Psoriasis

Tumor necrosis factor α (TNF-α) inhibitor–induced psoriasis is a known paradoxical adverse effect of this family of medications, which includes infliximab, adalimumab, etanercept, golimumab, and certolizumab. In the pediatric population, these therapies recently gained approval for nondermatologic conditions—meaning that this phenomenon is encountered more frequently.¹ In a systematic review of TNF-α inhibitor–induced psoriasis, severe scalp involvement was associated with alopecia in 7.5% of cases.² Onset of scalp psoriasis with alopecia in patients being treated with a TNF-α inhibitor should lead to consideration of this condition.

Psoriatic alopecia is an uncommon presentation of psoriasis. Although well described, alopecia as a clinical manifestation of scalp psoriasis is not a well-known concept among clinicians and has never been widely accepted. Adding to the diagnostic challenge is that psoriatic alopecia secondary to TNF-α inhibitor–induced psoriasis rarely has been reported in adults or children.^3-5 Including our case, our review of the literature yielded 7 pediatric cases (≤18 years) of TNF-α inhibitor–induced psoriatic alopecia.^6,7 A primary literature search of PubMed articles indexed for MEDLINE was conducted using the terms psoriatic alopecia, psoriasiform alopecia, TNF-α inhibitors, infliximab, adalimumab, etanercept, golimumab, and certolizumab.

We present the case of a pediatric patient with psoriatic alopecia secondary to treatment with adalimumab for Crohn disease (CD). We also provide a review of reported cases of psoriatic alopecia induced by a TNF-α inhibitor in the literature.

Case Report

A 12-year-old girl presented to our dermatology clinic with erythematous scaly plaques on the trunk, scalp, arms, and legs of 2 months’ duration. The lesions involved approximately 15% of the body surface area. The patient’s medical history was remarkable for CD diagnosed 4 years prior to presentation of the skin lesions. She had been treated for the past 2 years with adalimumab 40 mg once every 2 weeks and azathioprine 100 mg once daily. Because her CD was poorly controlled, the dosage of adalimumab was increased to 40 mg once weekly 6 months prior to the current presentation.

Our diagnosis was TNF-α inhibitor-induced psoriasis secondary to treatment with adalimumab.

The patient was treated with mometasone lotion 0.1% for the scalp lesions and triamcinolone cream 0.1% for the body lesions. Because of the extent of the psoriasis, we recommended changing adalimumab to ustekinumab, which is approved for CD in adults but is off label in children.

At 1-month follow-up, after receiving the induction dose of ustekinumab, the patient presented with partial improvement of the skin lesions but had developed a large, alopecic, erythematous plaque with thick yellowish scales on the scalp (Figure 1). She also had a positive hair pull test. The presumptive initial diagnosis of the alopecic scalp lesion was tinea capitis, for which multiple potassium hydroxide preparations of scales were performed, all yielding negative results. In addition, histopathologic examination with hematoxylin and eosin staining was performed (Figures 2A and 2B). Sterile tissue cultures for bacteria, fungi, and acid-fast bacilli were obtained and showed no growth. Periodic acid–Schiff staining was negative for fungal structures.

Comment

Psoriatic alopecia induced by a TNF-α inhibitor was first reported in 2007 in a 30-year-old woman with ankylosing spondylitis who was being treated with adalimumab.⁸ She had erythematous, scaly, alopecic plaques on the scalp and palmoplantar pustulosis. Findings on skin biopsy were compatible with psoriasis. The patient’s severe scalp psoriasis failed to respond to topical steroid treatment and adalimumab cessation. The extensive hair loss responded to cyclosporine 3 mg/kg daily.⁸

After conducting an extensive literature review, we found 26 cases of TNF-α–induced psoriatic alopecia, including the current case (Table).^6-16 The mean age at diagnosis was 27.8 years (SD, 13.6 years; range, 7–60 years). The female-to-male ratio was 3.3:1. The most common underlying condition for which TNF-α inhibitors were prescribed was CD (77% [20/26]). Psoriatic alopecia most commonly was reported secondary to treatment with infliximab (54% [14/26]), followed by adalimumab (42% [11/26]). Golimumab was the causative drug in 1 (4%) case. We did not find reports of etanercept or certolizumab having induced this manifestation. The onset of the scalp lesions occurred 2 to 46 months after starting treatment with the causative medication.

Previously reported cases have demonstrated various treatment options that yielded improvement or resolution of TNF-α inhibitor–induced psoriatic alopecia. These include either continuation or discontinuation of the TNF-α inhibitor combined with topical or intralesional steroids, methotrexate, or cyclosporine. Another option is to switch the TNF-α inhibitor to another biologic. Outcomes vary from patient to patient, making the physician’s clinical judgment crucial in deciding which treatment route to take. Our patient showed notable improvement when she was switched from adalimumab to ustekinumab as well as the combination of ustekinumab and clobetasol lotion 0.05%.

Conclusion

We recommend an individualized approach that provides patients with the safest and least invasive treatment option for TNF-α inhibitor–induced psoriatic alopecia. In most reported cases, the problem resolved with treatment, thereby classifying this form of alopecia as noncicatricial alopecia.

Tumor necrosis factor α (TNF-α) inhibitor–induced psoriasis is a known paradoxical adverse effect of this family of medications, which includes infliximab, adalimumab, etanercept, golimumab, and certolizumab. In the pediatric population, these therapies recently gained approval for nondermatologic conditions—meaning that this phenomenon is encountered more frequently.¹ In a systematic review of TNF-α inhibitor–induced psoriasis, severe scalp involvement was associated with alopecia in 7.5% of cases.² Onset of scalp psoriasis with alopecia in patients being treated with a TNF-α inhibitor should lead to consideration of this condition.

Psoriatic alopecia is an uncommon presentation of psoriasis. Although well described, alopecia as a clinical manifestation of scalp psoriasis is not a well-known concept among clinicians and has never been widely accepted. Adding to the diagnostic challenge is that psoriatic alopecia secondary to TNF-α inhibitor–induced psoriasis rarely has been reported in adults or children.^3-5 Including our case, our review of the literature yielded 7 pediatric cases (≤18 years) of TNF-α inhibitor–induced psoriatic alopecia.^6,7 A primary literature search of PubMed articles indexed for MEDLINE was conducted using the terms psoriatic alopecia, psoriasiform alopecia, TNF-α inhibitors, infliximab, adalimumab, etanercept, golimumab, and certolizumab.

We present the case of a pediatric patient with psoriatic alopecia secondary to treatment with adalimumab for Crohn disease (CD). We also provide a review of reported cases of psoriatic alopecia induced by a TNF-α inhibitor in the literature.

Case Report

A 12-year-old girl presented to our dermatology clinic with erythematous scaly plaques on the trunk, scalp, arms, and legs of 2 months’ duration. The lesions involved approximately 15% of the body surface area. The patient’s medical history was remarkable for CD diagnosed 4 years prior to presentation of the skin lesions. She had been treated for the past 2 years with adalimumab 40 mg once every 2 weeks and azathioprine 100 mg once daily. Because her CD was poorly controlled, the dosage of adalimumab was increased to 40 mg once weekly 6 months prior to the current presentation.

Our diagnosis was TNF-α inhibitor-induced psoriasis secondary to treatment with adalimumab.

The patient was treated with mometasone lotion 0.1% for the scalp lesions and triamcinolone cream 0.1% for the body lesions. Because of the extent of the psoriasis, we recommended changing adalimumab to ustekinumab, which is approved for CD in adults but is off label in children.

At 1-month follow-up, after receiving the induction dose of ustekinumab, the patient presented with partial improvement of the skin lesions but had developed a large, alopecic, erythematous plaque with thick yellowish scales on the scalp (Figure 1). She also had a positive hair pull test. The presumptive initial diagnosis of the alopecic scalp lesion was tinea capitis, for which multiple potassium hydroxide preparations of scales were performed, all yielding negative results. In addition, histopathologic examination with hematoxylin and eosin staining was performed (Figures 2A and 2B). Sterile tissue cultures for bacteria, fungi, and acid-fast bacilli were obtained and showed no growth. Periodic acid–Schiff staining was negative for fungal structures.

Comment

Psoriatic alopecia induced by a TNF-α inhibitor was first reported in 2007 in a 30-year-old woman with ankylosing spondylitis who was being treated with adalimumab.⁸ She had erythematous, scaly, alopecic plaques on the scalp and palmoplantar pustulosis. Findings on skin biopsy were compatible with psoriasis. The patient’s severe scalp psoriasis failed to respond to topical steroid treatment and adalimumab cessation. The extensive hair loss responded to cyclosporine 3 mg/kg daily.⁸

After conducting an extensive literature review, we found 26 cases of TNF-α–induced psoriatic alopecia, including the current case (Table).^6-16 The mean age at diagnosis was 27.8 years (SD, 13.6 years; range, 7–60 years). The female-to-male ratio was 3.3:1. The most common underlying condition for which TNF-α inhibitors were prescribed was CD (77% [20/26]). Psoriatic alopecia most commonly was reported secondary to treatment with infliximab (54% [14/26]), followed by adalimumab (42% [11/26]). Golimumab was the causative drug in 1 (4%) case. We did not find reports of etanercept or certolizumab having induced this manifestation. The onset of the scalp lesions occurred 2 to 46 months after starting treatment with the causative medication.

Previously reported cases have demonstrated various treatment options that yielded improvement or resolution of TNF-α inhibitor–induced psoriatic alopecia. These include either continuation or discontinuation of the TNF-α inhibitor combined with topical or intralesional steroids, methotrexate, or cyclosporine. Another option is to switch the TNF-α inhibitor to another biologic. Outcomes vary from patient to patient, making the physician’s clinical judgment crucial in deciding which treatment route to take. Our patient showed notable improvement when she was switched from adalimumab to ustekinumab as well as the combination of ustekinumab and clobetasol lotion 0.05%.

Conclusion

We recommend an individualized approach that provides patients with the safest and least invasive treatment option for TNF-α inhibitor–induced psoriatic alopecia. In most reported cases, the problem resolved with treatment, thereby classifying this form of alopecia as noncicatricial alopecia.

Tumor necrosis factor α (TNF-α) inhibitor–induced psoriasis is a known paradoxical adverse effect of this family of medications, which includes infliximab, adalimumab, etanercept, golimumab, and certolizumab. In the pediatric population, these therapies recently gained approval for nondermatologic conditions—meaning that this phenomenon is encountered more frequently.¹ In a systematic review of TNF-α inhibitor–induced psoriasis, severe scalp involvement was associated with alopecia in 7.5% of cases.² Onset of scalp psoriasis with alopecia in patients being treated with a TNF-α inhibitor should lead to consideration of this condition.

Psoriatic alopecia is an uncommon presentation of psoriasis. Although well described, alopecia as a clinical manifestation of scalp psoriasis is not a well-known concept among clinicians and has never been widely accepted. Adding to the diagnostic challenge is that psoriatic alopecia secondary to TNF-α inhibitor–induced psoriasis rarely has been reported in adults or children.^3-5 Including our case, our review of the literature yielded 7 pediatric cases (≤18 years) of TNF-α inhibitor–induced psoriatic alopecia.^6,7 A primary literature search of PubMed articles indexed for MEDLINE was conducted using the terms psoriatic alopecia, psoriasiform alopecia, TNF-α inhibitors, infliximab, adalimumab, etanercept, golimumab, and certolizumab.

We present the case of a pediatric patient with psoriatic alopecia secondary to treatment with adalimumab for Crohn disease (CD). We also provide a review of reported cases of psoriatic alopecia induced by a TNF-α inhibitor in the literature.

