Metabolomic and Lipidomic Alterations in Patients with Atopic Dermatitis with Dupilumab-Associated Ocular Surface Disease

Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic pruritic eczema with an estimated prevalence of 10% in adults and 50% of them suffering from moderate-to-severe manifestations. Dupilumab, an IL-4/IL-13 inhibitor, is approved for treating moderate-to-severe AD. However, dupilumab-associated ocular surface disease (DAOSD) emerges in up to 60% of dupilumab-treated patients, constituting a major AD-specific adverse event. DAOSD pathogenesis has not been fully understood yet. To elucidate the metabolic changes occurring after dupilumab treatment in patients with AD, we focused in this prospective single-center cohort study particularly on patients who developed DAOSD. In total, 20 patients with AD underwent dupilumab therapy, with 6 developing DAOSD. Plasma and serum samples were collected at baseline, 4 and 16 weeks after treatment initiation, and during the conjunctivitis episode. In addition, 10 age- and sex-matched healthy controls were sampled solely at baseline. High-resolution mass spectrometry was employed for metabolomic and lipidomic analysis of all blood samples. Targeted metabolomics and lipidomic with multivariate analysis unveiled significant metabolic and lipidic disparities (such as increased activity of benzoic acid, tyrosine and indole metabolism, and others) between AD patients with and those without DAOSD. Metabolomics and lipidomic analysis further deepen our comprehension of DAOSD pathogenesis.