Dermatology

The patient was diagnosed with lichen nitidus, given the characteristic clinical presentation.

Lichen nitidus is a rare chronic inflammatory condition of the skin that most commonly presents in children and young adults and does not seem to be restricted to any sex or race. The classic lesions are described as asymptomatic to slightly pruritic, small (1 mm), skin-colored to hypopigmented flat-topped papules.

Koebner phenomenon is usually seen in which the skin lesions appear in areas of traumatized healthy skin. The extremities, abdomen, chest, and penis are common locations for the lesions to occur. Rarely, the oral mucosa or nails can be involved. It has been described in patients with a diagnosis of Crohn’s disease, Niemann-Pick disease, Down syndrome, and HIV. The rare, generalized purpuric variant has been reported in a few cases associated with interferon and ribavirin treatment for hepatitis C infection and nivolumab treatment for cancer. The pathophysiology of lichen nitidus is unknown.

Lichen nitidus can occur in the presence of other skin conditions like lichen planus, atopic dermatitis, vitiligo, erythema nodosum, and lichen spinulosus. Histopathologic characteristics of lichen nitidus are described as a “ball and claw” of epidermal rete around a lymphohistiocytic infiltrate. Parakeratosis overlying epidermal atrophy and focal basal liquefaction degeneration is also seen.

The differential diagnosis of lichen nitidus includes flat warts, which can present as clusters of small flat-topped papules that can show a pseudo-Koebner phenomenon (where the virus is seeded in traumatized skin). The morphological difference between the condition is that lichen nitidus lesions are usually monomorphic, compared with flat warts, which usually present with different sizes and shapes.

Patients with a history of allergic contact dermatitis may present with a generalized monomorphic eruption of skin-colored papules (known as ID reaction) that can sometimes be very similar to lichen nitidus. Allergic contact dermatitis tends to respond fairly quickly to topical or systemic corticosteroids, unlike lichen nitidus. There are a few reports that consider lichen nitidus to be a variant of lichen planus, although they have different histopathologic findings. Lichen planus lesions are described as polygonal, pruritic, purple to pink papules most commonly seen on the wrists, lower back, and ankles. Lichen planus can be seen in patients with hepatitis C and may also occur secondary to medication.

Milia are small keratin cysts on the skin that are commonly seen in babies as primary milia and can be seen in older children secondary to trauma (commonly on the eyelids) or medications. Given their size and monomorphic appearance, they can sometimes be confused with lichen nitidus.

Lichen nitidus is often asymptomatic and the lesions resolve within a few months to years. Topical corticosteroids can be helpful to alleviate the symptoms in patients who present with pruritus. In more persistent and generalized cases, phototherapy, systemic corticosteroids, acitretin, isotretinoin, or cyclosporine can be considered.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Chu J and Lam JM. CMAJ. 2014 Dec 9;186(18):E688.

Lestringant G et al. Dermatology 1996;192:171-3.

Peterson JA et al. Proc (Bayl Univ Med Cent). 2021 Aug 25;35(1):70-2.

Schwartz C and Goodman MB. “Lichen nitidus,” in StatPearls. Treasure Island, Fla.: StatPearls Publishing, 2022.

The patient was diagnosed with lichen nitidus, given the characteristic clinical presentation.

Lichen nitidus is a rare chronic inflammatory condition of the skin that most commonly presents in children and young adults and does not seem to be restricted to any sex or race. The classic lesions are described as asymptomatic to slightly pruritic, small (1 mm), skin-colored to hypopigmented flat-topped papules.

Koebner phenomenon is usually seen in which the skin lesions appear in areas of traumatized healthy skin. The extremities, abdomen, chest, and penis are common locations for the lesions to occur. Rarely, the oral mucosa or nails can be involved. It has been described in patients with a diagnosis of Crohn’s disease, Niemann-Pick disease, Down syndrome, and HIV. The rare, generalized purpuric variant has been reported in a few cases associated with interferon and ribavirin treatment for hepatitis C infection and nivolumab treatment for cancer. The pathophysiology of lichen nitidus is unknown.

Lichen nitidus can occur in the presence of other skin conditions like lichen planus, atopic dermatitis, vitiligo, erythema nodosum, and lichen spinulosus. Histopathologic characteristics of lichen nitidus are described as a “ball and claw” of epidermal rete around a lymphohistiocytic infiltrate. Parakeratosis overlying epidermal atrophy and focal basal liquefaction degeneration is also seen.

The differential diagnosis of lichen nitidus includes flat warts, which can present as clusters of small flat-topped papules that can show a pseudo-Koebner phenomenon (where the virus is seeded in traumatized skin). The morphological difference between the condition is that lichen nitidus lesions are usually monomorphic, compared with flat warts, which usually present with different sizes and shapes.

Patients with a history of allergic contact dermatitis may present with a generalized monomorphic eruption of skin-colored papules (known as ID reaction) that can sometimes be very similar to lichen nitidus. Allergic contact dermatitis tends to respond fairly quickly to topical or systemic corticosteroids, unlike lichen nitidus. There are a few reports that consider lichen nitidus to be a variant of lichen planus, although they have different histopathologic findings. Lichen planus lesions are described as polygonal, pruritic, purple to pink papules most commonly seen on the wrists, lower back, and ankles. Lichen planus can be seen in patients with hepatitis C and may also occur secondary to medication.

Milia are small keratin cysts on the skin that are commonly seen in babies as primary milia and can be seen in older children secondary to trauma (commonly on the eyelids) or medications. Given their size and monomorphic appearance, they can sometimes be confused with lichen nitidus.

Lichen nitidus is often asymptomatic and the lesions resolve within a few months to years. Topical corticosteroids can be helpful to alleviate the symptoms in patients who present with pruritus. In more persistent and generalized cases, phototherapy, systemic corticosteroids, acitretin, isotretinoin, or cyclosporine can be considered.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Chu J and Lam JM. CMAJ. 2014 Dec 9;186(18):E688.

Lestringant G et al. Dermatology 1996;192:171-3.

Peterson JA et al. Proc (Bayl Univ Med Cent). 2021 Aug 25;35(1):70-2.

Schwartz C and Goodman MB. “Lichen nitidus,” in StatPearls. Treasure Island, Fla.: StatPearls Publishing, 2022.

The patient was diagnosed with lichen nitidus, given the characteristic clinical presentation.

Lichen nitidus is a rare chronic inflammatory condition of the skin that most commonly presents in children and young adults and does not seem to be restricted to any sex or race. The classic lesions are described as asymptomatic to slightly pruritic, small (1 mm), skin-colored to hypopigmented flat-topped papules.

Koebner phenomenon is usually seen in which the skin lesions appear in areas of traumatized healthy skin. The extremities, abdomen, chest, and penis are common locations for the lesions to occur. Rarely, the oral mucosa or nails can be involved. It has been described in patients with a diagnosis of Crohn’s disease, Niemann-Pick disease, Down syndrome, and HIV. The rare, generalized purpuric variant has been reported in a few cases associated with interferon and ribavirin treatment for hepatitis C infection and nivolumab treatment for cancer. The pathophysiology of lichen nitidus is unknown.

Lichen nitidus can occur in the presence of other skin conditions like lichen planus, atopic dermatitis, vitiligo, erythema nodosum, and lichen spinulosus. Histopathologic characteristics of lichen nitidus are described as a “ball and claw” of epidermal rete around a lymphohistiocytic infiltrate. Parakeratosis overlying epidermal atrophy and focal basal liquefaction degeneration is also seen.

The differential diagnosis of lichen nitidus includes flat warts, which can present as clusters of small flat-topped papules that can show a pseudo-Koebner phenomenon (where the virus is seeded in traumatized skin). The morphological difference between the condition is that lichen nitidus lesions are usually monomorphic, compared with flat warts, which usually present with different sizes and shapes.

Patients with a history of allergic contact dermatitis may present with a generalized monomorphic eruption of skin-colored papules (known as ID reaction) that can sometimes be very similar to lichen nitidus. Allergic contact dermatitis tends to respond fairly quickly to topical or systemic corticosteroids, unlike lichen nitidus. There are a few reports that consider lichen nitidus to be a variant of lichen planus, although they have different histopathologic findings. Lichen planus lesions are described as polygonal, pruritic, purple to pink papules most commonly seen on the wrists, lower back, and ankles. Lichen planus can be seen in patients with hepatitis C and may also occur secondary to medication.

Milia are small keratin cysts on the skin that are commonly seen in babies as primary milia and can be seen in older children secondary to trauma (commonly on the eyelids) or medications. Given their size and monomorphic appearance, they can sometimes be confused with lichen nitidus.

Lichen nitidus is often asymptomatic and the lesions resolve within a few months to years. Topical corticosteroids can be helpful to alleviate the symptoms in patients who present with pruritus. In more persistent and generalized cases, phototherapy, systemic corticosteroids, acitretin, isotretinoin, or cyclosporine can be considered.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Chu J and Lam JM. CMAJ. 2014 Dec 9;186(18):E688.

Lestringant G et al. Dermatology 1996;192:171-3.

Peterson JA et al. Proc (Bayl Univ Med Cent). 2021 Aug 25;35(1):70-2.

Schwartz C and Goodman MB. “Lichen nitidus,” in StatPearls. Treasure Island, Fla.: StatPearls Publishing, 2022.

In December 2021, major changes took effect in the iPLEDGE program, the Food and Drug Administration–required safety program for managing the risks of isotretinoin’s teratogenicity and preventing exposure during pregnancy. Now, more modifications may be coming to the acne drug’s safety program.

The FDA has scheduled a joint meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee for March 28-29 to discuss proposed changes to the iPLEDGE risk evaluation and mitigation strategy (REMS) requirements. The aim, according to the FDA meeting announcement, is “to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of isotretinoin oral capsules for patients.”

Ocskay Bence/Fotolia.com

Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane. Its former brand name was Accutane.

Problems began to surface days after a new, gender-neutral approach to the risk mitigation program was launched on Dec. 13, 2021. That program had been approved earlier by the FDA.

However, the problems that were encountered were a result of glitches in changes in the platform that had been planned, and were not related to the gender-neutral changes. The iPLEDGE program had transitioned to the new platform, and the rollout was far from smooth. Dermatologists, pharmacists, patients, parents of patients, and others were frustrated and angry that they could not access the new platform and obtain the medication promptly. Reaching the help line to sort out problems was another exercise in frustration. Wait times while on hold were unbearably long, or problems were not resolved over the phone.

(The new gender-neutral approach, which advocates said was needed to preserve inclusiveness of their patients, including transgender patients, places potential patients into two categories: those who can become pregnant, and those who cannot. Previously, there were three categories into which patients were classified: females who have reproductive potential, females who do not have reproductive potential, and males.)

Before pharmacists can fill a prescription for isotretinoin, a medical provider must confirm a patient’s negative pregnancy test and inform a patient with reproductive potential of the risks of the medication.

In January 2022, to deal with the chaotic launch and subsequent problems, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve the problems reported by clinicians, pharmacists, and patients.

The American Academy of Dermatology Association formed an iPLEDGE work group to address the issues and suggest solutions. It has made several requests of and suggestions for the IPMG, which manages the program, according to Andrea L. Zaenglein, MD, professor of dermatology and pediatrics at Penn State Hershey (Pa.) Medical Center, and a member of the work group.

“We are asking them to eliminate the monthly attestation for patients who can’t get pregnant and to review and modify restrictive and punitive waiting and lockout periods for all patients,” she told this news organization.

As of February 2023, most of the platform glitches had been smoothed out, Dr. Zaenglein said. Still, “improvements to the design of the website could improve the user interface,” she added.


The FDA has established a docket for the public to submit comments before the meeting. The docket number is FDA-2022-N-3071. The electronic filing system will accept comments until 11:59 p.m. Eastern time on March 27. Background material and a link to the live webcast of the panel meeting will be available to the public no later than 2 days before the meeting and will be posted on the FDA web page or at the time of the meeting.

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

In December 2021, major changes took effect in the iPLEDGE program, the Food and Drug Administration–required safety program for managing the risks of isotretinoin’s teratogenicity and preventing exposure during pregnancy. Now, more modifications may be coming to the acne drug’s safety program.

The FDA has scheduled a joint meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee for March 28-29 to discuss proposed changes to the iPLEDGE risk evaluation and mitigation strategy (REMS) requirements. The aim, according to the FDA meeting announcement, is “to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of isotretinoin oral capsules for patients.”

Ocskay Bence/Fotolia.com

Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane. Its former brand name was Accutane.

Problems began to surface days after a new, gender-neutral approach to the risk mitigation program was launched on Dec. 13, 2021. That program had been approved earlier by the FDA.

However, the problems that were encountered were a result of glitches in changes in the platform that had been planned, and were not related to the gender-neutral changes. The iPLEDGE program had transitioned to the new platform, and the rollout was far from smooth. Dermatologists, pharmacists, patients, parents of patients, and others were frustrated and angry that they could not access the new platform and obtain the medication promptly. Reaching the help line to sort out problems was another exercise in frustration. Wait times while on hold were unbearably long, or problems were not resolved over the phone.

(The new gender-neutral approach, which advocates said was needed to preserve inclusiveness of their patients, including transgender patients, places potential patients into two categories: those who can become pregnant, and those who cannot. Previously, there were three categories into which patients were classified: females who have reproductive potential, females who do not have reproductive potential, and males.)

Before pharmacists can fill a prescription for isotretinoin, a medical provider must confirm a patient’s negative pregnancy test and inform a patient with reproductive potential of the risks of the medication.

In January 2022, to deal with the chaotic launch and subsequent problems, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve the problems reported by clinicians, pharmacists, and patients.

The American Academy of Dermatology Association formed an iPLEDGE work group to address the issues and suggest solutions. It has made several requests of and suggestions for the IPMG, which manages the program, according to Andrea L. Zaenglein, MD, professor of dermatology and pediatrics at Penn State Hershey (Pa.) Medical Center, and a member of the work group.

“We are asking them to eliminate the monthly attestation for patients who can’t get pregnant and to review and modify restrictive and punitive waiting and lockout periods for all patients,” she told this news organization.

As of February 2023, most of the platform glitches had been smoothed out, Dr. Zaenglein said. Still, “improvements to the design of the website could improve the user interface,” she added.


The FDA has established a docket for the public to submit comments before the meeting. The docket number is FDA-2022-N-3071. The electronic filing system will accept comments until 11:59 p.m. Eastern time on March 27. Background material and a link to the live webcast of the panel meeting will be available to the public no later than 2 days before the meeting and will be posted on the FDA web page or at the time of the meeting.

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

In December 2021, major changes took effect in the iPLEDGE program, the Food and Drug Administration–required safety program for managing the risks of isotretinoin’s teratogenicity and preventing exposure during pregnancy. Now, more modifications may be coming to the acne drug’s safety program.

The FDA has scheduled a joint meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee for March 28-29 to discuss proposed changes to the iPLEDGE risk evaluation and mitigation strategy (REMS) requirements. The aim, according to the FDA meeting announcement, is “to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of isotretinoin oral capsules for patients.”

