A distinct psoriasis-atopic dermatitis overlapping phenotype in adults with dual type 2 and type 3 immune features and favorable response to Janus kinase 1 inhibition.

Abstract

Patients exhibiting overlapping histopathologic features of psoriasis (Pso) and atopic dermatitis (AD) present a diagnostic and therapeutic challenge. To delineate the clinicopathological and immunologic portrait of psoriasis-atopic dermatitis overlapping (Pso-Ec) for integrated diagnosis and therapeutic decision-making. We conducted a 2-center prospective study comparing 30 Pso-Ec patients with typical Pso and AD cohorts. Clinicopathological characteristics and immunologic profiling of lesional skin and peripheral blood were analyzed, and treatment courses were assessed. Pso-Ec patients (aged 13-72 years; mean age: 49.7 years) presented with ill-defined erythematous plaques with thin scales, excoriation, intense itching, and mixed psoriatic-eczematous histology. Immune profiling showed co-existence of helper T cell 2/cytotoxic T cell 2 and helper T cell 17/cytotoxic T cell 17 in skin and blood, with Janus kinase (JAK) 1 signal transducer and activator of transcription 2/6 signaling involvement. Responses to prior Pso-targeted (n = 18) and AD-targeted (n = 15) biologics were often inadequate. In contrast, JAK1 inhibitors achieved minimal disease activity (body surface area ≤ 2, numerical rating scale ≤1) during a median follow-up of 17 months. No progression to classic Pso or AD phenotypes was observed. Sample size was limited and immunologic analyses were performed in a representative subset of patients. Pso-Ec represents a distinct, predominantly adult-onset phenotype driven by dual type 2 and type 3 inflammation, and JAK1 inhibitors appear as an effective option.