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

Sep 30, 2026

Patients with chronic inflammatory dermatoses, particularly psoriasis and atopic dermatitis, benefit from modern biological agents and small-molecule drugs, which markedly improve cutaneous lesions. Despite generally favorable safety, these therapies can trigger adverse effects that range from mild and off-therapy to clinically significant and decisive. This review explains, at the molecular level, common drug-related complications, detailing target pathways and mechanisms for TNFα, IL-17/23, IL-4/13, and JAK inhibitors, and links them to infections, paradoxical disease, ocular and musculoskeletal findings, and other systemic events.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Introduction

Psoriasis: clinical features and pathogenesis

Atopic dermatitis: barrier dysfunction and pathogenesis

Biological and small-molecular therapies

AnnAls of Medicine 2026, Vol. 58, no. 1, 2611461 [https://doi.org/10.1080/07853890.2025.261](https://doi.org/10.1080/07853890.2025.261)1461 REVIEW ARTICLE 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 Patrycja Lemiesz, Julia Nowowiejska-Purpurowicz and Iwona Flisiak department of dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland 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, andreactivation 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. Introduction ARTICLE HISTORY Received 28 October 2025 Accepted 28 December 2025 KEYWORDS Atopic dermatitis; psoriasis; dupilumab; upadacitinib; conjunctivitis; TNFα inhibitors; JAK inhibitor Psoriasis is a chronic, incurable, inflammatory skin disease that affects an average of 3% of the global population [1] . It is one of the most common reasons for appointments in the dermatological office. The pathogenesis of psoriasis is complex and still not fully elucidated; it encompasses genetic background, immunological disorders, and the influence of modulating environmental factors [2,3] . Currently, more than 60 chromosomal loci determining predisposition to the disease have been identified [2] . Psoriasis is also undoubtedly an autoimmune disease, which can be provoked and exacerbated by external factors, e.g. trauma, infection, stress, and drugs [1,2] . Clinically, the most common variant of psoriasis – plaque – is manifested by the presence of papules which merge forming exfoliative psoriatic plaques in upright locations of the extremities, lumbar and sacral regions, and in the intragluteal fold. The diagnosis is usually made based on the clinical picture [1,3] . Atopic dermatitis (AD) is also one of the most common chronic skin diseases. As with psoriasis, the pathogenesis of AD is complex and includes genetic background, immunological disorders, and modulating environmental factors [4] . The essence of AD is epidermal barrier dysfunction, resulting in water loss and subsequent severe dryness, which in turn leads to easier penetration of pathogens and allergens [4] . The clinical picture depends on the age of the patient; adults have erythematous and exfoliative lesions with lichenification on the flexor surfaces of the extremities, while in children the lesions are CONTACT Julia nowowiejska-Purpurowicz [julia.nowowiejska@umb.edu.pl](julia.nowowiejska@umb.edu.pl) department of dermatology and Venereology, Medical

FAQs

Which molecular targets do biological therapies use in psoriasis and atopic dermatitis?

In psoriasis, biologics predominantly target TNFα and IL-17/IL-23 pathways. In atopic dermatitis, therapy more commonly inhibits IL-4 and IL-13 signaling.

What adverse effects are associated with TNFα inhibitors and IL-17 inhibitors?

TNFα inhibitors are linked to higher infection susceptibility, paradoxical psoriasis, eczematoid lesions, and tuberculosis reactivation. IL-17 inhibitors may cause fungal infections and may possibly trigger inflammatory bowel disease.

How do JAK inhibitors relate to adverse events in both conditions?

JAK inhibitors may cause infections and acne, can be associated with dyslipidemia, and in selected cases may relate to cardiovascular events. They are effective small-molecule therapies for both psoriasis and atopic dermatitis, with a stronger emphasis in AD.

Sep 30, 2026

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