A Novel IL6ST Variant in an Adolescent with Recurrent Abscesses and Eczema Treated with Dupilumab

We present the case of a 17-year-old male with a long-standing history of recurrent and persistent cutaneous abscesses beginning at 6 years of age. Lesions were widespread, affecting the scalp, trunk, buttocks, and extremities, and characterized by painful, indurated nodules that drained purulent fluid spontaneously and resolved over 5–10 days, often with pruritus and residual scarring. He denied fevers or other systemic symptoms. Multiple antibiotic courses provided no sustained improvement. A punch biopsy at age 14 years demonstrated a suppurative granulomatous infiltrate. Bacterial cultures grew Staphylococcus aureus on two occasions, while fungal and Acid-Fast Bacillus (AFB) cultures remained negative. Partial clinical improvement on rifampin and azithromycin raised suspicion for an atypical acid-fast bacillary infection and potential underlying immunodeficiency; however, repeat cultures for nontuberculous mycobacteria were persistently negative, and the diagnosis was not confirmed.Past medical history was also notable only for several otitis media episodes as a child. There was no history of pneumonia, fractures, dysmorphic features, delayed dentition, joint hypermobility, candida infections, or childhood eczema. Family history included severe acne and recurrent boils in the father, atopic disease in the mother, and two healthy siblings.Immunologic evaluation revealed normal lymphocyte subsets, intact mitogen and antigen proliferation responses, normal neutrophil oxidative burst, and normal quantitative immunoglobulins. He had adequate vaccine responses to protein and polysaccharide antigens. IgE was markedly elevated at 6,757 IU/mL with mild eosinophilia.A comprehensive primary immunodeficiency genetic panel identified a variant of uncertain significance in IL6ST at c.1405G>C (p.Asp469His), a gene associated with autosomal-dominant and autosomal recessive Hyper-IgE syndrome. This missense variant is absent from population databases and has not been previously reported in individuals with IL6ST-related disease. It is population frequency on gnomAD (v4.1.0) is 0.0000006199, Combined Annotation Dependent Depletion (CADD) score of 25.9, and a PolyPhen score of 0.940 (which categorizes it as probably damaging).He subsequently developed atopic dermatitis involving the scalp and flexural regions of his extremities. Although never used in patients with IL6ST, dupilumab was initiated in light of emerging evidence that it can lead to marked improvement in cutaneous and systemic symptoms in select Hyper-IgE phenotypes. His clinical response is being closely monitored.