Ocskay Bence/Fotolia.com

Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane. Its former brand name was Accutane.

Problems began to surface days after a new, gender-neutral approach to the risk mitigation program was launched on Dec. 13, 2021. That program had been approved earlier by the FDA.

However, the problems that were encountered were a result of glitches in changes in the platform that had been planned, and were not related to the gender-neutral changes. The iPLEDGE program had transitioned to the new platform, and the rollout was far from smooth. Dermatologists, pharmacists, patients, parents of patients, and others were frustrated and angry that they could not access the new platform and obtain the medication promptly. Reaching the help line to sort out problems was another exercise in frustration. Wait times while on hold were unbearably long, or problems were not resolved over the phone.

(The new gender-neutral approach, which advocates said was needed to preserve inclusiveness of their patients, including transgender patients, places potential patients into two categories: those who can become pregnant, and those who cannot. Previously, there were three categories into which patients were classified: females who have reproductive potential, females who do not have reproductive potential, and males.)

Before pharmacists can fill a prescription for isotretinoin, a medical provider must confirm a patient’s negative pregnancy test and inform a patient with reproductive potential of the risks of the medication.

In January 2022, to deal with the chaotic launch and subsequent problems, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve the problems reported by clinicians, pharmacists, and patients.

The American Academy of Dermatology Association formed an iPLEDGE work group to address the issues and suggest solutions. It has made several requests of and suggestions for the IPMG, which manages the program, according to Andrea L. Zaenglein, MD, professor of dermatology and pediatrics at Penn State Hershey (Pa.) Medical Center, and a member of the work group.

“We are asking them to eliminate the monthly attestation for patients who can’t get pregnant and to review and modify restrictive and punitive waiting and lockout periods for all patients,” she told this news organization.

As of February 2023, most of the platform glitches had been smoothed out, Dr. Zaenglein said. Still, “improvements to the design of the website could improve the user interface,” she added.


The FDA has established a docket for the public to submit comments before the meeting. The docket number is FDA-2022-N-3071. The electronic filing system will accept comments until 11:59 p.m. Eastern time on March 27. Background material and a link to the live webcast of the panel meeting will be available to the public no later than 2 days before the meeting and will be posted on the FDA web page or at the time of the meeting.

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

The U.S. Food and Drug Administration today expanded the indication for Pfizer’s oral Janus kinase (JAK) inhibitor for atopic dermatitis (AD), abrocitinib (Cibinqo), to include adolescents aged 12 through 17 years.

Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.

It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.

The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.

Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.

The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.

Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.

Select JADE TEEN findings include the following:

• IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
• EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
• Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.

Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.

In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.

He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.

Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.

AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.

JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.

Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.

Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.

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

The U.S. Food and Drug Administration today expanded the indication for Pfizer’s oral Janus kinase (JAK) inhibitor for atopic dermatitis (AD), abrocitinib (Cibinqo), to include adolescents aged 12 through 17 years.

Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.

It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.

The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.

Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.

The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.

Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.

Select JADE TEEN findings include the following:

• IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
• EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
• Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.

Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.

In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.

He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.

Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.

AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.

JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.

Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.

Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.

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

The U.S. Food and Drug Administration today expanded the indication for Pfizer’s oral Janus kinase (JAK) inhibitor for atopic dermatitis (AD), abrocitinib (Cibinqo), to include adolescents aged 12 through 17 years.

Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.

It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.

The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.

Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.

The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.

Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.

Select JADE TEEN findings include the following:

• IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
• EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
• Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.

Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.

In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.

He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.

Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.

AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.

JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.

Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.

Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.

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

The incidence of acne in preadolescents was higher in girls than in boys, and was associated with higher body mass index (BMI) percentiles, in a large population-based retrospective study that used age- and sex-matched controls.

The investigators also identified “a potential association” with precocious puberty that they said “should be considered, especially among those presenting [with acne] under 8 or 9 years old.” The study was published in Pediatric Dermatology .

Senior author Megha M. Tollefson, MD, and coauthors used resources of the Rochester Epidemiology Project to identify all residents of Olmstead County, Minn., who were diagnosed with acne between the ages of 7 and 12 years during 2010-2018. They then randomly selected two age and sex-matched community controls in order to evaluate the relationship of preadolescent acne and BMI.

They confirmed 643 acne cases, and calculated an annual age- and sex-adjusted incidence rate for ages 7-12 of 58 per 10,000 person-years (95% confidence interval, 53.5-62.5). The incidence rate was significantly higher in females than males (89.2 vs. 28.2 per 10,000 person-years; P < .001), and it significantly increased with age (incidence rates of 4.3, 24.4, and 144.3 per 10,000 person-years among those ages 7-8, 9-10, and 11-12 years, respectively).

The median BMI percentile among children with acne was significantly higher than those without an acne diagnosis (75.0 vs. 65.0; P <.001). They also were much more likely to be obese: 16.7% of the children with acne had a BMI in at least the 95th percentile, compared with 12.2% among controls with no acne diagnosis (P = .01). (The qualifying 581 acne cases for this analysis had BMIs recorded within 8 months of the index data, in addition to not having pre-existing acne-relevant endocrine disorders.)

“High BMI is a strong risk factor for acne development and severity in adults, but until now pediatric studies have revealed mixed information ... [and have been] largely retrospective reviews without controls,” Dr. Tollefson, professor of pediatrics and dermatology at the Mayo Clinic, Rochester, Minn., and colleagues wrote.


 

‘Valuable’ data

Leah Lalor, MD, a pediatric dermatologist not involved with the research, said she is happy to see it. “It’s really valuable,” she said in an interview. “It’s actually the first study that gives us incidence data for preadolescent acne. We all have [had our estimates], but this study quantifies it ... and it will set the stage for further studies of preadolescents in the future.”

The study also documents that “girls are more likely to present to the clinic with acne, and to do so at younger ages, which we’ve suspected and which makes physiologic sense since girls tend to go through puberty earlier than boys,” said Dr. Lalor, assistant professor of dermatology and pediatrics at the Medical College of Wisconsin and the Children’s Wisconsin Clinics, both in Milwaukee. “And most interestingly, it really reveals that BMI is higher among preadolescents with acne than those without.”

The important caveat, she emphasized, is that the study population in Olmstead County, Minn. has a relatively higher level of education, wealth, and employment than the rest of the United States.

The investigators also found that use of systemic acne medications increased with increasing BMI (odds ratio, 1.43 per 5 kg/m² increase in BMI; 95% CI, 1.07-1.92; P = .015). Approximately 5% of underweight or normal children were prescribed systemic acne medications, compared with 8.1% of overweight children, and 10.3% of those who were obese – data that suggest that most preadolescents with acne had mild to moderate disease and that more severe acne may be associated with increasing BMI percentiles, the authors wrote.

Approximately 4% of the 643 preadolescents with acne were diagnosed with an acne-relevant endocrine disorder prior to or at the time of acne diagnosis – most commonly precocious puberty. Of the 24 diagnoses of precocious puberty, 22 were in females, with a mean age at diagnosis of 7.3 years.

Puberty before age 8 in girls and 9 in boys is classified as precocious puberty. “Thus, a thorough review of systems and exam should be done in this population [with acne] to look for precocious puberty with a low threshold for systemic evaluation if indicated,” the authors wrote, also noting that 19 or the 482 female patients with acne were subsequently diagnosed with polycystic ovary syndrome.

Dr. Lalor said she “automatically” refers children with acne who are younger than 7 for an endocrine workup, but not necessarily children ages 7, 8, or 9 because “that’s considered within the normal realm of starting to get some acne.” Acne in the context of other symptoms such as body odor, hair, or thelarche may prompt referral in these ages, however, she said.
 

Future research

Obesity may influence preadolescent acne development through its effect on puberty, as overweight and obese girls achieve puberty earlier than those with normal BMI. And “insulin resistance, which may be related to obesity, has been implicated with inducing or worsening acne potentially related to shifts in IGF-1 [insulin-like growth factor 1] signaling and hyperandrogenemia,” Dr. Tollefson and colleagues wrote. Nutrition is also a possible confounder in the study.

“Patients and families have long felt that certain foods or practices contribute to acne, though this has been difficult to prove,” Dr. Lalor said. “We know that excess skim milk seems to contribute ... and there’s a correlation between high glycemic load diets [and acne].”

Assessing dietary habits in conjunction with BMI, and acne incidence and severity, would be valuable. So would research to determine “if decreasing the BMI percentile [in children with acne] would improve or prevent acne, without doing any acne treatments,” she said.

The study was supported by the National Institute on Aging and the Rochester Epidemiology Project. The authors reported no conflicts of interest. Dr. Lalor also reported no conflicts of interest.

The incidence of acne in preadolescents was higher in girls than in boys, and was associated with higher body mass index (BMI) percentiles, in a large population-based retrospective study that used age- and sex-matched controls.

The investigators also identified “a potential association” with precocious puberty that they said “should be considered, especially among those presenting [with acne] under 8 or 9 years old.” The study was published in Pediatric Dermatology .

Senior author Megha M. Tollefson, MD, and coauthors used resources of the Rochester Epidemiology Project to identify all residents of Olmstead County, Minn., who were diagnosed with acne between the ages of 7 and 12 years during 2010-2018. They then randomly selected two age and sex-matched community controls in order to evaluate the relationship of preadolescent acne and BMI.

They confirmed 643 acne cases, and calculated an annual age- and sex-adjusted incidence rate for ages 7-12 of 58 per 10,000 person-years (95% confidence interval, 53.5-62.5). The incidence rate was significantly higher in females than males (89.2 vs. 28.2 per 10,000 person-years; P < .001), and it significantly increased with age (incidence rates of 4.3, 24.4, and 144.3 per 10,000 person-years among those ages 7-8, 9-10, and 11-12 years, respectively).

The median BMI percentile among children with acne was significantly higher than those without an acne diagnosis (75.0 vs. 65.0; P <.001). They also were much more likely to be obese: 16.7% of the children with acne had a BMI in at least the 95th percentile, compared with 12.2% among controls with no acne diagnosis (P = .01). (The qualifying 581 acne cases for this analysis had BMIs recorded within 8 months of the index data, in addition to not having pre-existing acne-relevant endocrine disorders.)

“High BMI is a strong risk factor for acne development and severity in adults, but until now pediatric studies have revealed mixed information ... [and have been] largely retrospective reviews without controls,” Dr. Tollefson, professor of pediatrics and dermatology at the Mayo Clinic, Rochester, Minn., and colleagues wrote.


 

‘Valuable’ data

Leah Lalor, MD, a pediatric dermatologist not involved with the research, said she is happy to see it. “It’s really valuable,” she said in an interview. “It’s actually the first study that gives us incidence data for preadolescent acne. We all have [had our estimates], but this study quantifies it ... and it will set the stage for further studies of preadolescents in the future.”

The study also documents that “girls are more likely to present to the clinic with acne, and to do so at younger ages, which we’ve suspected and which makes physiologic sense since girls tend to go through puberty earlier than boys,” said Dr. Lalor, assistant professor of dermatology and pediatrics at the Medical College of Wisconsin and the Children’s Wisconsin Clinics, both in Milwaukee. “And most interestingly, it really reveals that BMI is higher among preadolescents with acne than those without.”

The important caveat, she emphasized, is that the study population in Olmstead County, Minn. has a relatively higher level of education, wealth, and employment than the rest of the United States.

The investigators also found that use of systemic acne medications increased with increasing BMI (odds ratio, 1.43 per 5 kg/m² increase in BMI; 95% CI, 1.07-1.92; P = .015). Approximately 5% of underweight or normal children were prescribed systemic acne medications, compared with 8.1% of overweight children, and 10.3% of those who were obese – data that suggest that most preadolescents with acne had mild to moderate disease and that more severe acne may be associated with increasing BMI percentiles, the authors wrote.

Approximately 4% of the 643 preadolescents with acne were diagnosed with an acne-relevant endocrine disorder prior to or at the time of acne diagnosis – most commonly precocious puberty. Of the 24 diagnoses of precocious puberty, 22 were in females, with a mean age at diagnosis of 7.3 years.

Puberty before age 8 in girls and 9 in boys is classified as precocious puberty. “Thus, a thorough review of systems and exam should be done in this population [with acne] to look for precocious puberty with a low threshold for systemic evaluation if indicated,” the authors wrote, also noting that 19 or the 482 female patients with acne were subsequently diagnosed with polycystic ovary syndrome.

Dr. Lalor said she “automatically” refers children with acne who are younger than 7 for an endocrine workup, but not necessarily children ages 7, 8, or 9 because “that’s considered within the normal realm of starting to get some acne.” Acne in the context of other symptoms such as body odor, hair, or thelarche may prompt referral in these ages, however, she said.
 

Future research

Obesity may influence preadolescent acne development through its effect on puberty, as overweight and obese girls achieve puberty earlier than those with normal BMI. And “insulin resistance, which may be related to obesity, has been implicated with inducing or worsening acne potentially related to shifts in IGF-1 [insulin-like growth factor 1] signaling and hyperandrogenemia,” Dr. Tollefson and colleagues wrote. Nutrition is also a possible confounder in the study.

“Patients and families have long felt that certain foods or practices contribute to acne, though this has been difficult to prove,” Dr. Lalor said. “We know that excess skim milk seems to contribute ... and there’s a correlation between high glycemic load diets [and acne].”

Assessing dietary habits in conjunction with BMI, and acne incidence and severity, would be valuable. So would research to determine “if decreasing the BMI percentile [in children with acne] would improve or prevent acne, without doing any acne treatments,” she said.

The study was supported by the National Institute on Aging and the Rochester Epidemiology Project. The authors reported no conflicts of interest. Dr. Lalor also reported no conflicts of interest.

The incidence of acne in preadolescents was higher in girls than in boys, and was associated with higher body mass index (BMI) percentiles, in a large population-based retrospective study that used age- and sex-matched controls.

The investigators also identified “a potential association” with precocious puberty that they said “should be considered, especially among those presenting [with acne] under 8 or 9 years old.” The study was published in Pediatric Dermatology .

Senior author Megha M. Tollefson, MD, and coauthors used resources of the Rochester Epidemiology Project to identify all residents of Olmstead County, Minn., who were diagnosed with acne between the ages of 7 and 12 years during 2010-2018. They then randomly selected two age and sex-matched community controls in order to evaluate the relationship of preadolescent acne and BMI.

They confirmed 643 acne cases, and calculated an annual age- and sex-adjusted incidence rate for ages 7-12 of 58 per 10,000 person-years (95% confidence interval, 53.5-62.5). The incidence rate was significantly higher in females than males (89.2 vs. 28.2 per 10,000 person-years; P < .001), and it significantly increased with age (incidence rates of 4.3, 24.4, and 144.3 per 10,000 person-years among those ages 7-8, 9-10, and 11-12 years, respectively).

