Immunopathogenetic basis of paradoxical cutaneous reactions during treatment with TNF-α inhibitors
https://doi.org/10.33667/2078-5631-2026-3-8-13
Abstract
Long-term therapy with tumor necrosis factor-alpha (TNF-α) inhibitors – a cornerstone in the treatment of severe immune-mediated inflammatory diseases – can induce paradoxical reactions (PR): the de novo onset or exacerbation of immune-mediated dermatoses that are pathogenetically related to the conditions for which the drug was prescribed. The pathogenesis of PR arises from a disruption of systemic immune homeostasis following blockade of TNF-α, a pleiotropic cytokine with diverse regulatory functions. This leads to cytokine imbalance, a shift in the dominant T-helper immune response, and hyperactivation of alternative pro-inflammatory pathways. Clinically, PR are highly heterogeneous, encompassing psoriasiform, eczematous, lichenoid, and granulomatous reactions, as well as paradoxical neutrophilic dermatoses – each characterized by distinct epidemiological and clinicomorphological features. The development of PR is determined by the interplay between pharmacological intervention and the patient’s individual genetic background. The study of PR is of considerable interest not only in the context of pharmacovigilance but also as a unique in vivo model for investigating human immune homeostasis, illustrating the high degree of compensatory capacity and nonlinearity inherent in cytokine networks.
Purpose of the review: to systematize current understanding of the pathogenesis of paradoxical reactions (PR) occurring during genetically engineered biological therapy with tumor necrosis factor-alpha (TNF-α) inhibitors.
About the Authors
D. B. Churkina
Central State Medical Academy of the Administrative Department of the President of the Russian Federation
Russian Federation
Russian Federation
Churkina Daria B., postgraduate student at Det of Dermatovenereology and Cosmetology
Moscow
E. A. Shatokhina
Central State Medical Academy of the Administrative Department of the President of the Russian Federation ; Research and Educational Institute of Lomonosov Moscow State University
Russian Federation
Russian Federation
Shatokhina Evgeniya A., Dr Med Sci (habil.), professor at Dept of Dermatovenereology and Cosmetology, leading researcher at Dept of Internal Medicine
Moscow
A. V. Kagramanova
A.S. Loginov Moscow Clinical Scientific and Practical Center of the Moscow Department of Healthcare ; Research Institute for Healthcare Organization and Medical Management of the Moscow Department of Healthcare
Russian Federation
Russian Federation
Kagramanova Anna V., Dr Med Sci (habil.), senior researcher at Dept of Inflammatory Bowel Diseases, leading specialist at Dept of Proctology
Moscow
L. S. Kruglova
Central State Medical Academy of the Administrative Department of the President of the Russian Federation
Russian Federation
Russian Federation
Kruglova Larisa S., Dr Med Sci (habil.), professor, head of Dept of Dermatovenereology and Cosmetology
Moscow
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For citations:
Churkina D.B., Shatokhina E.A., Kagramanova A.V., Kruglova L.S. Immunopathogenetic basis of paradoxical cutaneous reactions during treatment with TNF-α inhibitors. Medical alphabet. 2026;(3):8-13. (In Russ.) https://doi.org/10.33667/2078-5631-2026-3-8-13
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