Abstract

Enfortumab vedotin (EV), a nectin-4-directed antibody drug conjugate, was FDA-approved in 2019 as third-line treatment of locally advanced/metastatic urothelial cancer. Nectin-4 plays a role in adherens junctions expressed in the skin, bladder, and several epithelial malignancies. Reports of idiosyncratic reactions to EV are sparse given its novelty. Herein, we describe a unique non-autoimmune bullous dermatitis reaction to EV. A 78-year-old male with metastatic urothelial cancer progressing on platinum-based chemotherapy and pembrolizumab presented with rapid onset rash approximately 3 weeks after initiating EV. The rash covered approximately 25% of his body surface area with minimally pruritic erythematous patches on dorsal forearms, intact bullae on the dorsal hands, and erythema involving the hips, buttocks, and medial thighs with exfoliative scaling and epidermal fragility. No fever or mucosal involvement were noted. Biopsies of dorsal hand and medial thigh revealed a pauci-inflammatory subepidermal split with squamous dysmaturation and dyskeratosis with non-specific weak granular immunoglobulin A deposition along the basement membrane. He subsequently experienced significant exfoliation and was treated with triamcinolone 0.1% ointment without rash progression. We recommended against EV discontinuation given his refractory malignancy. In this case of EV-associated cutaneous toxicity, the eruption had overlapping clinical features of  SDRIFE and a bullous dermatitis with prominent exfoliation. Prior reports have shown a clinical spectrum including toxic erythema of chemotherapy,  Stevens Johnson syndrome/TEN-like eruptions, and vesicular eruptions. The postulated etiopathogenesis is theorized to involve the interruption of cutaneous nectin-4—expressed in the suprabasal epidermis—combined with microtubule disruption, resulting in non-specific vesiculobullous eruptions and exfoliative dermatitis.