Case Report

A 12-year-old girl presented to our dermatology clinic with erythematous scaly plaques on the trunk, scalp, arms, and legs of 2 months’ duration. The lesions involved approximately 15% of the body surface area. The patient’s medical history was remarkable for CD diagnosed 4 years prior to presentation of the skin lesions. She had been treated for the past 2 years with adalimumab 40 mg once every 2 weeks and azathioprine 100 mg once daily. Because her CD was poorly controlled, the dosage of adalimumab was increased to 40 mg once weekly 6 months prior to the current presentation.

Our diagnosis was TNF-α inhibitor-induced psoriasis secondary to treatment with adalimumab.

The patient was treated with mometasone lotion 0.1% for the scalp lesions and triamcinolone cream 0.1% for the body lesions. Because of the extent of the psoriasis, we recommended changing adalimumab to ustekinumab, which is approved for CD in adults but is off label in children.

At 1-month follow-up, after receiving the induction dose of ustekinumab, the patient presented with partial improvement of the skin lesions but had developed a large, alopecic, erythematous plaque with thick yellowish scales on the scalp (Figure 1). She also had a positive hair pull test. The presumptive initial diagnosis of the alopecic scalp lesion was tinea capitis, for which multiple potassium hydroxide preparations of scales were performed, all yielding negative results. In addition, histopathologic examination with hematoxylin and eosin staining was performed (Figures 2A and 2B). Sterile tissue cultures for bacteria, fungi, and acid-fast bacilli were obtained and showed no growth. Periodic acid–Schiff staining was negative for fungal structures.

Comment

Psoriatic alopecia induced by a TNF-α inhibitor was first reported in 2007 in a 30-year-old woman with ankylosing spondylitis who was being treated with adalimumab.⁸ She had erythematous, scaly, alopecic plaques on the scalp and palmoplantar pustulosis. Findings on skin biopsy were compatible with psoriasis. The patient’s severe scalp psoriasis failed to respond to topical steroid treatment and adalimumab cessation. The extensive hair loss responded to cyclosporine 3 mg/kg daily.⁸

After conducting an extensive literature review, we found 26 cases of TNF-α–induced psoriatic alopecia, including the current case (Table).^6-16 The mean age at diagnosis was 27.8 years (SD, 13.6 years; range, 7–60 years). The female-to-male ratio was 3.3:1. The most common underlying condition for which TNF-α inhibitors were prescribed was CD (77% [20/26]). Psoriatic alopecia most commonly was reported secondary to treatment with infliximab (54% [14/26]), followed by adalimumab (42% [11/26]). Golimumab was the causative drug in 1 (4%) case. We did not find reports of etanercept or certolizumab having induced this manifestation. The onset of the scalp lesions occurred 2 to 46 months after starting treatment with the causative medication.

Previously reported cases have demonstrated various treatment options that yielded improvement or resolution of TNF-α inhibitor–induced psoriatic alopecia. These include either continuation or discontinuation of the TNF-α inhibitor combined with topical or intralesional steroids, methotrexate, or cyclosporine. Another option is to switch the TNF-α inhibitor to another biologic. Outcomes vary from patient to patient, making the physician’s clinical judgment crucial in deciding which treatment route to take. Our patient showed notable improvement when she was switched from adalimumab to ustekinumab as well as the combination of ustekinumab and clobetasol lotion 0.05%.

Conclusion

We recommend an individualized approach that provides patients with the safest and least invasive treatment option for TNF-α inhibitor–induced psoriatic alopecia. In most reported cases, the problem resolved with treatment, thereby classifying this form of alopecia as noncicatricial alopecia.

Key studies on psoriasis presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2021included data on new topical treatments and biological therapies.

Dr Steven Feldman, of Wake Forest School of Medicine, reviews trial data demonstrating the efficacy of a topical formulation of roflumilast, a phosphodiesterase type 4 (PDE-4) inhibitor previously used in oral systemic form to treat psoriasis.

He also discusses a meta-analysis of the efficacy of biologics favoring newer treatments, such as drugs targeting IL-17 and IL-23.

Dr Feldman reviews the results of two pivotal phase 3 trials presented at the meeting. The POETYK study examined deucravacitinib, a TYK2 inhibitor. In a head-to-head comparison, deucravacitinib was found to be more effective and better tolerated than apremilast in treating psoriasis. BE RADIANT, another head-to-head study, compared the IL-17 blockers bimekizumab and secukinumab. The year-long study favored bimekizumab, though it was associated with a higher risk for candidiasis.

Finally, Dr Feldman discusses the significance of a study showing that psoriasis patients have an approximately 20% higher risk for COVID-19 infection compared with a control group.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

Key studies on psoriasis presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2021included data on new topical treatments and biological therapies.

Dr Steven Feldman, of Wake Forest School of Medicine, reviews trial data demonstrating the efficacy of a topical formulation of roflumilast, a phosphodiesterase type 4 (PDE-4) inhibitor previously used in oral systemic form to treat psoriasis.

He also discusses a meta-analysis of the efficacy of biologics favoring newer treatments, such as drugs targeting IL-17 and IL-23.

Dr Feldman reviews the results of two pivotal phase 3 trials presented at the meeting. The POETYK study examined deucravacitinib, a TYK2 inhibitor. In a head-to-head comparison, deucravacitinib was found to be more effective and better tolerated than apremilast in treating psoriasis. BE RADIANT, another head-to-head study, compared the IL-17 blockers bimekizumab and secukinumab. The year-long study favored bimekizumab, though it was associated with a higher risk for candidiasis.

Finally, Dr Feldman discusses the significance of a study showing that psoriasis patients have an approximately 20% higher risk for COVID-19 infection compared with a control group.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

Key studies on psoriasis presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2021included data on new topical treatments and biological therapies.

Dr Steven Feldman, of Wake Forest School of Medicine, reviews trial data demonstrating the efficacy of a topical formulation of roflumilast, a phosphodiesterase type 4 (PDE-4) inhibitor previously used in oral systemic form to treat psoriasis.

He also discusses a meta-analysis of the efficacy of biologics favoring newer treatments, such as drugs targeting IL-17 and IL-23.

Dr Feldman reviews the results of two pivotal phase 3 trials presented at the meeting. The POETYK study examined deucravacitinib, a TYK2 inhibitor. In a head-to-head comparison, deucravacitinib was found to be more effective and better tolerated than apremilast in treating psoriasis. BE RADIANT, another head-to-head study, compared the IL-17 blockers bimekizumab and secukinumab. The year-long study favored bimekizumab, though it was associated with a higher risk for candidiasis.

Finally, Dr Feldman discusses the significance of a study showing that psoriasis patients have an approximately 20% higher risk for COVID-19 infection compared with a control group.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

The Diagnosis: Demodicosis 

A clinical diagnosis of facial demodicosis triggered by topical corticosteroid therapy was suspected in our patient. A 3-mm punch biopsy of the right forehead demonstrated a follicular infundibulum rich in Demodex folliculorum with a discrete mononuclear infiltrate in the dermis (Figure 1), confirming the diagnosis. The patient was prescribed metronidazole gel 2% twice daily. Complete clearance of the facial rash was observed at 1-week follow-up (Figure 2). 

Demodex folliculorum is a mite that parasitizes the pilosebaceous follicles of human skin, becoming pathogenic with excessive colonization.^1-3 Facial demodicosis presents as pruritic papules and pustules in a pilosebaceous distribution on the face.^2,3 The diagnosis of facial demodicosis can be difficult due to similarities with many other common facial rashes such as acne, rosacea, contact dermatitis, and folliculitis.  

Similar to facial demodicosis, rosacea can present with erythema, papules, and pustules on the face. Patients with rosacea also have a higher prevalence and degree of Demodex mite infestation.⁴ However, these facial rashes can be differentiated when symptom acuity and personal and family histories are considered. In patients with a long-standing personal and/or family history of erythema, papules, and pustules, the chronicity of disease implies a diagnosis of rosacea. The acute onset of symptomatology and absence of personal or family history of rosacea in our patient favored a diagnosis of demodicosis. 

Pityrosporum folliculitis is an eruption caused by Malassezia furfur, the organism implicated in tinea versicolor. It can present similarly to Demodex folliculitis with follicular papules and pustules on the forehead and back. Features that help to differentiate Pityrosporum folliculitis from Demodex folliculitis include involvement of the upper trunk and onset after antibiotic usage.⁵ Diagnosis of Pityrosporum folliculitis can be confirmed by potassium hydroxide preparation, which demonstrates spaghetti-and-meatball-like hyphae and spores. 

Eosinophilic folliculitis is a chronic sterile folliculitis that usually presents as intensely pruritic papules and pustules on the face with an eruptive onset. There are 3 variants of disease: the classic form (also known as Ofuji disease), immunosuppression-associated disease, and infancy-associated disease.⁶ Eosinophilic folliculitis also may present with annular plaques and peripheral blood eosinophilia, and it is more prevalent in patients of Japanese descent. Differentiation from Demodex folliculitis can be done by histologic examination, which demonstrates spongiosis with exocytosis of eosinophils into the epithelium and a clear deficiency of infiltrating mites.⁶ 

Miliaria, also known as sweat rash, is a common condition that occurs due to occlusion of eccrine sweat glands.⁷ Clinically, miliaria is characterized by erythematous papules ranging from 2 to 4 mm in size that may be vesicular or pustular. Miliaria and demodicosis may have similar clinical presentations; however, several characteristic differences can be noted. Based on the pathophysiology, miliaria will not be folliculocentric, which differs from demodicosis. Additionally, miliaria most commonly occurs in areas of occlusion, such as in skin folds or on the trunk under tight clothing. Miliaria rarely can appear confluent and sunburnlike.⁸ Furthermore, miliaria is less common on the face, while demodicosis almost exclusively is found on the face. 

We present the case of an otherwise healthy patient with acute onset of pruritic papules and pustules involving the superior face following topical corticosteroid use. Similar cases frequently are encountered by dermatologists and require broad differential diagnoses. 

The Diagnosis: Demodicosis 

A clinical diagnosis of facial demodicosis triggered by topical corticosteroid therapy was suspected in our patient. A 3-mm punch biopsy of the right forehead demonstrated a follicular infundibulum rich in Demodex folliculorum with a discrete mononuclear infiltrate in the dermis (Figure 1), confirming the diagnosis. The patient was prescribed metronidazole gel 2% twice daily. Complete clearance of the facial rash was observed at 1-week follow-up (Figure 2). 

Demodex folliculorum is a mite that parasitizes the pilosebaceous follicles of human skin, becoming pathogenic with excessive colonization.^1-3 Facial demodicosis presents as pruritic papules and pustules in a pilosebaceous distribution on the face.^2,3 The diagnosis of facial demodicosis can be difficult due to similarities with many other common facial rashes such as acne, rosacea, contact dermatitis, and folliculitis.  

Similar to facial demodicosis, rosacea can present with erythema, papules, and pustules on the face. Patients with rosacea also have a higher prevalence and degree of Demodex mite infestation.⁴ However, these facial rashes can be differentiated when symptom acuity and personal and family histories are considered. In patients with a long-standing personal and/or family history of erythema, papules, and pustules, the chronicity of disease implies a diagnosis of rosacea. The acute onset of symptomatology and absence of personal or family history of rosacea in our patient favored a diagnosis of demodicosis. 

Pityrosporum folliculitis is an eruption caused by Malassezia furfur, the organism implicated in tinea versicolor. It can present similarly to Demodex folliculitis with follicular papules and pustules on the forehead and back. Features that help to differentiate Pityrosporum folliculitis from Demodex folliculitis include involvement of the upper trunk and onset after antibiotic usage.⁵ Diagnosis of Pityrosporum folliculitis can be confirmed by potassium hydroxide preparation, which demonstrates spaghetti-and-meatball-like hyphae and spores. 

