Targeting IL-17 in fibrosing skin disease: a review of evidence in systemic sclerosis & morphea

Systemic sclerosis (SSc) and morphea are fibrosing skin conditions with limited treatment options and often unpredictable responses. Interleukin-17 (IL-17), a pro-inflammatory cytokine, has emerged as a potential target given its complex role in fibrosis. Early studies of brodalumab have suggested potential improvement in SSc skin scores, though results remain preliminary and unpublished. Secukinumab has shown benefit in several case reports involving morphea and stiff skin syndrome. However, concerns remain about long-term safety, including cardiovascular risks and rare cases of drug-induced scleroderma-like illness. In this narrative review, we summarize the current clinical and translational literature on IL-17 blockade in fibrosing skin disease, including two phase II trials and five case reports published between 2019 and 2024. Across these studies, IL-17 inhibitors were associated with improvements in skin thickening, disease activity, and quality-of-life scores in select patients. We also explore the immunologic rationale for IL-17 inhibition and its interplay with TGF-β and fibroblast activation. While current data remain limited, IL-17 blockade shows early promise as a targeted therapy for fibrosing skin disease. Further investigation is needed to clarify patient selection criteria, validate long-term efficacy, and ensure safety. As our understanding of immune-mediated fibrosis deepens, IL-17 inhibitors may offer a novel therapeutic approach for patients with refractory or progressive skin fibrosis.