
• Intercurrent infections were significantly associated with minor SLE flares (hazard ratio, 1.9; 95% CI, 1.2-3.0) but not with major flares.
• Major infections were linked to a 7.4 times higher risk for major SLE flares within 3 months (95% CI, 2.2-24.6).

IN PRACTICE:

“This finding stresses the importance of awareness and strict monitoring of disease activity in patients with SLE suffering a major infection and prompt adequate treatment in case of the development of a disease flare,” the authors wrote.

SOURCE:

The study was led by Fatma el Hadiyen, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center in the Netherlands. It was published online on July 1, 2024, in Lupus Science & Medicine.

LIMITATIONS:

The reliance on patient recall for minor infections may have introduced recall bias. The small number of patients with identified causative organisms limited the generalizability of the findings. The Bootsma criteria were used for defining SLE flares, which may not align with more recent international standards.

DISCLOSURES:

No specific funding source was reported. One author reported receiving personal fees from various pharmaceutical companies outside the submitted work.

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:

Intercurrent infections are associated with an increased risk for systemic lupus erythematosus (SLE) flares within 3 months, with major infections associated with a 7.4 times higher risk for major flares.

METHODOLOGY:

• The researchers prospectively examined the association between intercurrent infections and subsequent SLE flares in 203 patients (median age, 40 years; 91% women) with SLE from the Amsterdam SLE cohort study.
• SLE flares were defined as an increase in disease activity combined with an intensification of immunosuppressive therapy. They were categorized into minor and major flares according to the severity and required treatment.
• Major infections were defined as those requiring hospital admission or intravenous antibiotic therapy, while minor infections did not require hospital admission.
• The risk interval for the occurrence of a disease flare was defined as 3 months from the index date of an infection.
• Patients were followed for a median duration of 6 years.

TAKEAWAY:

• The incidence of major and minor infections was 5.3 (95% CI, 4.1-6.9) and 63.9 per 100 patient-years (95% CI, 59.3-69.0), respectively.
• Intercurrent infections were associated with a 1.9 times higher risk for SLE flares within 3 months (95% CI, 1.3-2.9).
• Intercurrent infections were significantly associated with minor SLE flares (hazard ratio, 1.9; 95% CI, 1.2-3.0) but not with major flares.
• Major infections were linked to a 7.4 times higher risk for major SLE flares within 3 months (95% CI, 2.2-24.6).

IN PRACTICE:

“This finding stresses the importance of awareness and strict monitoring of disease activity in patients with SLE suffering a major infection and prompt adequate treatment in case of the development of a disease flare,” the authors wrote.

SOURCE:

The study was led by Fatma el Hadiyen, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center in the Netherlands. It was published online on July 1, 2024, in Lupus Science & Medicine.

LIMITATIONS:

The reliance on patient recall for minor infections may have introduced recall bias. The small number of patients with identified causative organisms limited the generalizability of the findings. The Bootsma criteria were used for defining SLE flares, which may not align with more recent international standards.

DISCLOSURES:

No specific funding source was reported. One author reported receiving personal fees from various pharmaceutical companies outside the submitted work.

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:

Intercurrent infections are associated with an increased risk for systemic lupus erythematosus (SLE) flares within 3 months, with major infections associated with a 7.4 times higher risk for major flares.

METHODOLOGY:

• The researchers prospectively examined the association between intercurrent infections and subsequent SLE flares in 203 patients (median age, 40 years; 91% women) with SLE from the Amsterdam SLE cohort study.
• SLE flares were defined as an increase in disease activity combined with an intensification of immunosuppressive therapy. They were categorized into minor and major flares according to the severity and required treatment.
• Major infections were defined as those requiring hospital admission or intravenous antibiotic therapy, while minor infections did not require hospital admission.
• The risk interval for the occurrence of a disease flare was defined as 3 months from the index date of an infection.
• Patients were followed for a median duration of 6 years.

TAKEAWAY:

• The incidence of major and minor infections was 5.3 (95% CI, 4.1-6.9) and 63.9 per 100 patient-years (95% CI, 59.3-69.0), respectively.
• Intercurrent infections were associated with a 1.9 times higher risk for SLE flares within 3 months (95% CI, 1.3-2.9).
• Intercurrent infections were significantly associated with minor SLE flares (hazard ratio, 1.9; 95% CI, 1.2-3.0) but not with major flares.
• Major infections were linked to a 7.4 times higher risk for major SLE flares within 3 months (95% CI, 2.2-24.6).

IN PRACTICE:

“This finding stresses the importance of awareness and strict monitoring of disease activity in patients with SLE suffering a major infection and prompt adequate treatment in case of the development of a disease flare,” the authors wrote.

SOURCE:

The study was led by Fatma el Hadiyen, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center in the Netherlands. It was published online on July 1, 2024, in Lupus Science & Medicine.

LIMITATIONS:

The reliance on patient recall for minor infections may have introduced recall bias. The small number of patients with identified causative organisms limited the generalizability of the findings. The Bootsma criteria were used for defining SLE flares, which may not align with more recent international standards.

DISCLOSURES:

No specific funding source was reported. One author reported receiving personal fees from various pharmaceutical companies outside the submitted work.

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.

Recognizing cutaneous drug eruptions is important for treatment and prevention of recurrence. Fixed drug eruptions (FDEs) typically are harmless but can have major negative cosmetic consequences for patients. In its more severe forms, patients are at risk for widespread epithelial necrosis with accompanying complications. We report 1 patient with generalized FDE and 2 with generalized bullous FDE. We also discuss the recognition and treatment of the condition. Two patients previously had been diagnosed with systemic lupus erythematosus (SLE).

Case Series

Patient 1—A 60-year-old woman presented to dermatology with a rash on the trunk and groin folds of 4 days’ duration. She had a history of SLE and cutaneous lupus treated with hydroxychloroquine 200 mg twice daily and topical corticosteroids. She had started sulfamethoxazole-trimethoprim for a urinary tract infection with a rash appearing 1 day later. She reported burning skin pain with progression to blisters that “sloughed” off. She denied any known history of allergy to sulfa drugs. Prior to evaluation by dermatology, she visited an urgent care facility and was prescribed hydroxyzine and intramuscular corticosteroids. At presentation to dermatology 3 days after taking sulfamethoxazole-trimethoprim, she had annular flaccid bullae and superficial erosions with dusky borders on the right posterior thigh, right side of the chest, left inframammary fold, and right inguinal fold (Figure 1). She had no ocular, oral, or vaginal erosions. A diagnosis of generalized bullous FDE was favored over erythema multiforme or Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Shave biopsies from lesions on the right posterior thigh and right inguinal fold demonstrated interface dermatitis with epidermal necrosis, pigment incontinence, and numerous eosinophils. Direct immunofluorescence of the perilesional skin was negative for immunoprotein deposition. These findings were consistent with the clinical impression of generalized bullous FDE. Prior to receiving the histopathology report, the patient was initiated on a regimen of cyclosporine 5 mg/kg/d in the setting of normal renal function and followed until the eruption resolved completely. Cyclosporine was tapered at 2 weeks and discontinued at 3 weeks.

Patient 2—A 32-year-old woman presented for follow-up management of discoid lupus erythematosus. She had a history of systemic and cutaneous lupus, juvenile rheumatoid arthritis, and mixed connective tissue disease managed with prednisone, hydroxychloroquine, azathioprine, and belimumab. Physical examination revealed scarring alopecia with dyspigmentation and active inflammation consistent with uncontrolled cutaneous lupus. However, she also had oval-shaped hyperpigmented patches over the left breast, clavicle, and anterior chest consistent with a generalized FDE (Figure 2). The patient did not recall a history of similar lesions and could not identify a possible trigger. She was counseled on possible culprits and advised to avoid unnecessary medications. She had an unremarkable clinical course; therefore, no further intervention was necessary.

 

Patient 3—A 33-year-old man presented to the emergency department with a painful rash on the chest and back of 2 days’ duration that began 1 hour after taking naproxen (dosage unknown) for back pain. He had no notable medical history. The patient stated that the rash had slowly worsened and started to develop blisters. He visited an urgent care facility 1 day prior to the current presentation and was started on a 5-day course of prednisone 40 mg daily; the first 2 doses did not help. He denied any mucosal involvement apart from a tender lesion on the penis. He reported a history of an allergic reaction to penicillin. Physical examination revealed extensive dusky violaceous annular plaques with erythematous borders across the anterior and posterior trunk (Figure 3). Multiple flaccid bullae developed within these plaques, involving 15% of the body surface area. He was diagnosed with generalized bullous FDE based on the clinical history and histopathology. He was admitted to the burn intensive care unit and treated with cyclosporine 3 mg/kg/d with subsequent resolution of the eruption.

Comment

Presentation of FDEs—A fixed drug eruption manifests with 1 or more well-demarcated, red or violaceous, annular patches that resolve with postinflammatory hyperpigmentation; it occasionally may manifest with bullae. Initial eruptions may occur up to 2 weeks following medication exposure, but recurrent eruptions usually happen within minutes to hours later. They often are in the same location as prior lesions. A fixed drug eruption can be solitary, scattered, or generalized; a generalized FDE typically demonstrates multiple bilateral lesions that may itch, burn, or cause no symptoms. Patients can experience an FDE at any age, though the median age is reported as 35 to 60 years of age.¹ A fixed drug eruption usually occurs after ingestion of oral medications, though there have been a few reports with iodinated contrast.² Well-known culprits include antibiotics (eg, sulfamethoxazole-trimethoprim, tetracyclines, penicillins/cephalosporins, quinolones, dapsone), nonsteroidal anti-inflammatory drugs, acetaminophen (eg, paracetamol), barbiturates, antimalarials, and anticonvulsants. It also can occur with vaccines or with certain foods (fixed food eruption).^3,4 Clinicians may try an oral drug challenge to identify the cause of an FDE, but in patients with a history of a generalized FDE, the risk for developing an increasingly severe reaction with repeated exposure to the medication is too high.⁵

Histopathology—Patch testing at the site of prior eruption with suspected drug culprits may be useful.⁶ Histopathology of FDE typically demonstrates vacuolar changes at the dermoepidermal junction with a lichenoid lymphocytic infiltrate. Early lesions often show a predominance of eosinophils. Subepidermal clefting is a feature of the bullous variant. In an active lesion, there are large numbers of CD8+ T lymphocytes expressing natural killer cell–associated molecules.⁷ The pathologic mechanism is not well understood, though it has been hypothesized that memory CD8+ cells are maintained in specific regions of the epidermis by IL-15 produced in the microenvironment and are activated upon rechallenge.⁷Considerations in Generalized Bullous FDE—Generalized FDE is defined in the literature as an FDE with involvement of 3 of 6 body areas: head, neck, trunk, upper limbs, lower limbs, and genital area. It may cover more or less than 10% of the body surface area.^8-10 Although an isolated FDE frequently is asymptomatic and may not be cause for alarm, recurring drug eruptions increase the risk for development of generalized bullous FDE. Generalized bullous FDE is a rare subset. It is frequently misdiagnosed, and data on its incidence are uncertain.¹¹ Of note, several pathologies causing bullous lesions may be in the differential diagnosis, including bullous pemphigoid; pemphigus vulgaris; bullous SLE; or bullae from cutaneous lupus, staphylococcal scalded skin syndrome, erythema multiforme, or SJS/TEN.¹² When matched for body surface area involvement with SJS/TEN, generalized bullous FDE shares nearly identical mortality rates¹⁰; therefore, these patients should be treated with the same level of urgency and admitted to a critical care or burn unit, as they are at serious risk for infection and other complications.¹³

Clinical history and presentation along with histopathologic findings help to narrow down the differential diagnosis. Clinically, generalized bullous FDE does not affect the surrounding skin and manifests sooner after drug exposure (1–24 hours) with less mucosal involvement than SJS/TEN.⁹ Additionally, SJS/TEN patients frequently have generalized malaise and/or fever, while generalized bullous FDE patients do not. Finally, patients with generalized bullous FDE may report a history of a cutaneous eruption similar in morphology or in the same location.

Histopathologically, generalized bullous FDE may be similar to FDE with the addition of a subepidermal blister. Generalized bullous FDE patients have greater eosinophil infiltration and dermal melanophages than patients with SJS/TEN.⁹ Cellular infiltrates in generalized bullous FDE include more dermal CD41 cells, such as Foxp31 regulatory T cells; fewer intraepidermal CD561 cells; and fewer intraepidermal cells with granulysin.⁹ Occasionally, generalized bullous FDE causes full-thickness necrosis. In those cases, generalized bullous FDE cannot reliably be distinguished from other conditions with epidermal necrolysis on histopathology.¹³

FDE Diagnostics—A cytotoxin produced by cytotoxic T lymphocytes, granulysin can be measured to aid in diagnosis of FDE, though this test may not be widely available. High levels of granulysin in the blister fluid and serum can be used to distinguish SJS/TEN, erythema multiforme, and localized and generalized bullous FDE from other non–cytotoxic T lymphocyte–mediated bullous skin disorders, such as bullous pemphigoid, pemphigus, and bullous SLE.¹⁴ Blister granulysin levels are notably lower in generalized bullous FDE than in SJS/TEN.^9,14 Chen et al¹⁴ also found that granulysin levels can be used to gauge disease progression given that the levels sharply decrease after patients have reached maximal skin detachment.

Management—Avoidance of the inciting drug often is sufficient for patients with an FDE, as demonstrated in patient 2 in our case series. Clinicians also should counsel patients on avoidance of potential cross-reacting drugs. Symptomatic treatment for itch or pain is appropriate and may include antihistamines or topical steroids. Nonsteroidal anti-inflammatory drugs may exacerbate or be causative of FDE. For generalized bullous FDE, cyclosporine is favored in the literature^15,16 and was used to successfully treat both patients 1 and 3 in our case series. A short course of systemic corticosteroids or intravenous immunoglobulin also may be considered. Mild cases of generalized bullous FDE may be treated with close outpatient follow-up (patient 1), while severe cases require inpatient or even critical care monitoring with aggressive medical management to prevent the progression of skin desquamation (patient 3). Patients with severe oral lesions may require inpatient support for fluid maintenance.

Lupus History—Two patients in our case series had a history of lupus. Lupus itself can cause primary bullous lesions. Similar to FDE, bullous SLE can involve sun-exposed and nonexposed areas of the skin as well as the mucous membranes with a predilection for the lower vermilion lip.¹⁷ In bullous SLE, tense subepidermal blisters with a neutrophil-rich infiltrate form due to circulating antibodies to type VII collagen. These blisters have an erythematous or urticated base, most commonly on the face, upper trunk, and proximal extremities.¹⁸ In both SLE with skin manifestations and lupus limited to the skin, bullae may form due to extensive vacuolar degeneration. Similar to TEN, they can form rapidly in a widespread distribution.¹⁷ However, there is limited mucosal involvement, no clear drug association, and a better prognosis. Bullae caused by lupus will frequently demonstrate deposition of immunoproteins IgG, IgM, IgA, and complement component 3 at the basement membrane zone in perilesional skin on direct immunofluorescence. However, negative direct immunofluorescence does not rule out lupus.¹² At the same time, patients with lupus frequently have comorbidities requiring multiple medications; the need for these medications may predispose patients to higher rates of cutaneous drug eruptions.¹⁹ To our knowledge, there is no known association between FDE and lupus.