Eosinophilic folliculitis is a chronic sterile folliculitis that usually presents as intensely pruritic papules and pustules on the face with an eruptive onset. There are 3 variants of disease: the classic form (also known as Ofuji disease), immunosuppression-associated disease, and infancy-associated disease.⁶ Eosinophilic folliculitis also may present with annular plaques and peripheral blood eosinophilia, and it is more prevalent in patients of Japanese descent. Differentiation from Demodex folliculitis can be done by histologic examination, which demonstrates spongiosis with exocytosis of eosinophils into the epithelium and a clear deficiency of infiltrating mites.⁶ 

Miliaria, also known as sweat rash, is a common condition that occurs due to occlusion of eccrine sweat glands.⁷ Clinically, miliaria is characterized by erythematous papules ranging from 2 to 4 mm in size that may be vesicular or pustular. Miliaria and demodicosis may have similar clinical presentations; however, several characteristic differences can be noted. Based on the pathophysiology, miliaria will not be folliculocentric, which differs from demodicosis. Additionally, miliaria most commonly occurs in areas of occlusion, such as in skin folds or on the trunk under tight clothing. Miliaria rarely can appear confluent and sunburnlike.⁸ Furthermore, miliaria is less common on the face, while demodicosis almost exclusively is found on the face. 

We present the case of an otherwise healthy patient with acute onset of pruritic papules and pustules involving the superior face following topical corticosteroid use. Similar cases frequently are encountered by dermatologists and require broad differential diagnoses. 

The Diagnosis: Demodicosis 

A clinical diagnosis of facial demodicosis triggered by topical corticosteroid therapy was suspected in our patient. A 3-mm punch biopsy of the right forehead demonstrated a follicular infundibulum rich in Demodex folliculorum with a discrete mononuclear infiltrate in the dermis (Figure 1), confirming the diagnosis. The patient was prescribed metronidazole gel 2% twice daily. Complete clearance of the facial rash was observed at 1-week follow-up (Figure 2). 

Demodex folliculorum is a mite that parasitizes the pilosebaceous follicles of human skin, becoming pathogenic with excessive colonization.^1-3 Facial demodicosis presents as pruritic papules and pustules in a pilosebaceous distribution on the face.^2,3 The diagnosis of facial demodicosis can be difficult due to similarities with many other common facial rashes such as acne, rosacea, contact dermatitis, and folliculitis.  

Similar to facial demodicosis, rosacea can present with erythema, papules, and pustules on the face. Patients with rosacea also have a higher prevalence and degree of Demodex mite infestation.⁴ However, these facial rashes can be differentiated when symptom acuity and personal and family histories are considered. In patients with a long-standing personal and/or family history of erythema, papules, and pustules, the chronicity of disease implies a diagnosis of rosacea. The acute onset of symptomatology and absence of personal or family history of rosacea in our patient favored a diagnosis of demodicosis. 

Pityrosporum folliculitis is an eruption caused by Malassezia furfur, the organism implicated in tinea versicolor. It can present similarly to Demodex folliculitis with follicular papules and pustules on the forehead and back. Features that help to differentiate Pityrosporum folliculitis from Demodex folliculitis include involvement of the upper trunk and onset after antibiotic usage.⁵ Diagnosis of Pityrosporum folliculitis can be confirmed by potassium hydroxide preparation, which demonstrates spaghetti-and-meatball-like hyphae and spores. 

Eosinophilic folliculitis is a chronic sterile folliculitis that usually presents as intensely pruritic papules and pustules on the face with an eruptive onset. There are 3 variants of disease: the classic form (also known as Ofuji disease), immunosuppression-associated disease, and infancy-associated disease.⁶ Eosinophilic folliculitis also may present with annular plaques and peripheral blood eosinophilia, and it is more prevalent in patients of Japanese descent. Differentiation from Demodex folliculitis can be done by histologic examination, which demonstrates spongiosis with exocytosis of eosinophils into the epithelium and a clear deficiency of infiltrating mites.⁶ 

Miliaria, also known as sweat rash, is a common condition that occurs due to occlusion of eccrine sweat glands.⁷ Clinically, miliaria is characterized by erythematous papules ranging from 2 to 4 mm in size that may be vesicular or pustular. Miliaria and demodicosis may have similar clinical presentations; however, several characteristic differences can be noted. Based on the pathophysiology, miliaria will not be folliculocentric, which differs from demodicosis. Additionally, miliaria most commonly occurs in areas of occlusion, such as in skin folds or on the trunk under tight clothing. Miliaria rarely can appear confluent and sunburnlike.⁸ Furthermore, miliaria is less common on the face, while demodicosis almost exclusively is found on the face. 

We present the case of an otherwise healthy patient with acute onset of pruritic papules and pustules involving the superior face following topical corticosteroid use. Similar cases frequently are encountered by dermatologists and require broad differential diagnoses. 

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

To the Editor:

Psoriasis vulgaris is a chronic autoimmune inflammatory disease and biologic agents, such as anti–tumor necrosis factor α (TNF-α), are alternative drugs in case of resistance or adverse events to conventional ones.¹ The limitation of these agents is immunosuppression that may cause infections such as tuberculosis (TB). Prophylaxis is indicated to latent TB diseases if the purified protein derivative (tuberculin) skin test is higher than 5 mm before starting these treatments. The challenge in TB treatment is adverse drug reactions (ADRs) that are reported in 4% to 6% of cases.^2,3

Erythema multiforme–like dermatitis is a rare skin rash that develops due to isoniazid (INH). The clinical presentation includes erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH. Skin biopsy and patch tests are the supportive diagnostic methods. Isoniazid-associated skin rashes rarely are reported and generally are not severe enough to terminate the drug. We present a patient with psoriasis who received TB prophylaxis before anti–TNF-α use. He presented with erythema multiforme–like dermatitis due to INH. Withdrawal of the drug and treatment of the lesions were the first steps of intolerance, followed by a patch test with the culprit drug after recovery. We discuss the diagnostic drug allergy evaluation and treatment approach.

A 37-year-old man presented with a 15-year history of severe psoriasis with frequent flares. He was treated with various topical and systemic agents including acitretin and methotrexate at 4-year intervals. Despite the addition of phototherapy, he underwent a new treatment with anti–TNF-α, as the disease control with other treatments was insufficient. Before starting anti–TNF-α, preventive treatment against TB with INH (300 mg/d) was indicated with 20 mm of purified protein derivative. On approximately the 20th day of treatment, he developed pruritic erythema with desquamation and exfoliation localized to the hands and feet (Figure 1). Isoniazid was discontinued and a topical steroid was initiated. After 3 weeks, the skin lesions were completely improved and INH was reinitiated at the same dose with antihistamine prophylaxis (oral levocetirizine 5 mg/d). Seven days later, similar skin lesions presented that were more extensive on the arms and legs (Figure 2). Complete blood cell counts, renal and hepatic function tests, and hepatitis markers were within reference range in consultation with the allergy division. To distinguish the lesions from a psoriasis attack, a punch biopsy of the eruptive dermatitis showed erythema multiforme–like dermatitis including dermal edema and perivascular lymphocytic infiltration with no relation to psoriasis but consistent with a drug eruption. Isoniazid was discontinued, and the skin lesions resolved after 4 weeks of topical steroid and oral antihistamine use (Figure 3). There was no other drug use except INH, and a skin patch test with INH was positive at 72 hours (Figure 4). Skin tests with INH were done to 5 healthy lesions that were negative. Finally, TB prophylaxis was performed with rifampicin (10 mg/kg/d [600 mg/d]) for 4 months with no ADRs. The patient’s psoriasis lesions improved with anti–TNF-α that was initiated 1 month after starting TB prevention with rifampicin.

This case of erythema multiforme–like dermatitis was diagnosed with acral involvement, a positive patch test to INH, and lymphocytic inflammation in a skin biopsy. It was a drug-induced reaction, as skin lesions developed during INH intake and improved after drug withdrawal.

Isoniazid, also known as isonicotinylhydrazide, is an oral antibiotic used for the treatment of TB and other mycobacteria. Protective treatment against latent TB primarily is done with daily INH for 6 or 9 months; alternatively, INH may be taken weekly with rifapentine for 3 months or daily with rifampicin for 4 months. Daily rifampicin alone for 4 months also is an option. In general, these regimens have similar efficacy; however, in terms of safety, the rifampicin and rifapentine combination regimens have fewer hepatotoxicity events compared to the INH alone regimen, but there are more cutaneous and flulike reactions and gastrointestinal intolerance.⁴ Cutaneous ADRs to TB treatment such as mild itchiness and cutaneous eruptions usually are observed within 2 months of drug initiation. Pyrazinamide was reported as the most common drug associated with cutaneous ADRs, and INH was the rarest offending drug.⁵

The frequency of ADRs to INH is approximately 5.4%, and the most prevalent ADRs include asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy, and hepatotoxicity, and skin lesions are less common.² Our patient’s laboratory test results excluded vitamin B deficiency, hepatic and renal dysfunction, and neuropathy.

Previously reported skin reactions related to INH were late-type reactions such as maculopapular rash, dermatitis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis.^5,6 The concerning prediagnosis of psoriatic exacerbation in our patient was ruled out by the absence of typical skin lesions such as well-defined, erythematous plaques and pustules and atypical localization such as the dorsal hands and feet rather than the knees, elbows, lumbosacral region, scalp, and abdomen, which is typical of psoriasis. DRESS syndrome was unlikely with the absence of fever, lymphadenopathy, hypereosinophilia, leukocytosis, and renal and hepatic dysfunction.⁷ There were no widespread blisters, epidermal detachment, or mucosal involvement on the trunk or face typically associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.^7,8 A possible diagnosis of contact dermatitis was suspected with likely skin lesions as exfoliation and chapping, typical localization on the hands and feet, and positive patch test that supported sensitization to the drug. However, the patient’s skin lesions were not eczematous (characterized by erythema, vesiculation, exudation, or bullous edema in the acute phase), and were not localized to areas of irritant exposure.³ In our patient, erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH was compatible with erythema multiforme, whereas the absence of target appearance, positive patch test, and late appearance were incompatible with erythema multiforme.⁸

Because the clinical picture did not fit contact dermatitis or erythema multiforme, a diagnosis of erythema multiforme–like noneczematous dermatitis was suggested. Noneczematous dermatitis has subtypes that include purpuric, lichenoid, pustular, lymphomatoid, dyshidrosiform, and pigmented, as well as erythema multiforme–like contact eruptions.⁹ These clinical entities are not associated with contact exposure, but are related to systemic exposure, as seen in our patient.¹⁰ The patch test positivity and skin biopsy report also supported the diagnosis of erythema multiforme–like dermatitis. Erythema multiforme–like dermatitis is thought to be caused by medications or infections inducing immunocomplexes and lymphocytic infiltration in the dermis and subepidermis. Nevertheless, the prognosis was self-limiting in both.⁸ The clinical polymorphism caused by INH in this patient was suggested to be related with individual susceptibility, variability of contact-activating modalities, and the targeted cutaneous structures. Furthermore, among the risk factors for cutaneous ADRs—HIV, polypharmacy, older age, and preexisting renal and liver impairment—the only notable factor in this patient was psoriasis as an autoimmune disorder.

Patients with skin diseases such as psoriasis should be followed up by closer monitoring during INH use. Withdrawal of the drug and symptomatic treatment of the lesions with corticosteroid and antihistamine are the first steps of drug intolerance. After complete recovery and termination of antiallergic drugs, diagnostic tests are recommended if the drug reaction was not life-threatening. Skin prick and intradermal tests are useful in early-type drug reactions, whereas patch testing and late evaluation of an intradermal test may be helpful in the diagnosis of delayed-type reactions. The full dose of INH is avoided in an intradermal test against irritation. A patch test with INH was performed by diluting a 100-mg tablet with 1 mL of distilled water, and used as 1/100, 1/10, and 1/1 dilutions.⁸ Patch testing with INH also was done in 5 healthy control patients to exclude the irritation effect in this case. The rechallenge of INH was done in a controlled manner in our patient to rule out psoriasis activation since it was a localized skin reaction with no serious ADR. An oral provocation test with the culprit drug is the gold standard of drug allergy diagnosis that should be done in a tertiary hospital with an intensive care unit.

