The molecular mechanism of the adverse effects of the biological and small molecular drugs in the therapy of inflammatory skin diseases – psoriasis and atopic dermatitis

TL;DR

This review explains the molecular reasons behind side effects of drugs used to treat psoriasis and atopic dermatitis.

Contribution

The paper provides a comprehensive summary of the molecular mechanisms underlying adverse effects of biologics and small molecule drugs in inflammatory skin diseases.

Findings

TNFα inhibitors increase infection risk and may cause paradoxical psoriasis.

IL-17 inhibitors are linked to fungal infections and inflammatory bowel disease.

JAK inhibitors can lead to infections, acne, and cardiovascular events.

Abstract

Patients with the most common chronic inflammatory dermatoses, namely psoriasis and atopic dermatitis, gained access to state-of-the-art therapeutic options providing spectacular improvement of skin lesions. Although generally safe, biological agents and small molecular drugs have also side effects which may be mild and irrelevant to the therapy course, but sometimes, of a greater extent and influencing further therapeutic decisions. In this review, we summarize the molecular explanation for the most common adverse effects of drugs used in the treatment of psoriasis and atopic dermatitis. Biologics used in psoriasis predominantly target TNFα, IL-17, 23, while in AD inhibit IL-4,13,31. Janus kinase (JAK) inhibitors represent small-molecule therapies effective in both conditions, although more prominently in AD. TNFα inhibitors are associated with increased susceptibility to infections, paradoxical psoriasis, eczematoid lesions, and reactivation of tuberculosis. IL-17 inhibitors may cause fungal infections and possibly trigger inflammatory bowel disease. IL-4/13 blockade in AD treatment has been linked to eosinophilia, conjunctivitis, arthritis, and facial erythema, likely due to a shift toward IL-17-driven inflammation. JAK inhibitors may cause infections, acne, dyslipidemia, and, in selected cases, cardiovascular events. This review emphasizes the importance of understanding the pathogenetic background of drug-related complications to introduce appropriate clinical management and patient selection.

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