Conclusion

Patients with acute eruptions following the initiation of a new prescription or over-the-counter medication require urgent evaluation. Generalized bullous FDE requires timely diagnosis and intervention. Patients with lupus have an increased risk for cutaneous drug eruptions due to polypharmacy. Further investigation is necessary to determine if there is a pathophysiologic mechanism responsible for the development of FDE in lupus patients.

Recognizing cutaneous drug eruptions is important for treatment and prevention of recurrence. Fixed drug eruptions (FDEs) typically are harmless but can have major negative cosmetic consequences for patients. In its more severe forms, patients are at risk for widespread epithelial necrosis with accompanying complications. We report 1 patient with generalized FDE and 2 with generalized bullous FDE. We also discuss the recognition and treatment of the condition. Two patients previously had been diagnosed with systemic lupus erythematosus (SLE).

Case Series

Patient 1—A 60-year-old woman presented to dermatology with a rash on the trunk and groin folds of 4 days’ duration. She had a history of SLE and cutaneous lupus treated with hydroxychloroquine 200 mg twice daily and topical corticosteroids. She had started sulfamethoxazole-trimethoprim for a urinary tract infection with a rash appearing 1 day later. She reported burning skin pain with progression to blisters that “sloughed” off. She denied any known history of allergy to sulfa drugs. Prior to evaluation by dermatology, she visited an urgent care facility and was prescribed hydroxyzine and intramuscular corticosteroids. At presentation to dermatology 3 days after taking sulfamethoxazole-trimethoprim, she had annular flaccid bullae and superficial erosions with dusky borders on the right posterior thigh, right side of the chest, left inframammary fold, and right inguinal fold (Figure 1). She had no ocular, oral, or vaginal erosions. A diagnosis of generalized bullous FDE was favored over erythema multiforme or Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Shave biopsies from lesions on the right posterior thigh and right inguinal fold demonstrated interface dermatitis with epidermal necrosis, pigment incontinence, and numerous eosinophils. Direct immunofluorescence of the perilesional skin was negative for immunoprotein deposition. These findings were consistent with the clinical impression of generalized bullous FDE. Prior to receiving the histopathology report, the patient was initiated on a regimen of cyclosporine 5 mg/kg/d in the setting of normal renal function and followed until the eruption resolved completely. Cyclosporine was tapered at 2 weeks and discontinued at 3 weeks.

Patient 2—A 32-year-old woman presented for follow-up management of discoid lupus erythematosus. She had a history of systemic and cutaneous lupus, juvenile rheumatoid arthritis, and mixed connective tissue disease managed with prednisone, hydroxychloroquine, azathioprine, and belimumab. Physical examination revealed scarring alopecia with dyspigmentation and active inflammation consistent with uncontrolled cutaneous lupus. However, she also had oval-shaped hyperpigmented patches over the left breast, clavicle, and anterior chest consistent with a generalized FDE (Figure 2). The patient did not recall a history of similar lesions and could not identify a possible trigger. She was counseled on possible culprits and advised to avoid unnecessary medications. She had an unremarkable clinical course; therefore, no further intervention was necessary.

 

Patient 3—A 33-year-old man presented to the emergency department with a painful rash on the chest and back of 2 days’ duration that began 1 hour after taking naproxen (dosage unknown) for back pain. He had no notable medical history. The patient stated that the rash had slowly worsened and started to develop blisters. He visited an urgent care facility 1 day prior to the current presentation and was started on a 5-day course of prednisone 40 mg daily; the first 2 doses did not help. He denied any mucosal involvement apart from a tender lesion on the penis. He reported a history of an allergic reaction to penicillin. Physical examination revealed extensive dusky violaceous annular plaques with erythematous borders across the anterior and posterior trunk (Figure 3). Multiple flaccid bullae developed within these plaques, involving 15% of the body surface area. He was diagnosed with generalized bullous FDE based on the clinical history and histopathology. He was admitted to the burn intensive care unit and treated with cyclosporine 3 mg/kg/d with subsequent resolution of the eruption.

Comment

Presentation of FDEs—A fixed drug eruption manifests with 1 or more well-demarcated, red or violaceous, annular patches that resolve with postinflammatory hyperpigmentation; it occasionally may manifest with bullae. Initial eruptions may occur up to 2 weeks following medication exposure, but recurrent eruptions usually happen within minutes to hours later. They often are in the same location as prior lesions. A fixed drug eruption can be solitary, scattered, or generalized; a generalized FDE typically demonstrates multiple bilateral lesions that may itch, burn, or cause no symptoms. Patients can experience an FDE at any age, though the median age is reported as 35 to 60 years of age.¹ A fixed drug eruption usually occurs after ingestion of oral medications, though there have been a few reports with iodinated contrast.² Well-known culprits include antibiotics (eg, sulfamethoxazole-trimethoprim, tetracyclines, penicillins/cephalosporins, quinolones, dapsone), nonsteroidal anti-inflammatory drugs, acetaminophen (eg, paracetamol), barbiturates, antimalarials, and anticonvulsants. It also can occur with vaccines or with certain foods (fixed food eruption).^3,4 Clinicians may try an oral drug challenge to identify the cause of an FDE, but in patients with a history of a generalized FDE, the risk for developing an increasingly severe reaction with repeated exposure to the medication is too high.⁵

Histopathology—Patch testing at the site of prior eruption with suspected drug culprits may be useful.⁶ Histopathology of FDE typically demonstrates vacuolar changes at the dermoepidermal junction with a lichenoid lymphocytic infiltrate. Early lesions often show a predominance of eosinophils. Subepidermal clefting is a feature of the bullous variant. In an active lesion, there are large numbers of CD8+ T lymphocytes expressing natural killer cell–associated molecules.⁷ The pathologic mechanism is not well understood, though it has been hypothesized that memory CD8+ cells are maintained in specific regions of the epidermis by IL-15 produced in the microenvironment and are activated upon rechallenge.⁷Considerations in Generalized Bullous FDE—Generalized FDE is defined in the literature as an FDE with involvement of 3 of 6 body areas: head, neck, trunk, upper limbs, lower limbs, and genital area. It may cover more or less than 10% of the body surface area.^8-10 Although an isolated FDE frequently is asymptomatic and may not be cause for alarm, recurring drug eruptions increase the risk for development of generalized bullous FDE. Generalized bullous FDE is a rare subset. It is frequently misdiagnosed, and data on its incidence are uncertain.¹¹ Of note, several pathologies causing bullous lesions may be in the differential diagnosis, including bullous pemphigoid; pemphigus vulgaris; bullous SLE; or bullae from cutaneous lupus, staphylococcal scalded skin syndrome, erythema multiforme, or SJS/TEN.¹² When matched for body surface area involvement with SJS/TEN, generalized bullous FDE shares nearly identical mortality rates¹⁰; therefore, these patients should be treated with the same level of urgency and admitted to a critical care or burn unit, as they are at serious risk for infection and other complications.¹³

Clinical history and presentation along with histopathologic findings help to narrow down the differential diagnosis. Clinically, generalized bullous FDE does not affect the surrounding skin and manifests sooner after drug exposure (1–24 hours) with less mucosal involvement than SJS/TEN.⁹ Additionally, SJS/TEN patients frequently have generalized malaise and/or fever, while generalized bullous FDE patients do not. Finally, patients with generalized bullous FDE may report a history of a cutaneous eruption similar in morphology or in the same location.

Histopathologically, generalized bullous FDE may be similar to FDE with the addition of a subepidermal blister. Generalized bullous FDE patients have greater eosinophil infiltration and dermal melanophages than patients with SJS/TEN.⁹ Cellular infiltrates in generalized bullous FDE include more dermal CD41 cells, such as Foxp31 regulatory T cells; fewer intraepidermal CD561 cells; and fewer intraepidermal cells with granulysin.⁹ Occasionally, generalized bullous FDE causes full-thickness necrosis. In those cases, generalized bullous FDE cannot reliably be distinguished from other conditions with epidermal necrolysis on histopathology.¹³

FDE Diagnostics—A cytotoxin produced by cytotoxic T lymphocytes, granulysin can be measured to aid in diagnosis of FDE, though this test may not be widely available. High levels of granulysin in the blister fluid and serum can be used to distinguish SJS/TEN, erythema multiforme, and localized and generalized bullous FDE from other non–cytotoxic T lymphocyte–mediated bullous skin disorders, such as bullous pemphigoid, pemphigus, and bullous SLE.¹⁴ Blister granulysin levels are notably lower in generalized bullous FDE than in SJS/TEN.^9,14 Chen et al¹⁴ also found that granulysin levels can be used to gauge disease progression given that the levels sharply decrease after patients have reached maximal skin detachment.

Management—Avoidance of the inciting drug often is sufficient for patients with an FDE, as demonstrated in patient 2 in our case series. Clinicians also should counsel patients on avoidance of potential cross-reacting drugs. Symptomatic treatment for itch or pain is appropriate and may include antihistamines or topical steroids. Nonsteroidal anti-inflammatory drugs may exacerbate or be causative of FDE. For generalized bullous FDE, cyclosporine is favored in the literature^15,16 and was used to successfully treat both patients 1 and 3 in our case series. A short course of systemic corticosteroids or intravenous immunoglobulin also may be considered. Mild cases of generalized bullous FDE may be treated with close outpatient follow-up (patient 1), while severe cases require inpatient or even critical care monitoring with aggressive medical management to prevent the progression of skin desquamation (patient 3). Patients with severe oral lesions may require inpatient support for fluid maintenance.

Lupus History—Two patients in our case series had a history of lupus. Lupus itself can cause primary bullous lesions. Similar to FDE, bullous SLE can involve sun-exposed and nonexposed areas of the skin as well as the mucous membranes with a predilection for the lower vermilion lip.¹⁷ In bullous SLE, tense subepidermal blisters with a neutrophil-rich infiltrate form due to circulating antibodies to type VII collagen. These blisters have an erythematous or urticated base, most commonly on the face, upper trunk, and proximal extremities.¹⁸ In both SLE with skin manifestations and lupus limited to the skin, bullae may form due to extensive vacuolar degeneration. Similar to TEN, they can form rapidly in a widespread distribution.¹⁷ However, there is limited mucosal involvement, no clear drug association, and a better prognosis. Bullae caused by lupus will frequently demonstrate deposition of immunoproteins IgG, IgM, IgA, and complement component 3 at the basement membrane zone in perilesional skin on direct immunofluorescence. However, negative direct immunofluorescence does not rule out lupus.¹² At the same time, patients with lupus frequently have comorbidities requiring multiple medications; the need for these medications may predispose patients to higher rates of cutaneous drug eruptions.¹⁹ To our knowledge, there is no known association between FDE and lupus.

Conclusion

Patients with acute eruptions following the initiation of a new prescription or over-the-counter medication require urgent evaluation. Generalized bullous FDE requires timely diagnosis and intervention. Patients with lupus have an increased risk for cutaneous drug eruptions due to polypharmacy. Further investigation is necessary to determine if there is a pathophysiologic mechanism responsible for the development of FDE in lupus patients.

Recognizing cutaneous drug eruptions is important for treatment and prevention of recurrence. Fixed drug eruptions (FDEs) typically are harmless but can have major negative cosmetic consequences for patients. In its more severe forms, patients are at risk for widespread epithelial necrosis with accompanying complications. We report 1 patient with generalized FDE and 2 with generalized bullous FDE. We also discuss the recognition and treatment of the condition. Two patients previously had been diagnosed with systemic lupus erythematosus (SLE).

Case Series

Patient 1—A 60-year-old woman presented to dermatology with a rash on the trunk and groin folds of 4 days’ duration. She had a history of SLE and cutaneous lupus treated with hydroxychloroquine 200 mg twice daily and topical corticosteroids. She had started sulfamethoxazole-trimethoprim for a urinary tract infection with a rash appearing 1 day later. She reported burning skin pain with progression to blisters that “sloughed” off. She denied any known history of allergy to sulfa drugs. Prior to evaluation by dermatology, she visited an urgent care facility and was prescribed hydroxyzine and intramuscular corticosteroids. At presentation to dermatology 3 days after taking sulfamethoxazole-trimethoprim, she had annular flaccid bullae and superficial erosions with dusky borders on the right posterior thigh, right side of the chest, left inframammary fold, and right inguinal fold (Figure 1). She had no ocular, oral, or vaginal erosions. A diagnosis of generalized bullous FDE was favored over erythema multiforme or Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Shave biopsies from lesions on the right posterior thigh and right inguinal fold demonstrated interface dermatitis with epidermal necrosis, pigment incontinence, and numerous eosinophils. Direct immunofluorescence of the perilesional skin was negative for immunoprotein deposition. These findings were consistent with the clinical impression of generalized bullous FDE. Prior to receiving the histopathology report, the patient was initiated on a regimen of cyclosporine 5 mg/kg/d in the setting of normal renal function and followed until the eruption resolved completely. Cyclosporine was tapered at 2 weeks and discontinued at 3 weeks.

Patient 2—A 32-year-old woman presented for follow-up management of discoid lupus erythematosus. She had a history of systemic and cutaneous lupus, juvenile rheumatoid arthritis, and mixed connective tissue disease managed with prednisone, hydroxychloroquine, azathioprine, and belimumab. Physical examination revealed scarring alopecia with dyspigmentation and active inflammation consistent with uncontrolled cutaneous lupus. However, she also had oval-shaped hyperpigmented patches over the left breast, clavicle, and anterior chest consistent with a generalized FDE (Figure 2). The patient did not recall a history of similar lesions and could not identify a possible trigger. She was counseled on possible culprits and advised to avoid unnecessary medications. She had an unremarkable clinical course; therefore, no further intervention was necessary.

 

Patient 3—A 33-year-old man presented to the emergency department with a painful rash on the chest and back of 2 days’ duration that began 1 hour after taking naproxen (dosage unknown) for back pain. He had no notable medical history. The patient stated that the rash had slowly worsened and started to develop blisters. He visited an urgent care facility 1 day prior to the current presentation and was started on a 5-day course of prednisone 40 mg daily; the first 2 doses did not help. He denied any mucosal involvement apart from a tender lesion on the penis. He reported a history of an allergic reaction to penicillin. Physical examination revealed extensive dusky violaceous annular plaques with erythematous borders across the anterior and posterior trunk (Figure 3). Multiple flaccid bullae developed within these plaques, involving 15% of the body surface area. He was diagnosed with generalized bullous FDE based on the clinical history and histopathology. He was admitted to the burn intensive care unit and treated with cyclosporine 3 mg/kg/d with subsequent resolution of the eruption.