This case of erythema multiforme–like dermatitis due to INH is interesting due to systemic intake of INH, which resulted in dermatitis with localized involvement similar to erythema multiforme but with no immunologic processes or prior sensitization. With the increasing use of anti–TNF-α treatment, INH use will be more prevalent than in the past for the treatment of latent TB. Even though the skin-restricted ADRs of INH are rare and minor, particular attention should be paid to patients with dermatologic diseases. In our case, diagnostic drug allergy evaluation was performed to optimize the second-line treatment of TB infection, in addition to early withdrawal of the culprit drug.

To the Editor:

Psoriasis vulgaris is a chronic autoimmune inflammatory disease and biologic agents, such as anti–tumor necrosis factor α (TNF-α), are alternative drugs in case of resistance or adverse events to conventional ones.¹ The limitation of these agents is immunosuppression that may cause infections such as tuberculosis (TB). Prophylaxis is indicated to latent TB diseases if the purified protein derivative (tuberculin) skin test is higher than 5 mm before starting these treatments. The challenge in TB treatment is adverse drug reactions (ADRs) that are reported in 4% to 6% of cases.^2,3

Erythema multiforme–like dermatitis is a rare skin rash that develops due to isoniazid (INH). The clinical presentation includes erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH. Skin biopsy and patch tests are the supportive diagnostic methods. Isoniazid-associated skin rashes rarely are reported and generally are not severe enough to terminate the drug. We present a patient with psoriasis who received TB prophylaxis before anti–TNF-α use. He presented with erythema multiforme–like dermatitis due to INH. Withdrawal of the drug and treatment of the lesions were the first steps of intolerance, followed by a patch test with the culprit drug after recovery. We discuss the diagnostic drug allergy evaluation and treatment approach.

A 37-year-old man presented with a 15-year history of severe psoriasis with frequent flares. He was treated with various topical and systemic agents including acitretin and methotrexate at 4-year intervals. Despite the addition of phototherapy, he underwent a new treatment with anti–TNF-α, as the disease control with other treatments was insufficient. Before starting anti–TNF-α, preventive treatment against TB with INH (300 mg/d) was indicated with 20 mm of purified protein derivative. On approximately the 20th day of treatment, he developed pruritic erythema with desquamation and exfoliation localized to the hands and feet (Figure 1). Isoniazid was discontinued and a topical steroid was initiated. After 3 weeks, the skin lesions were completely improved and INH was reinitiated at the same dose with antihistamine prophylaxis (oral levocetirizine 5 mg/d). Seven days later, similar skin lesions presented that were more extensive on the arms and legs (Figure 2). Complete blood cell counts, renal and hepatic function tests, and hepatitis markers were within reference range in consultation with the allergy division. To distinguish the lesions from a psoriasis attack, a punch biopsy of the eruptive dermatitis showed erythema multiforme–like dermatitis including dermal edema and perivascular lymphocytic infiltration with no relation to psoriasis but consistent with a drug eruption. Isoniazid was discontinued, and the skin lesions resolved after 4 weeks of topical steroid and oral antihistamine use (Figure 3). There was no other drug use except INH, and a skin patch test with INH was positive at 72 hours (Figure 4). Skin tests with INH were done to 5 healthy lesions that were negative. Finally, TB prophylaxis was performed with rifampicin (10 mg/kg/d [600 mg/d]) for 4 months with no ADRs. The patient’s psoriasis lesions improved with anti–TNF-α that was initiated 1 month after starting TB prevention with rifampicin.

This case of erythema multiforme–like dermatitis was diagnosed with acral involvement, a positive patch test to INH, and lymphocytic inflammation in a skin biopsy. It was a drug-induced reaction, as skin lesions developed during INH intake and improved after drug withdrawal.

Isoniazid, also known as isonicotinylhydrazide, is an oral antibiotic used for the treatment of TB and other mycobacteria. Protective treatment against latent TB primarily is done with daily INH for 6 or 9 months; alternatively, INH may be taken weekly with rifapentine for 3 months or daily with rifampicin for 4 months. Daily rifampicin alone for 4 months also is an option. In general, these regimens have similar efficacy; however, in terms of safety, the rifampicin and rifapentine combination regimens have fewer hepatotoxicity events compared to the INH alone regimen, but there are more cutaneous and flulike reactions and gastrointestinal intolerance.⁴ Cutaneous ADRs to TB treatment such as mild itchiness and cutaneous eruptions usually are observed within 2 months of drug initiation. Pyrazinamide was reported as the most common drug associated with cutaneous ADRs, and INH was the rarest offending drug.⁵

The frequency of ADRs to INH is approximately 5.4%, and the most prevalent ADRs include asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy, and hepatotoxicity, and skin lesions are less common.² Our patient’s laboratory test results excluded vitamin B deficiency, hepatic and renal dysfunction, and neuropathy.

Previously reported skin reactions related to INH were late-type reactions such as maculopapular rash, dermatitis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis.^5,6 The concerning prediagnosis of psoriatic exacerbation in our patient was ruled out by the absence of typical skin lesions such as well-defined, erythematous plaques and pustules and atypical localization such as the dorsal hands and feet rather than the knees, elbows, lumbosacral region, scalp, and abdomen, which is typical of psoriasis. DRESS syndrome was unlikely with the absence of fever, lymphadenopathy, hypereosinophilia, leukocytosis, and renal and hepatic dysfunction.⁷ There were no widespread blisters, epidermal detachment, or mucosal involvement on the trunk or face typically associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.^7,8 A possible diagnosis of contact dermatitis was suspected with likely skin lesions as exfoliation and chapping, typical localization on the hands and feet, and positive patch test that supported sensitization to the drug. However, the patient’s skin lesions were not eczematous (characterized by erythema, vesiculation, exudation, or bullous edema in the acute phase), and were not localized to areas of irritant exposure.³ In our patient, erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH was compatible with erythema multiforme, whereas the absence of target appearance, positive patch test, and late appearance were incompatible with erythema multiforme.⁸

Because the clinical picture did not fit contact dermatitis or erythema multiforme, a diagnosis of erythema multiforme–like noneczematous dermatitis was suggested. Noneczematous dermatitis has subtypes that include purpuric, lichenoid, pustular, lymphomatoid, dyshidrosiform, and pigmented, as well as erythema multiforme–like contact eruptions.⁹ These clinical entities are not associated with contact exposure, but are related to systemic exposure, as seen in our patient.¹⁰ The patch test positivity and skin biopsy report also supported the diagnosis of erythema multiforme–like dermatitis. Erythema multiforme–like dermatitis is thought to be caused by medications or infections inducing immunocomplexes and lymphocytic infiltration in the dermis and subepidermis. Nevertheless, the prognosis was self-limiting in both.⁸ The clinical polymorphism caused by INH in this patient was suggested to be related with individual susceptibility, variability of contact-activating modalities, and the targeted cutaneous structures. Furthermore, among the risk factors for cutaneous ADRs—HIV, polypharmacy, older age, and preexisting renal and liver impairment—the only notable factor in this patient was psoriasis as an autoimmune disorder.

Patients with skin diseases such as psoriasis should be followed up by closer monitoring during INH use. Withdrawal of the drug and symptomatic treatment of the lesions with corticosteroid and antihistamine are the first steps of drug intolerance. After complete recovery and termination of antiallergic drugs, diagnostic tests are recommended if the drug reaction was not life-threatening. Skin prick and intradermal tests are useful in early-type drug reactions, whereas patch testing and late evaluation of an intradermal test may be helpful in the diagnosis of delayed-type reactions. The full dose of INH is avoided in an intradermal test against irritation. A patch test with INH was performed by diluting a 100-mg tablet with 1 mL of distilled water, and used as 1/100, 1/10, and 1/1 dilutions.⁸ Patch testing with INH also was done in 5 healthy control patients to exclude the irritation effect in this case. The rechallenge of INH was done in a controlled manner in our patient to rule out psoriasis activation since it was a localized skin reaction with no serious ADR. An oral provocation test with the culprit drug is the gold standard of drug allergy diagnosis that should be done in a tertiary hospital with an intensive care unit.

This case of erythema multiforme–like dermatitis due to INH is interesting due to systemic intake of INH, which resulted in dermatitis with localized involvement similar to erythema multiforme but with no immunologic processes or prior sensitization. With the increasing use of anti–TNF-α treatment, INH use will be more prevalent than in the past for the treatment of latent TB. Even though the skin-restricted ADRs of INH are rare and minor, particular attention should be paid to patients with dermatologic diseases. In our case, diagnostic drug allergy evaluation was performed to optimize the second-line treatment of TB infection, in addition to early withdrawal of the culprit drug.

To the Editor:

Psoriasis vulgaris is a chronic autoimmune inflammatory disease and biologic agents, such as anti–tumor necrosis factor α (TNF-α), are alternative drugs in case of resistance or adverse events to conventional ones.¹ The limitation of these agents is immunosuppression that may cause infections such as tuberculosis (TB). Prophylaxis is indicated to latent TB diseases if the purified protein derivative (tuberculin) skin test is higher than 5 mm before starting these treatments. The challenge in TB treatment is adverse drug reactions (ADRs) that are reported in 4% to 6% of cases.^2,3

Erythema multiforme–like dermatitis is a rare skin rash that develops due to isoniazid (INH). The clinical presentation includes erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH. Skin biopsy and patch tests are the supportive diagnostic methods. Isoniazid-associated skin rashes rarely are reported and generally are not severe enough to terminate the drug. We present a patient with psoriasis who received TB prophylaxis before anti–TNF-α use. He presented with erythema multiforme–like dermatitis due to INH. Withdrawal of the drug and treatment of the lesions were the first steps of intolerance, followed by a patch test with the culprit drug after recovery. We discuss the diagnostic drug allergy evaluation and treatment approach.

A 37-year-old man presented with a 15-year history of severe psoriasis with frequent flares. He was treated with various topical and systemic agents including acitretin and methotrexate at 4-year intervals. Despite the addition of phototherapy, he underwent a new treatment with anti–TNF-α, as the disease control with other treatments was insufficient. Before starting anti–TNF-α, preventive treatment against TB with INH (300 mg/d) was indicated with 20 mm of purified protein derivative. On approximately the 20th day of treatment, he developed pruritic erythema with desquamation and exfoliation localized to the hands and feet (Figure 1). Isoniazid was discontinued and a topical steroid was initiated. After 3 weeks, the skin lesions were completely improved and INH was reinitiated at the same dose with antihistamine prophylaxis (oral levocetirizine 5 mg/d). Seven days later, similar skin lesions presented that were more extensive on the arms and legs (Figure 2). Complete blood cell counts, renal and hepatic function tests, and hepatitis markers were within reference range in consultation with the allergy division. To distinguish the lesions from a psoriasis attack, a punch biopsy of the eruptive dermatitis showed erythema multiforme–like dermatitis including dermal edema and perivascular lymphocytic infiltration with no relation to psoriasis but consistent with a drug eruption. Isoniazid was discontinued, and the skin lesions resolved after 4 weeks of topical steroid and oral antihistamine use (Figure 3). There was no other drug use except INH, and a skin patch test with INH was positive at 72 hours (Figure 4). Skin tests with INH were done to 5 healthy lesions that were negative. Finally, TB prophylaxis was performed with rifampicin (10 mg/kg/d [600 mg/d]) for 4 months with no ADRs. The patient’s psoriasis lesions improved with anti–TNF-α that was initiated 1 month after starting TB prevention with rifampicin.

