Broad range of adverse cutaneous eruptions in patients on TNF‐alpha antagonists

Abstract

Biologic therapies targeting tumor necrosis factor (TNF)-alpha have become a mainstay in the management of a number of autoimmune diseases. We report a series of adverse skin eruptions in six patients (four females, two males, age: 21-58 years, mean: 39) receiving 4 months to 10 years (mean 3.1 years) of anti-TNF-alpha therapies (infliximab, n = 4; adalimumab, n = 1 or etanercept, n = 1). The following drug-associated diagnoses were made in eight skin biopsies performed at Massachusetts General Hospital between 3/2007 and 10/2010: pustular folliculitis, psoriasis, interface dermatitis, neutrophilic eccrine hidradenitis, Sweet's syndrome, lupus, vasculitis and palmoplantar pustulosis. The descriptions of neutrophilic eccrine hidradenitis-like and Sweet's-like hypersensitivity eruptions induced by anti-TNF-alpha therapies are the first such cases described in the literature. Each cutaneous eruption improved or resolved with switching to a different TNF-alpha inhibitor, discontinuation of the anti-TNF-alpha agent, and/or topical or systemic steroids. There was a clear chronologic relationship with, and clinical remission upon withdrawal or steroid suppression of the anti-TNF-alpha agents. The mechanism for such diverse cutaneous eruptions among this class of medications remains poorly understood. The cutaneous adverse reaction profile of TNF-alpha inhibitors is broad and should be considered in the histopathologic differential in this clinical setting.

Skin Side Effects of Inflammatory Bowel Disease Therapy

“…30 All anti-TNF have been associated with a broad spectrum of dermatologic conditions (Table 1), such as cutaneous viral or bacterial infections, urticaria, alopecia areata, granulomatous reactions, atopic dermatitis, cutaneous lymphoma, vitiligo, acne, lichenoid drug reactions, leucocytoclastic vascultis, purpura, etc. [31][32][33] We must realize, however, that (1) many of these reactions have been described only as case reports or small case series, which, even if well documented, are not sufficient to establish a cause-effect assumption; (2) often patients were taking concomitant medications; and (3) some of these manifestations could eventually be associated with disease itself. The correct approach to these skin reactions, and the decision to stop or to continue the supposedly offending anti-TNF, should therefore be based on the severity of the skin lesion, on the impact on patient's quality of life, and on the need to maintain the anti-TNF.…”

TNFα and IL‐17A are differentially expressed in psoriasis‐like vs eczema‐like drug reactions to TNFα antagonists

“…However, the widening use of these drugs is mirrored by an increasing number of cases with paradoxical skin lesions resembling psoriasis, eczematiform‐like reactions and other conditions that occur during treatment with TNFα inhibitors—even in patients who had never had psoriasis or eczema before. Evidence for the hypothesis that it is a specific drug effect of TNFα inhibitors includes (1) the absence of a personal or family history of psoriasis; (2) the temporal relationship between anti‐TNF treatment and the appearance of cutaneous lesions; (3) clinical improvement observed after discontinuation of therapy; and (4) subsequent recurrence of psoriatic lesions after switching to another anti‐TNF agent.…”

Tumour necrosis factor-α-inhibitor-induced neutrophilic folliculitis presenting with strong lesional expression of interleukin-36γ

“…Biologic drugs targeting tumour necrosis factor (TNF)‐α, such as infliximab, adalimumab and etanercept, are frequently used to treat many common autoimmune and cutaneous disorders, including inflammatory bowel disease (IBD) and psoriasis. However, a large number of paradoxical cutaneous drug reactions in patients receiving anti‐TNF‐α treatment have been reported, including psoriasiform skin reactions, lupus‐like disorders, vasculitis, palmoplantar pustulosis, dermatological infections and pustular folliculitis …”