Comment

Presentation of FDEs—A fixed drug eruption manifests with 1 or more well-demarcated, red or violaceous, annular patches that resolve with postinflammatory hyperpigmentation; it occasionally may manifest with bullae. Initial eruptions may occur up to 2 weeks following medication exposure, but recurrent eruptions usually happen within minutes to hours later. They often are in the same location as prior lesions. A fixed drug eruption can be solitary, scattered, or generalized; a generalized FDE typically demonstrates multiple bilateral lesions that may itch, burn, or cause no symptoms. Patients can experience an FDE at any age, though the median age is reported as 35 to 60 years of age.¹ A fixed drug eruption usually occurs after ingestion of oral medications, though there have been a few reports with iodinated contrast.² Well-known culprits include antibiotics (eg, sulfamethoxazole-trimethoprim, tetracyclines, penicillins/cephalosporins, quinolones, dapsone), nonsteroidal anti-inflammatory drugs, acetaminophen (eg, paracetamol), barbiturates, antimalarials, and anticonvulsants. It also can occur with vaccines or with certain foods (fixed food eruption).^3,4 Clinicians may try an oral drug challenge to identify the cause of an FDE, but in patients with a history of a generalized FDE, the risk for developing an increasingly severe reaction with repeated exposure to the medication is too high.⁵

Histopathology—Patch testing at the site of prior eruption with suspected drug culprits may be useful.⁶ Histopathology of FDE typically demonstrates vacuolar changes at the dermoepidermal junction with a lichenoid lymphocytic infiltrate. Early lesions often show a predominance of eosinophils. Subepidermal clefting is a feature of the bullous variant. In an active lesion, there are large numbers of CD8+ T lymphocytes expressing natural killer cell–associated molecules.⁷ The pathologic mechanism is not well understood, though it has been hypothesized that memory CD8+ cells are maintained in specific regions of the epidermis by IL-15 produced in the microenvironment and are activated upon rechallenge.⁷Considerations in Generalized Bullous FDE—Generalized FDE is defined in the literature as an FDE with involvement of 3 of 6 body areas: head, neck, trunk, upper limbs, lower limbs, and genital area. It may cover more or less than 10% of the body surface area.^8-10 Although an isolated FDE frequently is asymptomatic and may not be cause for alarm, recurring drug eruptions increase the risk for development of generalized bullous FDE. Generalized bullous FDE is a rare subset. It is frequently misdiagnosed, and data on its incidence are uncertain.¹¹ Of note, several pathologies causing bullous lesions may be in the differential diagnosis, including bullous pemphigoid; pemphigus vulgaris; bullous SLE; or bullae from cutaneous lupus, staphylococcal scalded skin syndrome, erythema multiforme, or SJS/TEN.¹² When matched for body surface area involvement with SJS/TEN, generalized bullous FDE shares nearly identical mortality rates¹⁰; therefore, these patients should be treated with the same level of urgency and admitted to a critical care or burn unit, as they are at serious risk for infection and other complications.¹³

Clinical history and presentation along with histopathologic findings help to narrow down the differential diagnosis. Clinically, generalized bullous FDE does not affect the surrounding skin and manifests sooner after drug exposure (1–24 hours) with less mucosal involvement than SJS/TEN.⁹ Additionally, SJS/TEN patients frequently have generalized malaise and/or fever, while generalized bullous FDE patients do not. Finally, patients with generalized bullous FDE may report a history of a cutaneous eruption similar in morphology or in the same location.

Histopathologically, generalized bullous FDE may be similar to FDE with the addition of a subepidermal blister. Generalized bullous FDE patients have greater eosinophil infiltration and dermal melanophages than patients with SJS/TEN.⁹ Cellular infiltrates in generalized bullous FDE include more dermal CD41 cells, such as Foxp31 regulatory T cells; fewer intraepidermal CD561 cells; and fewer intraepidermal cells with granulysin.⁹ Occasionally, generalized bullous FDE causes full-thickness necrosis. In those cases, generalized bullous FDE cannot reliably be distinguished from other conditions with epidermal necrolysis on histopathology.¹³

FDE Diagnostics—A cytotoxin produced by cytotoxic T lymphocytes, granulysin can be measured to aid in diagnosis of FDE, though this test may not be widely available. High levels of granulysin in the blister fluid and serum can be used to distinguish SJS/TEN, erythema multiforme, and localized and generalized bullous FDE from other non–cytotoxic T lymphocyte–mediated bullous skin disorders, such as bullous pemphigoid, pemphigus, and bullous SLE.¹⁴ Blister granulysin levels are notably lower in generalized bullous FDE than in SJS/TEN.^9,14 Chen et al¹⁴ also found that granulysin levels can be used to gauge disease progression given that the levels sharply decrease after patients have reached maximal skin detachment.

Management—Avoidance of the inciting drug often is sufficient for patients with an FDE, as demonstrated in patient 2 in our case series. Clinicians also should counsel patients on avoidance of potential cross-reacting drugs. Symptomatic treatment for itch or pain is appropriate and may include antihistamines or topical steroids. Nonsteroidal anti-inflammatory drugs may exacerbate or be causative of FDE. For generalized bullous FDE, cyclosporine is favored in the literature^15,16 and was used to successfully treat both patients 1 and 3 in our case series. A short course of systemic corticosteroids or intravenous immunoglobulin also may be considered. Mild cases of generalized bullous FDE may be treated with close outpatient follow-up (patient 1), while severe cases require inpatient or even critical care monitoring with aggressive medical management to prevent the progression of skin desquamation (patient 3). Patients with severe oral lesions may require inpatient support for fluid maintenance.

Lupus History—Two patients in our case series had a history of lupus. Lupus itself can cause primary bullous lesions. Similar to FDE, bullous SLE can involve sun-exposed and nonexposed areas of the skin as well as the mucous membranes with a predilection for the lower vermilion lip.¹⁷ In bullous SLE, tense subepidermal blisters with a neutrophil-rich infiltrate form due to circulating antibodies to type VII collagen. These blisters have an erythematous or urticated base, most commonly on the face, upper trunk, and proximal extremities.¹⁸ In both SLE with skin manifestations and lupus limited to the skin, bullae may form due to extensive vacuolar degeneration. Similar to TEN, they can form rapidly in a widespread distribution.¹⁷ However, there is limited mucosal involvement, no clear drug association, and a better prognosis. Bullae caused by lupus will frequently demonstrate deposition of immunoproteins IgG, IgM, IgA, and complement component 3 at the basement membrane zone in perilesional skin on direct immunofluorescence. However, negative direct immunofluorescence does not rule out lupus.¹² At the same time, patients with lupus frequently have comorbidities requiring multiple medications; the need for these medications may predispose patients to higher rates of cutaneous drug eruptions.¹⁹ To our knowledge, there is no known association between FDE and lupus.

Conclusion

Patients with acute eruptions following the initiation of a new prescription or over-the-counter medication require urgent evaluation. Generalized bullous FDE requires timely diagnosis and intervention. Patients with lupus have an increased risk for cutaneous drug eruptions due to polypharmacy. Further investigation is necessary to determine if there is a pathophysiologic mechanism responsible for the development of FDE in lupus patients.

To the Editor:

A 48-year-old man presented with nodular lesions in a sporotrichoid pattern on the right hand and forearm of 3 months’ duration (Figure). There were no lymphadeno-pathies, and he had no notable medical history. He denied fever and other systemic symptoms. The patient recently had manipulated a warm water fish aquarium. Although he did not recall a clear injury, inadvertent mild trauma was a possibility. He denied other contact or trauma in relation to animals or vegetables.

Histopathology from a punch biopsy of the forearm revealed a granulomatous infiltrate with necrosis at the deep dermis level at the interface with the subcutaneous cellular tissue that was composed of mainly epithelioid cells with a few multinucleated giant cells. No acid-fast bacilli or fungi were observed with special stains.

A polymerase chain reaction assay for atypical mycobacteria was positive for Mycobacterium interjectum. The culture of the skin biopsy was negative for fungi and mycobacteria after long incubation (6 weeks) on 2 occasions, and an antibiogram was not available. Complementary tests including hemogram, HIV serology, and chest and upper extremity radiographs did not reveal any abnormalities.

To the Editor:

A 48-year-old man presented with nodular lesions in a sporotrichoid pattern on the right hand and forearm of 3 months’ duration (Figure). There were no lymphadeno-pathies, and he had no notable medical history. He denied fever and other systemic symptoms. The patient recently had manipulated a warm water fish aquarium. Although he did not recall a clear injury, inadvertent mild trauma was a possibility. He denied other contact or trauma in relation to animals or vegetables.

Histopathology from a punch biopsy of the forearm revealed a granulomatous infiltrate with necrosis at the deep dermis level at the interface with the subcutaneous cellular tissue that was composed of mainly epithelioid cells with a few multinucleated giant cells. No acid-fast bacilli or fungi were observed with special stains.

A polymerase chain reaction assay for atypical mycobacteria was positive for Mycobacterium interjectum. The culture of the skin biopsy was negative for fungi and mycobacteria after long incubation (6 weeks) on 2 occasions, and an antibiogram was not available. Complementary tests including hemogram, HIV serology, and chest and upper extremity radiographs did not reveal any abnormalities.

To the Editor:

A 48-year-old man presented with nodular lesions in a sporotrichoid pattern on the right hand and forearm of 3 months’ duration (Figure). There were no lymphadeno-pathies, and he had no notable medical history. He denied fever and other systemic symptoms. The patient recently had manipulated a warm water fish aquarium. Although he did not recall a clear injury, inadvertent mild trauma was a possibility. He denied other contact or trauma in relation to animals or vegetables.

Histopathology from a punch biopsy of the forearm revealed a granulomatous infiltrate with necrosis at the deep dermis level at the interface with the subcutaneous cellular tissue that was composed of mainly epithelioid cells with a few multinucleated giant cells. No acid-fast bacilli or fungi were observed with special stains.

A polymerase chain reaction assay for atypical mycobacteria was positive for Mycobacterium interjectum. The culture of the skin biopsy was negative for fungi and mycobacteria after long incubation (6 weeks) on 2 occasions, and an antibiogram was not available. Complementary tests including hemogram, HIV serology, and chest and upper extremity radiographs did not reveal any abnormalities.

WASHINGTON — The chronic, excessive fragility of aging and sun-damaged skin has a name in the medical literature: dermatoporosis. This identification is helpful because it validates patients’ suffering and conveys the skin’s vulnerability to serious medical complications, said Adam Friedman, MD, at the ElderDerm conference on dermatology in the older patient.

Key features of dermatoporosis include atrophic skin, solar purpura, white pseudoscars, easily acquired skin lacerations and tears, bruises, and delayed healing. “We’re going to see more of this, and it will more and more be a chief complaint of patients,” said Dr. Friedman, professor and chair of dermatology at George Washington University (GWU) in Washington, and co-chair of the meeting. GWU hosted the conference, describing it as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Likely Pathophysiology

Advancing age and chronic ultraviolet (UV) radiation exposure are the chief drivers of dermatoporosis. In addition to UVA and UVB light, other secondary drivers include genetic susceptibility, topical and systematic corticosteroid use, and anticoagulant treatment.

Its pathogenesis is not well described in the literature but is easy to envision, Dr. Friedman said. For one, both advancing age and exposure to UV light lead to a reduction in hygroscopic glycosaminoglycans, including hyaluronate (HA), and the impact of this diminishment is believed to go “beyond [the loss of] buoyancy,” he noted. Researchers have “been showing these are not just water-loving molecules, they also have some biologic properties” relating to keratinocyte production and epidermal turnover that appear to be intricately linked to the pathogenesis of dermatoporosis. 

HAs have been shown to interact with the cell surface receptor CD44 to stimulate keratinocyte proliferation, and low levels of CD44 have been reported in skin with dermatoporosis compared with a younger control population. (A newly characterized organelle, the hyaluronosome, serves as an HA factory and contains CD44 and heparin-binding epidermal growth factor, Dr. Friedman noted. Inadequate functioning may be involved in skin atrophy.) 

Advancing age also brings an increase in matrix metalloproteinases (MMPs)–1, –2, and –3, which are “the demolition workers of the skin,” and downregulation of a tissue inhibitor of MMPs, he said. 

Adding insult to injury, dermis-penetrating UVA also activates MMPs, “obliterating collagen and elastin.” UVB generates DNA photoproducts, including oxidative stress and damaging skin cell DNA. “That UV light induces breakdown [of the skin] through different mechanisms and inhibits buildup is a simple concept I think our patients can understand,” Dr. Friedman said.
 

Multifaceted Treatment

For an older adult, “there is never a wrong time to start sun-protective measures” to prevent or try to halt the progression of dermatoporosis, Dr. Friedman said, noting that “UV radiation is an immunosuppressant, so there are many good reasons to start” if the adult is not already taking measures on a regular basis.

Potential treatments for the syndrome of dermatoporosis are backed by few clinical studies, but dermatologists are skilled at translating the use of products from one disease state to another based on understandings of pathophysiology and mechanistic pathways, Dr. Friedman commented in an interview after the meeting. 

For instance, “from decades of research, we know what retinoids will do to the skin,” he said in the interview. “We know they will turn on collagen-1 and -3 genes in the skin, and that they will increase the production of glycosaminoglycans ... By understanding the biology, we can translate this to dermatoporosis.” These changes were demonstrated, for instance, in a small study of topical retinol in older adults.

Studies of topical alpha hydroxy acid (AHA), moreover, have demonstrated epidermal thickening and firmness, and “some studies show they can limit steroid-induced atrophy,” Dr. Friedman said at the meeting. “And things like lactic acid and urea are super accessible.”

Topical dehydroepiandrosterone is backed by even less data than retinoids or AHAs are, “but it’s still something to consider” as part of a multimechanistic approach to dermatoporosis, Dr. Friedman shared, noting that a small study demonstrated beneficial effects on epidermal atrophy in aging skin. 

The use of vitamin D analogues such as calcipotriene, which is approved for the treatment of psoriasis, may also be promising. “One concept is that [vitamin D analogues] increase calcium concentrations in the epidermis, and calcium is so central to keratinocyte differentiation” and epidermal function that calcipotriene in combination with topical steroid therapy has been shown to limit skin atrophy, he noted.

Nutritionally, low protein intake is a known problem in the older population and is associated with increased skin fragility and poorer healing. From a prevention and treatment standpoint, therefore, patients can be counseled to be attentive to their diets, Dr. Friedman said. Experts have recommended a higher protein intake for older adults than for younger adults; in 2013, an international group recommended a protein intake of 1-1.5 g/kg/d for healthy older adults and more for those with acute or chronic illness.

“Patients love talking about diet and skin disease ... and they love over-the-counter nutraceuticals as well because they want something natural,” Dr. Friedman said. “I like using bioflavonoids in combination with vitamin C, which can be effective especially for solar purpura.”

Courtesy Dr. Adam Friedman

Skin Injury and Wound Prevention

In addition to recommending gentle skin cleansers and daily moisturizing, dermatologists should talk to their older patients with dermatoporosis about their home environments. “What is it like? Is there furniture with sharp edges?” Dr. Friedman advised. If so, could they use sleeves or protectors on their arms or legs “to protect against injury?”

In a later meeting session about lower-extremity wounds on geriatric patients, Michael Stempel, DPM, assistant professor of medicine and surgery and chief of podiatry at GWU, said that he was happy to hear the term dermatoporosis being used because like diabetes, it’s a risk factor for developing lower-extremity wounds and poor wound healing. 

