Demodex Infestation in Patients With Atopic Dermatitis Treated With Dupilumab: A Case–Control Study

ABSTRACT Atopic dermatitis (AD) is a chronic inflammatory skin disease in which dupilumab, an interleukin‐4 receptor alpha antagonist, has become a cornerstone therapy for moderate‐to‐severe disease. However, persistent facial and neck erythema and related symptoms have been increasingly reported during dupilumab treatment, and the underlying mechanisms remain incompletely understood. Demodex species, common components of the cutaneous microbiota, have been proposed as potential contributing factors. This retrospective case–control study evaluated Demodex infestation in patients with moderate‐to‐severe AD receiving dupilumab therapy compared with AD patients not receiving systemic immunosuppressive treatment. A total of 61 patients were included: 31 dupilumab‐treated patients and 30 controls. Demodex density was assessed using standardized skin surface biopsy, with ≥ 5 mites/cm 2 considered positive infestation. Clinical features, laboratory parameters, and treatment characteristics were analyzed. Demodex positivity was significantly more frequent in dupilumab‐treated patients than in controls (45.2% vs. 6.7%, p = 0.001). All dupilumab‐treated patients had achieved at least a 75% improvement in Eczema Area and Severity Index at the time of assessment. Within the dupilumab group, Demodex‐positive patients were older than Demodex‐negative patients, while no significant differences were observed regarding sex, eosinophil counts, or total IgE levels. Most Demodex‐positive patients reported persistent facial erythema and pruritus, often accompanied by ocular symptoms. Although a causal relationship cannot be established due to the retrospective design, these findings suggest that Demodex infestation may coexist with persistent head‐and‐neck symptoms in AD patients receiving dupilumab. Evaluation for Demodex infestation may be considered clinically relevant in patients presenting with atypical or treatment‐resistant facial involvement during dupilumab therapy.