Dissecting Cellulitis of the Scalp Associated With Dupilumab: A Paradoxical Neutrophilic Reaction

We report the case of a 27-year-old Caucasian man with chronic type-2 upper-airway disease treated with dupilumab at a dosage of 300 mg every 2 weeks. The first five injections were well tolerated. A few days after the fifth dose, the patient developed tender papules on the vertex scalp that rapidly progressed within 1 week into deep inflammatory nodules and abscesses with multiple draining sinus tracts. Pain, swelling, and purulent discharge intensified quickly, while the remainder of the skin examination was unremarkable (Figure 1a,b). Laboratory evaluation revealed leukocytosis (13.19 × 103/μL) with neutrophilia and moderately elevated C-reactive protein levels. Hepatic and renal function tests, creatine kinase, lipid profile, and serologic screening for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) were within normal limits. Repeated cultures from purulent drainage were negative. A scalp biopsy demonstrated follicular rupture, a dense neutrophil-rich inflammatory infiltrate, early sinus tract formation, and perifollicular fibrosis, consistent with a diagnosis of dissecting cellulitis of the scalp (DCS) (Figure 2). Dupilumab was discontinued, and treatment with isotretinoin (20 mg/day) and a short course of oral prednisone (25 mg/day for 20 days) was initiated. Clinical improvement was rapid, with marked reduction of inflammatory activity and pain within 2 weeks and no new lesion development by 4 weeks. At 3 months of follow-up, the patient remained stable on isotretinoin monotherapy, with residual inactive cicatricial alopecia (Figure 1c,d). Given the severity of disease and persistent inflammatory potential, therapy with adalimumab, a tumor necrosis factor-alpha (TNF-α) inhibitor, was subsequently initiated. To our knowledge, this represents the first reported case of dissecting cellulitis of the scalp occurring in association with dupilumab therapy. Dupilumab, a monoclonal antibody targeting the interleukin-4 (IL-4) receptor alpha subunit and inhibiting IL-4 and IL-13 signaling, is widely regarded as one of the safest biologic agents in dermatology. However, increasing evidence indicates that IL-4 and IL-13 are not only effector cytokines of type-2 immunity but also important regulators of the IL-23/Th17 axis, exerting inhibitory effects on Th17 differentiation and neutrophilic inflammation [1]. Inhibition of these cytokines may favor a relative immune deviation toward Th1/Th17-skewed responses. This hypothesis should be regarded as a conceptual immunologic model rather than a definitive causal mechanism, as no direct immunophenotyping was performed. Similar immune deviations have been proposed to explain paradoxical inflammatory reactions during dupilumab therapy, including de novo psoriasis [2] and seronegative inflammatory arthritis or enthesitis [3]. DCS is a chronic neutrophilic disorder belonging to the follicular occlusion spectrum, in which IL-23/IL-17 and TNF signaling pathways play a central pathogenic role. Within this framework, DCS can be viewed as part of a broader spectrum of follicular and neutrophilic dermatoses that may emerge as paradoxical inflammatory reactions during biologic therapy [4, 5]. Given the substantial risk of irreversible cicatricial alopecia, early recognition of new-onset scalp nodules, abscesses, or sinus tracts in patients receiving dupilumab is essential to prevent permanent sequelae. The authors have nothing to report. The patients in this manuscript have given written informed consent to publication of their case details. This study follows the ethics guidelines. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.