He shared the case of an older woman with dermatoporosis who “tripped and skinned her knee against a step and then self-treated it for over a month by pouring hydrogen peroxide over it and letting air get to it.” The wound developed into “full-thickness tissue loss,” said Dr. Stempel, also medical director of the Wound Healing and Limb Preservation Center at GWU Hospital. 

Misperceptions are common among older patients about how a simple wound should be managed; for instance, the adage “just let it get air” is not uncommon. This makes anticipatory guidance about basic wound care — such as the importance of a moist and occlusive environment and the safe use of hydrogen peroxide — especially important for patients with dermatoporosis, Dr. Friedman commented after the meeting.

Dermatoporosis is quantifiable, Dr. Friedman said during the meeting, with a scoring system having been developed by the researchers in Switzerland who originally coined the term. Its use in practice is unnecessary, but its existence is “nice to share with patients who feel bothered because oftentimes, patients feel it’s been dismissed by other providers,” he said. “Telling your patients there’s an actual name for their problem, and that there are ways to quantify and measure changes over time, is validating.” 

Its recognition as a medical condition, Dr. Friedman added, also enables the dermatologist to bring it up and counsel appropriately — without a patient feeling shame — when it is identified in the context of a skin excision, treatment of a primary inflammatory skin disease, or management of another dermatologic problem.

Dr. Friedman disclosed that he is a consultant/advisory board member for L’Oréal, La Roche-Posay, Galderma, and other companies; a speaker for Regeneron/Sanofi, Incyte, BMD, and Janssen; and has grants from Pfizer, Lilly, Incyte, and other companies. Dr. Stempel reported no disclosures.

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

WASHINGTON — The chronic, excessive fragility of aging and sun-damaged skin has a name in the medical literature: dermatoporosis. This identification is helpful because it validates patients’ suffering and conveys the skin’s vulnerability to serious medical complications, said Adam Friedman, MD, at the ElderDerm conference on dermatology in the older patient.

Key features of dermatoporosis include atrophic skin, solar purpura, white pseudoscars, easily acquired skin lacerations and tears, bruises, and delayed healing. “We’re going to see more of this, and it will more and more be a chief complaint of patients,” said Dr. Friedman, professor and chair of dermatology at George Washington University (GWU) in Washington, and co-chair of the meeting. GWU hosted the conference, describing it as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Likely Pathophysiology

Advancing age and chronic ultraviolet (UV) radiation exposure are the chief drivers of dermatoporosis. In addition to UVA and UVB light, other secondary drivers include genetic susceptibility, topical and systematic corticosteroid use, and anticoagulant treatment.

Its pathogenesis is not well described in the literature but is easy to envision, Dr. Friedman said. For one, both advancing age and exposure to UV light lead to a reduction in hygroscopic glycosaminoglycans, including hyaluronate (HA), and the impact of this diminishment is believed to go “beyond [the loss of] buoyancy,” he noted. Researchers have “been showing these are not just water-loving molecules, they also have some biologic properties” relating to keratinocyte production and epidermal turnover that appear to be intricately linked to the pathogenesis of dermatoporosis. 

HAs have been shown to interact with the cell surface receptor CD44 to stimulate keratinocyte proliferation, and low levels of CD44 have been reported in skin with dermatoporosis compared with a younger control population. (A newly characterized organelle, the hyaluronosome, serves as an HA factory and contains CD44 and heparin-binding epidermal growth factor, Dr. Friedman noted. Inadequate functioning may be involved in skin atrophy.) 

Advancing age also brings an increase in matrix metalloproteinases (MMPs)–1, –2, and –3, which are “the demolition workers of the skin,” and downregulation of a tissue inhibitor of MMPs, he said. 

Adding insult to injury, dermis-penetrating UVA also activates MMPs, “obliterating collagen and elastin.” UVB generates DNA photoproducts, including oxidative stress and damaging skin cell DNA. “That UV light induces breakdown [of the skin] through different mechanisms and inhibits buildup is a simple concept I think our patients can understand,” Dr. Friedman said.
 

Multifaceted Treatment

For an older adult, “there is never a wrong time to start sun-protective measures” to prevent or try to halt the progression of dermatoporosis, Dr. Friedman said, noting that “UV radiation is an immunosuppressant, so there are many good reasons to start” if the adult is not already taking measures on a regular basis.

Potential treatments for the syndrome of dermatoporosis are backed by few clinical studies, but dermatologists are skilled at translating the use of products from one disease state to another based on understandings of pathophysiology and mechanistic pathways, Dr. Friedman commented in an interview after the meeting. 

For instance, “from decades of research, we know what retinoids will do to the skin,” he said in the interview. “We know they will turn on collagen-1 and -3 genes in the skin, and that they will increase the production of glycosaminoglycans ... By understanding the biology, we can translate this to dermatoporosis.” These changes were demonstrated, for instance, in a small study of topical retinol in older adults.

Studies of topical alpha hydroxy acid (AHA), moreover, have demonstrated epidermal thickening and firmness, and “some studies show they can limit steroid-induced atrophy,” Dr. Friedman said at the meeting. “And things like lactic acid and urea are super accessible.”

Topical dehydroepiandrosterone is backed by even less data than retinoids or AHAs are, “but it’s still something to consider” as part of a multimechanistic approach to dermatoporosis, Dr. Friedman shared, noting that a small study demonstrated beneficial effects on epidermal atrophy in aging skin. 

The use of vitamin D analogues such as calcipotriene, which is approved for the treatment of psoriasis, may also be promising. “One concept is that [vitamin D analogues] increase calcium concentrations in the epidermis, and calcium is so central to keratinocyte differentiation” and epidermal function that calcipotriene in combination with topical steroid therapy has been shown to limit skin atrophy, he noted.

Nutritionally, low protein intake is a known problem in the older population and is associated with increased skin fragility and poorer healing. From a prevention and treatment standpoint, therefore, patients can be counseled to be attentive to their diets, Dr. Friedman said. Experts have recommended a higher protein intake for older adults than for younger adults; in 2013, an international group recommended a protein intake of 1-1.5 g/kg/d for healthy older adults and more for those with acute or chronic illness.

“Patients love talking about diet and skin disease ... and they love over-the-counter nutraceuticals as well because they want something natural,” Dr. Friedman said. “I like using bioflavonoids in combination with vitamin C, which can be effective especially for solar purpura.”

Courtesy Dr. Adam Friedman

Skin Injury and Wound Prevention

In addition to recommending gentle skin cleansers and daily moisturizing, dermatologists should talk to their older patients with dermatoporosis about their home environments. “What is it like? Is there furniture with sharp edges?” Dr. Friedman advised. If so, could they use sleeves or protectors on their arms or legs “to protect against injury?”

In a later meeting session about lower-extremity wounds on geriatric patients, Michael Stempel, DPM, assistant professor of medicine and surgery and chief of podiatry at GWU, said that he was happy to hear the term dermatoporosis being used because like diabetes, it’s a risk factor for developing lower-extremity wounds and poor wound healing. 

He shared the case of an older woman with dermatoporosis who “tripped and skinned her knee against a step and then self-treated it for over a month by pouring hydrogen peroxide over it and letting air get to it.” The wound developed into “full-thickness tissue loss,” said Dr. Stempel, also medical director of the Wound Healing and Limb Preservation Center at GWU Hospital. 

Misperceptions are common among older patients about how a simple wound should be managed; for instance, the adage “just let it get air” is not uncommon. This makes anticipatory guidance about basic wound care — such as the importance of a moist and occlusive environment and the safe use of hydrogen peroxide — especially important for patients with dermatoporosis, Dr. Friedman commented after the meeting.

Dermatoporosis is quantifiable, Dr. Friedman said during the meeting, with a scoring system having been developed by the researchers in Switzerland who originally coined the term. Its use in practice is unnecessary, but its existence is “nice to share with patients who feel bothered because oftentimes, patients feel it’s been dismissed by other providers,” he said. “Telling your patients there’s an actual name for their problem, and that there are ways to quantify and measure changes over time, is validating.” 

Its recognition as a medical condition, Dr. Friedman added, also enables the dermatologist to bring it up and counsel appropriately — without a patient feeling shame — when it is identified in the context of a skin excision, treatment of a primary inflammatory skin disease, or management of another dermatologic problem.

Dr. Friedman disclosed that he is a consultant/advisory board member for L’Oréal, La Roche-Posay, Galderma, and other companies; a speaker for Regeneron/Sanofi, Incyte, BMD, and Janssen; and has grants from Pfizer, Lilly, Incyte, and other companies. Dr. Stempel reported no disclosures.

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

WASHINGTON — The chronic, excessive fragility of aging and sun-damaged skin has a name in the medical literature: dermatoporosis. This identification is helpful because it validates patients’ suffering and conveys the skin’s vulnerability to serious medical complications, said Adam Friedman, MD, at the ElderDerm conference on dermatology in the older patient.

Key features of dermatoporosis include atrophic skin, solar purpura, white pseudoscars, easily acquired skin lacerations and tears, bruises, and delayed healing. “We’re going to see more of this, and it will more and more be a chief complaint of patients,” said Dr. Friedman, professor and chair of dermatology at George Washington University (GWU) in Washington, and co-chair of the meeting. GWU hosted the conference, describing it as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Likely Pathophysiology

Advancing age and chronic ultraviolet (UV) radiation exposure are the chief drivers of dermatoporosis. In addition to UVA and UVB light, other secondary drivers include genetic susceptibility, topical and systematic corticosteroid use, and anticoagulant treatment.

Its pathogenesis is not well described in the literature but is easy to envision, Dr. Friedman said. For one, both advancing age and exposure to UV light lead to a reduction in hygroscopic glycosaminoglycans, including hyaluronate (HA), and the impact of this diminishment is believed to go “beyond [the loss of] buoyancy,” he noted. Researchers have “been showing these are not just water-loving molecules, they also have some biologic properties” relating to keratinocyte production and epidermal turnover that appear to be intricately linked to the pathogenesis of dermatoporosis. 

HAs have been shown to interact with the cell surface receptor CD44 to stimulate keratinocyte proliferation, and low levels of CD44 have been reported in skin with dermatoporosis compared with a younger control population. (A newly characterized organelle, the hyaluronosome, serves as an HA factory and contains CD44 and heparin-binding epidermal growth factor, Dr. Friedman noted. Inadequate functioning may be involved in skin atrophy.) 

Advancing age also brings an increase in matrix metalloproteinases (MMPs)–1, –2, and –3, which are “the demolition workers of the skin,” and downregulation of a tissue inhibitor of MMPs, he said. 

Adding insult to injury, dermis-penetrating UVA also activates MMPs, “obliterating collagen and elastin.” UVB generates DNA photoproducts, including oxidative stress and damaging skin cell DNA. “That UV light induces breakdown [of the skin] through different mechanisms and inhibits buildup is a simple concept I think our patients can understand,” Dr. Friedman said.
 

Multifaceted Treatment

For an older adult, “there is never a wrong time to start sun-protective measures” to prevent or try to halt the progression of dermatoporosis, Dr. Friedman said, noting that “UV radiation is an immunosuppressant, so there are many good reasons to start” if the adult is not already taking measures on a regular basis.

Potential treatments for the syndrome of dermatoporosis are backed by few clinical studies, but dermatologists are skilled at translating the use of products from one disease state to another based on understandings of pathophysiology and mechanistic pathways, Dr. Friedman commented in an interview after the meeting. 

For instance, “from decades of research, we know what retinoids will do to the skin,” he said in the interview. “We know they will turn on collagen-1 and -3 genes in the skin, and that they will increase the production of glycosaminoglycans ... By understanding the biology, we can translate this to dermatoporosis.” These changes were demonstrated, for instance, in a small study of topical retinol in older adults.

Studies of topical alpha hydroxy acid (AHA), moreover, have demonstrated epidermal thickening and firmness, and “some studies show they can limit steroid-induced atrophy,” Dr. Friedman said at the meeting. “And things like lactic acid and urea are super accessible.”

Topical dehydroepiandrosterone is backed by even less data than retinoids or AHAs are, “but it’s still something to consider” as part of a multimechanistic approach to dermatoporosis, Dr. Friedman shared, noting that a small study demonstrated beneficial effects on epidermal atrophy in aging skin. 

The use of vitamin D analogues such as calcipotriene, which is approved for the treatment of psoriasis, may also be promising. “One concept is that [vitamin D analogues] increase calcium concentrations in the epidermis, and calcium is so central to keratinocyte differentiation” and epidermal function that calcipotriene in combination with topical steroid therapy has been shown to limit skin atrophy, he noted.

Nutritionally, low protein intake is a known problem in the older population and is associated with increased skin fragility and poorer healing. From a prevention and treatment standpoint, therefore, patients can be counseled to be attentive to their diets, Dr. Friedman said. Experts have recommended a higher protein intake for older adults than for younger adults; in 2013, an international group recommended a protein intake of 1-1.5 g/kg/d for healthy older adults and more for those with acute or chronic illness.

“Patients love talking about diet and skin disease ... and they love over-the-counter nutraceuticals as well because they want something natural,” Dr. Friedman said. “I like using bioflavonoids in combination with vitamin C, which can be effective especially for solar purpura.”

Courtesy Dr. Adam Friedman

Skin Injury and Wound Prevention

In addition to recommending gentle skin cleansers and daily moisturizing, dermatologists should talk to their older patients with dermatoporosis about their home environments. “What is it like? Is there furniture with sharp edges?” Dr. Friedman advised. If so, could they use sleeves or protectors on their arms or legs “to protect against injury?”

In a later meeting session about lower-extremity wounds on geriatric patients, Michael Stempel, DPM, assistant professor of medicine and surgery and chief of podiatry at GWU, said that he was happy to hear the term dermatoporosis being used because like diabetes, it’s a risk factor for developing lower-extremity wounds and poor wound healing. 

He shared the case of an older woman with dermatoporosis who “tripped and skinned her knee against a step and then self-treated it for over a month by pouring hydrogen peroxide over it and letting air get to it.” The wound developed into “full-thickness tissue loss,” said Dr. Stempel, also medical director of the Wound Healing and Limb Preservation Center at GWU Hospital. 

Misperceptions are common among older patients about how a simple wound should be managed; for instance, the adage “just let it get air” is not uncommon. This makes anticipatory guidance about basic wound care — such as the importance of a moist and occlusive environment and the safe use of hydrogen peroxide — especially important for patients with dermatoporosis, Dr. Friedman commented after the meeting.

Dermatoporosis is quantifiable, Dr. Friedman said during the meeting, with a scoring system having been developed by the researchers in Switzerland who originally coined the term. Its use in practice is unnecessary, but its existence is “nice to share with patients who feel bothered because oftentimes, patients feel it’s been dismissed by other providers,” he said. “Telling your patients there’s an actual name for their problem, and that there are ways to quantify and measure changes over time, is validating.” 

Its recognition as a medical condition, Dr. Friedman added, also enables the dermatologist to bring it up and counsel appropriately — without a patient feeling shame — when it is identified in the context of a skin excision, treatment of a primary inflammatory skin disease, or management of another dermatologic problem.