The median BMI percentile among children with acne was significantly higher than those without an acne diagnosis (75.0 vs. 65.0; P <.001). They also were much more likely to be obese: 16.7% of the children with acne had a BMI in at least the 95th percentile, compared with 12.2% among controls with no acne diagnosis (P = .01). (The qualifying 581 acne cases for this analysis had BMIs recorded within 8 months of the index data, in addition to not having pre-existing acne-relevant endocrine disorders.)

“High BMI is a strong risk factor for acne development and severity in adults, but until now pediatric studies have revealed mixed information ... [and have been] largely retrospective reviews without controls,” Dr. Tollefson, professor of pediatrics and dermatology at the Mayo Clinic, Rochester, Minn., and colleagues wrote.


 

‘Valuable’ data

Leah Lalor, MD, a pediatric dermatologist not involved with the research, said she is happy to see it. “It’s really valuable,” she said in an interview. “It’s actually the first study that gives us incidence data for preadolescent acne. We all have [had our estimates], but this study quantifies it ... and it will set the stage for further studies of preadolescents in the future.”

The study also documents that “girls are more likely to present to the clinic with acne, and to do so at younger ages, which we’ve suspected and which makes physiologic sense since girls tend to go through puberty earlier than boys,” said Dr. Lalor, assistant professor of dermatology and pediatrics at the Medical College of Wisconsin and the Children’s Wisconsin Clinics, both in Milwaukee. “And most interestingly, it really reveals that BMI is higher among preadolescents with acne than those without.”

The important caveat, she emphasized, is that the study population in Olmstead County, Minn. has a relatively higher level of education, wealth, and employment than the rest of the United States.

The investigators also found that use of systemic acne medications increased with increasing BMI (odds ratio, 1.43 per 5 kg/m² increase in BMI; 95% CI, 1.07-1.92; P = .015). Approximately 5% of underweight or normal children were prescribed systemic acne medications, compared with 8.1% of overweight children, and 10.3% of those who were obese – data that suggest that most preadolescents with acne had mild to moderate disease and that more severe acne may be associated with increasing BMI percentiles, the authors wrote.

Approximately 4% of the 643 preadolescents with acne were diagnosed with an acne-relevant endocrine disorder prior to or at the time of acne diagnosis – most commonly precocious puberty. Of the 24 diagnoses of precocious puberty, 22 were in females, with a mean age at diagnosis of 7.3 years.

Puberty before age 8 in girls and 9 in boys is classified as precocious puberty. “Thus, a thorough review of systems and exam should be done in this population [with acne] to look for precocious puberty with a low threshold for systemic evaluation if indicated,” the authors wrote, also noting that 19 or the 482 female patients with acne were subsequently diagnosed with polycystic ovary syndrome.

Dr. Lalor said she “automatically” refers children with acne who are younger than 7 for an endocrine workup, but not necessarily children ages 7, 8, or 9 because “that’s considered within the normal realm of starting to get some acne.” Acne in the context of other symptoms such as body odor, hair, or thelarche may prompt referral in these ages, however, she said.
 

Future research

Obesity may influence preadolescent acne development through its effect on puberty, as overweight and obese girls achieve puberty earlier than those with normal BMI. And “insulin resistance, which may be related to obesity, has been implicated with inducing or worsening acne potentially related to shifts in IGF-1 [insulin-like growth factor 1] signaling and hyperandrogenemia,” Dr. Tollefson and colleagues wrote. Nutrition is also a possible confounder in the study.

“Patients and families have long felt that certain foods or practices contribute to acne, though this has been difficult to prove,” Dr. Lalor said. “We know that excess skim milk seems to contribute ... and there’s a correlation between high glycemic load diets [and acne].”

Assessing dietary habits in conjunction with BMI, and acne incidence and severity, would be valuable. So would research to determine “if decreasing the BMI percentile [in children with acne] would improve or prevent acne, without doing any acne treatments,” she said.

The study was supported by the National Institute on Aging and the Rochester Epidemiology Project. The authors reported no conflicts of interest. Dr. Lalor also reported no conflicts of interest.

Isotretinoin was not associated with a 1-year risk of incident inflammatory bowel disease (IBD) in a large population-based cohort study that also found no significant association of oral tetracycline-class antibiotics with IBD – and a small but statistically significant association of acne itself with the inflammatory disorders that make up IBD.

For the study, senior author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, and his colleagues used data from the TriNetX global research platform, which mines patient-level electronic medical record data from dozens of health care organizations, mainly in the United States. The network includes over 106 million patients. They looked at four cohorts: Patients without acne; those with acne but no current or prior use of systemic medications; those with acne managed with isotretinoin (and no prior use of oral tetracycline-class antibiotics); and those with acne managed with oral tetracycline-class antibiotics (and no exposure to isotretinoin).

Ocskay Bence/Fotolia.com

For the acne cohorts, the investigators captured first encounters with a diagnosis of acne and first prescriptions of interest. And studywide, they used propensity score matching to balance cohorts for age, sex, race, ethnicity, and combined oral contraceptive use.

“These data should provide more reassurance to patients and prescribers that isotretinoin does not appear to result in a meaningfully increased risk of inflammatory bowel disease,” they wrote in the study, published online in the Journal of the American Academy of Dermatology.

“These are important findings as isotretinoin is a valuable treatment for acne that can result in a durable remission of disease activity, prevent acne scarring, and reduce our overreliance on oral antibiotics for acne,” they added.

Indeed, dermatologist Jonathan S. Weiss, MD, who was not involved in the research and was asked to comment on the study, said that the findings “are reassuring given the large numbers of patients evaluated and treated.” The smallest cohort – the isotretinoin group – had over 11,000 patients, and the other cohorts had over 100,000 patients each, he said in an interview.

“At this point, I’m not sure we need any other immediate information to feel comfortable using isotretinoin with respect to a potential to cause IBD, but it would be nice to see some longitudinal follow-up data for longer-term reassurance,” added Dr. Weiss, who practices in Snellville, Georgia, and is on the board of the directors of the American Acne and Rosacea Society.

 

The findings: Risk with acne

To assess the potential association between acne and IBD, the researchers identified more than 350,000 patients with acne managed without systemic medications, and propensity score matched them with patients who did not have acne. Altogether, their mean age was 22; 32.1% were male, and 59.6% were White.

Compared with the controls who did not have acne, they found a statistically significant association between acne and risk of incident IBD (odds ratio, 1.42; 95% confidence interval, 1.23-1.65) and an absolute risk difference of .04%. Separated into Crohn’s disease (CD) and ulcerative colitis (UC), ORs were 1.56 and 1.62, respectively.
 

Tetracyclines

To assess the association of oral tetracycline use and IBD, they compared more than 144,000 patients whose acne was managed with antibiotics with patients whose acne was managed without systemic medications. The patients had a mean age of 24.4; 34.7% were male, and 68.2% were White.

Compared with the patients who were not on systemic medications, there were no significant associations among those on oral tetracyclines, with an OR for incident IBD of 1 (95% CI, 0.82-1.22), an OR for incident CD of 1.09 (95% CI, 0.86-1.38), and an OR for UC of 0.78 (95% CI, 0.61-1.00).
 

Isotretinoin

To evaluate the association of isotretinoin and IBD, the researchers compared more than 11,000 patients treated with isotretinoin with two matched groups: patients with acne managed without systemic medications, and patients with acne managed with oral tetracyclines. The latter comparison was made to minimize potential confounding by acne severity. These patients had a mean age of 21.1; 49.5% were male, and 75.3% were White.

In the first comparison, compared with patients not treated with systemic medications, the OR for 1-year incidence of IBD among patients treated with isotretinoin was 1.29 (95% CI, 0.64-2.59), with an absolute risk difference of .036%. The ORs for CD and UC were 1.00 (95% CI, 0.45-2.23) and 1.27 (95% CI, .58-2.80), respectively.

And compared with the antibiotic-managed group, the OR for incident IBD among those on isotretinoin was 1.13 (95% CI, 0.57-2.21), with an absolute risk difference of .018%. The OR for CD was 1.00 (95% CI, 0.45-2.23). The OR for UC could not be accurately estimated because of an insufficient number of events in the tetracycline-treated group.
 

‘Challenging’ area of research

Researching acne treatments and the potential risk of IBD has been a methodologically “challenging topic to study” because of possible confounding and surveillance bias depending on study designs, Dr. Barbieri, director of the Brigham and Women’s Advanced Acne Therapeutics Clinic, said in an interview.

Studies that have identified a potential association between isotretinoin and IBD often have not adequately controlled for prior antibiotic exposure, for instance. And other studies, including a retrospective cohort study also published recently in JAAD using the same TriNetX database, have found 6-month isotretinoin-related risks of IBD but no increased risk at 1 year or more of follow-up – a finding that suggests a role of surveillance bias, Dr. Barbieri said.

The follow-up period of 1 year in their new study was chosen to minimize the risk of such bias. “Since patients on isotretinoin are seen more often, and since there are historical concerns about isotretinoin and IBD, patients on isotretinoin may be more likely to be screened earlier and thus could be diagnosed sooner than those not on [the medication],” he said.

He and his coauthors considered similar potential bias in designing the no-acne cohort, choosing patients who had routine primary care visits without abnormal findings in order to “reduce potential for bias due to frequency of interaction with the health care system,” they noted in their paper. (Patients had no prior encounters for acne and no history of acne treatments.)
 

Antibiotics, acne itself

Research on antibiotic use for acne and risk of IBD is scant, and the few studies that have been published show conflicting findings, Dr. Barbieri noted. In the meantime, studies and meta-analyses in the general medical literature – not involving acne – have identified an association between lifetime oral antibiotic exposure and IBD, he said.

While the results of the new study “are reassuring that oral tetracycline-class exposure for acne may not be associated with a significant absolute risk of inflammatory bowel disease, given the potential for antibiotic resistance and other antibiotic-associated complications, it remains important to be judicious” with their use in acne management, he and his coauthors wrote in the study.

The potential association between antibiotics for acne and IBD needs further study, preferably with longer follow-up duration, Dr. Barbieri said in the interview, but researchers are challenged by the lack of datasets with high-quality longitudinal data “beyond a few years of follow-up.”

The extent to which acne itself is associated with IBD is another area ripe for more research. Thus far, it seems that IBD and acne – and other chronic inflammatory skin diseases such as psoriasis – involve similar pathogenic pathways. “We know that in IBD Th17 and TNF immunologic pathways are important, so it’s not surprising that there may be associations,” he said.

In their paper, Dr. Barbieri and his coauthors emphasize, however, that the absolute risk difference between acne and IBD is small. It’s “unlikely that population level screening is warranted among patients with acne,” they wrote.

A second new study

The other study, also published recently in JAAD, used the same TriNetX research platform to identify approximately 77,000 patients with acne starting isotretinoin and matched them with patients starting oral antibiotics.

The investigators, Khalaf Kridin MD, PhD, and Ralf J. Ludwig, MD, of the Lübeck Institute of Experimental Dermatology, University of Lübeck (Germany), found that the lifetime risks (greater than 6 months) for patients on isotretinoin were not significantly elevated, compared with those on oral antibiotics for either CD (hazard ratio 1.05; 95% CI, 0.89-1.24, P = .583) or UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) They also looked at the risk of irritable bowel syndrome (IBS) and found a lower lifetime risk in the isotretinoin group.

In the short term, during the first 6 months after drug initiation, there was a significant, but slight increase in UC in the isotretinoin group. But this risk decreased to the level of the antibiotic group with longer follow up. “The absolute incidence rates [of IBD] and the risk difference of UC within the first 6 months are of limited clinical significance,” they wrote.

It may be, Dr. Weiss said in commenting on this study, “that isotretinoin unmasks an already-existing genetic tendency to UC early on in the course of treatment, but that it does not truly cause an increased incidence of any type of IBD.”

Both studies, said Dr. Barbieri, “add to an extensive body of literature that supports that isotretinoin is not associated with IBD.”

Dr. Barbieri had no disclosures for the study, for which Matthew T. Taylor served as first author. Coauthor Shawn Kwatra, MD, disclosed that he is an advisory board member/consultant for numerous pharmaceutical companies and has served as an investigator for several. Both are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The other authors had no disclosures. Dr. Kridin and Dr. Ludwig had no disclosures for their study. Dr. Weiss had no disclosures.

Isotretinoin was not associated with a 1-year risk of incident inflammatory bowel disease (IBD) in a large population-based cohort study that also found no significant association of oral tetracycline-class antibiotics with IBD – and a small but statistically significant association of acne itself with the inflammatory disorders that make up IBD.

For the study, senior author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, and his colleagues used data from the TriNetX global research platform, which mines patient-level electronic medical record data from dozens of health care organizations, mainly in the United States. The network includes over 106 million patients. They looked at four cohorts: Patients without acne; those with acne but no current or prior use of systemic medications; those with acne managed with isotretinoin (and no prior use of oral tetracycline-class antibiotics); and those with acne managed with oral tetracycline-class antibiotics (and no exposure to isotretinoin).

Ocskay Bence/Fotolia.com

For the acne cohorts, the investigators captured first encounters with a diagnosis of acne and first prescriptions of interest. And studywide, they used propensity score matching to balance cohorts for age, sex, race, ethnicity, and combined oral contraceptive use.

“These data should provide more reassurance to patients and prescribers that isotretinoin does not appear to result in a meaningfully increased risk of inflammatory bowel disease,” they wrote in the study, published online in the Journal of the American Academy of Dermatology.

“These are important findings as isotretinoin is a valuable treatment for acne that can result in a durable remission of disease activity, prevent acne scarring, and reduce our overreliance on oral antibiotics for acne,” they added.

Indeed, dermatologist Jonathan S. Weiss, MD, who was not involved in the research and was asked to comment on the study, said that the findings “are reassuring given the large numbers of patients evaluated and treated.” The smallest cohort – the isotretinoin group – had over 11,000 patients, and the other cohorts had over 100,000 patients each, he said in an interview.

“At this point, I’m not sure we need any other immediate information to feel comfortable using isotretinoin with respect to a potential to cause IBD, but it would be nice to see some longitudinal follow-up data for longer-term reassurance,” added Dr. Weiss, who practices in Snellville, Georgia, and is on the board of the directors of the American Acne and Rosacea Society.

 

The findings: Risk with acne

To assess the potential association between acne and IBD, the researchers identified more than 350,000 patients with acne managed without systemic medications, and propensity score matched them with patients who did not have acne. Altogether, their mean age was 22; 32.1% were male, and 59.6% were White.

Compared with the controls who did not have acne, they found a statistically significant association between acne and risk of incident IBD (odds ratio, 1.42; 95% confidence interval, 1.23-1.65) and an absolute risk difference of .04%. Separated into Crohn’s disease (CD) and ulcerative colitis (UC), ORs were 1.56 and 1.62, respectively.
 

Tetracyclines

To assess the association of oral tetracycline use and IBD, they compared more than 144,000 patients whose acne was managed with antibiotics with patients whose acne was managed without systemic medications. The patients had a mean age of 24.4; 34.7% were male, and 68.2% were White.

