P031 Granulomatous eruptions in patients treated with dupilumab

Abstract

Dupilumab, a monoclonal antibody targeting interleukin-4 and interleukin-13 signalling, has transformed the management of severe atopic eczema. While dupilumab is generally well tolerated, granulomatous reactions are increasingly recognized as a rare adverse effect. We present three patients with severe atopic eczema who developed granulomatous eruptions after prolonged dupilumab therapy. Case 1. A 54-year-old woman developed erythematous papules and plaques around the ear and neck 3 years after starting dupilumab. Biopsy revealed naked epithelioid granulomas, and investigations for systemic sarcoidosis were negative. The eruption persisted for 15 months but resolved spontaneously without discontinuation of dupilumab. Case 2. A 38-year-old man presented with reddish plaques and patches on the upper arms 5 years into treatment. Histology demonstrated interstitial and epithelioid granulomas with central necrobiotic collagen. The eruption settled without intervention, and dupilumab was continued. Case 3. A 63-year-old man developed shiny red–brown papules on background telangiectatic skin on the chest and arms after 2 years and 7 months of therapy. Histopathology showed well-formed non-necrotizing epithelioid granulomas in a perifollicular and superficial dermal distribution. He remains under review. In all cases the special stains alcian blue, periodic acid–Schiff, Grocott, Ziehl-Neelson and Wade–Fite were negative for pathogens. These cases expand the spectrum of dupilumab-associated granulomatous cutaneous eruptions, which may present as granuloma annulare, sarcoid-like eruptions, lichenoid-granulomatous dermatitis or rosacea-like changes. The proposed mechanism involves T helper (Th)2 blockade with compensatory Th1/Th17 hyper-response, driving granulomatous inflammation. However, this may be reversible, and our cases demonstrate that it may be possible to continue dupilumab as these cutaneous eruptions can resolve without drug cessation. Importantly, clinicians using dupilumab should remain vigilant for systemic granulomatous conditions such as drug-induced ­sarcoidosis-like reactions, which may require broader evaluation beyond the skin.