Dr. Friedman disclosed that he is a consultant/advisory board member for L’Oréal, La Roche-Posay, Galderma, and other companies; a speaker for Regeneron/Sanofi, Incyte, BMD, and Janssen; and has grants from Pfizer, Lilly, Incyte, and other companies. Dr. Stempel reported no disclosures.

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

Ahmad Reza Djalali, an Iranian-Swedish physician specializing in disaster medicine, has begun a hunger strike after being sentenced to death in 2017.

Last year, Iran set a grim record, leading the world in executions. The country carried out at least 853 executions, which accounted for three quarters of the officially recorded executions worldwide. The Iranian government uses the death penalty to intimidate political opponents, especially since the women’s uprising in 2022, and to exert pressure on Western states in diplomatic standoffs.

Among the thousands of political prisoners currently on death row in Tehran’s notorious Evin prison is Dr. Djalali, a 52-year-old physician.

He emigrated to Sweden in 2009 and joined the Karolinska Institutet in Stockholm, Sweden. Over the years, he became one of Europe’s leading experts in disaster medicine. His work has been cited more than 700 times in medical literature, and he played a key role in establishing the emergency and disaster research center at the University of Piedmont.

In Italy, Denmark, and Sweden, Dr. Djalali helped hospitals and healthcare professionals in preparing for earthquakes, nuclear accidents, and terrorist attacks and designed several disaster medicine training programs.
 

‘Spreading Corruption’

Despite settling in Sweden with his family, Dr. Djalali never forgot his Iranian roots. His doctoral thesis was dedicated to the victims of the 2003 Bam earthquake in Iran, which killed 23,000 people. He expressed a desire to share his knowledge with his Iranian colleagues to help people. So when he was invited to participate in a 2016 conference at the University of Tehran, he accepted without hesitation.

Unfortunately, this decision had severe consequences. On April 25, 2016, as he was concluding his trip to Iran, the researcher was arrested by intelligence agents. After being held incommunicado for several days, he was officially accused of passing confidential information to Israeli intelligence services. According to his family, this accusation was baseless. They believed he was targeted for refusing to work for Iranian intelligence services in Europe.

On October 21, 2017, Dr. Djalali was sentenced to death for “spreading corruption on Earth,” a vague charge often used by Islamic courts against those who allegedly have challenged the regime. A few days later, a video of his “confessions” was broadcast on Iranian television. These confessions were coerced; Dr. Djalali later revealed that Iranian police had threatened to harm his mother in Iran and his family in Sweden.

Since then, Dr. Djalali and his loved ones have anxiously awaited the moment when the regime might carry out the sentence. Several times over the years, he has seemed on the verge of execution, only to receive a last-minute reprieve each time.

His imprisonment has taken a severe toll on his physical and mental health. He has reportedly lost 24 kg since his incarceration, and his family, who receive sporadic updates, suspect he has leukemia. Despite his deteriorating condition, the authorities have refused him access to a hematologist.
 

‘Forgotten’ in Exchange

The international medical community has rallied to secure Dr. Djalali’s release, but their efforts have so far been fruitless. The United Nations, the European Union, Amnesty International, several universities, and the World Medical Association have called for his release. In 2018, Sweden granted him citizenship in an attempt to increase pressure on Tehran, but Iranian law does not recognize dual citizenship.

On June 16, after nearly 7 years on death row, Dr. Djalali informed his family that he had begun a hunger strike. “It’s the only way to make my voice heard in the world,” he explained. “As a doctor, Ahmad Reza knows all too well that his fragile physical state makes a hunger strike potentially fatal, but he sees no other option. He suffers from cardiac arrhythmia, bradycardia, hypotension, chronic gastritis, anemia, and extreme weight loss following his two previous hunger strikes,” his wife told the press.

Aside from a potential (and unlikely) act of clemency by the Iranian authorities, Dr. Djalali’s best hope lies in a prisoner exchange. The Iranian government often imprisons foreign nationals to exchange them for Iranians detained in Western countries.

On June 15, Sweden agreed to release an Iranian dignitary serving a life sentence in exchange for the release of Swedish nationals detained in Iran. For a long time, Dr. Djalali’s family had hoped he would be included in this exchange.

However, to avoid jeopardizing the deal, the Swedish prime minister chose to accept the release of only two other Swedish nationals, leaving Dr. Djalali to his grim fate. “Mr Prime Minister, you have decided to abandon me at the enormous risk of being executed,” Dr. Djalali responded bitterly, knowing he could be hanged at any moment.
 

This story was translated from JIM 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.

Ahmad Reza Djalali, an Iranian-Swedish physician specializing in disaster medicine, has begun a hunger strike after being sentenced to death in 2017.

Last year, Iran set a grim record, leading the world in executions. The country carried out at least 853 executions, which accounted for three quarters of the officially recorded executions worldwide. The Iranian government uses the death penalty to intimidate political opponents, especially since the women’s uprising in 2022, and to exert pressure on Western states in diplomatic standoffs.

Among the thousands of political prisoners currently on death row in Tehran’s notorious Evin prison is Dr. Djalali, a 52-year-old physician.

He emigrated to Sweden in 2009 and joined the Karolinska Institutet in Stockholm, Sweden. Over the years, he became one of Europe’s leading experts in disaster medicine. His work has been cited more than 700 times in medical literature, and he played a key role in establishing the emergency and disaster research center at the University of Piedmont.

In Italy, Denmark, and Sweden, Dr. Djalali helped hospitals and healthcare professionals in preparing for earthquakes, nuclear accidents, and terrorist attacks and designed several disaster medicine training programs.
 

‘Spreading Corruption’

Despite settling in Sweden with his family, Dr. Djalali never forgot his Iranian roots. His doctoral thesis was dedicated to the victims of the 2003 Bam earthquake in Iran, which killed 23,000 people. He expressed a desire to share his knowledge with his Iranian colleagues to help people. So when he was invited to participate in a 2016 conference at the University of Tehran, he accepted without hesitation.

Unfortunately, this decision had severe consequences. On April 25, 2016, as he was concluding his trip to Iran, the researcher was arrested by intelligence agents. After being held incommunicado for several days, he was officially accused of passing confidential information to Israeli intelligence services. According to his family, this accusation was baseless. They believed he was targeted for refusing to work for Iranian intelligence services in Europe.

On October 21, 2017, Dr. Djalali was sentenced to death for “spreading corruption on Earth,” a vague charge often used by Islamic courts against those who allegedly have challenged the regime. A few days later, a video of his “confessions” was broadcast on Iranian television. These confessions were coerced; Dr. Djalali later revealed that Iranian police had threatened to harm his mother in Iran and his family in Sweden.

Since then, Dr. Djalali and his loved ones have anxiously awaited the moment when the regime might carry out the sentence. Several times over the years, he has seemed on the verge of execution, only to receive a last-minute reprieve each time.

His imprisonment has taken a severe toll on his physical and mental health. He has reportedly lost 24 kg since his incarceration, and his family, who receive sporadic updates, suspect he has leukemia. Despite his deteriorating condition, the authorities have refused him access to a hematologist.
 

‘Forgotten’ in Exchange

The international medical community has rallied to secure Dr. Djalali’s release, but their efforts have so far been fruitless. The United Nations, the European Union, Amnesty International, several universities, and the World Medical Association have called for his release. In 2018, Sweden granted him citizenship in an attempt to increase pressure on Tehran, but Iranian law does not recognize dual citizenship.

On June 16, after nearly 7 years on death row, Dr. Djalali informed his family that he had begun a hunger strike. “It’s the only way to make my voice heard in the world,” he explained. “As a doctor, Ahmad Reza knows all too well that his fragile physical state makes a hunger strike potentially fatal, but he sees no other option. He suffers from cardiac arrhythmia, bradycardia, hypotension, chronic gastritis, anemia, and extreme weight loss following his two previous hunger strikes,” his wife told the press.

Aside from a potential (and unlikely) act of clemency by the Iranian authorities, Dr. Djalali’s best hope lies in a prisoner exchange. The Iranian government often imprisons foreign nationals to exchange them for Iranians detained in Western countries.

On June 15, Sweden agreed to release an Iranian dignitary serving a life sentence in exchange for the release of Swedish nationals detained in Iran. For a long time, Dr. Djalali’s family had hoped he would be included in this exchange.

However, to avoid jeopardizing the deal, the Swedish prime minister chose to accept the release of only two other Swedish nationals, leaving Dr. Djalali to his grim fate. “Mr Prime Minister, you have decided to abandon me at the enormous risk of being executed,” Dr. Djalali responded bitterly, knowing he could be hanged at any moment.
 

This story was translated from JIM 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.

Ahmad Reza Djalali, an Iranian-Swedish physician specializing in disaster medicine, has begun a hunger strike after being sentenced to death in 2017.

Last year, Iran set a grim record, leading the world in executions. The country carried out at least 853 executions, which accounted for three quarters of the officially recorded executions worldwide. The Iranian government uses the death penalty to intimidate political opponents, especially since the women’s uprising in 2022, and to exert pressure on Western states in diplomatic standoffs.

Among the thousands of political prisoners currently on death row in Tehran’s notorious Evin prison is Dr. Djalali, a 52-year-old physician.

He emigrated to Sweden in 2009 and joined the Karolinska Institutet in Stockholm, Sweden. Over the years, he became one of Europe’s leading experts in disaster medicine. His work has been cited more than 700 times in medical literature, and he played a key role in establishing the emergency and disaster research center at the University of Piedmont.

In Italy, Denmark, and Sweden, Dr. Djalali helped hospitals and healthcare professionals in preparing for earthquakes, nuclear accidents, and terrorist attacks and designed several disaster medicine training programs.
 

‘Spreading Corruption’

Despite settling in Sweden with his family, Dr. Djalali never forgot his Iranian roots. His doctoral thesis was dedicated to the victims of the 2003 Bam earthquake in Iran, which killed 23,000 people. He expressed a desire to share his knowledge with his Iranian colleagues to help people. So when he was invited to participate in a 2016 conference at the University of Tehran, he accepted without hesitation.

Unfortunately, this decision had severe consequences. On April 25, 2016, as he was concluding his trip to Iran, the researcher was arrested by intelligence agents. After being held incommunicado for several days, he was officially accused of passing confidential information to Israeli intelligence services. According to his family, this accusation was baseless. They believed he was targeted for refusing to work for Iranian intelligence services in Europe.

On October 21, 2017, Dr. Djalali was sentenced to death for “spreading corruption on Earth,” a vague charge often used by Islamic courts against those who allegedly have challenged the regime. A few days later, a video of his “confessions” was broadcast on Iranian television. These confessions were coerced; Dr. Djalali later revealed that Iranian police had threatened to harm his mother in Iran and his family in Sweden.

Since then, Dr. Djalali and his loved ones have anxiously awaited the moment when the regime might carry out the sentence. Several times over the years, he has seemed on the verge of execution, only to receive a last-minute reprieve each time.

His imprisonment has taken a severe toll on his physical and mental health. He has reportedly lost 24 kg since his incarceration, and his family, who receive sporadic updates, suspect he has leukemia. Despite his deteriorating condition, the authorities have refused him access to a hematologist.
 

‘Forgotten’ in Exchange

The international medical community has rallied to secure Dr. Djalali’s release, but their efforts have so far been fruitless. The United Nations, the European Union, Amnesty International, several universities, and the World Medical Association have called for his release. In 2018, Sweden granted him citizenship in an attempt to increase pressure on Tehran, but Iranian law does not recognize dual citizenship.

On June 16, after nearly 7 years on death row, Dr. Djalali informed his family that he had begun a hunger strike. “It’s the only way to make my voice heard in the world,” he explained. “As a doctor, Ahmad Reza knows all too well that his fragile physical state makes a hunger strike potentially fatal, but he sees no other option. He suffers from cardiac arrhythmia, bradycardia, hypotension, chronic gastritis, anemia, and extreme weight loss following his two previous hunger strikes,” his wife told the press.

Aside from a potential (and unlikely) act of clemency by the Iranian authorities, Dr. Djalali’s best hope lies in a prisoner exchange. The Iranian government often imprisons foreign nationals to exchange them for Iranians detained in Western countries.

On June 15, Sweden agreed to release an Iranian dignitary serving a life sentence in exchange for the release of Swedish nationals detained in Iran. For a long time, Dr. Djalali’s family had hoped he would be included in this exchange.

However, to avoid jeopardizing the deal, the Swedish prime minister chose to accept the release of only two other Swedish nationals, leaving Dr. Djalali to his grim fate. “Mr Prime Minister, you have decided to abandon me at the enormous risk of being executed,” Dr. Djalali responded bitterly, knowing he could be hanged at any moment.
 

This story was translated from JIM 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.

WASHINGTON, DC — The onset of atopic dermatitis (AD) in older adulthood — even in adults aged ≥ 90 years — is a phenomenon documented in the literature in recent years, with reports showing age-related immune differences and differences in risk factors, Jonathan I. Silverberg, MD, PhD, MPH, said at the ElderDerm Conference on dermatology in the older patient hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC. 

“I walked out of residency under the impression that if it didn’t start in the first year or two of life, it’s not AD,” said Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University. “The numbers tell us a very different story.” 

Dr. Silverberg

The prevalence of AD in the United States fluctuates between 6% and 8% through adulthood, including age categories up to 81-85 years, according to 2012 National Health Interview Survey data. And while persistence of childhood-onset AD is common, a systematic review and meta-analysis published in 2018 concluded that one in four adults with AD report adult-onset disease. 

The investigators, including Dr. Silverberg, identified 25 observational studies — studies conducted across 16 countries and published during 1956-2017 — that included an analysis of age of onset beyond 10 years of age, and other inclusion criteria. Of the 25 studies, 17 reported age of onset after 16 years of age and had sufficient data for the meta-analysis. Using random-effects weighting, the investigators found a pooled proportion of adult-onset AD of 26.1% (95% CI, 16.5%-37.2%).

The research demonstrates that “the age of onset is distributed well throughout the lifespan,” Dr. Silverberg said, with the data “indicating there are many elderly-onset cases of true AD as well.” (Thirteen of the studies analyzed an age of onset from age ≥ 65, and several looked beyond age 80). 

A 2021 study of a primary care database in the United Kingdom of 3.85 million children and adults found a “fascinating” bimodal distribution of incidence across the lifespan, with peaks in both infancy and older adulthood, he said. Incidence in adulthood was relatively stable from ages 18-49 years, after which, “into the 50s, 60s and beyond, you started to see a steady climb again.” 

Also intriguing, Dr. Silverberg continued, are findings from a study of outpatient healthcare utilization for AD in which he and his coinvestigator analyzed data from the National Ambulatory Medical Care Survey (NAMCS). In the article, published in 2023 covering data from the 1993-2015 NAMCS, they reported that AD visits were more common among children aged 0-4 years (32.0%) and 5-9 years of age (10.6%), then decreased in adolescents aged 10-19 years (11.6%), remained fairly steady in patients aged 20-89 years (1.0%-4.7%), and increased in patients aged > 90 years (20.7%).

