Increased IL-23 is Associated to Heliotrope Sign in Multivariate Model on Idiopathic Inflammatory Myopathies

Heliotrope rash is a pathognomonic feature of dermatomyositis (DM); however, the molecular pathways implicated in cutaneous involvement have not been fully explored. Although the IL-23/Th17 axis has been implicated in inflammatory and autoimmune diseases, the clinical significance of circulating IL-23 across the idiopathic inflammatory myopathy (IIM) spectrum, particularly in cutaneous disease expression, remains insufficiently defined. In this cross-sectional study, we aimed to quantify serum IL-23 levels in patients with IIM and evaluate their association with cutaneous involvement, including overall skin disease activity assessed by the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and the presence of specific skin manifestations, particularly pathognomonic lesions, using a univariate analysis. Serum IL-23 levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) in patients with IIM and healthy controls (HCs), and their relationships with clinical and cutaneous variables were analyzed using univariable and multivariable approaches. Higher IL-23 levels were associated with cutaneous involvement, especially with pathognomonic skin manifestations and, most notably, heliotrope sign. IL-23 also showed a positive correlation with CDASI activity; the relationship with heliotrope sign remained consistent. Applying a multivariate model, heliotrope rash remained the only independent factor associated with IL-23 levels: in other words, IL-23 increases by 437.3 pg/mL when heliotrope is present. These findings suggest that IL-23 may be preferentially associated with a cutaneous phenotype characterized by heliotrope rash, rather than with global skin burden alone.