This case of erythema multiforme–like dermatitis was diagnosed with acral involvement, a positive patch test to INH, and lymphocytic inflammation in a skin biopsy. It was a drug-induced reaction, as skin lesions developed during INH intake and improved after drug withdrawal.

Isoniazid, also known as isonicotinylhydrazide, is an oral antibiotic used for the treatment of TB and other mycobacteria. Protective treatment against latent TB primarily is done with daily INH for 6 or 9 months; alternatively, INH may be taken weekly with rifapentine for 3 months or daily with rifampicin for 4 months. Daily rifampicin alone for 4 months also is an option. In general, these regimens have similar efficacy; however, in terms of safety, the rifampicin and rifapentine combination regimens have fewer hepatotoxicity events compared to the INH alone regimen, but there are more cutaneous and flulike reactions and gastrointestinal intolerance.⁴ Cutaneous ADRs to TB treatment such as mild itchiness and cutaneous eruptions usually are observed within 2 months of drug initiation. Pyrazinamide was reported as the most common drug associated with cutaneous ADRs, and INH was the rarest offending drug.⁵

The frequency of ADRs to INH is approximately 5.4%, and the most prevalent ADRs include asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy, and hepatotoxicity, and skin lesions are less common.² Our patient’s laboratory test results excluded vitamin B deficiency, hepatic and renal dysfunction, and neuropathy.

Previously reported skin reactions related to INH were late-type reactions such as maculopapular rash, dermatitis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis.^5,6 The concerning prediagnosis of psoriatic exacerbation in our patient was ruled out by the absence of typical skin lesions such as well-defined, erythematous plaques and pustules and atypical localization such as the dorsal hands and feet rather than the knees, elbows, lumbosacral region, scalp, and abdomen, which is typical of psoriasis. DRESS syndrome was unlikely with the absence of fever, lymphadenopathy, hypereosinophilia, leukocytosis, and renal and hepatic dysfunction.⁷ There were no widespread blisters, epidermal detachment, or mucosal involvement on the trunk or face typically associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.^7,8 A possible diagnosis of contact dermatitis was suspected with likely skin lesions as exfoliation and chapping, typical localization on the hands and feet, and positive patch test that supported sensitization to the drug. However, the patient’s skin lesions were not eczematous (characterized by erythema, vesiculation, exudation, or bullous edema in the acute phase), and were not localized to areas of irritant exposure.³ In our patient, erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH was compatible with erythema multiforme, whereas the absence of target appearance, positive patch test, and late appearance were incompatible with erythema multiforme.⁸

Because the clinical picture did not fit contact dermatitis or erythema multiforme, a diagnosis of erythema multiforme–like noneczematous dermatitis was suggested. Noneczematous dermatitis has subtypes that include purpuric, lichenoid, pustular, lymphomatoid, dyshidrosiform, and pigmented, as well as erythema multiforme–like contact eruptions.⁹ These clinical entities are not associated with contact exposure, but are related to systemic exposure, as seen in our patient.¹⁰ The patch test positivity and skin biopsy report also supported the diagnosis of erythema multiforme–like dermatitis. Erythema multiforme–like dermatitis is thought to be caused by medications or infections inducing immunocomplexes and lymphocytic infiltration in the dermis and subepidermis. Nevertheless, the prognosis was self-limiting in both.⁸ The clinical polymorphism caused by INH in this patient was suggested to be related with individual susceptibility, variability of contact-activating modalities, and the targeted cutaneous structures. Furthermore, among the risk factors for cutaneous ADRs—HIV, polypharmacy, older age, and preexisting renal and liver impairment—the only notable factor in this patient was psoriasis as an autoimmune disorder.

Patients with skin diseases such as psoriasis should be followed up by closer monitoring during INH use. Withdrawal of the drug and symptomatic treatment of the lesions with corticosteroid and antihistamine are the first steps of drug intolerance. After complete recovery and termination of antiallergic drugs, diagnostic tests are recommended if the drug reaction was not life-threatening. Skin prick and intradermal tests are useful in early-type drug reactions, whereas patch testing and late evaluation of an intradermal test may be helpful in the diagnosis of delayed-type reactions. The full dose of INH is avoided in an intradermal test against irritation. A patch test with INH was performed by diluting a 100-mg tablet with 1 mL of distilled water, and used as 1/100, 1/10, and 1/1 dilutions.⁸ Patch testing with INH also was done in 5 healthy control patients to exclude the irritation effect in this case. The rechallenge of INH was done in a controlled manner in our patient to rule out psoriasis activation since it was a localized skin reaction with no serious ADR. An oral provocation test with the culprit drug is the gold standard of drug allergy diagnosis that should be done in a tertiary hospital with an intensive care unit.

This case of erythema multiforme–like dermatitis due to INH is interesting due to systemic intake of INH, which resulted in dermatitis with localized involvement similar to erythema multiforme but with no immunologic processes or prior sensitization. With the increasing use of anti–TNF-α treatment, INH use will be more prevalent than in the past for the treatment of latent TB. Even though the skin-restricted ADRs of INH are rare and minor, particular attention should be paid to patients with dermatologic diseases. In our case, diagnostic drug allergy evaluation was performed to optimize the second-line treatment of TB infection, in addition to early withdrawal of the culprit drug.

To the Editor:

The term tinea incognito was introduced by Ive and Marks¹ in 1968 and refers to unusual clinical presentations of tinea due to the application of topical corticosteroids. Tinea incognito, which does not feature the classical clinical characteristics of tinea corporis such as well-defined, erythematous, scaly patches and elevated borders, is regularly misdiagnosed as inflammatory dermatosis.² Immunosuppression caused by topical and/or systemic steroids predisposes patients to the development of tinea.³ Herein, a case of widespread pustular tinea incognito mimicking pustular psoriasis along with failure of tumor necrosis factor (TNF) inhibitor treatment is reported in a patient with chronic plaque psoriasis and steroid-induced Cushing syndrome.

A 46-year-old man with a 25-year history of psoriasis was referred to the dermatologic outpatient clinic with a severe flare-up of chronic plaque psoriasis. Prior treatments included methotrexate and acitretin without response. Narrowband UVB treatment was discontinued due to claustrophobia. Topical treatment with calcipotriol 0.005%–betamethasone dipropionate 0.05% gel was reported to be ineffective. The patient was administered prednisone over several months in a primary care setting at a dosage of 35 mg daily when he presented to the dermatology clinic. Physical examination revealed widespread chronic plaque psoriasis of the trunk and extremities, and a psoriasis area and severity index score of 15 was calculated. The patient had onychodystrophy with subungual hyperkeratosis of all toenails. Signs of prednisone-induced Cushing syndrome, including central obesity, lipodystrophy, and red striae, were noted.

Treatment was started by dermatology with the TNF inhibitor adalimumab at an initial dose of 80 mg, followed by subsequent 40-mg doses every other week; prednisone was tapered off. Topical treatment with a 4-week course of clobetasol propionate cream 0.05% daily for psoriatic lesions was initiated.

Six weeks after the initial consultation, the patient presented to the hospital’s emergency department with worsening symptoms of itchy, burning, and painful skin after good initial improvement. The patient’s skin started to burn upon application of clobetasol and the rash worsened. The patient did not use emollients. At that point, the patient was on a daily dose of 15 mg of prednisone. On dermatologic review, multiple partially annular lesions with subtle scaling and multiple pustules on the arms and legs as well as the buttocks and groin were noticed. These lesions were confined to sites of prior psoriasis as marked by postinflammatory hyperpigmentation (Figure 1). Widespread tinea was assumed, and treatment with fluconazole 50 mg daily was administered for 4 weeks. Direct examination of skin scrapings from the patient’s thigh showed hyphae, and fungal culture was positive for Trichophyton rubrum. Scrapings from the patient’s hallux nail remained inconclusive due to bacterial overgrowth. At 4-week follow-up, the patient’s skin had cleared entirely and showed only postinflammatory changes (Figure 2). Healthy proximal nail growth was observed. Fluconazole was continued at a once-weekly dose of 150 mg together with adalimumab at a dose of 40 mg every 2 weeks and a prednisone tapering schedule.

Apart from psoriasis, tinea incognito most commonly is mistaken for other inflammatory conditions such as eczema, folliculitis, rosacea, granuloma annulare, and discoid lupus erythematosus.² Inflammatory tinea can present with pustules due to the increased occurrence of neutrophil invasion.¹¹This patient’s symptoms worsened 4 weeks after the initiation of TNF inhibitor treatment, which suggested treatment failure. However, clearance of the preexisting psoriatic lesions with remnant hyperpigmentation only argued for good response to TNF inhibitor treatment. The main differential diagnosis of this case of tinea incognito was generalized pustular psoriasis. The patient also was being treated with systemic and topical steroids, both known for their potential to trigger pustular psoriasis.^12,13 Furthermore, TNF inhibitors have been described as a trigger for predominantly palmoplantar pustulosis but also are additionally associated with generalized pustular psoriasis.¹⁴

This case aims to raise awareness that tinea incognito can imitate both pustular psoriasis and TNF inhibitor treatment failure. Furthermore, the presented findings highlight risks associated with the treatment of psoriasis with systemic steroids. Pustular tinea incognito should be considered in the differential diagnosis of pustular psoriasis, especially in the setting of immunosuppression. After initial improvement, worsening of symptoms such as itching and burning as well as extension of the lesions upon application of topical steroids are regularly described in tinea incognito and can be present in addition to the more typical annular presentation of lesions as a clue to the diagnosis.

To the Editor:

The term tinea incognito was introduced by Ive and Marks¹ in 1968 and refers to unusual clinical presentations of tinea due to the application of topical corticosteroids. Tinea incognito, which does not feature the classical clinical characteristics of tinea corporis such as well-defined, erythematous, scaly patches and elevated borders, is regularly misdiagnosed as inflammatory dermatosis.² Immunosuppression caused by topical and/or systemic steroids predisposes patients to the development of tinea.³ Herein, a case of widespread pustular tinea incognito mimicking pustular psoriasis along with failure of tumor necrosis factor (TNF) inhibitor treatment is reported in a patient with chronic plaque psoriasis and steroid-induced Cushing syndrome.

A 46-year-old man with a 25-year history of psoriasis was referred to the dermatologic outpatient clinic with a severe flare-up of chronic plaque psoriasis. Prior treatments included methotrexate and acitretin without response. Narrowband UVB treatment was discontinued due to claustrophobia. Topical treatment with calcipotriol 0.005%–betamethasone dipropionate 0.05% gel was reported to be ineffective. The patient was administered prednisone over several months in a primary care setting at a dosage of 35 mg daily when he presented to the dermatology clinic. Physical examination revealed widespread chronic plaque psoriasis of the trunk and extremities, and a psoriasis area and severity index score of 15 was calculated. The patient had onychodystrophy with subungual hyperkeratosis of all toenails. Signs of prednisone-induced Cushing syndrome, including central obesity, lipodystrophy, and red striae, were noted.

Treatment was started by dermatology with the TNF inhibitor adalimumab at an initial dose of 80 mg, followed by subsequent 40-mg doses every other week; prednisone was tapered off. Topical treatment with a 4-week course of clobetasol propionate cream 0.05% daily for psoriatic lesions was initiated.

