Targeted Therapy, Untargeted Rash: Insights From a GRAPPA Workshop on Immune Shifts in Psoriatic Disease

The increasing use of targeted immunomodulatory therapies for psoriasis and atopic dermatitis has transformed disease management. However, paradoxical and treatment-induced cutaneous adverse and musculoskeletal events are being increasingly recognized that often mimic or deviate from the primary disease phenotype. This review summarizes current evidence on the clinical manifestations, underlying pathophysiological mechanisms, and therapeutic strategies for biologic-induced cutaneous and articular reactions in immune-mediated dermatoses. We highlight reactions associated with tumor necrosis factor, interleukin (IL)-17, IL-23, and IL-4/IL-13 inhibitors, discussing diagnostic challenges and immunologic shifts underlying these phenomena. Recognition of these distinct entities is critical to avoid misinterpretation as treatment failure and to optimize patient care through tailored management strategies and shared decision making.