Compared with the patients who were not on systemic medications, there were no significant associations among those on oral tetracyclines, with an OR for incident IBD of 1 (95% CI, 0.82-1.22), an OR for incident CD of 1.09 (95% CI, 0.86-1.38), and an OR for UC of 0.78 (95% CI, 0.61-1.00).
 

Isotretinoin

To evaluate the association of isotretinoin and IBD, the researchers compared more than 11,000 patients treated with isotretinoin with two matched groups: patients with acne managed without systemic medications, and patients with acne managed with oral tetracyclines. The latter comparison was made to minimize potential confounding by acne severity. These patients had a mean age of 21.1; 49.5% were male, and 75.3% were White.

In the first comparison, compared with patients not treated with systemic medications, the OR for 1-year incidence of IBD among patients treated with isotretinoin was 1.29 (95% CI, 0.64-2.59), with an absolute risk difference of .036%. The ORs for CD and UC were 1.00 (95% CI, 0.45-2.23) and 1.27 (95% CI, .58-2.80), respectively.

And compared with the antibiotic-managed group, the OR for incident IBD among those on isotretinoin was 1.13 (95% CI, 0.57-2.21), with an absolute risk difference of .018%. The OR for CD was 1.00 (95% CI, 0.45-2.23). The OR for UC could not be accurately estimated because of an insufficient number of events in the tetracycline-treated group.
 

‘Challenging’ area of research

Researching acne treatments and the potential risk of IBD has been a methodologically “challenging topic to study” because of possible confounding and surveillance bias depending on study designs, Dr. Barbieri, director of the Brigham and Women’s Advanced Acne Therapeutics Clinic, said in an interview.

Studies that have identified a potential association between isotretinoin and IBD often have not adequately controlled for prior antibiotic exposure, for instance. And other studies, including a retrospective cohort study also published recently in JAAD using the same TriNetX database, have found 6-month isotretinoin-related risks of IBD but no increased risk at 1 year or more of follow-up – a finding that suggests a role of surveillance bias, Dr. Barbieri said.

The follow-up period of 1 year in their new study was chosen to minimize the risk of such bias. “Since patients on isotretinoin are seen more often, and since there are historical concerns about isotretinoin and IBD, patients on isotretinoin may be more likely to be screened earlier and thus could be diagnosed sooner than those not on [the medication],” he said.

He and his coauthors considered similar potential bias in designing the no-acne cohort, choosing patients who had routine primary care visits without abnormal findings in order to “reduce potential for bias due to frequency of interaction with the health care system,” they noted in their paper. (Patients had no prior encounters for acne and no history of acne treatments.)
 

Antibiotics, acne itself

Research on antibiotic use for acne and risk of IBD is scant, and the few studies that have been published show conflicting findings, Dr. Barbieri noted. In the meantime, studies and meta-analyses in the general medical literature – not involving acne – have identified an association between lifetime oral antibiotic exposure and IBD, he said.

While the results of the new study “are reassuring that oral tetracycline-class exposure for acne may not be associated with a significant absolute risk of inflammatory bowel disease, given the potential for antibiotic resistance and other antibiotic-associated complications, it remains important to be judicious” with their use in acne management, he and his coauthors wrote in the study.

The potential association between antibiotics for acne and IBD needs further study, preferably with longer follow-up duration, Dr. Barbieri said in the interview, but researchers are challenged by the lack of datasets with high-quality longitudinal data “beyond a few years of follow-up.”

The extent to which acne itself is associated with IBD is another area ripe for more research. Thus far, it seems that IBD and acne – and other chronic inflammatory skin diseases such as psoriasis – involve similar pathogenic pathways. “We know that in IBD Th17 and TNF immunologic pathways are important, so it’s not surprising that there may be associations,” he said.

In their paper, Dr. Barbieri and his coauthors emphasize, however, that the absolute risk difference between acne and IBD is small. It’s “unlikely that population level screening is warranted among patients with acne,” they wrote.

A second new study

The other study, also published recently in JAAD, used the same TriNetX research platform to identify approximately 77,000 patients with acne starting isotretinoin and matched them with patients starting oral antibiotics.

The investigators, Khalaf Kridin MD, PhD, and Ralf J. Ludwig, MD, of the Lübeck Institute of Experimental Dermatology, University of Lübeck (Germany), found that the lifetime risks (greater than 6 months) for patients on isotretinoin were not significantly elevated, compared with those on oral antibiotics for either CD (hazard ratio 1.05; 95% CI, 0.89-1.24, P = .583) or UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) They also looked at the risk of irritable bowel syndrome (IBS) and found a lower lifetime risk in the isotretinoin group.

In the short term, during the first 6 months after drug initiation, there was a significant, but slight increase in UC in the isotretinoin group. But this risk decreased to the level of the antibiotic group with longer follow up. “The absolute incidence rates [of IBD] and the risk difference of UC within the first 6 months are of limited clinical significance,” they wrote.

It may be, Dr. Weiss said in commenting on this study, “that isotretinoin unmasks an already-existing genetic tendency to UC early on in the course of treatment, but that it does not truly cause an increased incidence of any type of IBD.”

Both studies, said Dr. Barbieri, “add to an extensive body of literature that supports that isotretinoin is not associated with IBD.”

Dr. Barbieri had no disclosures for the study, for which Matthew T. Taylor served as first author. Coauthor Shawn Kwatra, MD, disclosed that he is an advisory board member/consultant for numerous pharmaceutical companies and has served as an investigator for several. Both are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The other authors had no disclosures. Dr. Kridin and Dr. Ludwig had no disclosures for their study. Dr. Weiss had no disclosures.

Isotretinoin was not associated with a 1-year risk of incident inflammatory bowel disease (IBD) in a large population-based cohort study that also found no significant association of oral tetracycline-class antibiotics with IBD – and a small but statistically significant association of acne itself with the inflammatory disorders that make up IBD.

For the study, senior author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, and his colleagues used data from the TriNetX global research platform, which mines patient-level electronic medical record data from dozens of health care organizations, mainly in the United States. The network includes over 106 million patients. They looked at four cohorts: Patients without acne; those with acne but no current or prior use of systemic medications; those with acne managed with isotretinoin (and no prior use of oral tetracycline-class antibiotics); and those with acne managed with oral tetracycline-class antibiotics (and no exposure to isotretinoin).

Ocskay Bence/Fotolia.com

For the acne cohorts, the investigators captured first encounters with a diagnosis of acne and first prescriptions of interest. And studywide, they used propensity score matching to balance cohorts for age, sex, race, ethnicity, and combined oral contraceptive use.

“These data should provide more reassurance to patients and prescribers that isotretinoin does not appear to result in a meaningfully increased risk of inflammatory bowel disease,” they wrote in the study, published online in the Journal of the American Academy of Dermatology.

“These are important findings as isotretinoin is a valuable treatment for acne that can result in a durable remission of disease activity, prevent acne scarring, and reduce our overreliance on oral antibiotics for acne,” they added.

Indeed, dermatologist Jonathan S. Weiss, MD, who was not involved in the research and was asked to comment on the study, said that the findings “are reassuring given the large numbers of patients evaluated and treated.” The smallest cohort – the isotretinoin group – had over 11,000 patients, and the other cohorts had over 100,000 patients each, he said in an interview.

“At this point, I’m not sure we need any other immediate information to feel comfortable using isotretinoin with respect to a potential to cause IBD, but it would be nice to see some longitudinal follow-up data for longer-term reassurance,” added Dr. Weiss, who practices in Snellville, Georgia, and is on the board of the directors of the American Acne and Rosacea Society.

 

The findings: Risk with acne

To assess the potential association between acne and IBD, the researchers identified more than 350,000 patients with acne managed without systemic medications, and propensity score matched them with patients who did not have acne. Altogether, their mean age was 22; 32.1% were male, and 59.6% were White.

Compared with the controls who did not have acne, they found a statistically significant association between acne and risk of incident IBD (odds ratio, 1.42; 95% confidence interval, 1.23-1.65) and an absolute risk difference of .04%. Separated into Crohn’s disease (CD) and ulcerative colitis (UC), ORs were 1.56 and 1.62, respectively.
 

Tetracyclines

To assess the association of oral tetracycline use and IBD, they compared more than 144,000 patients whose acne was managed with antibiotics with patients whose acne was managed without systemic medications. The patients had a mean age of 24.4; 34.7% were male, and 68.2% were White.

Compared with the patients who were not on systemic medications, there were no significant associations among those on oral tetracyclines, with an OR for incident IBD of 1 (95% CI, 0.82-1.22), an OR for incident CD of 1.09 (95% CI, 0.86-1.38), and an OR for UC of 0.78 (95% CI, 0.61-1.00).
 

Isotretinoin

To evaluate the association of isotretinoin and IBD, the researchers compared more than 11,000 patients treated with isotretinoin with two matched groups: patients with acne managed without systemic medications, and patients with acne managed with oral tetracyclines. The latter comparison was made to minimize potential confounding by acne severity. These patients had a mean age of 21.1; 49.5% were male, and 75.3% were White.

In the first comparison, compared with patients not treated with systemic medications, the OR for 1-year incidence of IBD among patients treated with isotretinoin was 1.29 (95% CI, 0.64-2.59), with an absolute risk difference of .036%. The ORs for CD and UC were 1.00 (95% CI, 0.45-2.23) and 1.27 (95% CI, .58-2.80), respectively.

And compared with the antibiotic-managed group, the OR for incident IBD among those on isotretinoin was 1.13 (95% CI, 0.57-2.21), with an absolute risk difference of .018%. The OR for CD was 1.00 (95% CI, 0.45-2.23). The OR for UC could not be accurately estimated because of an insufficient number of events in the tetracycline-treated group.
 

‘Challenging’ area of research

Researching acne treatments and the potential risk of IBD has been a methodologically “challenging topic to study” because of possible confounding and surveillance bias depending on study designs, Dr. Barbieri, director of the Brigham and Women’s Advanced Acne Therapeutics Clinic, said in an interview.

Studies that have identified a potential association between isotretinoin and IBD often have not adequately controlled for prior antibiotic exposure, for instance. And other studies, including a retrospective cohort study also published recently in JAAD using the same TriNetX database, have found 6-month isotretinoin-related risks of IBD but no increased risk at 1 year or more of follow-up – a finding that suggests a role of surveillance bias, Dr. Barbieri said.

The follow-up period of 1 year in their new study was chosen to minimize the risk of such bias. “Since patients on isotretinoin are seen more often, and since there are historical concerns about isotretinoin and IBD, patients on isotretinoin may be more likely to be screened earlier and thus could be diagnosed sooner than those not on [the medication],” he said.

He and his coauthors considered similar potential bias in designing the no-acne cohort, choosing patients who had routine primary care visits without abnormal findings in order to “reduce potential for bias due to frequency of interaction with the health care system,” they noted in their paper. (Patients had no prior encounters for acne and no history of acne treatments.)
 

Antibiotics, acne itself

Research on antibiotic use for acne and risk of IBD is scant, and the few studies that have been published show conflicting findings, Dr. Barbieri noted. In the meantime, studies and meta-analyses in the general medical literature – not involving acne – have identified an association between lifetime oral antibiotic exposure and IBD, he said.

While the results of the new study “are reassuring that oral tetracycline-class exposure for acne may not be associated with a significant absolute risk of inflammatory bowel disease, given the potential for antibiotic resistance and other antibiotic-associated complications, it remains important to be judicious” with their use in acne management, he and his coauthors wrote in the study.

The potential association between antibiotics for acne and IBD needs further study, preferably with longer follow-up duration, Dr. Barbieri said in the interview, but researchers are challenged by the lack of datasets with high-quality longitudinal data “beyond a few years of follow-up.”

The extent to which acne itself is associated with IBD is another area ripe for more research. Thus far, it seems that IBD and acne – and other chronic inflammatory skin diseases such as psoriasis – involve similar pathogenic pathways. “We know that in IBD Th17 and TNF immunologic pathways are important, so it’s not surprising that there may be associations,” he said.

In their paper, Dr. Barbieri and his coauthors emphasize, however, that the absolute risk difference between acne and IBD is small. It’s “unlikely that population level screening is warranted among patients with acne,” they wrote.

A second new study

The other study, also published recently in JAAD, used the same TriNetX research platform to identify approximately 77,000 patients with acne starting isotretinoin and matched them with patients starting oral antibiotics.

The investigators, Khalaf Kridin MD, PhD, and Ralf J. Ludwig, MD, of the Lübeck Institute of Experimental Dermatology, University of Lübeck (Germany), found that the lifetime risks (greater than 6 months) for patients on isotretinoin were not significantly elevated, compared with those on oral antibiotics for either CD (hazard ratio 1.05; 95% CI, 0.89-1.24, P = .583) or UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) They also looked at the risk of irritable bowel syndrome (IBS) and found a lower lifetime risk in the isotretinoin group.

In the short term, during the first 6 months after drug initiation, there was a significant, but slight increase in UC in the isotretinoin group. But this risk decreased to the level of the antibiotic group with longer follow up. “The absolute incidence rates [of IBD] and the risk difference of UC within the first 6 months are of limited clinical significance,” they wrote.

It may be, Dr. Weiss said in commenting on this study, “that isotretinoin unmasks an already-existing genetic tendency to UC early on in the course of treatment, but that it does not truly cause an increased incidence of any type of IBD.”

Both studies, said Dr. Barbieri, “add to an extensive body of literature that supports that isotretinoin is not associated with IBD.”

Dr. Barbieri had no disclosures for the study, for which Matthew T. Taylor served as first author. Coauthor Shawn Kwatra, MD, disclosed that he is an advisory board member/consultant for numerous pharmaceutical companies and has served as an investigator for several. Both are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The other authors had no disclosures. Dr. Kridin and Dr. Ludwig had no disclosures for their study. Dr. Weiss had no disclosures.

Leprosy, also known as Hansen’s disease (HD), is a historically stigmatized infection caused by acid-fast bacilli Mycobacterium leprae, and M. lepromatosis. Paucibacillary tuberculoid leprosy is characterized by few anesthetic hypo- or hyperpigmented lesions and can be accompanied by palpable peripheral nerve enlargements.

Tuberculoid leprosy presents histologically with epithelioid histiocytes with lymphocytes and Langhans giant cells. Neurotropic granulomas are also characteristic of tuberculoid leprosy. Fite staining allows for the identification of the acid-fast bacilli of M. leprae, which in some cases are quite few in number. The standard mycobacterium stain, Ziehl-Neelsen, is a good option for M. tuberculosis, but because of the relative weak mycolic acid coat of M. leprae, the Fite stain is more appropriate for identifying M. leprae.

Clinically, other than the presence of fewer than five hypoesthetic lesions that are either hypopigmented or erythematous, tuberculoid leprosy often presents with additional peripheral nerve involvement that manifests as numbness and tingling in hands and feet.¹ This patient denied any tingling, weakness, or numbness, outside of the anesthetic lesion on his posterior upper arm.

The patient, born in the United States, had a remote history of military travel to Iraq, Kuwait, and the Philippines, but had not traveled internationally within the last 15 years, apart from a cruise to the Bahamas. He denied any known contact with individuals with similar lesions. He denied a history of contact with armadillos, but acknowledged that they are native to where he resides in central Florida, and that he had seen them in his yard.