Six weeks after the initial consultation, the patient presented to the hospital’s emergency department with worsening symptoms of itchy, burning, and painful skin after good initial improvement. The patient’s skin started to burn upon application of clobetasol and the rash worsened. The patient did not use emollients. At that point, the patient was on a daily dose of 15 mg of prednisone. On dermatologic review, multiple partially annular lesions with subtle scaling and multiple pustules on the arms and legs as well as the buttocks and groin were noticed. These lesions were confined to sites of prior psoriasis as marked by postinflammatory hyperpigmentation (Figure 1). Widespread tinea was assumed, and treatment with fluconazole 50 mg daily was administered for 4 weeks. Direct examination of skin scrapings from the patient’s thigh showed hyphae, and fungal culture was positive for Trichophyton rubrum. Scrapings from the patient’s hallux nail remained inconclusive due to bacterial overgrowth. At 4-week follow-up, the patient’s skin had cleared entirely and showed only postinflammatory changes (Figure 2). Healthy proximal nail growth was observed. Fluconazole was continued at a once-weekly dose of 150 mg together with adalimumab at a dose of 40 mg every 2 weeks and a prednisone tapering schedule.

Apart from psoriasis, tinea incognito most commonly is mistaken for other inflammatory conditions such as eczema, folliculitis, rosacea, granuloma annulare, and discoid lupus erythematosus.² Inflammatory tinea can present with pustules due to the increased occurrence of neutrophil invasion.¹¹This patient’s symptoms worsened 4 weeks after the initiation of TNF inhibitor treatment, which suggested treatment failure. However, clearance of the preexisting psoriatic lesions with remnant hyperpigmentation only argued for good response to TNF inhibitor treatment. The main differential diagnosis of this case of tinea incognito was generalized pustular psoriasis. The patient also was being treated with systemic and topical steroids, both known for their potential to trigger pustular psoriasis.^12,13 Furthermore, TNF inhibitors have been described as a trigger for predominantly palmoplantar pustulosis but also are additionally associated with generalized pustular psoriasis.¹⁴

This case aims to raise awareness that tinea incognito can imitate both pustular psoriasis and TNF inhibitor treatment failure. Furthermore, the presented findings highlight risks associated with the treatment of psoriasis with systemic steroids. Pustular tinea incognito should be considered in the differential diagnosis of pustular psoriasis, especially in the setting of immunosuppression. After initial improvement, worsening of symptoms such as itching and burning as well as extension of the lesions upon application of topical steroids are regularly described in tinea incognito and can be present in addition to the more typical annular presentation of lesions as a clue to the diagnosis.

To the Editor:

The term tinea incognito was introduced by Ive and Marks¹ in 1968 and refers to unusual clinical presentations of tinea due to the application of topical corticosteroids. Tinea incognito, which does not feature the classical clinical characteristics of tinea corporis such as well-defined, erythematous, scaly patches and elevated borders, is regularly misdiagnosed as inflammatory dermatosis.² Immunosuppression caused by topical and/or systemic steroids predisposes patients to the development of tinea.³ Herein, a case of widespread pustular tinea incognito mimicking pustular psoriasis along with failure of tumor necrosis factor (TNF) inhibitor treatment is reported in a patient with chronic plaque psoriasis and steroid-induced Cushing syndrome.

A 46-year-old man with a 25-year history of psoriasis was referred to the dermatologic outpatient clinic with a severe flare-up of chronic plaque psoriasis. Prior treatments included methotrexate and acitretin without response. Narrowband UVB treatment was discontinued due to claustrophobia. Topical treatment with calcipotriol 0.005%–betamethasone dipropionate 0.05% gel was reported to be ineffective. The patient was administered prednisone over several months in a primary care setting at a dosage of 35 mg daily when he presented to the dermatology clinic. Physical examination revealed widespread chronic plaque psoriasis of the trunk and extremities, and a psoriasis area and severity index score of 15 was calculated. The patient had onychodystrophy with subungual hyperkeratosis of all toenails. Signs of prednisone-induced Cushing syndrome, including central obesity, lipodystrophy, and red striae, were noted.

Treatment was started by dermatology with the TNF inhibitor adalimumab at an initial dose of 80 mg, followed by subsequent 40-mg doses every other week; prednisone was tapered off. Topical treatment with a 4-week course of clobetasol propionate cream 0.05% daily for psoriatic lesions was initiated.

Six weeks after the initial consultation, the patient presented to the hospital’s emergency department with worsening symptoms of itchy, burning, and painful skin after good initial improvement. The patient’s skin started to burn upon application of clobetasol and the rash worsened. The patient did not use emollients. At that point, the patient was on a daily dose of 15 mg of prednisone. On dermatologic review, multiple partially annular lesions with subtle scaling and multiple pustules on the arms and legs as well as the buttocks and groin were noticed. These lesions were confined to sites of prior psoriasis as marked by postinflammatory hyperpigmentation (Figure 1). Widespread tinea was assumed, and treatment with fluconazole 50 mg daily was administered for 4 weeks. Direct examination of skin scrapings from the patient’s thigh showed hyphae, and fungal culture was positive for Trichophyton rubrum. Scrapings from the patient’s hallux nail remained inconclusive due to bacterial overgrowth. At 4-week follow-up, the patient’s skin had cleared entirely and showed only postinflammatory changes (Figure 2). Healthy proximal nail growth was observed. Fluconazole was continued at a once-weekly dose of 150 mg together with adalimumab at a dose of 40 mg every 2 weeks and a prednisone tapering schedule.

Apart from psoriasis, tinea incognito most commonly is mistaken for other inflammatory conditions such as eczema, folliculitis, rosacea, granuloma annulare, and discoid lupus erythematosus.² Inflammatory tinea can present with pustules due to the increased occurrence of neutrophil invasion.¹¹This patient’s symptoms worsened 4 weeks after the initiation of TNF inhibitor treatment, which suggested treatment failure. However, clearance of the preexisting psoriatic lesions with remnant hyperpigmentation only argued for good response to TNF inhibitor treatment. The main differential diagnosis of this case of tinea incognito was generalized pustular psoriasis. The patient also was being treated with systemic and topical steroids, both known for their potential to trigger pustular psoriasis.^12,13 Furthermore, TNF inhibitors have been described as a trigger for predominantly palmoplantar pustulosis but also are additionally associated with generalized pustular psoriasis.¹⁴

This case aims to raise awareness that tinea incognito can imitate both pustular psoriasis and TNF inhibitor treatment failure. Furthermore, the presented findings highlight risks associated with the treatment of psoriasis with systemic steroids. Pustular tinea incognito should be considered in the differential diagnosis of pustular psoriasis, especially in the setting of immunosuppression. After initial improvement, worsening of symptoms such as itching and burning as well as extension of the lesions upon application of topical steroids are regularly described in tinea incognito and can be present in addition to the more typical annular presentation of lesions as a clue to the diagnosis.

A cohort study of psoriasis patients in Denmark found that a nonmedical switch from brand name adalimumab to adalimumab biosimilars was not associated with drug retention at 1 year. And another study, a small, single-center retrospective study of patients with hidradenitis suppurativa (HS), found that administration of infliximab and biosimilar infliximab were associated with similar and significant improvement in disease.

Both studies were published online in April in JAMA Dermatology and add to mounting evidence that biosimilars may be interchangeable in certain dermatologic conditions.

“Biosimilars are an exciting innovation in the field,” Joseph Zahn, MD, assistant professor of dermatology at George Washington University, Washington, said in an interview. “Their efficacy and price point will allow patients greater access to effective treatment.” To date, biosimilars approved in the United States that could be prescribed by dermatologists include those for rituximab, etanercept, adalimumab, and infliximab.

In the trial from Denmark, Nikolai Loft, MD, of the University of Copenhagen and colleagues evaluated outcomes following a mandatory medical switch from the brand name adalimumab, referred to as adalimumab originator, to adalimumab biosimilars among 726 individuals who were enrolled in a Danish nationwide registry of patients treated with biologics since 2007. The primary outcome was 1-year drug retention in patients switching to adalimumab biosimilars compared with patients treated with adalimumab originator.

The study population consisted of 348 patients with at least 2 years of exposure to adalimumab who had switched from originator to adalimumab biosimilars (a mean age of 52 and 72% male) and 378 patients who served as the adalimumab cohort (a mean age of 51 and 71% male). When the researchers compared the 1-year drug retention rates between the adalimumab biosimilar cohort and the adalimumab originator cohort, the rates were similar (92% vs. 92.1%, respectively).

The hazard ratios for other outcomes were similar as well. Specifically, the crude hazard ratios were 1.02 (P = .94) for all causes of drug discontinuation, 0.82 (P = .60) for insufficient effect, and 1.41 (P = .50) for adverse events (AEs) in the adalimumab biosimilar cohort, compared with the adalimumab originator cohort.

“Overall, results for any AEs were contradicting, but certain AEs were more prevalent in the adalimumab biosimilar cohort,” the authors wrote. Dermatologic AEs and AEs in the “other” category “were more prevalent, which could be attributable to more patients experiencing injection site reactions as a result of larger volumes and differences in excipients and syringes in the adalimumab biosimilars and the adalimumab originator.” Other potential explanations they offered were the nocebo effect and greater awareness of AEs among practitioners and patients.

“This study concludes that, when switched to a biosimilar medication, patients do not have worse control of their psoriasis nor do they switch to other medications,” Dr. Zahn, who was asked to comment about these results, said in the interview. “However, there was a trend toward a higher number of side effects in the biosimilar group. The main takeaway point from this study is that biosimilars of adalimumab seem to be relatively interchangeable in patients with psoriasis without loss of efficacy or significant increase in side effects that lead to a medication change for the patient.”

The researchers acknowledged certain limitations of their study, including the fact that it was limited to Danish patients and that individual AEs could not be examined. “Moreover, the surveillance of AEs is not as vigilant as in clinical trials, and AEs are most likely underreported,” they wrote. “Although no major differences were found when switching from adalimumab originator to adalimumab biosimilar versions, it was not possible to assess the performance of individual adalimumab biosimilar versions in this study.”

In the second study, Christopher Sayed, MD, associate professor of dermatology, University of North Carolina, Chapel Hill, and colleagues retrospectively evaluated the effectiveness of infliximab-abda versus infliximab administration in the treatment of 34 patients with HS who were cared for at the university’s dermatology clinic. Patients were treated with either agent for at least 10 weeks. The infliximab treatment group consisted of 20 patients with a mean age of 42 years who were mostly female (17; 85%), while the infliximab-abda treatment group included 14 patients with a mean age of 36 years who also were mostly female (13; 93%).

Both groups received loading doses of 10 mg/kg at weeks 0, 2, and 6, and treatment was continued with a maintenance dose administered every 4-8 weeks. The patients were followed between February 2016 and June 2020 and the primary outcome measure was Hidradenitis Suppurative Clinical Response (HiSCR), which was defined as at least a 50% decrease in inflammatory nodule count without any increase in the number of abscesses or draining sinuses.

The researchers found that 71% of patients in the infliximab-abda treatment group achieved a HiSCR, compared with 60% of their counterparts in the infliximab treatment group, a difference that did not reach statistical significance (P = .47). Three patients in the infliximab treatment group experienced AEs, compared with none in the infliximab-abda treatment group.

“The data are promising,” Dr. Zahn said. “Although this is a small study with a limited number of patients, it suggests that this particular biosimilar may be a reasonable or possibly even equivalent alternative to infliximab. A larger, prospective trial will be needed before we can be sure the results are equivalent.”

Dr. Sayed and colleagues noted certain limitations of their study, including the retrospective design and the use of concomitant medications by some participants. “There is also a risk of selection bias because copay and medication assistance programs are not available for infliximab-abda for patients with HS,” they wrote.

In an editorial accompanying the two studies, Mark Lebwohl, MD, professor of dermatology, Icahn School of Medicine at Mount Sinai, New York, wrote that the introduction of biosimilars have been justified by “the hope that lower costs” will increase availability of treatments to patients with moderate to severe psoriasis. “Inroads in the U.S. market, however, have been limited,” he added, and there is concern that they “may be used to prevent access to newer interleukin-17 blockers and interleukin-23 blockers for which biosimilars are available and that do not carry the boxed warnings found on tumor necrosis factor blockers.”