“The peak usage for dermatologists, primary care physicians, etc., is happening in the first few years of life, partially because that’s when the disease is more common and more severe but also partially because that’s when parents and caregivers are first learning [about] the disease and trying to understand how to gain control,” Dr. Silverberg said at the meeting, presenting data from an expanded, unpublished analysis of NAMCS data showing these same outpatient utilization patterns. 

“It’s fascinating — there’s a much greater utilization in the elderly population. Why? The short answer is, we don’t know,” he said. 
 

Risk Factors, Immune Differences

People with adult-onset AD were more likely to be women, smokers in adulthood, and have a lower childhood socioeconomic status than those whose AD started in childhood in a longitudinal study of two large birth cohorts from the United Kingdom , Dr. Silverberg pointed out.

Patients with childhood-onset AD, meanwhile, were more likely to have asthma, allergen-specific immunoglobulin E (IgE), and known genetic polymorphisms previously associated with AD. (Each cohort — the 1958 British Cohort Study and the 1970 British Cohort Study — had more than 17,000 participants who were followed from birth through middle age.)

Data is limited, but “mechanistically,” AD in much older adults appears to have a unique serum cytokine pattern, Dr. Silverberg said. He pointed to a cross-sectional study in China of 1312 children and adults with AD in which researchers analyzed clinical features, serum samples, and skin biopsy samples.

Adults aged > 60 years showed more lesions on the trunk and extensor sites of the extremities and lower levels of serum IgE and peripheral eosinophil counts than those in younger age groups. And “interestingly,” compared with healthy controls, older patients with AD had “higher levels of serum expression of a variety of cytokines, including IL [interleukin]-4 but also high TARC levels ... and a variety of cytokines related to the Th17, TH1 axes, etc.,” he said. 

“So, we’re seeing a fascinating new profile that may be a little different than younger-onset cases,” he said, noting that TARC (thymus and activation-regulated chemokine) is regarded as a “decent biomarker” for AD.

In addition to higher levels of IL-4 and TARC, the study investigators reported significantly higher levels of IL-17A, IL-6, IL-22, IL-33, and thymic stromal lymphopoietin in older patients, compared with healthy controls.

Research also suggests that air pollution may play a role in the onset of AD in older age, Dr. Silverberg said, referencing a 2023 study that explored the association of air pollution and genetic risk with the onset of AD after age 50. The study analyzed 337,910 participants from the UK Biobank, with a median 12-year follow-up. Genetic risks were assessed as low, intermediate, and high, based on tertiles of polygenic risk scores. Exposure to various air pollutants was assessed using weighted quantile sum and also categorized into tertiles.

The incidence of older adult-onset AD was associated with medium and high air pollution compared with low air pollution, with hazard ratios (HRs) of 1.182 (P = .003) and 1.359 (P < .001), respectively. And “to a lesser extent,” Dr. Silverberg said, incidence was associated with medium and high genetic susceptibility, with HRs of 1.065 (P = .249) and 1.153 (P = .008).

The researchers calculated a greater population-attributable fraction of air pollution (15.5%) than genetic risk (6.4%). “This means that yes, genetics can contribute even to later-onset disease ... but environment may play an even more important role,” Dr. Silverberg said.

In the Clinic

In all patients, and especially in older adults, sleep disturbance associated with AD is a consideration for care. Data collected at the eczema clinic of Northwestern University, Chicago, Illinois, between 2014 and 2019 through previsit, self-administered questionnaires show that patients ≥ 65 years of age have more profound sleep disturbance (especially trouble staying asleep) than patients aged 18-64 years, despite having similar AD severity, said Dr. Silverberg, a coinvestigator of the study.

Older age was associated with having an increased number of nights of sleep disturbance (3-7 nights in the previous week) because of eczema (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16-3.92). It was also associated with itching-attributed delays in falling asleep and nighttime awakenings in the prior 2 weeks (aOR, 1.88; 95% CI, 1.05-3.39). 

“The aging population has dysregulated sleep patterns and altered circadian rhythms, so some of this is just natural predisposition,” Dr. Silverberg said. “But it’s amplified [with AD and itching], and it becomes a big clinical problem when we get into treatment because it’s our natural inclination to prescribe antihistamines for their sedative properties.”

Antihistamines can cause more profound sedation, more forgetfulness, and more anticholinergic side effects, he said, noting that “there’s some evidence that high-dose antihistamines may exacerbate dementia.”

Medication side effects and medication interactions, comorbidities, and decreased renal and hepatic clearance all can complicate treatment of AD in older adults. So can mobility, the extent of social/caregiving support, and other aspects of aging. For example, “I’m a big fan of ‘soak and smears’ ... but you have to ask, can you get out of a bathtub safely?” Dr. Silverberg said. “And you have to ask, can you reach the areas you need to [in order] to apply topicals?”

With oral Janus kinase inhibitors and other systemic medications, as with other drugs, “our older population is the most vulnerable from a safety perspective,” he said. A recently published post hoc analysis of four randomized trials of dupilumab in adults ≥ 60 years of age with moderate to severe AD demonstrated efficacy comparable with that in younger patients and “a really clean safety profile,” said Dr. Silverberg, the lead author. “We really need more of these types of post hocs to have some relative contextualization” for older adults.

Dr. Silverberg reported being a speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; a consultant and/or advisory board member for Regeneron, Sanofi-Genzyme, and other companies; and an investigator for several companies.

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

WASHINGTON, DC — The onset of atopic dermatitis (AD) in older adulthood — even in adults aged ≥ 90 years — is a phenomenon documented in the literature in recent years, with reports showing age-related immune differences and differences in risk factors, Jonathan I. Silverberg, MD, PhD, MPH, said at the ElderDerm Conference on dermatology in the older patient hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC. 

“I walked out of residency under the impression that if it didn’t start in the first year or two of life, it’s not AD,” said Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University. “The numbers tell us a very different story.” 

Dr. Silverberg

The prevalence of AD in the United States fluctuates between 6% and 8% through adulthood, including age categories up to 81-85 years, according to 2012 National Health Interview Survey data. And while persistence of childhood-onset AD is common, a systematic review and meta-analysis published in 2018 concluded that one in four adults with AD report adult-onset disease. 

The investigators, including Dr. Silverberg, identified 25 observational studies — studies conducted across 16 countries and published during 1956-2017 — that included an analysis of age of onset beyond 10 years of age, and other inclusion criteria. Of the 25 studies, 17 reported age of onset after 16 years of age and had sufficient data for the meta-analysis. Using random-effects weighting, the investigators found a pooled proportion of adult-onset AD of 26.1% (95% CI, 16.5%-37.2%).

The research demonstrates that “the age of onset is distributed well throughout the lifespan,” Dr. Silverberg said, with the data “indicating there are many elderly-onset cases of true AD as well.” (Thirteen of the studies analyzed an age of onset from age ≥ 65, and several looked beyond age 80). 

A 2021 study of a primary care database in the United Kingdom of 3.85 million children and adults found a “fascinating” bimodal distribution of incidence across the lifespan, with peaks in both infancy and older adulthood, he said. Incidence in adulthood was relatively stable from ages 18-49 years, after which, “into the 50s, 60s and beyond, you started to see a steady climb again.” 

Also intriguing, Dr. Silverberg continued, are findings from a study of outpatient healthcare utilization for AD in which he and his coinvestigator analyzed data from the National Ambulatory Medical Care Survey (NAMCS). In the article, published in 2023 covering data from the 1993-2015 NAMCS, they reported that AD visits were more common among children aged 0-4 years (32.0%) and 5-9 years of age (10.6%), then decreased in adolescents aged 10-19 years (11.6%), remained fairly steady in patients aged 20-89 years (1.0%-4.7%), and increased in patients aged > 90 years (20.7%).

“The peak usage for dermatologists, primary care physicians, etc., is happening in the first few years of life, partially because that’s when the disease is more common and more severe but also partially because that’s when parents and caregivers are first learning [about] the disease and trying to understand how to gain control,” Dr. Silverberg said at the meeting, presenting data from an expanded, unpublished analysis of NAMCS data showing these same outpatient utilization patterns. 

“It’s fascinating — there’s a much greater utilization in the elderly population. Why? The short answer is, we don’t know,” he said. 
 

Risk Factors, Immune Differences

People with adult-onset AD were more likely to be women, smokers in adulthood, and have a lower childhood socioeconomic status than those whose AD started in childhood in a longitudinal study of two large birth cohorts from the United Kingdom , Dr. Silverberg pointed out.

Patients with childhood-onset AD, meanwhile, were more likely to have asthma, allergen-specific immunoglobulin E (IgE), and known genetic polymorphisms previously associated with AD. (Each cohort — the 1958 British Cohort Study and the 1970 British Cohort Study — had more than 17,000 participants who were followed from birth through middle age.)

Data is limited, but “mechanistically,” AD in much older adults appears to have a unique serum cytokine pattern, Dr. Silverberg said. He pointed to a cross-sectional study in China of 1312 children and adults with AD in which researchers analyzed clinical features, serum samples, and skin biopsy samples.

Adults aged > 60 years showed more lesions on the trunk and extensor sites of the extremities and lower levels of serum IgE and peripheral eosinophil counts than those in younger age groups. And “interestingly,” compared with healthy controls, older patients with AD had “higher levels of serum expression of a variety of cytokines, including IL [interleukin]-4 but also high TARC levels ... and a variety of cytokines related to the Th17, TH1 axes, etc.,” he said. 

“So, we’re seeing a fascinating new profile that may be a little different than younger-onset cases,” he said, noting that TARC (thymus and activation-regulated chemokine) is regarded as a “decent biomarker” for AD.

In addition to higher levels of IL-4 and TARC, the study investigators reported significantly higher levels of IL-17A, IL-6, IL-22, IL-33, and thymic stromal lymphopoietin in older patients, compared with healthy controls.

Research also suggests that air pollution may play a role in the onset of AD in older age, Dr. Silverberg said, referencing a 2023 study that explored the association of air pollution and genetic risk with the onset of AD after age 50. The study analyzed 337,910 participants from the UK Biobank, with a median 12-year follow-up. Genetic risks were assessed as low, intermediate, and high, based on tertiles of polygenic risk scores. Exposure to various air pollutants was assessed using weighted quantile sum and also categorized into tertiles.

The incidence of older adult-onset AD was associated with medium and high air pollution compared with low air pollution, with hazard ratios (HRs) of 1.182 (P = .003) and 1.359 (P < .001), respectively. And “to a lesser extent,” Dr. Silverberg said, incidence was associated with medium and high genetic susceptibility, with HRs of 1.065 (P = .249) and 1.153 (P = .008).

The researchers calculated a greater population-attributable fraction of air pollution (15.5%) than genetic risk (6.4%). “This means that yes, genetics can contribute even to later-onset disease ... but environment may play an even more important role,” Dr. Silverberg said.

In the Clinic

In all patients, and especially in older adults, sleep disturbance associated with AD is a consideration for care. Data collected at the eczema clinic of Northwestern University, Chicago, Illinois, between 2014 and 2019 through previsit, self-administered questionnaires show that patients ≥ 65 years of age have more profound sleep disturbance (especially trouble staying asleep) than patients aged 18-64 years, despite having similar AD severity, said Dr. Silverberg, a coinvestigator of the study.

Older age was associated with having an increased number of nights of sleep disturbance (3-7 nights in the previous week) because of eczema (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16-3.92). It was also associated with itching-attributed delays in falling asleep and nighttime awakenings in the prior 2 weeks (aOR, 1.88; 95% CI, 1.05-3.39). 

“The aging population has dysregulated sleep patterns and altered circadian rhythms, so some of this is just natural predisposition,” Dr. Silverberg said. “But it’s amplified [with AD and itching], and it becomes a big clinical problem when we get into treatment because it’s our natural inclination to prescribe antihistamines for their sedative properties.”

Antihistamines can cause more profound sedation, more forgetfulness, and more anticholinergic side effects, he said, noting that “there’s some evidence that high-dose antihistamines may exacerbate dementia.”

Medication side effects and medication interactions, comorbidities, and decreased renal and hepatic clearance all can complicate treatment of AD in older adults. So can mobility, the extent of social/caregiving support, and other aspects of aging. For example, “I’m a big fan of ‘soak and smears’ ... but you have to ask, can you get out of a bathtub safely?” Dr. Silverberg said. “And you have to ask, can you reach the areas you need to [in order] to apply topicals?”

With oral Janus kinase inhibitors and other systemic medications, as with other drugs, “our older population is the most vulnerable from a safety perspective,” he said. A recently published post hoc analysis of four randomized trials of dupilumab in adults ≥ 60 years of age with moderate to severe AD demonstrated efficacy comparable with that in younger patients and “a really clean safety profile,” said Dr. Silverberg, the lead author. “We really need more of these types of post hocs to have some relative contextualization” for older adults.

Dr. Silverberg reported being a speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; a consultant and/or advisory board member for Regeneron, Sanofi-Genzyme, and other companies; and an investigator for several companies.

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

WASHINGTON, DC — The onset of atopic dermatitis (AD) in older adulthood — even in adults aged ≥ 90 years — is a phenomenon documented in the literature in recent years, with reports showing age-related immune differences and differences in risk factors, Jonathan I. Silverberg, MD, PhD, MPH, said at the ElderDerm Conference on dermatology in the older patient hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC. 

“I walked out of residency under the impression that if it didn’t start in the first year or two of life, it’s not AD,” said Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University. “The numbers tell us a very different story.” 

Dr. Silverberg

The prevalence of AD in the United States fluctuates between 6% and 8% through adulthood, including age categories up to 81-85 years, according to 2012 National Health Interview Survey data. And while persistence of childhood-onset AD is common, a systematic review and meta-analysis published in 2018 concluded that one in four adults with AD report adult-onset disease. 

The investigators, including Dr. Silverberg, identified 25 observational studies — studies conducted across 16 countries and published during 1956-2017 — that included an analysis of age of onset beyond 10 years of age, and other inclusion criteria. Of the 25 studies, 17 reported age of onset after 16 years of age and had sufficient data for the meta-analysis. Using random-effects weighting, the investigators found a pooled proportion of adult-onset AD of 26.1% (95% CI, 16.5%-37.2%).

The research demonstrates that “the age of onset is distributed well throughout the lifespan,” Dr. Silverberg said, with the data “indicating there are many elderly-onset cases of true AD as well.” (Thirteen of the studies analyzed an age of onset from age ≥ 65, and several looked beyond age 80). 

A 2021 study of a primary care database in the United Kingdom of 3.85 million children and adults found a “fascinating” bimodal distribution of incidence across the lifespan, with peaks in both infancy and older adulthood, he said. Incidence in adulthood was relatively stable from ages 18-49 years, after which, “into the 50s, 60s and beyond, you started to see a steady climb again.” 

Also intriguing, Dr. Silverberg continued, are findings from a study of outpatient healthcare utilization for AD in which he and his coinvestigator analyzed data from the National Ambulatory Medical Care Survey (NAMCS). In the article, published in 2023 covering data from the 1993-2015 NAMCS, they reported that AD visits were more common among children aged 0-4 years (32.0%) and 5-9 years of age (10.6%), then decreased in adolescents aged 10-19 years (11.6%), remained fairly steady in patients aged 20-89 years (1.0%-4.7%), and increased in patients aged > 90 years (20.7%).