Histopathological examination revealed an unremarkable epidermis with a superficial and deep perivascular, periadnexal, and perineural lymphohistiocytic infiltrate. Fite stain revealed rare rod-shaped organisms (Figure 2). These findings are consistent with a diagnosis of paucibacillary, tuberculoid leprosy.

The patient’s travel history to highly endemic areas (Middle East), as well as possible environmental contact with armadillos – including contact with soil that the armadillos occupied – could explain plausible modes of transmission. Following consultation with our infectious disease department and the National Hansen’s Disease Program, our patient began a planned course of therapy with 18 months of minocycline, rifampin, and moxifloxacin.

Human-to-human transmission of HD has been well documented; however, zoonotic transmission – specifically via the nine-banded armadillo (Dasypus novemcinctus) – serves as another suggested means of transmission, especially in the Southeastern United States.^2-6 Travel to highly-endemic areas increases the risk of contracting HD, which may take up to 20 years following contact with the bacteria to manifest clinically.

While central Florida was previously thought to be a nonendemic area of disease, the incidence of the disease in this region has increased in recent years.⁷ Human-to-human transmission, which remains a concern with immigration from highly-endemic regions^, occurs via long-term contact with nasal droplets of an infected person.^8,9

Many patients in regions with very few cases of leprosy deny travel to other endemic regions and contact with infected people. Thus, zoonotic transmission remains a legitimate concern in the Southeastern United States – accounting, at least in part, for many of the non–human-transmitted cases of leprosy.^2,10 We encourage clinicians to maintain a high level of clinical suspicion for leprosy when evaluating patients presenting with hypoesthetic cutaneous lesions and to obtain a travel history and to ask about armadillo exposure.

This case and the photos were submitted by Ms. Smith, from the University of South Florida, Tampa; Dr. Hatch and Dr. Sarriera-Lazaro, from the department of dermatology and cutaneous surgery, University of South Florida; and Dr. Turner and Dr. Beachkofsky, from the department of pathology and laboratory medicine at the James A. Haley Veterans’ Hospital, Tampa. Dr. Bilu Martin edited this case. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Leprosy (Hansen’s Disease), in: “Goldman’s Cecil Medicine,” 24th ed. (Philadelphia: W.B. Saunders, 2012: pp. 1950-4.

2. Sharma R et al. Emerg Infect Dis. 2015 Dec;21(12):2127-34.

3. Lane JE et al. J Am Acad Dermatol. 2006 Oct;55(4):714-6.

4. Clark BM et al. Am J Trop Med Hyg. 2008 Jun;78(6):962-7.

5. Bruce S et al. J Am Acad Dermatol. 2000 Aug;43(2 Pt 1):223-8.

6. Loughry WJ et al. J Wildl Dis. 2009 Jan;45(1):144-52.

7. FDo H. Florida charts: Hansen’s Disease (Leprosy). Health FDo. 2019. https://www.flhealthcharts.gov/ChartsReports/rdPage.aspx?rdReport=NonVitalIndNoGrpCounts.DataViewer&cid=174.

8. Maymone MBC et al. J Am Acad Dermatol. 2020 Jul;83(1):1-14.

9. Scollard DM et al. Clin Microbiol Rev. 2006 Apr;19(2):338-81.

10. Domozych R et al. JAAD Case Rep. 2016 May 12;2(3):189-92.




 

Leprosy, also known as Hansen’s disease (HD), is a historically stigmatized infection caused by acid-fast bacilli Mycobacterium leprae, and M. lepromatosis. Paucibacillary tuberculoid leprosy is characterized by few anesthetic hypo- or hyperpigmented lesions and can be accompanied by palpable peripheral nerve enlargements.

Tuberculoid leprosy presents histologically with epithelioid histiocytes with lymphocytes and Langhans giant cells. Neurotropic granulomas are also characteristic of tuberculoid leprosy. Fite staining allows for the identification of the acid-fast bacilli of M. leprae, which in some cases are quite few in number. The standard mycobacterium stain, Ziehl-Neelsen, is a good option for M. tuberculosis, but because of the relative weak mycolic acid coat of M. leprae, the Fite stain is more appropriate for identifying M. leprae.

Clinically, other than the presence of fewer than five hypoesthetic lesions that are either hypopigmented or erythematous, tuberculoid leprosy often presents with additional peripheral nerve involvement that manifests as numbness and tingling in hands and feet.¹ This patient denied any tingling, weakness, or numbness, outside of the anesthetic lesion on his posterior upper arm.

The patient, born in the United States, had a remote history of military travel to Iraq, Kuwait, and the Philippines, but had not traveled internationally within the last 15 years, apart from a cruise to the Bahamas. He denied any known contact with individuals with similar lesions. He denied a history of contact with armadillos, but acknowledged that they are native to where he resides in central Florida, and that he had seen them in his yard.

Histopathological examination revealed an unremarkable epidermis with a superficial and deep perivascular, periadnexal, and perineural lymphohistiocytic infiltrate. Fite stain revealed rare rod-shaped organisms (Figure 2). These findings are consistent with a diagnosis of paucibacillary, tuberculoid leprosy.

The patient’s travel history to highly endemic areas (Middle East), as well as possible environmental contact with armadillos – including contact with soil that the armadillos occupied – could explain plausible modes of transmission. Following consultation with our infectious disease department and the National Hansen’s Disease Program, our patient began a planned course of therapy with 18 months of minocycline, rifampin, and moxifloxacin.

Human-to-human transmission of HD has been well documented; however, zoonotic transmission – specifically via the nine-banded armadillo (Dasypus novemcinctus) – serves as another suggested means of transmission, especially in the Southeastern United States.^2-6 Travel to highly-endemic areas increases the risk of contracting HD, which may take up to 20 years following contact with the bacteria to manifest clinically.

While central Florida was previously thought to be a nonendemic area of disease, the incidence of the disease in this region has increased in recent years.⁷ Human-to-human transmission, which remains a concern with immigration from highly-endemic regions^, occurs via long-term contact with nasal droplets of an infected person.^8,9

Many patients in regions with very few cases of leprosy deny travel to other endemic regions and contact with infected people. Thus, zoonotic transmission remains a legitimate concern in the Southeastern United States – accounting, at least in part, for many of the non–human-transmitted cases of leprosy.^2,10 We encourage clinicians to maintain a high level of clinical suspicion for leprosy when evaluating patients presenting with hypoesthetic cutaneous lesions and to obtain a travel history and to ask about armadillo exposure.

This case and the photos were submitted by Ms. Smith, from the University of South Florida, Tampa; Dr. Hatch and Dr. Sarriera-Lazaro, from the department of dermatology and cutaneous surgery, University of South Florida; and Dr. Turner and Dr. Beachkofsky, from the department of pathology and laboratory medicine at the James A. Haley Veterans’ Hospital, Tampa. Dr. Bilu Martin edited this case. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Leprosy (Hansen’s Disease), in: “Goldman’s Cecil Medicine,” 24th ed. (Philadelphia: W.B. Saunders, 2012: pp. 1950-4.

2. Sharma R et al. Emerg Infect Dis. 2015 Dec;21(12):2127-34.

3. Lane JE et al. J Am Acad Dermatol. 2006 Oct;55(4):714-6.

4. Clark BM et al. Am J Trop Med Hyg. 2008 Jun;78(6):962-7.

5. Bruce S et al. J Am Acad Dermatol. 2000 Aug;43(2 Pt 1):223-8.

6. Loughry WJ et al. J Wildl Dis. 2009 Jan;45(1):144-52.

7. FDo H. Florida charts: Hansen’s Disease (Leprosy). Health FDo. 2019. https://www.flhealthcharts.gov/ChartsReports/rdPage.aspx?rdReport=NonVitalIndNoGrpCounts.DataViewer&cid=174.

8. Maymone MBC et al. J Am Acad Dermatol. 2020 Jul;83(1):1-14.

9. Scollard DM et al. Clin Microbiol Rev. 2006 Apr;19(2):338-81.

10. Domozych R et al. JAAD Case Rep. 2016 May 12;2(3):189-92.




 

Leprosy, also known as Hansen’s disease (HD), is a historically stigmatized infection caused by acid-fast bacilli Mycobacterium leprae, and M. lepromatosis. Paucibacillary tuberculoid leprosy is characterized by few anesthetic hypo- or hyperpigmented lesions and can be accompanied by palpable peripheral nerve enlargements.

Tuberculoid leprosy presents histologically with epithelioid histiocytes with lymphocytes and Langhans giant cells. Neurotropic granulomas are also characteristic of tuberculoid leprosy. Fite staining allows for the identification of the acid-fast bacilli of M. leprae, which in some cases are quite few in number. The standard mycobacterium stain, Ziehl-Neelsen, is a good option for M. tuberculosis, but because of the relative weak mycolic acid coat of M. leprae, the Fite stain is more appropriate for identifying M. leprae.

Clinically, other than the presence of fewer than five hypoesthetic lesions that are either hypopigmented or erythematous, tuberculoid leprosy often presents with additional peripheral nerve involvement that manifests as numbness and tingling in hands and feet.¹ This patient denied any tingling, weakness, or numbness, outside of the anesthetic lesion on his posterior upper arm.

The patient, born in the United States, had a remote history of military travel to Iraq, Kuwait, and the Philippines, but had not traveled internationally within the last 15 years, apart from a cruise to the Bahamas. He denied any known contact with individuals with similar lesions. He denied a history of contact with armadillos, but acknowledged that they are native to where he resides in central Florida, and that he had seen them in his yard.

Histopathological examination revealed an unremarkable epidermis with a superficial and deep perivascular, periadnexal, and perineural lymphohistiocytic infiltrate. Fite stain revealed rare rod-shaped organisms (Figure 2). These findings are consistent with a diagnosis of paucibacillary, tuberculoid leprosy.

The patient’s travel history to highly endemic areas (Middle East), as well as possible environmental contact with armadillos – including contact with soil that the armadillos occupied – could explain plausible modes of transmission. Following consultation with our infectious disease department and the National Hansen’s Disease Program, our patient began a planned course of therapy with 18 months of minocycline, rifampin, and moxifloxacin.

Human-to-human transmission of HD has been well documented; however, zoonotic transmission – specifically via the nine-banded armadillo (Dasypus novemcinctus) – serves as another suggested means of transmission, especially in the Southeastern United States.^2-6 Travel to highly-endemic areas increases the risk of contracting HD, which may take up to 20 years following contact with the bacteria to manifest clinically.

While central Florida was previously thought to be a nonendemic area of disease, the incidence of the disease in this region has increased in recent years.⁷ Human-to-human transmission, which remains a concern with immigration from highly-endemic regions^, occurs via long-term contact with nasal droplets of an infected person.^8,9

Many patients in regions with very few cases of leprosy deny travel to other endemic regions and contact with infected people. Thus, zoonotic transmission remains a legitimate concern in the Southeastern United States – accounting, at least in part, for many of the non–human-transmitted cases of leprosy.^2,10 We encourage clinicians to maintain a high level of clinical suspicion for leprosy when evaluating patients presenting with hypoesthetic cutaneous lesions and to obtain a travel history and to ask about armadillo exposure.

This case and the photos were submitted by Ms. Smith, from the University of South Florida, Tampa; Dr. Hatch and Dr. Sarriera-Lazaro, from the department of dermatology and cutaneous surgery, University of South Florida; and Dr. Turner and Dr. Beachkofsky, from the department of pathology and laboratory medicine at the James A. Haley Veterans’ Hospital, Tampa. Dr. Bilu Martin edited this case. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Leprosy (Hansen’s Disease), in: “Goldman’s Cecil Medicine,” 24th ed. (Philadelphia: W.B. Saunders, 2012: pp. 1950-4.

2. Sharma R et al. Emerg Infect Dis. 2015 Dec;21(12):2127-34.

3. Lane JE et al. J Am Acad Dermatol. 2006 Oct;55(4):714-6.

4. Clark BM et al. Am J Trop Med Hyg. 2008 Jun;78(6):962-7.

5. Bruce S et al. J Am Acad Dermatol. 2000 Aug;43(2 Pt 1):223-8.

6. Loughry WJ et al. J Wildl Dis. 2009 Jan;45(1):144-52.

7. FDo H. Florida charts: Hansen’s Disease (Leprosy). Health FDo. 2019. https://www.flhealthcharts.gov/ChartsReports/rdPage.aspx?rdReport=NonVitalIndNoGrpCounts.DataViewer&cid=174.

8. Maymone MBC et al. J Am Acad Dermatol. 2020 Jul;83(1):1-14.

9. Scollard DM et al. Clin Microbiol Rev. 2006 Apr;19(2):338-81.

10. Domozych R et al. JAAD Case Rep. 2016 May 12;2(3):189-92.




 

People with untreatable dystrophic epidermolysis bullosa (DEB) may soon have access to an investigational gene therapy delivered in a topical gel that is currently under review by the Food and Drug Administration.

In a phase 3 study of patients with DEB, “we found that repeated topical application of B-VEC [beremagene geperpavec], an HSV-1–based gene therapy, resulted in a greater likelihood of complete wound healing than the topical application of placebo at up to 6 months,” the authors wrote. The study was published in The New England Journal of Medicine. “Longer and larger trials are warranted to determine the durability of effect and risks of this approach,” the authors noted.

“The results prove that B-VEC, the first topical in vivo gene therapy to reach late-stage development, can heal DEB,” senior author M. Peter Marinkovich, MD, associate professor of dermatology at Stanford University, Redwood City, Calif., said in an interview.

“In the past, DEB was a very specialized disease that only a handful of dermatologists would see but could not do much to treat,” he said. “With gene therapy, many more dermatologists who may not be familiar with DEB will be able to treat these patients in their offices.” It is expected that nurses will be able to administer the treatment to patients at home, he added.
 

Rare, life-threatening, genetic blistering disease

DEB, a rare disease that affects one to three persons per million in the United States, is caused by mutations in the COL7A1 gene that encodes the alpha-1 chain of collagen type VII (C7) protein. C7 forms the anchoring fibrils that attach the epidermis to the underlying dermal connective tissue.

COL71A mutations that lead to defective, decreased, or absent C7 can make the skin so fragile it tears with the slightest touch. This has led to patients being called “butterfly children.” Epithelial tissues blister and scar, causing esophageal and genitourinary strictures, adhesion of digits, malnutrition, anemia, infection, and bothersome itch and pain. Morbidity and mortality are high. The leading cause of death in adults is chronic wounds leading to aggressive squamous cell cancers.
 

The first therapy for DEB, under FDA review

B-VEC restores C7 protein by using an engineered replication-defective herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells to restore functional C7 protein fibrils that stabilize the skin structure.

On the basis of manufacturing information submitted to the FDA in December 2022, the agency extended the date for a decision on approval by 3 months, to May 19, 2023, according to a statement from Krystal Biotech, the developer of B-VEC and the sponsor of the NEJM study.