Dr. Loft reported receiving personal fees from Eli Lilly and Janssen outside of the submitted work. Many of his coauthors reporting having numerous financial conflicts of interest with the pharmaceutical industry. The HS study was supported by a public health service research award from the National Institutes of Health. Dr. Sayed reported receiving personal fees or personal fees paid to the institution from AbbVie, Novartis, Chemocentryx, GlaxoSmithKline, Incyte, InflaRx, and UCB. No other disclosures were reported. Dr. Lebwohl disclosed receiving research funds from companies including AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, and Incyte; and receiving personal fees from multiple companies, outside of the submitted work. Dr. Zahn reported having no disclosures.

[email protected]

A cohort study of psoriasis patients in Denmark found that a nonmedical switch from brand name adalimumab to adalimumab biosimilars was not associated with drug retention at 1 year. And another study, a small, single-center retrospective study of patients with hidradenitis suppurativa (HS), found that administration of infliximab and biosimilar infliximab were associated with similar and significant improvement in disease.

Both studies were published online in April in JAMA Dermatology and add to mounting evidence that biosimilars may be interchangeable in certain dermatologic conditions.

“Biosimilars are an exciting innovation in the field,” Joseph Zahn, MD, assistant professor of dermatology at George Washington University, Washington, said in an interview. “Their efficacy and price point will allow patients greater access to effective treatment.” To date, biosimilars approved in the United States that could be prescribed by dermatologists include those for rituximab, etanercept, adalimumab, and infliximab.

In the trial from Denmark, Nikolai Loft, MD, of the University of Copenhagen and colleagues evaluated outcomes following a mandatory medical switch from the brand name adalimumab, referred to as adalimumab originator, to adalimumab biosimilars among 726 individuals who were enrolled in a Danish nationwide registry of patients treated with biologics since 2007. The primary outcome was 1-year drug retention in patients switching to adalimumab biosimilars compared with patients treated with adalimumab originator.

The study population consisted of 348 patients with at least 2 years of exposure to adalimumab who had switched from originator to adalimumab biosimilars (a mean age of 52 and 72% male) and 378 patients who served as the adalimumab cohort (a mean age of 51 and 71% male). When the researchers compared the 1-year drug retention rates between the adalimumab biosimilar cohort and the adalimumab originator cohort, the rates were similar (92% vs. 92.1%, respectively).

The hazard ratios for other outcomes were similar as well. Specifically, the crude hazard ratios were 1.02 (P = .94) for all causes of drug discontinuation, 0.82 (P = .60) for insufficient effect, and 1.41 (P = .50) for adverse events (AEs) in the adalimumab biosimilar cohort, compared with the adalimumab originator cohort.

“Overall, results for any AEs were contradicting, but certain AEs were more prevalent in the adalimumab biosimilar cohort,” the authors wrote. Dermatologic AEs and AEs in the “other” category “were more prevalent, which could be attributable to more patients experiencing injection site reactions as a result of larger volumes and differences in excipients and syringes in the adalimumab biosimilars and the adalimumab originator.” Other potential explanations they offered were the nocebo effect and greater awareness of AEs among practitioners and patients.

“This study concludes that, when switched to a biosimilar medication, patients do not have worse control of their psoriasis nor do they switch to other medications,” Dr. Zahn, who was asked to comment about these results, said in the interview. “However, there was a trend toward a higher number of side effects in the biosimilar group. The main takeaway point from this study is that biosimilars of adalimumab seem to be relatively interchangeable in patients with psoriasis without loss of efficacy or significant increase in side effects that lead to a medication change for the patient.”

The researchers acknowledged certain limitations of their study, including the fact that it was limited to Danish patients and that individual AEs could not be examined. “Moreover, the surveillance of AEs is not as vigilant as in clinical trials, and AEs are most likely underreported,” they wrote. “Although no major differences were found when switching from adalimumab originator to adalimumab biosimilar versions, it was not possible to assess the performance of individual adalimumab biosimilar versions in this study.”

In the second study, Christopher Sayed, MD, associate professor of dermatology, University of North Carolina, Chapel Hill, and colleagues retrospectively evaluated the effectiveness of infliximab-abda versus infliximab administration in the treatment of 34 patients with HS who were cared for at the university’s dermatology clinic. Patients were treated with either agent for at least 10 weeks. The infliximab treatment group consisted of 20 patients with a mean age of 42 years who were mostly female (17; 85%), while the infliximab-abda treatment group included 14 patients with a mean age of 36 years who also were mostly female (13; 93%).

Both groups received loading doses of 10 mg/kg at weeks 0, 2, and 6, and treatment was continued with a maintenance dose administered every 4-8 weeks. The patients were followed between February 2016 and June 2020 and the primary outcome measure was Hidradenitis Suppurative Clinical Response (HiSCR), which was defined as at least a 50% decrease in inflammatory nodule count without any increase in the number of abscesses or draining sinuses.

The researchers found that 71% of patients in the infliximab-abda treatment group achieved a HiSCR, compared with 60% of their counterparts in the infliximab treatment group, a difference that did not reach statistical significance (P = .47). Three patients in the infliximab treatment group experienced AEs, compared with none in the infliximab-abda treatment group.

“The data are promising,” Dr. Zahn said. “Although this is a small study with a limited number of patients, it suggests that this particular biosimilar may be a reasonable or possibly even equivalent alternative to infliximab. A larger, prospective trial will be needed before we can be sure the results are equivalent.”

Dr. Sayed and colleagues noted certain limitations of their study, including the retrospective design and the use of concomitant medications by some participants. “There is also a risk of selection bias because copay and medication assistance programs are not available for infliximab-abda for patients with HS,” they wrote.

In an editorial accompanying the two studies, Mark Lebwohl, MD, professor of dermatology, Icahn School of Medicine at Mount Sinai, New York, wrote that the introduction of biosimilars have been justified by “the hope that lower costs” will increase availability of treatments to patients with moderate to severe psoriasis. “Inroads in the U.S. market, however, have been limited,” he added, and there is concern that they “may be used to prevent access to newer interleukin-17 blockers and interleukin-23 blockers for which biosimilars are available and that do not carry the boxed warnings found on tumor necrosis factor blockers.”

Dr. Loft reported receiving personal fees from Eli Lilly and Janssen outside of the submitted work. Many of his coauthors reporting having numerous financial conflicts of interest with the pharmaceutical industry. The HS study was supported by a public health service research award from the National Institutes of Health. Dr. Sayed reported receiving personal fees or personal fees paid to the institution from AbbVie, Novartis, Chemocentryx, GlaxoSmithKline, Incyte, InflaRx, and UCB. No other disclosures were reported. Dr. Lebwohl disclosed receiving research funds from companies including AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, and Incyte; and receiving personal fees from multiple companies, outside of the submitted work. Dr. Zahn reported having no disclosures.

[email protected]

A cohort study of psoriasis patients in Denmark found that a nonmedical switch from brand name adalimumab to adalimumab biosimilars was not associated with drug retention at 1 year. And another study, a small, single-center retrospective study of patients with hidradenitis suppurativa (HS), found that administration of infliximab and biosimilar infliximab were associated with similar and significant improvement in disease.

Both studies were published online in April in JAMA Dermatology and add to mounting evidence that biosimilars may be interchangeable in certain dermatologic conditions.

“Biosimilars are an exciting innovation in the field,” Joseph Zahn, MD, assistant professor of dermatology at George Washington University, Washington, said in an interview. “Their efficacy and price point will allow patients greater access to effective treatment.” To date, biosimilars approved in the United States that could be prescribed by dermatologists include those for rituximab, etanercept, adalimumab, and infliximab.

In the trial from Denmark, Nikolai Loft, MD, of the University of Copenhagen and colleagues evaluated outcomes following a mandatory medical switch from the brand name adalimumab, referred to as adalimumab originator, to adalimumab biosimilars among 726 individuals who were enrolled in a Danish nationwide registry of patients treated with biologics since 2007. The primary outcome was 1-year drug retention in patients switching to adalimumab biosimilars compared with patients treated with adalimumab originator.

The study population consisted of 348 patients with at least 2 years of exposure to adalimumab who had switched from originator to adalimumab biosimilars (a mean age of 52 and 72% male) and 378 patients who served as the adalimumab cohort (a mean age of 51 and 71% male). When the researchers compared the 1-year drug retention rates between the adalimumab biosimilar cohort and the adalimumab originator cohort, the rates were similar (92% vs. 92.1%, respectively).

The hazard ratios for other outcomes were similar as well. Specifically, the crude hazard ratios were 1.02 (P = .94) for all causes of drug discontinuation, 0.82 (P = .60) for insufficient effect, and 1.41 (P = .50) for adverse events (AEs) in the adalimumab biosimilar cohort, compared with the adalimumab originator cohort.

“Overall, results for any AEs were contradicting, but certain AEs were more prevalent in the adalimumab biosimilar cohort,” the authors wrote. Dermatologic AEs and AEs in the “other” category “were more prevalent, which could be attributable to more patients experiencing injection site reactions as a result of larger volumes and differences in excipients and syringes in the adalimumab biosimilars and the adalimumab originator.” Other potential explanations they offered were the nocebo effect and greater awareness of AEs among practitioners and patients.

“This study concludes that, when switched to a biosimilar medication, patients do not have worse control of their psoriasis nor do they switch to other medications,” Dr. Zahn, who was asked to comment about these results, said in the interview. “However, there was a trend toward a higher number of side effects in the biosimilar group. The main takeaway point from this study is that biosimilars of adalimumab seem to be relatively interchangeable in patients with psoriasis without loss of efficacy or significant increase in side effects that lead to a medication change for the patient.”

The researchers acknowledged certain limitations of their study, including the fact that it was limited to Danish patients and that individual AEs could not be examined. “Moreover, the surveillance of AEs is not as vigilant as in clinical trials, and AEs are most likely underreported,” they wrote. “Although no major differences were found when switching from adalimumab originator to adalimumab biosimilar versions, it was not possible to assess the performance of individual adalimumab biosimilar versions in this study.”

In the second study, Christopher Sayed, MD, associate professor of dermatology, University of North Carolina, Chapel Hill, and colleagues retrospectively evaluated the effectiveness of infliximab-abda versus infliximab administration in the treatment of 34 patients with HS who were cared for at the university’s dermatology clinic. Patients were treated with either agent for at least 10 weeks. The infliximab treatment group consisted of 20 patients with a mean age of 42 years who were mostly female (17; 85%), while the infliximab-abda treatment group included 14 patients with a mean age of 36 years who also were mostly female (13; 93%).

Both groups received loading doses of 10 mg/kg at weeks 0, 2, and 6, and treatment was continued with a maintenance dose administered every 4-8 weeks. The patients were followed between February 2016 and June 2020 and the primary outcome measure was Hidradenitis Suppurative Clinical Response (HiSCR), which was defined as at least a 50% decrease in inflammatory nodule count without any increase in the number of abscesses or draining sinuses.

The researchers found that 71% of patients in the infliximab-abda treatment group achieved a HiSCR, compared with 60% of their counterparts in the infliximab treatment group, a difference that did not reach statistical significance (P = .47). Three patients in the infliximab treatment group experienced AEs, compared with none in the infliximab-abda treatment group.

“The data are promising,” Dr. Zahn said. “Although this is a small study with a limited number of patients, it suggests that this particular biosimilar may be a reasonable or possibly even equivalent alternative to infliximab. A larger, prospective trial will be needed before we can be sure the results are equivalent.”

Dr. Sayed and colleagues noted certain limitations of their study, including the retrospective design and the use of concomitant medications by some participants. “There is also a risk of selection bias because copay and medication assistance programs are not available for infliximab-abda for patients with HS,” they wrote.