“The peak usage for dermatologists, primary care physicians, etc., is happening in the first few years of life, partially because that’s when the disease is more common and more severe but also partially because that’s when parents and caregivers are first learning [about] the disease and trying to understand how to gain control,” Dr. Silverberg said at the meeting, presenting data from an expanded, unpublished analysis of NAMCS data showing these same outpatient utilization patterns. 

“It’s fascinating — there’s a much greater utilization in the elderly population. Why? The short answer is, we don’t know,” he said. 
 

Risk Factors, Immune Differences

People with adult-onset AD were more likely to be women, smokers in adulthood, and have a lower childhood socioeconomic status than those whose AD started in childhood in a longitudinal study of two large birth cohorts from the United Kingdom , Dr. Silverberg pointed out.

Patients with childhood-onset AD, meanwhile, were more likely to have asthma, allergen-specific immunoglobulin E (IgE), and known genetic polymorphisms previously associated with AD. (Each cohort — the 1958 British Cohort Study and the 1970 British Cohort Study — had more than 17,000 participants who were followed from birth through middle age.)

Data is limited, but “mechanistically,” AD in much older adults appears to have a unique serum cytokine pattern, Dr. Silverberg said. He pointed to a cross-sectional study in China of 1312 children and adults with AD in which researchers analyzed clinical features, serum samples, and skin biopsy samples.

Adults aged > 60 years showed more lesions on the trunk and extensor sites of the extremities and lower levels of serum IgE and peripheral eosinophil counts than those in younger age groups. And “interestingly,” compared with healthy controls, older patients with AD had “higher levels of serum expression of a variety of cytokines, including IL [interleukin]-4 but also high TARC levels ... and a variety of cytokines related to the Th17, TH1 axes, etc.,” he said. 

“So, we’re seeing a fascinating new profile that may be a little different than younger-onset cases,” he said, noting that TARC (thymus and activation-regulated chemokine) is regarded as a “decent biomarker” for AD.

In addition to higher levels of IL-4 and TARC, the study investigators reported significantly higher levels of IL-17A, IL-6, IL-22, IL-33, and thymic stromal lymphopoietin in older patients, compared with healthy controls.

Research also suggests that air pollution may play a role in the onset of AD in older age, Dr. Silverberg said, referencing a 2023 study that explored the association of air pollution and genetic risk with the onset of AD after age 50. The study analyzed 337,910 participants from the UK Biobank, with a median 12-year follow-up. Genetic risks were assessed as low, intermediate, and high, based on tertiles of polygenic risk scores. Exposure to various air pollutants was assessed using weighted quantile sum and also categorized into tertiles.

The incidence of older adult-onset AD was associated with medium and high air pollution compared with low air pollution, with hazard ratios (HRs) of 1.182 (P = .003) and 1.359 (P < .001), respectively. And “to a lesser extent,” Dr. Silverberg said, incidence was associated with medium and high genetic susceptibility, with HRs of 1.065 (P = .249) and 1.153 (P = .008).

The researchers calculated a greater population-attributable fraction of air pollution (15.5%) than genetic risk (6.4%). “This means that yes, genetics can contribute even to later-onset disease ... but environment may play an even more important role,” Dr. Silverberg said.

In the Clinic

In all patients, and especially in older adults, sleep disturbance associated with AD is a consideration for care. Data collected at the eczema clinic of Northwestern University, Chicago, Illinois, between 2014 and 2019 through previsit, self-administered questionnaires show that patients ≥ 65 years of age have more profound sleep disturbance (especially trouble staying asleep) than patients aged 18-64 years, despite having similar AD severity, said Dr. Silverberg, a coinvestigator of the study.

Older age was associated with having an increased number of nights of sleep disturbance (3-7 nights in the previous week) because of eczema (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16-3.92). It was also associated with itching-attributed delays in falling asleep and nighttime awakenings in the prior 2 weeks (aOR, 1.88; 95% CI, 1.05-3.39). 

“The aging population has dysregulated sleep patterns and altered circadian rhythms, so some of this is just natural predisposition,” Dr. Silverberg said. “But it’s amplified [with AD and itching], and it becomes a big clinical problem when we get into treatment because it’s our natural inclination to prescribe antihistamines for their sedative properties.”

Antihistamines can cause more profound sedation, more forgetfulness, and more anticholinergic side effects, he said, noting that “there’s some evidence that high-dose antihistamines may exacerbate dementia.”

Medication side effects and medication interactions, comorbidities, and decreased renal and hepatic clearance all can complicate treatment of AD in older adults. So can mobility, the extent of social/caregiving support, and other aspects of aging. For example, “I’m a big fan of ‘soak and smears’ ... but you have to ask, can you get out of a bathtub safely?” Dr. Silverberg said. “And you have to ask, can you reach the areas you need to [in order] to apply topicals?”

With oral Janus kinase inhibitors and other systemic medications, as with other drugs, “our older population is the most vulnerable from a safety perspective,” he said. A recently published post hoc analysis of four randomized trials of dupilumab in adults ≥ 60 years of age with moderate to severe AD demonstrated efficacy comparable with that in younger patients and “a really clean safety profile,” said Dr. Silverberg, the lead author. “We really need more of these types of post hocs to have some relative contextualization” for older adults.

Dr. Silverberg reported being a speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; a consultant and/or advisory board member for Regeneron, Sanofi-Genzyme, and other companies; and an investigator for several companies.

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

SEATTLE — Musculoskeletal (MSK) symptoms are common in patients with psoriasis, but should they be primarily handled by dermatologists or should rheumatologists be “in the driver’s seat?” That was the subject of a debate between a dermatologist and a rheumatologist at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

Fabian Proft, MD, the rheumatologist, spoke first and emphasized the potential that MSK symptoms are a sign of psoriatic arthritis (PsA) and therefore should be managed by a rheumatologist.

“Obviously, the rheumatologist perspective [is that] I should be in the driver’s seat when taking care of patient with psoriasis and MSK symptoms, but I will still need to have a copilot there: [The dermatologist] will have a slot,” said Dr. Proft, who is a rheumatologist at Charité — Universitätsmedizin Berlin.

“It’s so important that we make the correct and early diagnosis of [psoriatic arthritis and psoriasis] symptoms,” said Dr. Proft. He specifically called out cases where patients have symptoms that are difficult to determine, whether the cause is inflammatory, and when experience with imaging can be a key factor in the diagnosis.

It’s important not to overdiagnose or overtreat patients, he said, providing an example of a patient with psoriasis who had been training for a marathon. The MRI image suggested that his Achilles tendonitis pain was related to his athletic training, not PsA-associated inflammation. “So I think this is very important that you have the knowledge to read MRIs, and especially also carefully assessing them so as not to overdiagnose patients,” said Dr. Proft.

Dermatologist Rebuttal

In her rebuttal, Laura Savage, MD, PhD, emphasized the need for more of a coequal partnership between the two specialties because of the ability of dermatologists to intervene early in the treatment and prevention of PsA.

“Traditionally, I agree rheumatologists would solely be responsible for the assessment and the management of psoriatic arthritis, but I think that paradigm has shifted in part due to the increased recognition of the need for earlier intervention to limit disease progression and to reduce or even prevent functional limitation,” said Dr. Savage, who is a consultant dermatologist at Leeds Teaching Hospitals NHS Trust and a senior lecturer at the University of Leeds, Leeds, England.

Ideally, molecular biomarkers would be available to predict the development of PsA, but there aren’t any. Still, “we have a huge biomarker in the form of the skin, and it’s recognized that the majority of patients who will develop psoriatic arthritis will have antecedent psoriasis in about 70% of cases,” Dr. Savage said. “There’s a typical time delay of around 7-12 years between the onset of the skin [disease] and the patients developing psoriatic arthritis, and so many of them are going to be into the care of other healthcare practitioners, and particularly the care of dermatologists.”

Dermatologists may also be able to play a role in the prevention of PsA, according to Dr. Savage. In one retrospective study, treatment of skin lesions with biologics was associated with a reduced frequency of progression to PsA (11.1% vs 16.4%) over 10 years (P = .0006). Studies with tumor necrosis factor inhibitors and other interventions have shown similar results.

Such findings have led to the treat intercept strategy, which targets patients with psoriasis who have risk factors for transition to PsA — such as nail pitting, gluteal cleft disease, scalp disease, type 2 diabetes, obesity, and a first-degree relative with PsA — as well as symptoms of prodromal PSA, such as arthralgia and fatigue.

“I think dermatologists are aware of the need to not leave our patients languishing on these therapies and actually escalating them onto effective treatments that may also be able to treat early psoriatic arthritis. We could be more mindful about our choice of treatments for these patients, going on to thinking about their increased risk of PSA and trying to intercept,” Dr. Savage said. “What we don’t want is our patients to be developing these musculoskeletal symptoms of pain and stiffness and functional limitation and disability. We want to be treating the patients with musculoskeletal symptoms of that earlier prodromal phase when they’re developing arthralgia and fatigue.”

She conceded that more complicated patients are good candidates for care by the rheumatologist. “You can do your fancy imaging, and we’ll leave that to you, and the difficult-to-treat patients to [the rheumatologist], but actually we need to just get on and treat them,” she said. “One could argue as well that as a dermatologist, I’m likely to broaden my horizons in terms of choice of therapy and treat all of the domains of the patient. So I would argue that actually it should be the dermatologist who is in that driving seat, particularly when it comes to the management of early psoriatic arthritis, and actually what we should be doing is driving our patients and steering them to earlier intervention and better control for all domains of disease.”
 

Collaborative Care

During the follow-up discussion, both Dr. Proft and Dr. Savage agreed that dermatologists and rheumatologists should be working together in managing patients. “What we need to do is steer our patients toward collaborative care with our rheumatologists by trying to minimize delays to treatment, by working together in parallel clinics, combined clinics, and on virtual [multidisciplinary teams],” said Dr. Savage.

Dr. Proft agreed. “We should join forces and make decisions together.”

Dr. Savage and Dr. Proft did not provide any financial disclosures.

A version of this article appeared on Medscape.com.

SEATTLE — Musculoskeletal (MSK) symptoms are common in patients with psoriasis, but should they be primarily handled by dermatologists or should rheumatologists be “in the driver’s seat?” That was the subject of a debate between a dermatologist and a rheumatologist at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

Fabian Proft, MD, the rheumatologist, spoke first and emphasized the potential that MSK symptoms are a sign of psoriatic arthritis (PsA) and therefore should be managed by a rheumatologist.

“Obviously, the rheumatologist perspective [is that] I should be in the driver’s seat when taking care of patient with psoriasis and MSK symptoms, but I will still need to have a copilot there: [The dermatologist] will have a slot,” said Dr. Proft, who is a rheumatologist at Charité — Universitätsmedizin Berlin.

“It’s so important that we make the correct and early diagnosis of [psoriatic arthritis and psoriasis] symptoms,” said Dr. Proft. He specifically called out cases where patients have symptoms that are difficult to determine, whether the cause is inflammatory, and when experience with imaging can be a key factor in the diagnosis.

It’s important not to overdiagnose or overtreat patients, he said, providing an example of a patient with psoriasis who had been training for a marathon. The MRI image suggested that his Achilles tendonitis pain was related to his athletic training, not PsA-associated inflammation. “So I think this is very important that you have the knowledge to read MRIs, and especially also carefully assessing them so as not to overdiagnose patients,” said Dr. Proft.

Dermatologist Rebuttal

In her rebuttal, Laura Savage, MD, PhD, emphasized the need for more of a coequal partnership between the two specialties because of the ability of dermatologists to intervene early in the treatment and prevention of PsA.

“Traditionally, I agree rheumatologists would solely be responsible for the assessment and the management of psoriatic arthritis, but I think that paradigm has shifted in part due to the increased recognition of the need for earlier intervention to limit disease progression and to reduce or even prevent functional limitation,” said Dr. Savage, who is a consultant dermatologist at Leeds Teaching Hospitals NHS Trust and a senior lecturer at the University of Leeds, Leeds, England.

Ideally, molecular biomarkers would be available to predict the development of PsA, but there aren’t any. Still, “we have a huge biomarker in the form of the skin, and it’s recognized that the majority of patients who will develop psoriatic arthritis will have antecedent psoriasis in about 70% of cases,” Dr. Savage said. “There’s a typical time delay of around 7-12 years between the onset of the skin [disease] and the patients developing psoriatic arthritis, and so many of them are going to be into the care of other healthcare practitioners, and particularly the care of dermatologists.”

Dermatologists may also be able to play a role in the prevention of PsA, according to Dr. Savage. In one retrospective study, treatment of skin lesions with biologics was associated with a reduced frequency of progression to PsA (11.1% vs 16.4%) over 10 years (P = .0006). Studies with tumor necrosis factor inhibitors and other interventions have shown similar results.

Such findings have led to the treat intercept strategy, which targets patients with psoriasis who have risk factors for transition to PsA — such as nail pitting, gluteal cleft disease, scalp disease, type 2 diabetes, obesity, and a first-degree relative with PsA — as well as symptoms of prodromal PSA, such as arthralgia and fatigue.

“I think dermatologists are aware of the need to not leave our patients languishing on these therapies and actually escalating them onto effective treatments that may also be able to treat early psoriatic arthritis. We could be more mindful about our choice of treatments for these patients, going on to thinking about their increased risk of PSA and trying to intercept,” Dr. Savage said. “What we don’t want is our patients to be developing these musculoskeletal symptoms of pain and stiffness and functional limitation and disability. We want to be treating the patients with musculoskeletal symptoms of that earlier prodromal phase when they’re developing arthralgia and fatigue.”

She conceded that more complicated patients are good candidates for care by the rheumatologist. “You can do your fancy imaging, and we’ll leave that to you, and the difficult-to-treat patients to [the rheumatologist], but actually we need to just get on and treat them,” she said. “One could argue as well that as a dermatologist, I’m likely to broaden my horizons in terms of choice of therapy and treat all of the domains of the patient. So I would argue that actually it should be the dermatologist who is in that driving seat, particularly when it comes to the management of early psoriatic arthritis, and actually what we should be doing is driving our patients and steering them to earlier intervention and better control for all domains of disease.”
 

Collaborative Care

During the follow-up discussion, both Dr. Proft and Dr. Savage agreed that dermatologists and rheumatologists should be working together in managing patients. “What we need to do is steer our patients toward collaborative care with our rheumatologists by trying to minimize delays to treatment, by working together in parallel clinics, combined clinics, and on virtual [multidisciplinary teams],” said Dr. Savage.

Dr. Proft agreed. “We should join forces and make decisions together.”

Dr. Savage and Dr. Proft did not provide any financial disclosures.

A version of this article appeared on Medscape.com.

SEATTLE — Musculoskeletal (MSK) symptoms are common in patients with psoriasis, but should they be primarily handled by dermatologists or should rheumatologists be “in the driver’s seat?” That was the subject of a debate between a dermatologist and a rheumatologist at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

Fabian Proft, MD, the rheumatologist, spoke first and emphasized the potential that MSK symptoms are a sign of psoriatic arthritis (PsA) and therefore should be managed by a rheumatologist.

