Sweet Syndrome — SCE Dermatology MCQ

Correct answer: E — Anti-IL-1 (Anakinra/Canakinumab)

The correct answer is E, Anti-IL-1 (Anakinra/Canakinumab). This man has a classic presentation of Sweet syndrome (acute febrile neutrophilic dermatosis): a tender, rapidly expanding erythematous plaque with pseudovesiculation on the shin, neutrophilia, and a dense dermal neutrophilic infiltrate on biopsy without infection. The strong association with myelodysplastic syndrome points to malignancy-associated (paraneoplastic) neutrophilic dermatosis, a group increasingly recognised as IL-1 driven autoinflammatory disease. IL-1 (both alpha and beta) is a key upstream cytokine amplifying neutrophil recruitment and activation in Sweet syndrome and pyoderma gangrenosum, so blocking IL-1 with anakinra (IL-1 receptor antagonist) or canakinumab (anti-IL-1beta monoclonal) directly targets this pathway and has been used successfully in corticosteroid-refractory or recalcitrant disease. Why the other options are wrong: A. Anti-CD20 (Rituximab): targets B lymphocytes and is used in antibody-mediated disease (e.g. certain autoimmune blistering disorders); neutrophilic dermatoses are not B-cell or antibody driven, so B-cell depletion has no established mechanistic rationale here. C. Anti-IL-5 (Mepolizumab): IL-5 governs eosinophil maturation and survival, relevant to eosinophilic conditions such as severe eosinophilic asthma or hypereosinophilic syndrome, not neutrophil-driven dermatoses. D. Anti-IL-4R (Dupilumab): blocks IL-4/IL-13 signalling central to Th2 allergic and atopic disease (atopic dermatitis, asthma); it has no role in neutrophil-mediated autoinflammation. B. Anti-IgE (Omalizumab): targets IgE-mediated mast cell degranulation in allergic disease (urticaria, allergic asthma), which is pathogenically unrelated to a sterile neutrophilic infiltrate. Key point: In recalcitrant or malignancy-associated neutrophilic dermatoses (Sweet syndrome, pyoderma gangrenosum), IL-1 blockade with anakinra or canakinumab targets the core autoinflammatory driver when corticosteroids fail or are contraindicated.

Reference: O'Connor C, Gallagher C, Hollywood A, Paul L, O'Connell M. Anakinra for recalcitrant pyoderma gangrenosum. Clinical and Experimental Dermatology (British Association of Dermatologists journal), 2021;46(8):1558-1560. https://doi.org/10.1111/ced.14809