Dr. Marinkovich and his colleagues conducted the double-blind, randomized, controlled GEM-3 trial of B-VEC at three sites in the United States. The 31 study participants ranged in age from 1 to 44 years (median age, 16 years) and had genetically confirmed DEB (30 with the recessive form and 1 with the dominant form).

For each participant, a pair of wounds was chosen that were matched in size, region, and appearance. The wounds within each pair were randomly allocated to receive weekly applications of either B-VEC or placebo gel for 26 weeks.

The results of the study included the following:

• Complete healing at 6 months occurred in 67% of the wounds treated with B-VEC (including a wound in the patient with dominant DEB), vs. 22% of those who received placebo (95% confidence interval [CI], 24-68; P = .002).
• Complete healing at 3 months occurred in 71% of the wounds treated with B-VEC, vs. 20% of those who received placebo (95% CI, 29-73; P < .001).
• The mean change from baseline to week 22 in pain severity during wound-dressing changes for patients aged 6 years and older, as determined on the basis of a visual analogue scale, was –0.88 with B-VEC, vs. –0.71 with placebo (adjusted least-squares mean difference, –0.61; 95% CI, –1.10 to –0.13); similar mean changes were seen at weeks 24 and 26.
• Among all patients, 58% had at least one adverse event. Most adverse events were mild or moderate. The most common were pruritus, chills, and squamous cell carcinoma (SCC), which were reported in three patients each (SCC cases occurred at wound sites that had not been exposed to B-VEC or placebo). Serious adverse events, which were unrelated to the treatment, occurred in three patients: diarrhea, anemia, cellulitis, and a positive blood culture related to a hemodialysis catheter.

“With the ability to treat patients with topical gene therapy, dermatology is entering a new age of treatment possibilities,” Dr. Marinkovich said in the interview.

The researchers were surprised that the redosable in vivo gene therapy worked so well, he added. In vivo gene therapy has been plagued by the occurrence of immune reactions against the viral vectors used, Dr. Marinkovich explained. But because the herpes simplex virus has evolved to evade the immune system, his team could use the viral vector every week for 6 months without inflammatory reactions.

“The immune system’s inability to fight off or get rid of the herpes simplex vector makes it bad as a disease, but as a gene therapy vector, it provides a huge advantage,” he added.

Asked to comment on the results, Christen Ebens, MD, MPH, assistant professor in the department of pediatrics at the University of Minnesota, Minneapolis, whose clinical and research interests include EB, called the results exciting for patients, families, and doctors.

“Side effects were minimal, and importantly, use of the replication-incompetent HSV vector means that the payload gene does not integrate into the patient’s DNA,” Dr. Ebens, who was not involved in the study, said in an interview. “B-VEC is not a lifelong cure but potentially an effective maintenance therapy requiring repeated doses,” she added.

Although the researchers found no clinically important immune reactions to B-VEC, Dr. Ebens said she would like to see results from longer studies of the treatment. “We will want to see that patients do not produce neutralizing antibodies against B-VEC or its components, as such antibodies may yield the treatment ineffective or cause significant side effects.”

In an interview, Vanessa R. Holland, MD, associate clinical professor in the division of dermatology at UCLA Health, Burbank, Calif., who was not involved in the study, said that “topical replication-defective HSV-1 is a brilliant vector to deliver the depleted collagen.” She added that “such a vehicle may significantly alter management of these disorders and improve or extend lives by minimizing potentially fatal complications.”

Paras P. Vakharia, MD, PharmD, assistant professor of dermatology at Northwestern University, Chicago, who was not involved in the study, was surprised by the high percentage of healed wounds and wounds that remained healed over time.

B-VEC for treating other conditions

Dr. Marinkovich noted that an ongoing phase 1 clinical trial, also sponsored by Krystal Biotech, is using the HSV-1 vector to deliver a different biologic (KB105) to establish dose and safety in the treatment of ichthyosis. He added that he would like to explore the use of B-VEC to treat DEB at mucosal surfaces, including inside the mouth, the eye, and the esophagus.

Authors of two editorials that accompanied the study also referred to other conditions B-VEC might treat.

This study “highlights potential future investigations,” David V. Schaffer, PhD, professor of chemical and biomolecular engineering, bioengineering, and molecular and cell biology at the University of California, Berkeley, wrotes in one of the editorials.

Important considerations he mentioned include the likelihood of the treatment becoming lifelong; the inability of HSV to penetrate intact skin, making B-VEC unsuitable for preventing the development of new wounds; and the inability of this treatment to treat EB lesions along the digestive tract. “This important trial builds on and extends gene-therapy successes to new targets and vectors, an advance for patients,” he added.

In the second editorial, Aimee S. Payne, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia, raised the question of whether B-VEC’s clinical success for treating DEB can translate to other genetic diseases.

“Formulations for ophthalmic, oral-gastrointestinal, or respiratory delivery would be of great value to address the extracutaneous manifestations of epidermolysis bullosa and other genetic diseases,” she wrote.

Referring to an ongoing trial of a topical gene therapy for cystic fibrosis that is delivered by a nebulizer, Dr. Payne noted, “Ultimately, the completion of clinical trials such as this one will be required to determine whether HSV-1–mediated gene delivery can go more than skin deep.”

Earlier data and more details of the study were presented in a poster at the annual meeting of the Society for Pediatric Dermatology in July 2022.

Dr. Marinkovich has disclosed no relevant financial relationships. Several coauthors are employees of or have other financial relationships with Krystal Biotech, the study’s sponsor and the developer of beremagene geperpavec. Dr. Schaffer and Dr. Payne have financial relationships with the pharmaceutical industry. Dr. Ebens, Dr. Holland, and Dr. Vakharia have disclosed no relevant financial relationships.

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

People with untreatable dystrophic epidermolysis bullosa (DEB) may soon have access to an investigational gene therapy delivered in a topical gel that is currently under review by the Food and Drug Administration.

In a phase 3 study of patients with DEB, “we found that repeated topical application of B-VEC [beremagene geperpavec], an HSV-1–based gene therapy, resulted in a greater likelihood of complete wound healing than the topical application of placebo at up to 6 months,” the authors wrote. The study was published in The New England Journal of Medicine. “Longer and larger trials are warranted to determine the durability of effect and risks of this approach,” the authors noted.

“The results prove that B-VEC, the first topical in vivo gene therapy to reach late-stage development, can heal DEB,” senior author M. Peter Marinkovich, MD, associate professor of dermatology at Stanford University, Redwood City, Calif., said in an interview.

“In the past, DEB was a very specialized disease that only a handful of dermatologists would see but could not do much to treat,” he said. “With gene therapy, many more dermatologists who may not be familiar with DEB will be able to treat these patients in their offices.” It is expected that nurses will be able to administer the treatment to patients at home, he added.
 

Rare, life-threatening, genetic blistering disease

DEB, a rare disease that affects one to three persons per million in the United States, is caused by mutations in the COL7A1 gene that encodes the alpha-1 chain of collagen type VII (C7) protein. C7 forms the anchoring fibrils that attach the epidermis to the underlying dermal connective tissue.

COL71A mutations that lead to defective, decreased, or absent C7 can make the skin so fragile it tears with the slightest touch. This has led to patients being called “butterfly children.” Epithelial tissues blister and scar, causing esophageal and genitourinary strictures, adhesion of digits, malnutrition, anemia, infection, and bothersome itch and pain. Morbidity and mortality are high. The leading cause of death in adults is chronic wounds leading to aggressive squamous cell cancers.
 

The first therapy for DEB, under FDA review

B-VEC restores C7 protein by using an engineered replication-defective herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells to restore functional C7 protein fibrils that stabilize the skin structure.

On the basis of manufacturing information submitted to the FDA in December 2022, the agency extended the date for a decision on approval by 3 months, to May 19, 2023, according to a statement from Krystal Biotech, the developer of B-VEC and the sponsor of the NEJM study.

Dr. Marinkovich and his colleagues conducted the double-blind, randomized, controlled GEM-3 trial of B-VEC at three sites in the United States. The 31 study participants ranged in age from 1 to 44 years (median age, 16 years) and had genetically confirmed DEB (30 with the recessive form and 1 with the dominant form).

For each participant, a pair of wounds was chosen that were matched in size, region, and appearance. The wounds within each pair were randomly allocated to receive weekly applications of either B-VEC or placebo gel for 26 weeks.

The results of the study included the following:

• Complete healing at 6 months occurred in 67% of the wounds treated with B-VEC (including a wound in the patient with dominant DEB), vs. 22% of those who received placebo (95% confidence interval [CI], 24-68; P = .002).
• Complete healing at 3 months occurred in 71% of the wounds treated with B-VEC, vs. 20% of those who received placebo (95% CI, 29-73; P < .001).
• The mean change from baseline to week 22 in pain severity during wound-dressing changes for patients aged 6 years and older, as determined on the basis of a visual analogue scale, was –0.88 with B-VEC, vs. –0.71 with placebo (adjusted least-squares mean difference, –0.61; 95% CI, –1.10 to –0.13); similar mean changes were seen at weeks 24 and 26.
• Among all patients, 58% had at least one adverse event. Most adverse events were mild or moderate. The most common were pruritus, chills, and squamous cell carcinoma (SCC), which were reported in three patients each (SCC cases occurred at wound sites that had not been exposed to B-VEC or placebo). Serious adverse events, which were unrelated to the treatment, occurred in three patients: diarrhea, anemia, cellulitis, and a positive blood culture related to a hemodialysis catheter.

“With the ability to treat patients with topical gene therapy, dermatology is entering a new age of treatment possibilities,” Dr. Marinkovich said in the interview.

The researchers were surprised that the redosable in vivo gene therapy worked so well, he added. In vivo gene therapy has been plagued by the occurrence of immune reactions against the viral vectors used, Dr. Marinkovich explained. But because the herpes simplex virus has evolved to evade the immune system, his team could use the viral vector every week for 6 months without inflammatory reactions.

“The immune system’s inability to fight off or get rid of the herpes simplex vector makes it bad as a disease, but as a gene therapy vector, it provides a huge advantage,” he added.

Asked to comment on the results, Christen Ebens, MD, MPH, assistant professor in the department of pediatrics at the University of Minnesota, Minneapolis, whose clinical and research interests include EB, called the results exciting for patients, families, and doctors.

“Side effects were minimal, and importantly, use of the replication-incompetent HSV vector means that the payload gene does not integrate into the patient’s DNA,” Dr. Ebens, who was not involved in the study, said in an interview. “B-VEC is not a lifelong cure but potentially an effective maintenance therapy requiring repeated doses,” she added.

Although the researchers found no clinically important immune reactions to B-VEC, Dr. Ebens said she would like to see results from longer studies of the treatment. “We will want to see that patients do not produce neutralizing antibodies against B-VEC or its components, as such antibodies may yield the treatment ineffective or cause significant side effects.”

In an interview, Vanessa R. Holland, MD, associate clinical professor in the division of dermatology at UCLA Health, Burbank, Calif., who was not involved in the study, said that “topical replication-defective HSV-1 is a brilliant vector to deliver the depleted collagen.” She added that “such a vehicle may significantly alter management of these disorders and improve or extend lives by minimizing potentially fatal complications.”

Paras P. Vakharia, MD, PharmD, assistant professor of dermatology at Northwestern University, Chicago, who was not involved in the study, was surprised by the high percentage of healed wounds and wounds that remained healed over time.

B-VEC for treating other conditions

Dr. Marinkovich noted that an ongoing phase 1 clinical trial, also sponsored by Krystal Biotech, is using the HSV-1 vector to deliver a different biologic (KB105) to establish dose and safety in the treatment of ichthyosis. He added that he would like to explore the use of B-VEC to treat DEB at mucosal surfaces, including inside the mouth, the eye, and the esophagus.

Authors of two editorials that accompanied the study also referred to other conditions B-VEC might treat.

This study “highlights potential future investigations,” David V. Schaffer, PhD, professor of chemical and biomolecular engineering, bioengineering, and molecular and cell biology at the University of California, Berkeley, wrotes in one of the editorials.

Important considerations he mentioned include the likelihood of the treatment becoming lifelong; the inability of HSV to penetrate intact skin, making B-VEC unsuitable for preventing the development of new wounds; and the inability of this treatment to treat EB lesions along the digestive tract. “This important trial builds on and extends gene-therapy successes to new targets and vectors, an advance for patients,” he added.

In the second editorial, Aimee S. Payne, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia, raised the question of whether B-VEC’s clinical success for treating DEB can translate to other genetic diseases.

“Formulations for ophthalmic, oral-gastrointestinal, or respiratory delivery would be of great value to address the extracutaneous manifestations of epidermolysis bullosa and other genetic diseases,” she wrote.

Referring to an ongoing trial of a topical gene therapy for cystic fibrosis that is delivered by a nebulizer, Dr. Payne noted, “Ultimately, the completion of clinical trials such as this one will be required to determine whether HSV-1–mediated gene delivery can go more than skin deep.”

Earlier data and more details of the study were presented in a poster at the annual meeting of the Society for Pediatric Dermatology in July 2022.

Dr. Marinkovich has disclosed no relevant financial relationships. Several coauthors are employees of or have other financial relationships with Krystal Biotech, the study’s sponsor and the developer of beremagene geperpavec. Dr. Schaffer and Dr. Payne have financial relationships with the pharmaceutical industry. Dr. Ebens, Dr. Holland, and Dr. Vakharia have disclosed no relevant financial relationships.

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

People with untreatable dystrophic epidermolysis bullosa (DEB) may soon have access to an investigational gene therapy delivered in a topical gel that is currently under review by the Food and Drug Administration.

In a phase 3 study of patients with DEB, “we found that repeated topical application of B-VEC [beremagene geperpavec], an HSV-1–based gene therapy, resulted in a greater likelihood of complete wound healing than the topical application of placebo at up to 6 months,” the authors wrote. The study was published in The New England Journal of Medicine. “Longer and larger trials are warranted to determine the durability of effect and risks of this approach,” the authors noted.

“The results prove that B-VEC, the first topical in vivo gene therapy to reach late-stage development, can heal DEB,” senior author M. Peter Marinkovich, MD, associate professor of dermatology at Stanford University, Redwood City, Calif., said in an interview.

“In the past, DEB was a very specialized disease that only a handful of dermatologists would see but could not do much to treat,” he said. “With gene therapy, many more dermatologists who may not be familiar with DEB will be able to treat these patients in their offices.” It is expected that nurses will be able to administer the treatment to patients at home, he added.
 

Rare, life-threatening, genetic blistering disease

DEB, a rare disease that affects one to three persons per million in the United States, is caused by mutations in the COL7A1 gene that encodes the alpha-1 chain of collagen type VII (C7) protein. C7 forms the anchoring fibrils that attach the epidermis to the underlying dermal connective tissue.

