Track: Case Reports

Abstract:

A 53-year-old transgender female with stage IV urethral cancer, on enfortumab vedotin and pembrolizumab, presents for evaluation of a new blistering eruption. She initially developed a dermatitis on the trunk and upper arms which progressed to fragile bullae on the lower abdomen and superficial desquamation on the upper arms and proximal thighs. Two punch biopsies of a blister edge on the left thigh demonstrated vacuolar interface dermatitis with dyskeratosis, intraepidermal dysmaturation, and superficial to mid dermal perivascular lymphocytic inflammation. Eosinophils were not conspicuous. Direct immunofluorescence (DIF) was negative. The second biopsy showed intraepidermal vesiculation adjacent to an area with complete epidermal loss. A diagnosis of enfortumab vedotin-induced bullous reaction was made. The patient was placed on a prednisone taper followed by dupilumab.

Enfortumab vedotin, an antibody-drug conjugate targeting nectin-4 and disrupting microtubule function, is used with pembrolizumab for advanced urothelial carcinoma. Cutaneous toxicity is common, ranging from mild exanthem to severe dermatoses. Enfortumab vedotin induced bullous dermatitis has been described in small case series. Histopathology shows subepidermal vesiculation, dyskeratosis, spongiosis, apoptotic keratinocytes, and superficial perivascular inflammation with sporadic eosinophils. Intraepidermal vesiculation has rarely been described. DIF is characteristically negative, suggesting direct action against nectin-4, preferentially expressed in the basal layer. Dupilumab has been used successfully in a few cases, though the exact mechanism remains unknown. This case highlights the importance of recognizing the broad range of cutaneous reactions to cancer therapies and provides information on the novel use of dupilumab for enfortumab vedotin-induced bullous reaction.

Erich Karasko

Affiliation

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(132) Enfortumab Vedotin–Associated Bullous Dermatosis: An Emerging Cutaneous Toxicity with Distinct Histopathologic Features