Ustekinumab-associated morphoea: systematic review of the literature and a real-world case
Abstract
Ustekinumab, an IL-12/IL-23 inhibitor with an established safety profile, has recently been associated with paradoxical cutaneous immune reactions. Amongst these, morphoea developing during therapy represents a rare but mechanistically relevant phenomenon that highlights cytokine imbalance in skin homeostasis. We performed a systematic review of published cases of morphoea occurring in patients treated with ustekinumab to better define their clinical and therapeutic patterns, and coupled it to the description of a new case of morphoea in a patient receiving ustekinumab for Behçet disease. A search of PubMed, Web of Science and SciELO through October 2025 identified six eligible reports. Patients (median age 55.5 years) received ustekinumab for psoriasis, psoriatic arthritis or inflammatory bowel disease. Morphoea developed after 6–64 months of treatment and presented exclusively as plaque-type lesions with one showing overlap with lichen sclerosus. Discontinuation of ustekinumab led to improvement or remission in most patients, whilst continued therapy was associated with progression in one case. The temporal pattern, morphology and response to withdrawal support a drug-related effect, potentially reflecting a shift from a T helper 1 (TH1)/TH17 pathway towards profibrotic TH2 and TGFβ pathways. Interpretation is limited by the very small number of published cases, heterogeneity of clinical descriptions, and lack of standardized diagnostic or therapeutic criteria, restricting firm causal inference. Despite these limitations, awareness of this paradoxical reaction is important for timely recognition and management. Further mechanistic investigation and pharmacovigilance are needed.
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