“Obviously, the rheumatologist perspective [is that] I should be in the driver’s seat when taking care of patient with psoriasis and MSK symptoms, but I will still need to have a copilot there: [The dermatologist] will have a slot,” said Dr. Proft, who is a rheumatologist at Charité — Universitätsmedizin Berlin.

“It’s so important that we make the correct and early diagnosis of [psoriatic arthritis and psoriasis] symptoms,” said Dr. Proft. He specifically called out cases where patients have symptoms that are difficult to determine, whether the cause is inflammatory, and when experience with imaging can be a key factor in the diagnosis.

It’s important not to overdiagnose or overtreat patients, he said, providing an example of a patient with psoriasis who had been training for a marathon. The MRI image suggested that his Achilles tendonitis pain was related to his athletic training, not PsA-associated inflammation. “So I think this is very important that you have the knowledge to read MRIs, and especially also carefully assessing them so as not to overdiagnose patients,” said Dr. Proft.

Dermatologist Rebuttal

In her rebuttal, Laura Savage, MD, PhD, emphasized the need for more of a coequal partnership between the two specialties because of the ability of dermatologists to intervene early in the treatment and prevention of PsA.

“Traditionally, I agree rheumatologists would solely be responsible for the assessment and the management of psoriatic arthritis, but I think that paradigm has shifted in part due to the increased recognition of the need for earlier intervention to limit disease progression and to reduce or even prevent functional limitation,” said Dr. Savage, who is a consultant dermatologist at Leeds Teaching Hospitals NHS Trust and a senior lecturer at the University of Leeds, Leeds, England.

Ideally, molecular biomarkers would be available to predict the development of PsA, but there aren’t any. Still, “we have a huge biomarker in the form of the skin, and it’s recognized that the majority of patients who will develop psoriatic arthritis will have antecedent psoriasis in about 70% of cases,” Dr. Savage said. “There’s a typical time delay of around 7-12 years between the onset of the skin [disease] and the patients developing psoriatic arthritis, and so many of them are going to be into the care of other healthcare practitioners, and particularly the care of dermatologists.”

Dermatologists may also be able to play a role in the prevention of PsA, according to Dr. Savage. In one retrospective study, treatment of skin lesions with biologics was associated with a reduced frequency of progression to PsA (11.1% vs 16.4%) over 10 years (P = .0006). Studies with tumor necrosis factor inhibitors and other interventions have shown similar results.

Such findings have led to the treat intercept strategy, which targets patients with psoriasis who have risk factors for transition to PsA — such as nail pitting, gluteal cleft disease, scalp disease, type 2 diabetes, obesity, and a first-degree relative with PsA — as well as symptoms of prodromal PSA, such as arthralgia and fatigue.

“I think dermatologists are aware of the need to not leave our patients languishing on these therapies and actually escalating them onto effective treatments that may also be able to treat early psoriatic arthritis. We could be more mindful about our choice of treatments for these patients, going on to thinking about their increased risk of PSA and trying to intercept,” Dr. Savage said. “What we don’t want is our patients to be developing these musculoskeletal symptoms of pain and stiffness and functional limitation and disability. We want to be treating the patients with musculoskeletal symptoms of that earlier prodromal phase when they’re developing arthralgia and fatigue.”

She conceded that more complicated patients are good candidates for care by the rheumatologist. “You can do your fancy imaging, and we’ll leave that to you, and the difficult-to-treat patients to [the rheumatologist], but actually we need to just get on and treat them,” she said. “One could argue as well that as a dermatologist, I’m likely to broaden my horizons in terms of choice of therapy and treat all of the domains of the patient. So I would argue that actually it should be the dermatologist who is in that driving seat, particularly when it comes to the management of early psoriatic arthritis, and actually what we should be doing is driving our patients and steering them to earlier intervention and better control for all domains of disease.”
 

Collaborative Care

During the follow-up discussion, both Dr. Proft and Dr. Savage agreed that dermatologists and rheumatologists should be working together in managing patients. “What we need to do is steer our patients toward collaborative care with our rheumatologists by trying to minimize delays to treatment, by working together in parallel clinics, combined clinics, and on virtual [multidisciplinary teams],” said Dr. Savage.

Dr. Proft agreed. “We should join forces and make decisions together.”

Dr. Savage and Dr. Proft did not provide any financial disclosures.

A version of this article appeared on Medscape.com.

Two new studies focusing on the safety of benzoyl peroxide (BP)–containing acne products with typical everyday use found no reason for concern about either high blood levels of benzene, a breakdown product of BP, or cancer risk.

Earlier this year, controversy erupted after an independent lab Valisure petitioned the US Food and Drug Administration (FDA) to recall acne products with BP because it found extremely high levels of the carcinogen benzene. In the research, the lab directors contended that the products can form over 800 times the “conditionally restricted” FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter (OTC) products affected. The issue, according to the lab’s report, is one of degradation, not contamination; BP can decompose into benzene. Exposures to benzene have been linked with a higher risk for leukemia and other blood cancers.

Kittisak Kaewchalun/iStock/Getty Images

(“Conditionally restricted” means that the maximum of 2 ppm only applies to a drug product in which the use of benzene is unavoidable in order to produce a drug product with a significant therapeutic advance, according to FDA guidance.)

Critics of the report questioned the method used to test the products, calling for more “real-world” use data, and said the temperature used may not be what is expected with everyday use.

Now, both new studies are reassuring about the safety of the products, John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a telephone interview. He was a coauthor of both studies. A leading dermatologist not involved in the new research reviewed the findings and agreed.

Brigham and Women&#039;s Hospital

Dr. Lim

Further Details

Under high temperatures, or over a long period, BP can decompose to benzene, a colorless, flammable liquid with a sweet odor. Benzene is formed from natural processes such as forest fires and volcanoes, according to the American Cancer Society, and is found in the air, cigarette smoke, some foods (at low levels), and contaminated drinking water. It’s one of the 20 widely used chemicals involved in making plastics, resins, detergents, and pesticides, among other products.

In the study evaluating blood levels, the researchers matched 14 people who used BP products currently with 65 controls who did not. Five (36%) of those using the products had detectable blood levels; 21 (32%) of those who did not use them did. There was no association between BP exposure and detectable blood benzene levels (odds ratio, 1.12; P = .80).

In the larger study, the researchers used the TriNetX US Collaborative Network database, comparing more than 27,000 patients treated with BP products for acne with more than 27,000 patients aged 12-40 years who had a diagnosis of nevus or seborrheic keratosis with no exposure to prescribed BP or any diagnosis of acne, hidradenitis suppurativa, or rosacea. The researchers looked at the database over the subsequent 10 years to determine the risk for either blood cancers or internal malignancies.

Compared with patients diagnosed with nevus or seborrheic keratosis, those with acne treated with BP had no significant difference in the risk for lymphoma (hazard ratio [HR], 1.00), leukemia (HR, 0.91), any lymphoma or leukemia (HR, 1.04), and internal malignancies (HR, 0.93).

The findings suggest no increased risk for malignancy, the researchers said, although they acknowledged study limitations, such as possible misclassification of BP exposure due to OTC availability and other issues.

Value of BP Treatments

BP is the “go-to” acne treatment, as Dr. Barbieri pointed out. “It’s probably the number one treatment for acne,” and there’s no substitute for it and it’s one of the most effective topical acne treatments, he noted.

Despite the reassuring findings, Dr. Barbieri repeated advice he gave soon after the Valisure report was released. Use common sense and don’t store BP-containing products in hot cars or other hot environments. In warmer climates, refrigeration could be considered, he said. Discard old products. Manufacturers should use cold-chain storage from the manufacturing site to retail or pharmacy sale sites, he added.
 

FDA and Citizen Petition Status

Asked about the status of the petition from Valisure, an FDA spokesperson said: “The FDA does not comment on the status of pending petitions.”

Dr. Barbieri and Dr. Lim had no relevant disclosures. There were no funding sources for either of the two studies.
 

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

Two new studies focusing on the safety of benzoyl peroxide (BP)–containing acne products with typical everyday use found no reason for concern about either high blood levels of benzene, a breakdown product of BP, or cancer risk.

Earlier this year, controversy erupted after an independent lab Valisure petitioned the US Food and Drug Administration (FDA) to recall acne products with BP because it found extremely high levels of the carcinogen benzene. In the research, the lab directors contended that the products can form over 800 times the “conditionally restricted” FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter (OTC) products affected. The issue, according to the lab’s report, is one of degradation, not contamination; BP can decompose into benzene. Exposures to benzene have been linked with a higher risk for leukemia and other blood cancers.

Kittisak Kaewchalun/iStock/Getty Images

(“Conditionally restricted” means that the maximum of 2 ppm only applies to a drug product in which the use of benzene is unavoidable in order to produce a drug product with a significant therapeutic advance, according to FDA guidance.)

Critics of the report questioned the method used to test the products, calling for more “real-world” use data, and said the temperature used may not be what is expected with everyday use.

Now, both new studies are reassuring about the safety of the products, John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a telephone interview. He was a coauthor of both studies. A leading dermatologist not involved in the new research reviewed the findings and agreed.

Brigham and Women&#039;s Hospital

Dr. Lim

Further Details

Under high temperatures, or over a long period, BP can decompose to benzene, a colorless, flammable liquid with a sweet odor. Benzene is formed from natural processes such as forest fires and volcanoes, according to the American Cancer Society, and is found in the air, cigarette smoke, some foods (at low levels), and contaminated drinking water. It’s one of the 20 widely used chemicals involved in making plastics, resins, detergents, and pesticides, among other products.

In the study evaluating blood levels, the researchers matched 14 people who used BP products currently with 65 controls who did not. Five (36%) of those using the products had detectable blood levels; 21 (32%) of those who did not use them did. There was no association between BP exposure and detectable blood benzene levels (odds ratio, 1.12; P = .80).

In the larger study, the researchers used the TriNetX US Collaborative Network database, comparing more than 27,000 patients treated with BP products for acne with more than 27,000 patients aged 12-40 years who had a diagnosis of nevus or seborrheic keratosis with no exposure to prescribed BP or any diagnosis of acne, hidradenitis suppurativa, or rosacea. The researchers looked at the database over the subsequent 10 years to determine the risk for either blood cancers or internal malignancies.

Compared with patients diagnosed with nevus or seborrheic keratosis, those with acne treated with BP had no significant difference in the risk for lymphoma (hazard ratio [HR], 1.00), leukemia (HR, 0.91), any lymphoma or leukemia (HR, 1.04), and internal malignancies (HR, 0.93).

The findings suggest no increased risk for malignancy, the researchers said, although they acknowledged study limitations, such as possible misclassification of BP exposure due to OTC availability and other issues.

Value of BP Treatments

BP is the “go-to” acne treatment, as Dr. Barbieri pointed out. “It’s probably the number one treatment for acne,” and there’s no substitute for it and it’s one of the most effective topical acne treatments, he noted.

Despite the reassuring findings, Dr. Barbieri repeated advice he gave soon after the Valisure report was released. Use common sense and don’t store BP-containing products in hot cars or other hot environments. In warmer climates, refrigeration could be considered, he said. Discard old products. Manufacturers should use cold-chain storage from the manufacturing site to retail or pharmacy sale sites, he added.
 

FDA and Citizen Petition Status

Asked about the status of the petition from Valisure, an FDA spokesperson said: “The FDA does not comment on the status of pending petitions.”

Dr. Barbieri and Dr. Lim had no relevant disclosures. There were no funding sources for either of the two studies.
 

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

Two new studies focusing on the safety of benzoyl peroxide (BP)–containing acne products with typical everyday use found no reason for concern about either high blood levels of benzene, a breakdown product of BP, or cancer risk.

Earlier this year, controversy erupted after an independent lab Valisure petitioned the US Food and Drug Administration (FDA) to recall acne products with BP because it found extremely high levels of the carcinogen benzene. In the research, the lab directors contended that the products can form over 800 times the “conditionally restricted” FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter (OTC) products affected. The issue, according to the lab’s report, is one of degradation, not contamination; BP can decompose into benzene. Exposures to benzene have been linked with a higher risk for leukemia and other blood cancers.

Kittisak Kaewchalun/iStock/Getty Images

(“Conditionally restricted” means that the maximum of 2 ppm only applies to a drug product in which the use of benzene is unavoidable in order to produce a drug product with a significant therapeutic advance, according to FDA guidance.)

Critics of the report questioned the method used to test the products, calling for more “real-world” use data, and said the temperature used may not be what is expected with everyday use.

Now, both new studies are reassuring about the safety of the products, John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a telephone interview. He was a coauthor of both studies. A leading dermatologist not involved in the new research reviewed the findings and agreed.

Brigham and Women&#039;s Hospital

Dr. Lim

Further Details

Under high temperatures, or over a long period, BP can decompose to benzene, a colorless, flammable liquid with a sweet odor. Benzene is formed from natural processes such as forest fires and volcanoes, according to the American Cancer Society, and is found in the air, cigarette smoke, some foods (at low levels), and contaminated drinking water. It’s one of the 20 widely used chemicals involved in making plastics, resins, detergents, and pesticides, among other products.

In the study evaluating blood levels, the researchers matched 14 people who used BP products currently with 65 controls who did not. Five (36%) of those using the products had detectable blood levels; 21 (32%) of those who did not use them did. There was no association between BP exposure and detectable blood benzene levels (odds ratio, 1.12; P = .80).

In the larger study, the researchers used the TriNetX US Collaborative Network database, comparing more than 27,000 patients treated with BP products for acne with more than 27,000 patients aged 12-40 years who had a diagnosis of nevus or seborrheic keratosis with no exposure to prescribed BP or any diagnosis of acne, hidradenitis suppurativa, or rosacea. The researchers looked at the database over the subsequent 10 years to determine the risk for either blood cancers or internal malignancies.

Compared with patients diagnosed with nevus or seborrheic keratosis, those with acne treated with BP had no significant difference in the risk for lymphoma (hazard ratio [HR], 1.00), leukemia (HR, 0.91), any lymphoma or leukemia (HR, 1.04), and internal malignancies (HR, 0.93).

The findings suggest no increased risk for malignancy, the researchers said, although they acknowledged study limitations, such as possible misclassification of BP exposure due to OTC availability and other issues.

Value of BP Treatments

BP is the “go-to” acne treatment, as Dr. Barbieri pointed out. “It’s probably the number one treatment for acne,” and there’s no substitute for it and it’s one of the most effective topical acne treatments, he noted.

Despite the reassuring findings, Dr. Barbieri repeated advice he gave soon after the Valisure report was released. Use common sense and don’t store BP-containing products in hot cars or other hot environments. In warmer climates, refrigeration could be considered, he said. Discard old products. Manufacturers should use cold-chain storage from the manufacturing site to retail or pharmacy sale sites, he added.
 

FDA and Citizen Petition Status

Asked about the status of the petition from Valisure, an FDA spokesperson said: “The FDA does not comment on the status of pending petitions.”

Dr. Barbieri and Dr. Lim had no relevant disclosures. There were no funding sources for either of the two studies.
 

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