Jérémy Di Domizio, Antoine Girardin, Curdin Conrad, Teofila Seremet, M. Gilliet
Recent advances in immunology and transcriptomics have transformed dermatology, redefining inflammatory skin diseases as distinct molecular entities characterized by dominant immune pathways such as Th17, Th2, Th1, type I interferon (IFN) and myeloid modules. We transcriptionally delineated these immune modules, constructed a reference immune cartography to map patient skin biopsies and developed a digital platform that enables clinicians to analyse individual molecular profiles, facilitating precise diagnosis for clinically overlapping or diagnostically ambiguous dermatoses. Beyond diagnostic utility, this platform supports therapeutic decision-making by aligning each patient's dominant immune module with the most appropriate targeted treatment. Analyses of treatment failures reveal that discordance between therapy and immune module dominance, as well as immune shifts between modules, account for most cases of non-response. Realigning therapy with the patient's molecular profile restores efficacy and enables rational adaptation or repurposing of existing agents. By integrating molecular diagnostics with immune module-guided therapy, this approach establishes a precision medicine framework that optimizes outcomes and advances personalized care for patients with inflammatory skin disease.