Use of Dupilumab in HyperIgE syndrome with ERBIN-deficiency: case report

Abstract

HyperIgE Syndromes (HIES) are rare primary immunodeficiencies characterized by recurrent infections and Th2 clinical signature (elevated IgE, eosinophilia, asthma, and atopic dermatitis). The major genetic alterations concern loss of function mutations of the STAT3/ERBIN/SMAD2/3 complex. Patients with ERBIN-deficiency have a higher number of Treg and greater IL-4Rα expression on naïve lymphocytes, due to increased activation of the TGF-ß pathway. Dupilumab is an anti-IL-4Rα monoclonal antibody that inhibits IL-4 and IL-13 signalling and the expression of type 2 cytokines. We here discuss a case of Dupilumab treatment in a ERBB2IP mutated patient. At our Rare Diseases referral Centre, we have been following a 20-year-old patient with severe atopic dermatitis, history of recurrent sinopulmonary infections, asthma and IgE level of 8818kU/L. On physical examination, the patient presented diffuse eczema with areas of lichenization, Eczema Area and Severity Index 29, Numeric Rating Scale of itch 9/10, Dermatology Life Quality Index 28/30, saddle nose, prognathism and severe left-convex scoliosis with NIH-HIES score equal to 37. CD4T lymphocytes were mainly Th2 (52%); Th17 were 13%, with normal IgG, IgA and IgM levels. The NGS genetic study found the following mutation of ERBB2IP, which encodes for ERBIN protein, likely pathogenic for HIES, together with a TMC8 and a CASP10 variant, all in heterozygosis. Given the underlying immunodeficiency and the non-response to topical and systemic corticosteroids, therapy with cyclosporine was not considered. Dupilumab was instead started with an induction dose of 600 mg and maintenance of 300 mg every 15 days. At last follow-up (14 months after dupilumab initiation) the patient presents: subjective well-being, skin free from manifestations, EASI score 0, NRS 0/10, DLQI 0/30, normal lung function with optimal control of asthma, IgE still>5000 kU/L. Of note, no more infectious episodes were reported. In our patient, given the anamnestic context of immunodeficiency, the use of target therapy on IL-4/IL-13R signalling proved to be particularly effective and safe in the treatment of skin manifestations related to the loss of function mutation of the ERBIN gene, known for the functional relationship with STAT3 in the regulation of IL-4Rα expression on naïve lymphocytes and of the Th2 response.