Paradoxical Psoriasis: The Flip Side of TNF-α Inhibitors

Background: Tumor necrosis factor-alpha (TNF-α) inhibitors have revolutionized the management of chronic autoimmune diseases, including inflammatory bowel disease, rheumatoid arthritis, psoriasis, and psoriatic arthritis. Despite their efficacy, these agents have paradoxically been associated with the induction or exacerbation of psoriatic lesions, a phenomenon increasingly reported in the literature. Objective: This study aimed to describe the epidemiological and clinical characteristics of paradoxical psoriasis induced by anti-TNF-α therapy, analyze the therapeutic approaches employed, and assess patient outcomes. Methods: We conducted a retrospective analysis of 10 cases of paradoxical psoriasis reported to the National Center of Pharmacovigilance, Chalbi Belkahia (Tunis, Tunisia), between June 2018 and June 2023. Cases were selected from a database linked to VigiBase® and analyzed using the French method of causality assessment. Only cases in which anti-TNF-α agents were strongly suspected of inducing or exacerbating psoriasis were included. Results: The study included 10 patients (7 women, 3 men) with a mean age of 42.8 years. Eight patients had no history of psoriasis before starting anti-TNF-α therapy. Psoriatic lesions appeared, on average, 25.6 months (range: 2 months–6 years) after treatment initiation. Common clinical presentations included plaque psoriasis (4 patients) and pustular psoriasis (4 patients), while guttate and inverse forms were less frequent. The most frequent underlying conditions were ankylosing spondylitis (n = 3), rheumatoid arthritis (n = 3), psoriatic arthritis (n = 2), and Crohn’s disease (n = 2). Management strategies varied: anti-TNF-α therapy was discontinued in 8 patients, leading to remission in 7. Four patients were switched to another anti-TNF-α agent, and none experienced recurrence. Conclusion: Paradoxical psoriasis represents a significant adverse effect of anti-TNF-α therapy, with variable clinical presentations and management outcomes. Although switching to another anti–TNF-α agent may represent a viable therapeutic option, careful monitoring and individualized treatment strategies remain essential to achieving optimal outcomes. Further studies are needed to clarify underlying mechanisms and identify potential risk factors for this paradoxical reaction.