Paradoxical Psoriasis Induced by TNF Inhibitors and Beyond: A Review

Paradoxical psoriasis (PP) represents an uncommon but well-documented adverse effect that occurs following exposure to tumour necrosis factor-alpha (TNF-α) inhibitors. There is growing evidence that this reaction may not be class-specific, as the indications for biologic interventions (interleukin [IL]12/23, IL23, IL17, IL4/13) broaden in chronic inflammatory diseases. However, cumulative evidence amongst other classes remains limited to case reports. The pathogenesis of this reaction to TNF inhibitors has been postulated and experimentally supported as a switch toward interferon (IFN) production by antigen-presenting cells, however, the mechanism with other biologics remains elusive. The baseline association of classical psoriasis (non-drug induced) with the seronegative rheumatic and gastrointestinal inflammatory diseases treated by TNF inhibitors, initially made this reaction a challenge to define and study. As evidence has grown, PP has been defined as psoriatic lesions that arise de novo or as morphologically atypical exacerbations of pre-existing known psoriasis during TNF-α therapy. These lesions may persist and worsen unless treated, commonly requiring systemic therapeutic adjustments. This review explores the epidemiology, pathogenesis, clinical manifestations, and management of PP, with an emphasis on patient outcomes and recommendations based on primary data, systematic reviews, and contributions from key researchers in the field.