Treatment-associated phenotype switching between psoriasis and atopic dermatitis

Psoriasis and atopic dermatitis (AD) are traditionally viewed as distinct inflammatory skin diseases driven by type 17 and type 2 immune pathways, respectively. Increasing use of targeted therapies has revealed a treatment-associated phenotype switch between these conditions, the so-called 'flip-flop' phenomenon, characterized by sustained emergence of eczematous features in patients treated for psoriasis or psoriasiform disease in those treated for AD. Robust real-world data on this entity remain limited.

To characterize treatment-associated phenotype switching between psoriasis and AD in a large real-world cohort, focusing on clinical features, implicated therapies, management strategies and outcomes.

We conducted a retrospective, multicentre, multinational observational study across 17 dermatology centres in six countries. Patients with psoriasis or AD who developed a clinician-defined, persistent phenotype switch temporally associated with systemic or biologic therapy and requiring treatment modification were included. Demographic, clinical, therapeutic and outcome data were collected and analysed descriptively.

A total of 148 patients were included: 101 (68.2%) developed eczematous features while treated for psoriasis (PsO → eczematous), and 47 (31.8%) developed psoriasiform disease while treated for AD (AD → psoriasiform). PsO → eczematous patients were older and had more cardiometabolic comorbidities, whereas atopic comorbidities were more frequent in the AD → psoriasiform group. PsO → eczematous switches occurred mainly under interleukin (IL)-17 and IL-23 inhibitors, while AD → psoriasiform switches occurred exclusively during biologic therapies targeting type 2 inflammation, predominantly dupilumab. Treatment was modified in all patients. Janus kinase (JAK) inhibitors were the most frequently used strategy in both switch directions, particularly in PsO → eczematous cases. Marked clinical improvement was observed across phenotypes following therapeutic adjustment.

Treatment-associated phenotype switching between psoriasis and AD is a reproducible, bidirectional and clinically relevant real-world phenomenon reflecting immune plasticity rather than paradoxical disease induction. Recognition of this entity is essential to guide appropriate therapeutic adaptation, with JAK inhibitors emerging as a commonly effective management option.