COL71A mutations that lead to defective, decreased, or absent C7 can make the skin so fragile it tears with the slightest touch. This has led to patients being called “butterfly children.” Epithelial tissues blister and scar, causing esophageal and genitourinary strictures, adhesion of digits, malnutrition, anemia, infection, and bothersome itch and pain. Morbidity and mortality are high. The leading cause of death in adults is chronic wounds leading to aggressive squamous cell cancers.
 

The first therapy for DEB, under FDA review

B-VEC restores C7 protein by using an engineered replication-defective herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells to restore functional C7 protein fibrils that stabilize the skin structure.

On the basis of manufacturing information submitted to the FDA in December 2022, the agency extended the date for a decision on approval by 3 months, to May 19, 2023, according to a statement from Krystal Biotech, the developer of B-VEC and the sponsor of the NEJM study.

Dr. Marinkovich and his colleagues conducted the double-blind, randomized, controlled GEM-3 trial of B-VEC at three sites in the United States. The 31 study participants ranged in age from 1 to 44 years (median age, 16 years) and had genetically confirmed DEB (30 with the recessive form and 1 with the dominant form).

For each participant, a pair of wounds was chosen that were matched in size, region, and appearance. The wounds within each pair were randomly allocated to receive weekly applications of either B-VEC or placebo gel for 26 weeks.

The results of the study included the following:

• Complete healing at 6 months occurred in 67% of the wounds treated with B-VEC (including a wound in the patient with dominant DEB), vs. 22% of those who received placebo (95% confidence interval [CI], 24-68; P = .002).
• Complete healing at 3 months occurred in 71% of the wounds treated with B-VEC, vs. 20% of those who received placebo (95% CI, 29-73; P < .001).
• The mean change from baseline to week 22 in pain severity during wound-dressing changes for patients aged 6 years and older, as determined on the basis of a visual analogue scale, was –0.88 with B-VEC, vs. –0.71 with placebo (adjusted least-squares mean difference, –0.61; 95% CI, –1.10 to –0.13); similar mean changes were seen at weeks 24 and 26.
• Among all patients, 58% had at least one adverse event. Most adverse events were mild or moderate. The most common were pruritus, chills, and squamous cell carcinoma (SCC), which were reported in three patients each (SCC cases occurred at wound sites that had not been exposed to B-VEC or placebo). Serious adverse events, which were unrelated to the treatment, occurred in three patients: diarrhea, anemia, cellulitis, and a positive blood culture related to a hemodialysis catheter.

“With the ability to treat patients with topical gene therapy, dermatology is entering a new age of treatment possibilities,” Dr. Marinkovich said in the interview.

The researchers were surprised that the redosable in vivo gene therapy worked so well, he added. In vivo gene therapy has been plagued by the occurrence of immune reactions against the viral vectors used, Dr. Marinkovich explained. But because the herpes simplex virus has evolved to evade the immune system, his team could use the viral vector every week for 6 months without inflammatory reactions.

“The immune system’s inability to fight off or get rid of the herpes simplex vector makes it bad as a disease, but as a gene therapy vector, it provides a huge advantage,” he added.

Asked to comment on the results, Christen Ebens, MD, MPH, assistant professor in the department of pediatrics at the University of Minnesota, Minneapolis, whose clinical and research interests include EB, called the results exciting for patients, families, and doctors.

“Side effects were minimal, and importantly, use of the replication-incompetent HSV vector means that the payload gene does not integrate into the patient’s DNA,” Dr. Ebens, who was not involved in the study, said in an interview. “B-VEC is not a lifelong cure but potentially an effective maintenance therapy requiring repeated doses,” she added.

Although the researchers found no clinically important immune reactions to B-VEC, Dr. Ebens said she would like to see results from longer studies of the treatment. “We will want to see that patients do not produce neutralizing antibodies against B-VEC or its components, as such antibodies may yield the treatment ineffective or cause significant side effects.”

In an interview, Vanessa R. Holland, MD, associate clinical professor in the division of dermatology at UCLA Health, Burbank, Calif., who was not involved in the study, said that “topical replication-defective HSV-1 is a brilliant vector to deliver the depleted collagen.” She added that “such a vehicle may significantly alter management of these disorders and improve or extend lives by minimizing potentially fatal complications.”

Paras P. Vakharia, MD, PharmD, assistant professor of dermatology at Northwestern University, Chicago, who was not involved in the study, was surprised by the high percentage of healed wounds and wounds that remained healed over time.

B-VEC for treating other conditions

Dr. Marinkovich noted that an ongoing phase 1 clinical trial, also sponsored by Krystal Biotech, is using the HSV-1 vector to deliver a different biologic (KB105) to establish dose and safety in the treatment of ichthyosis. He added that he would like to explore the use of B-VEC to treat DEB at mucosal surfaces, including inside the mouth, the eye, and the esophagus.

Authors of two editorials that accompanied the study also referred to other conditions B-VEC might treat.

This study “highlights potential future investigations,” David V. Schaffer, PhD, professor of chemical and biomolecular engineering, bioengineering, and molecular and cell biology at the University of California, Berkeley, wrotes in one of the editorials.

Important considerations he mentioned include the likelihood of the treatment becoming lifelong; the inability of HSV to penetrate intact skin, making B-VEC unsuitable for preventing the development of new wounds; and the inability of this treatment to treat EB lesions along the digestive tract. “This important trial builds on and extends gene-therapy successes to new targets and vectors, an advance for patients,” he added.

In the second editorial, Aimee S. Payne, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia, raised the question of whether B-VEC’s clinical success for treating DEB can translate to other genetic diseases.

“Formulations for ophthalmic, oral-gastrointestinal, or respiratory delivery would be of great value to address the extracutaneous manifestations of epidermolysis bullosa and other genetic diseases,” she wrote.

Referring to an ongoing trial of a topical gene therapy for cystic fibrosis that is delivered by a nebulizer, Dr. Payne noted, “Ultimately, the completion of clinical trials such as this one will be required to determine whether HSV-1–mediated gene delivery can go more than skin deep.”

Earlier data and more details of the study were presented in a poster at the annual meeting of the Society for Pediatric Dermatology in July 2022.

Dr. Marinkovich has disclosed no relevant financial relationships. Several coauthors are employees of or have other financial relationships with Krystal Biotech, the study’s sponsor and the developer of beremagene geperpavec. Dr. Schaffer and Dr. Payne have financial relationships with the pharmaceutical industry. Dr. Ebens, Dr. Holland, and Dr. Vakharia have disclosed no relevant financial relationships.

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

ORLANDO – From new tools for diagnosis to new treatment options, the science on wound care continues to advance, providing clinicians with better options for their patients, Hadar Lev-Tov, MD, said at the ODAC Dermatology, Aesthetic & Surgery Conference.

At the meeting, Dr. Lev-Tov, associate professor of dermatology at the University of Miami, reviewed some of the latest developments in several conditions involving wound care.

ORLANDO – From new tools for diagnosis to new treatment options, the science on wound care continues to advance, providing clinicians with better options for their patients, Hadar Lev-Tov, MD, said at the ODAC Dermatology, Aesthetic & Surgery Conference.

At the meeting, Dr. Lev-Tov, associate professor of dermatology at the University of Miami, reviewed some of the latest developments in several conditions involving wound care.

ORLANDO – From new tools for diagnosis to new treatment options, the science on wound care continues to advance, providing clinicians with better options for their patients, Hadar Lev-Tov, MD, said at the ODAC Dermatology, Aesthetic & Surgery Conference.

At the meeting, Dr. Lev-Tov, associate professor of dermatology at the University of Miami, reviewed some of the latest developments in several conditions involving wound care.

ORLANDO – While less frequently seen dermatologic diseases do not get a “ton of attention” in expert talks and discussions, even one to two patients presenting with these conditions a month warrants continuing education, according to Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington.

These semi-forsaken diseases are important not to miss and can “also be quite challenging when we think about their management,” he said at the ODAC Dermatology, Aesthetic & Surgical Conference.

Dr. Friedman, also director of the GW dermatology residency program, reviewed several of these diseases – along with tips for management – during a session at the meeting.

Granuloma annulare (GA). This condition, Dr. Friedman said, can have “a lot of faces” – with a localized, general, perforating, subcutaneous, micropapular, or patchy appearance. It does not always have the classic ring pattern for which it is best known, he said. And in patients with darker skin tones, it is characterized by more of a brown or black color, rather than the pink-red color.

Dr. Friedman said that despite a kind of “Pavlovian response” linking GA with diabetes, this link might not be as strong as the field has come to believe, since the studies on which this belief was based included a patient population with narrow demographics. “Maybe GA and type 1 diabetes aren’t necessarily connected,” he said.

Dyslipidemia, on the other hand, has a strong connection with GA, he said. The disease is also linked to thyroid disease and is linked with malignancy, especially in older patients with generalized or atypical presentations of GA, he said.

Spontaneous resolution of the disease is seen within 2 years for 50% to 75% of patients, so “no treatment may be the best treatment,” but antimalarials can be effective, Dr. Friedman said. “I use antimalarials frequently in my practice,” he said. “The key is, they take time to work (4-5 months),” which should be explained to patients.

Antibiotics, he said, can be “somewhat effective,” but in the case of doxycycline at least, the disease can resolve within weeks but then may return when treatment is stopped.

There is some evidence to support using biologics and more recently, Janus kinase (JAK) inhibitors, off-label, to treat GA. Efficacy has been seen with the tumor necrosis factor (TNF) blocker infliximab and with the JAK inhibitor tofacitinib, he said.

 Lichen planus (LP). This is another common disease that can go off-script with its presentation. The disease is often described with the “six P’s” indicating the following characteristics: pruritic, polygonal, planar or flat-topped, purple papules, and plaques. But LP “didn’t read the textbook,” Dr. Friedman said.

“The clinical presentation of lichen planus can be quite broad,” he said. “The P’s aren’t always followed as there are a variety of colors and configurations which can be witnessed.”

With LP, there is a clear association with dyslipidemia and diabetes, so “asking the right questions is going to be important” when talking to the patient. There is also a higher risk of autoimmune diseases, especially of the thyroid type, associated with LP, he said.

No treatment has been Food and Drug Administration approved for LP, but some are expected in the future, he said.

For now, he emphasized creativity in the management of patients with LP. “I love oral retinoids for this,” he said. Antimalarials and methotrexate are also options.

In one case Dr. Friedman saw, nothing seemed to work: light therapy for a year; metronidazole; isotretinoin; halobetasol/tazarotene lotion; and the TNF-blocker adalimumab either weren’t effective or resulted in complications in the patient.

Knowing the recent implication of the interleukin (IL)-17 pathway in the pathophysiology of LP, he then tried the anti-IL17 antibody secukinumab. “This patient had a pretty robust response to treatment,” Dr. Friedman said. “He was very excited. The problem, as always, is access, especially for off-label therapies.”

Tumid lupus erythematosus. This disease is characterized by erythematous, edematous, nonscarring plaques on sun-exposed sites. For treatment, Dr. Friedman said antimalarials can be up to 90% effective, sometimes with rapid resolution of the lesions.

“You want to dose below that 5 mg per kg of true body weight to limit the small potential for ocular toxicity over time,” he said. And, he emphasized, “always combine treatment with good sun-protective measures.”

Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.

ORLANDO – While less frequently seen dermatologic diseases do not get a “ton of attention” in expert talks and discussions, even one to two patients presenting with these conditions a month warrants continuing education, according to Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington.

These semi-forsaken diseases are important not to miss and can “also be quite challenging when we think about their management,” he said at the ODAC Dermatology, Aesthetic & Surgical Conference.

Dr. Friedman, also director of the GW dermatology residency program, reviewed several of these diseases – along with tips for management – during a session at the meeting.

Granuloma annulare (GA). This condition, Dr. Friedman said, can have “a lot of faces” – with a localized, general, perforating, subcutaneous, micropapular, or patchy appearance. It does not always have the classic ring pattern for which it is best known, he said. And in patients with darker skin tones, it is characterized by more of a brown or black color, rather than the pink-red color.

Dr. Friedman said that despite a kind of “Pavlovian response” linking GA with diabetes, this link might not be as strong as the field has come to believe, since the studies on which this belief was based included a patient population with narrow demographics. “Maybe GA and type 1 diabetes aren’t necessarily connected,” he said.

Dyslipidemia, on the other hand, has a strong connection with GA, he said. The disease is also linked to thyroid disease and is linked with malignancy, especially in older patients with generalized or atypical presentations of GA, he said.

Spontaneous resolution of the disease is seen within 2 years for 50% to 75% of patients, so “no treatment may be the best treatment,” but antimalarials can be effective, Dr. Friedman said. “I use antimalarials frequently in my practice,” he said. “The key is, they take time to work (4-5 months),” which should be explained to patients.

Antibiotics, he said, can be “somewhat effective,” but in the case of doxycycline at least, the disease can resolve within weeks but then may return when treatment is stopped.

There is some evidence to support using biologics and more recently, Janus kinase (JAK) inhibitors, off-label, to treat GA. Efficacy has been seen with the tumor necrosis factor (TNF) blocker infliximab and with the JAK inhibitor tofacitinib, he said.

 Lichen planus (LP). This is another common disease that can go off-script with its presentation. The disease is often described with the “six P’s” indicating the following characteristics: pruritic, polygonal, planar or flat-topped, purple papules, and plaques. But LP “didn’t read the textbook,” Dr. Friedman said.

“The clinical presentation of lichen planus can be quite broad,” he said. “The P’s aren’t always followed as there are a variety of colors and configurations which can be witnessed.”

With LP, there is a clear association with dyslipidemia and diabetes, so “asking the right questions is going to be important” when talking to the patient. There is also a higher risk of autoimmune diseases, especially of the thyroid type, associated with LP, he said.

No treatment has been Food and Drug Administration approved for LP, but some are expected in the future, he said.

For now, he emphasized creativity in the management of patients with LP. “I love oral retinoids for this,” he said. Antimalarials and methotrexate are also options.

In one case Dr. Friedman saw, nothing seemed to work: light therapy for a year; metronidazole; isotretinoin; halobetasol/tazarotene lotion; and the TNF-blocker adalimumab either weren’t effective or resulted in complications in the patient.

Knowing the recent implication of the interleukin (IL)-17 pathway in the pathophysiology of LP, he then tried the anti-IL17 antibody secukinumab. “This patient had a pretty robust response to treatment,” Dr. Friedman said. “He was very excited. The problem, as always, is access, especially for off-label therapies.”

Tumid lupus erythematosus. This disease is characterized by erythematous, edematous, nonscarring plaques on sun-exposed sites. For treatment, Dr. Friedman said antimalarials can be up to 90% effective, sometimes with rapid resolution of the lesions.

“You want to dose below that 5 mg per kg of true body weight to limit the small potential for ocular toxicity over time,” he said. And, he emphasized, “always combine treatment with good sun-protective measures.”

Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.

ORLANDO – While less frequently seen dermatologic diseases do not get a “ton of attention” in expert talks and discussions, even one to two patients presenting with these conditions a month warrants continuing education, according to Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington.

These semi-forsaken diseases are important not to miss and can “also be quite challenging when we think about their management,” he said at the ODAC Dermatology, Aesthetic & Surgical Conference.