In an editorial accompanying the two studies, Mark Lebwohl, MD, professor of dermatology, Icahn School of Medicine at Mount Sinai, New York, wrote that the introduction of biosimilars have been justified by “the hope that lower costs” will increase availability of treatments to patients with moderate to severe psoriasis. “Inroads in the U.S. market, however, have been limited,” he added, and there is concern that they “may be used to prevent access to newer interleukin-17 blockers and interleukin-23 blockers for which biosimilars are available and that do not carry the boxed warnings found on tumor necrosis factor blockers.”

Dr. Loft reported receiving personal fees from Eli Lilly and Janssen outside of the submitted work. Many of his coauthors reporting having numerous financial conflicts of interest with the pharmaceutical industry. The HS study was supported by a public health service research award from the National Institutes of Health. Dr. Sayed reported receiving personal fees or personal fees paid to the institution from AbbVie, Novartis, Chemocentryx, GlaxoSmithKline, Incyte, InflaRx, and UCB. No other disclosures were reported. Dr. Lebwohl disclosed receiving research funds from companies including AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, and Incyte; and receiving personal fees from multiple companies, outside of the submitted work. Dr. Zahn reported having no disclosures.

[email protected]

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.

Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.

Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.

Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

Secukinumab is the latest adult plaque psoriasis treatment to be bested by a newcomer, the interleukin 17A and 17F blocker bimekizumab.

Rates of complete clearance were substantially higher with bimekizumab in a phase 3 trial with 743 patients with moderate-to-severe plaque psoriasis, but oral candidiasis (oral thrush) again emerged as a particular issue with the agent.

Clinical improvements seen with bimekizumab have exceeded those with two standard options for adult plaque psoriasis — the tumor necrosis factor blocker adalimumab and the interleukin (IL) 12/23 inhibitor ustekinumab

 — in phase 3 trials from manufacturer UCB Pharma, and it›s under review for the indication by the U.S. Food and Drug Administration and the European Medicines Agency.

The biologic is also being evaluated in phase 3 trials for treating psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa.

Results of the trial comparing bimekizumab to secukinumab, dubbed BE RADIANT, were presented at the American Academy of Dermatology Virtual Meeting Experience and published online concurrently April 23 in the New England Journal of Medicine.

The results “suggest that inhibition of both interleukin-17A and interleukin-17F with bimekizumab may provide greater clinical benefit for patients with moderate-to-severe plaque psoriasis than inhibition of interleukin-17A alone,” as with secukinumab, said the investigators, led by Kristian Reich, MD,  professor of dermatology at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.

The trial randomly assigned 373 adults to bimekizumab 320 mg every 4 weeks to week 16, then rerandomized them to maintenance dosing either every 4 weeks or every 8 weeks to week 48; another 370 adults were randomly assigned to secukinumab 300 mg weekly for the first 4 weeks, then every 4 weeks to week 48. Baseline Psoriasis Area and Severity Index (PASI) scores were about 20 points in both treatment groups.

At the 1-month point, 71% in the bimekizumab group, vs 47.3% on secukinumab, had a 75% or greater reduction from their baseline PASI score. At 4 months, 61.7% of those on bimekizumab but 48.9% in the secukinumab group had complete clearance with a PASI score of 100.

At 48 weeks, 67% of those on bimekizumab had a PASI 100 response — which was numerically similar between the two bimekizumab dosing regimens after week 16 — vs 46.2% of the secukinumab group (P for all < .001).

The incidence of serious adverse events was just under 6% in both groups, with adverse events leading to discontinuation in 3.5% of bimekizumab and 2.7% of secukinumab subjects. The rate of serious infections was similar in both groups.

However, as in past trials, oral candidiasis was an issue, occurring in 19.3% of bimekizumab subjects vs 3% on secukinumab. Half of the 72 bimekizumab cases were classified as mild, and all but two of the rest as moderate. Over 40% of affected subjects reported more than one case, but none led to treatment discontinuation.

More than 85% of oral candidiasis cases in the study were treated with antifungal therapy and resolved during the trial. Inflammatory bowel disease is a concern with IL-17 blockade, but this hasn’t emerged as a particular issue with bimekizumab. There was one case each of ulcerative colitis in both the bimekizumab and secukinumab groups, and just one case of ulcerative colitis in three previous phase 3 bimekizumab trials, according to the investigators.

Among the trial limitations: Patients who had been on bimekizumab or secukinumab previously were excluded, as were patients who had no response to an IL-17 biologic or more than one biologic agent of any other class within the previous 12 weeks. The limitations could reduce generalizability, the investigators said.

Patients in the trial were about 45 years old, on average, and about two thirds were men; over 90% were White.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Reich who reported grants and personal fees from companies including UCB Pharma. The full list of disclosures can be found with the New England Journal of Medicine article.

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

Secukinumab is the latest adult plaque psoriasis treatment to be bested by a newcomer, the interleukin 17A and 17F blocker bimekizumab.

Rates of complete clearance were substantially higher with bimekizumab in a phase 3 trial with 743 patients with moderate-to-severe plaque psoriasis, but oral candidiasis (oral thrush) again emerged as a particular issue with the agent.

Clinical improvements seen with bimekizumab have exceeded those with two standard options for adult plaque psoriasis — the tumor necrosis factor blocker adalimumab and the interleukin (IL) 12/23 inhibitor ustekinumab

 — in phase 3 trials from manufacturer UCB Pharma, and it›s under review for the indication by the U.S. Food and Drug Administration and the European Medicines Agency.

The biologic is also being evaluated in phase 3 trials for treating psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa.

Results of the trial comparing bimekizumab to secukinumab, dubbed BE RADIANT, were presented at the American Academy of Dermatology Virtual Meeting Experience and published online concurrently April 23 in the New England Journal of Medicine.

The results “suggest that inhibition of both interleukin-17A and interleukin-17F with bimekizumab may provide greater clinical benefit for patients with moderate-to-severe plaque psoriasis than inhibition of interleukin-17A alone,” as with secukinumab, said the investigators, led by Kristian Reich, MD,  professor of dermatology at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.

The trial randomly assigned 373 adults to bimekizumab 320 mg every 4 weeks to week 16, then rerandomized them to maintenance dosing either every 4 weeks or every 8 weeks to week 48; another 370 adults were randomly assigned to secukinumab 300 mg weekly for the first 4 weeks, then every 4 weeks to week 48. Baseline Psoriasis Area and Severity Index (PASI) scores were about 20 points in both treatment groups.

At the 1-month point, 71% in the bimekizumab group, vs 47.3% on secukinumab, had a 75% or greater reduction from their baseline PASI score. At 4 months, 61.7% of those on bimekizumab but 48.9% in the secukinumab group had complete clearance with a PASI score of 100.

At 48 weeks, 67% of those on bimekizumab had a PASI 100 response — which was numerically similar between the two bimekizumab dosing regimens after week 16 — vs 46.2% of the secukinumab group (P for all < .001).

The incidence of serious adverse events was just under 6% in both groups, with adverse events leading to discontinuation in 3.5% of bimekizumab and 2.7% of secukinumab subjects. The rate of serious infections was similar in both groups.

However, as in past trials, oral candidiasis was an issue, occurring in 19.3% of bimekizumab subjects vs 3% on secukinumab. Half of the 72 bimekizumab cases were classified as mild, and all but two of the rest as moderate. Over 40% of affected subjects reported more than one case, but none led to treatment discontinuation.

More than 85% of oral candidiasis cases in the study were treated with antifungal therapy and resolved during the trial. Inflammatory bowel disease is a concern with IL-17 blockade, but this hasn’t emerged as a particular issue with bimekizumab. There was one case each of ulcerative colitis in both the bimekizumab and secukinumab groups, and just one case of ulcerative colitis in three previous phase 3 bimekizumab trials, according to the investigators.

Among the trial limitations: Patients who had been on bimekizumab or secukinumab previously were excluded, as were patients who had no response to an IL-17 biologic or more than one biologic agent of any other class within the previous 12 weeks. The limitations could reduce generalizability, the investigators said.

Patients in the trial were about 45 years old, on average, and about two thirds were men; over 90% were White.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Reich who reported grants and personal fees from companies including UCB Pharma. The full list of disclosures can be found with the New England Journal of Medicine article.

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

Secukinumab is the latest adult plaque psoriasis treatment to be bested by a newcomer, the interleukin 17A and 17F blocker bimekizumab.

Rates of complete clearance were substantially higher with bimekizumab in a phase 3 trial with 743 patients with moderate-to-severe plaque psoriasis, but oral candidiasis (oral thrush) again emerged as a particular issue with the agent.

Clinical improvements seen with bimekizumab have exceeded those with two standard options for adult plaque psoriasis — the tumor necrosis factor blocker adalimumab and the interleukin (IL) 12/23 inhibitor ustekinumab

 — in phase 3 trials from manufacturer UCB Pharma, and it›s under review for the indication by the U.S. Food and Drug Administration and the European Medicines Agency.

The biologic is also being evaluated in phase 3 trials for treating psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa.

Results of the trial comparing bimekizumab to secukinumab, dubbed BE RADIANT, were presented at the American Academy of Dermatology Virtual Meeting Experience and published online concurrently April 23 in the New England Journal of Medicine.

The results “suggest that inhibition of both interleukin-17A and interleukin-17F with bimekizumab may provide greater clinical benefit for patients with moderate-to-severe plaque psoriasis than inhibition of interleukin-17A alone,” as with secukinumab, said the investigators, led by Kristian Reich, MD,  professor of dermatology at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.

The trial randomly assigned 373 adults to bimekizumab 320 mg every 4 weeks to week 16, then rerandomized them to maintenance dosing either every 4 weeks or every 8 weeks to week 48; another 370 adults were randomly assigned to secukinumab 300 mg weekly for the first 4 weeks, then every 4 weeks to week 48. Baseline Psoriasis Area and Severity Index (PASI) scores were about 20 points in both treatment groups.

At the 1-month point, 71% in the bimekizumab group, vs 47.3% on secukinumab, had a 75% or greater reduction from their baseline PASI score. At 4 months, 61.7% of those on bimekizumab but 48.9% in the secukinumab group had complete clearance with a PASI score of 100.

At 48 weeks, 67% of those on bimekizumab had a PASI 100 response — which was numerically similar between the two bimekizumab dosing regimens after week 16 — vs 46.2% of the secukinumab group (P for all < .001).

The incidence of serious adverse events was just under 6% in both groups, with adverse events leading to discontinuation in 3.5% of bimekizumab and 2.7% of secukinumab subjects. The rate of serious infections was similar in both groups.

However, as in past trials, oral candidiasis was an issue, occurring in 19.3% of bimekizumab subjects vs 3% on secukinumab. Half of the 72 bimekizumab cases were classified as mild, and all but two of the rest as moderate. Over 40% of affected subjects reported more than one case, but none led to treatment discontinuation.

More than 85% of oral candidiasis cases in the study were treated with antifungal therapy and resolved during the trial. Inflammatory bowel disease is a concern with IL-17 blockade, but this hasn’t emerged as a particular issue with bimekizumab. There was one case each of ulcerative colitis in both the bimekizumab and secukinumab groups, and just one case of ulcerative colitis in three previous phase 3 bimekizumab trials, according to the investigators.

Among the trial limitations: Patients who had been on bimekizumab or secukinumab previously were excluded, as were patients who had no response to an IL-17 biologic or more than one biologic agent of any other class within the previous 12 weeks. The limitations could reduce generalizability, the investigators said.

Patients in the trial were about 45 years old, on average, and about two thirds were men; over 90% were White.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Reich who reported grants and personal fees from companies including UCB Pharma. The full list of disclosures can be found with the New England Journal of Medicine article.

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