Dr. Friedman, also director of the GW dermatology residency program, reviewed several of these diseases – along with tips for management – during a session at the meeting.

Granuloma annulare (GA). This condition, Dr. Friedman said, can have “a lot of faces” – with a localized, general, perforating, subcutaneous, micropapular, or patchy appearance. It does not always have the classic ring pattern for which it is best known, he said. And in patients with darker skin tones, it is characterized by more of a brown or black color, rather than the pink-red color.

Dr. Friedman said that despite a kind of “Pavlovian response” linking GA with diabetes, this link might not be as strong as the field has come to believe, since the studies on which this belief was based included a patient population with narrow demographics. “Maybe GA and type 1 diabetes aren’t necessarily connected,” he said.

Dyslipidemia, on the other hand, has a strong connection with GA, he said. The disease is also linked to thyroid disease and is linked with malignancy, especially in older patients with generalized or atypical presentations of GA, he said.

Spontaneous resolution of the disease is seen within 2 years for 50% to 75% of patients, so “no treatment may be the best treatment,” but antimalarials can be effective, Dr. Friedman said. “I use antimalarials frequently in my practice,” he said. “The key is, they take time to work (4-5 months),” which should be explained to patients.

Antibiotics, he said, can be “somewhat effective,” but in the case of doxycycline at least, the disease can resolve within weeks but then may return when treatment is stopped.

There is some evidence to support using biologics and more recently, Janus kinase (JAK) inhibitors, off-label, to treat GA. Efficacy has been seen with the tumor necrosis factor (TNF) blocker infliximab and with the JAK inhibitor tofacitinib, he said.

 Lichen planus (LP). This is another common disease that can go off-script with its presentation. The disease is often described with the “six P’s” indicating the following characteristics: pruritic, polygonal, planar or flat-topped, purple papules, and plaques. But LP “didn’t read the textbook,” Dr. Friedman said.

“The clinical presentation of lichen planus can be quite broad,” he said. “The P’s aren’t always followed as there are a variety of colors and configurations which can be witnessed.”

With LP, there is a clear association with dyslipidemia and diabetes, so “asking the right questions is going to be important” when talking to the patient. There is also a higher risk of autoimmune diseases, especially of the thyroid type, associated with LP, he said.

No treatment has been Food and Drug Administration approved for LP, but some are expected in the future, he said.

For now, he emphasized creativity in the management of patients with LP. “I love oral retinoids for this,” he said. Antimalarials and methotrexate are also options.

In one case Dr. Friedman saw, nothing seemed to work: light therapy for a year; metronidazole; isotretinoin; halobetasol/tazarotene lotion; and the TNF-blocker adalimumab either weren’t effective or resulted in complications in the patient.

Knowing the recent implication of the interleukin (IL)-17 pathway in the pathophysiology of LP, he then tried the anti-IL17 antibody secukinumab. “This patient had a pretty robust response to treatment,” Dr. Friedman said. “He was very excited. The problem, as always, is access, especially for off-label therapies.”

Tumid lupus erythematosus. This disease is characterized by erythematous, edematous, nonscarring plaques on sun-exposed sites. For treatment, Dr. Friedman said antimalarials can be up to 90% effective, sometimes with rapid resolution of the lesions.

“You want to dose below that 5 mg per kg of true body weight to limit the small potential for ocular toxicity over time,” he said. And, he emphasized, “always combine treatment with good sun-protective measures.”

Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.

ORLANDO – Three weeks after a course of trimethoprim/sulfamethoxazole (Bactrim), a young female patient developed facial edema that involved “dusky erythematous papules” that were itchy. The eruption spread away from the head and her transaminase levels were “dramatic,” in the 700s, said Kalyani S. Marathe, MD, MPH, associate professor of dermatology and pediatrics at the University of Cincinnati.

Dr. Marathe, director of the division of dermatology at Cincinnati Children’s Hospital, reviewed this case in a presentation on pediatric dermatologic emergencies at the ODAC Dermatology, Aesthetic & Surgery Conference, pointing out potential pitfalls and important aspects that might require swift action.

The patient was diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS).

Facial involvement is common in pediatric cases of DRESS, but edema of the face is less common in children than adults, Dr. Marathe said.

Antiepileptic medications are the most common cause of DRESS, followed by antibiotics – most often, vancomycin and trimethoprim/sulfamethoxazole, she said. But sometimes the trigger is not clear, she noted, recalling a vexing case she once saw in which IV contrast was eventually identified as the cause.

When DRESS is suspected, she said, lab work should be done during the acute eruption and after resolution. This should include CBC, liver function tests, creatinine, and urinalysis, and human herpesvirus 6 (HHV-6) and thyroid testing.

Treatment typically includes supportive care, unless symptoms are systemic, or if there is impending liver failure, when steroids, cyclosporine, or IVIG can be used.

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): Mortality rates when these diseases overlap is 4%, Dr. Marathe said. Clues to diagnosing this other medication-induced condition include involvement of the palms and the soles of the feet; presence of the Nikolsky sign in which the top layers of the skin slip away from the lower layers when rubbed; mucosal involvement, which often precedes cutaneous involvement; and these symptoms occurring within the first 8 weeks of taking a medication, which are most commonly antibiotics and anti-epileptics.

Dr. Marathe underscored how important it is to get ophthalmology involved right away, because of the risk of vision loss. Amniotic membrane transfer to the eye at the time of diagnosis has been found to produce dramatically better outcomes, she said. The membrane has anti-inflammatory and antiscarring properties and can promote wound healing on the surface of the eye.

“I would recommend getting your ophthalmology team on board early because they have to advocate for these patients,” she said.

Corticosteroids and IVIG can improve ocular outcomes, but cyclosporine is associated with better mortality outcomes, she said. Emerging data on etanercept has also led to more use of that drug, she said.

Erythema multiforme (EM): unlike urticaria, multiforme EM can have mucosal involvement, Dr. Marathe said. Clinicians should look for three zones of color: A central duskiness, a rim of pallor, and a ring of erythema.

EM is triggered by a virus, which is usually herpes simplex virus (HSV). But she added that HSV is not always found. “So, there are certainly other triggers out there that we just haven’t identified,” she said.

If HSV is suspected, oral acyclovir is effective, she noted.

Other cases might not be as straightforward. Dr. Marathe said that during her fellowship, she saw a patient with EM that was controlled only by IVIG, so it was administered every 3 months. In that case, the trigger was never found.

Multisystem inflammatory syndrome in children (MIS-C): This syndrome can follow COVID-19 infection, and usually presents with 3-5 days of fever after COVID has resolved. It can include gastrointestinal, cardiorespiratory, and neurocognitive symptoms.

The skin presentation is mainly a morbilliform pattern, but clinicians might also see conjunctival involvement, mucosal involvement, and “COVID toes,” painful red or purple lesions on the toes.

Treatment is usually IVIG and systemic corticosteroids, with the treatment course depending on the severity.

MIS-C was initially thought to be Kawasaki’s disease, another autoinflammatory disorder, which is related but distinct, Dr. Marathe said.

Patients with MIS-C “are usually going to have COVID-positive antibodies,” she said. But since almost everybody may have COVID antibodies, “it’s not usually a helpful test for you now. But early on, that’s what we used as helpful indicator.”

Dr. Marathe reported no relevant financial relationships.

ORLANDO – Three weeks after a course of trimethoprim/sulfamethoxazole (Bactrim), a young female patient developed facial edema that involved “dusky erythematous papules” that were itchy. The eruption spread away from the head and her transaminase levels were “dramatic,” in the 700s, said Kalyani S. Marathe, MD, MPH, associate professor of dermatology and pediatrics at the University of Cincinnati.

Dr. Marathe, director of the division of dermatology at Cincinnati Children’s Hospital, reviewed this case in a presentation on pediatric dermatologic emergencies at the ODAC Dermatology, Aesthetic & Surgery Conference, pointing out potential pitfalls and important aspects that might require swift action.

The patient was diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS).

Facial involvement is common in pediatric cases of DRESS, but edema of the face is less common in children than adults, Dr. Marathe said.

Antiepileptic medications are the most common cause of DRESS, followed by antibiotics – most often, vancomycin and trimethoprim/sulfamethoxazole, she said. But sometimes the trigger is not clear, she noted, recalling a vexing case she once saw in which IV contrast was eventually identified as the cause.

When DRESS is suspected, she said, lab work should be done during the acute eruption and after resolution. This should include CBC, liver function tests, creatinine, and urinalysis, and human herpesvirus 6 (HHV-6) and thyroid testing.

Treatment typically includes supportive care, unless symptoms are systemic, or if there is impending liver failure, when steroids, cyclosporine, or IVIG can be used.

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): Mortality rates when these diseases overlap is 4%, Dr. Marathe said. Clues to diagnosing this other medication-induced condition include involvement of the palms and the soles of the feet; presence of the Nikolsky sign in which the top layers of the skin slip away from the lower layers when rubbed; mucosal involvement, which often precedes cutaneous involvement; and these symptoms occurring within the first 8 weeks of taking a medication, which are most commonly antibiotics and anti-epileptics.

Dr. Marathe underscored how important it is to get ophthalmology involved right away, because of the risk of vision loss. Amniotic membrane transfer to the eye at the time of diagnosis has been found to produce dramatically better outcomes, she said. The membrane has anti-inflammatory and antiscarring properties and can promote wound healing on the surface of the eye.

“I would recommend getting your ophthalmology team on board early because they have to advocate for these patients,” she said.

Corticosteroids and IVIG can improve ocular outcomes, but cyclosporine is associated with better mortality outcomes, she said. Emerging data on etanercept has also led to more use of that drug, she said.

Erythema multiforme (EM): unlike urticaria, multiforme EM can have mucosal involvement, Dr. Marathe said. Clinicians should look for three zones of color: A central duskiness, a rim of pallor, and a ring of erythema.

EM is triggered by a virus, which is usually herpes simplex virus (HSV). But she added that HSV is not always found. “So, there are certainly other triggers out there that we just haven’t identified,” she said.

If HSV is suspected, oral acyclovir is effective, she noted.

Other cases might not be as straightforward. Dr. Marathe said that during her fellowship, she saw a patient with EM that was controlled only by IVIG, so it was administered every 3 months. In that case, the trigger was never found.

Multisystem inflammatory syndrome in children (MIS-C): This syndrome can follow COVID-19 infection, and usually presents with 3-5 days of fever after COVID has resolved. It can include gastrointestinal, cardiorespiratory, and neurocognitive symptoms.

The skin presentation is mainly a morbilliform pattern, but clinicians might also see conjunctival involvement, mucosal involvement, and “COVID toes,” painful red or purple lesions on the toes.

Treatment is usually IVIG and systemic corticosteroids, with the treatment course depending on the severity.

MIS-C was initially thought to be Kawasaki’s disease, another autoinflammatory disorder, which is related but distinct, Dr. Marathe said.

Patients with MIS-C “are usually going to have COVID-positive antibodies,” she said. But since almost everybody may have COVID antibodies, “it’s not usually a helpful test for you now. But early on, that’s what we used as helpful indicator.”

Dr. Marathe reported no relevant financial relationships.

ORLANDO – Three weeks after a course of trimethoprim/sulfamethoxazole (Bactrim), a young female patient developed facial edema that involved “dusky erythematous papules” that were itchy. The eruption spread away from the head and her transaminase levels were “dramatic,” in the 700s, said Kalyani S. Marathe, MD, MPH, associate professor of dermatology and pediatrics at the University of Cincinnati.

Dr. Marathe, director of the division of dermatology at Cincinnati Children’s Hospital, reviewed this case in a presentation on pediatric dermatologic emergencies at the ODAC Dermatology, Aesthetic & Surgery Conference, pointing out potential pitfalls and important aspects that might require swift action.

The patient was diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS).

Facial involvement is common in pediatric cases of DRESS, but edema of the face is less common in children than adults, Dr. Marathe said.

Antiepileptic medications are the most common cause of DRESS, followed by antibiotics – most often, vancomycin and trimethoprim/sulfamethoxazole, she said. But sometimes the trigger is not clear, she noted, recalling a vexing case she once saw in which IV contrast was eventually identified as the cause.

When DRESS is suspected, she said, lab work should be done during the acute eruption and after resolution. This should include CBC, liver function tests, creatinine, and urinalysis, and human herpesvirus 6 (HHV-6) and thyroid testing.

Treatment typically includes supportive care, unless symptoms are systemic, or if there is impending liver failure, when steroids, cyclosporine, or IVIG can be used.

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): Mortality rates when these diseases overlap is 4%, Dr. Marathe said. Clues to diagnosing this other medication-induced condition include involvement of the palms and the soles of the feet; presence of the Nikolsky sign in which the top layers of the skin slip away from the lower layers when rubbed; mucosal involvement, which often precedes cutaneous involvement; and these symptoms occurring within the first 8 weeks of taking a medication, which are most commonly antibiotics and anti-epileptics.

Dr. Marathe underscored how important it is to get ophthalmology involved right away, because of the risk of vision loss. Amniotic membrane transfer to the eye at the time of diagnosis has been found to produce dramatically better outcomes, she said. The membrane has anti-inflammatory and antiscarring properties and can promote wound healing on the surface of the eye.

“I would recommend getting your ophthalmology team on board early because they have to advocate for these patients,” she said.

Corticosteroids and IVIG can improve ocular outcomes, but cyclosporine is associated with better mortality outcomes, she said. Emerging data on etanercept has also led to more use of that drug, she said.

Erythema multiforme (EM): unlike urticaria, multiforme EM can have mucosal involvement, Dr. Marathe said. Clinicians should look for three zones of color: A central duskiness, a rim of pallor, and a ring of erythema.

EM is triggered by a virus, which is usually herpes simplex virus (HSV). But she added that HSV is not always found. “So, there are certainly other triggers out there that we just haven’t identified,” she said.

If HSV is suspected, oral acyclovir is effective, she noted.

Other cases might not be as straightforward. Dr. Marathe said that during her fellowship, she saw a patient with EM that was controlled only by IVIG, so it was administered every 3 months. In that case, the trigger was never found.

Multisystem inflammatory syndrome in children (MIS-C): This syndrome can follow COVID-19 infection, and usually presents with 3-5 days of fever after COVID has resolved. It can include gastrointestinal, cardiorespiratory, and neurocognitive symptoms.

The skin presentation is mainly a morbilliform pattern, but clinicians might also see conjunctival involvement, mucosal involvement, and “COVID toes,” painful red or purple lesions on the toes.

Treatment is usually IVIG and systemic corticosteroids, with the treatment course depending on the severity.

MIS-C was initially thought to be Kawasaki’s disease, another autoinflammatory disorder, which is related but distinct, Dr. Marathe said.

Patients with MIS-C “are usually going to have COVID-positive antibodies,” she said. But since almost everybody may have COVID antibodies, “it’s not usually a helpful test for you now. But early on, that’s what we used as helpful indicator.”

Dr. Marathe reported no relevant financial relationships.