Inflammation-Mediated Dysregulation of Iron Homeostasis and Its Association with Anaemia Severity in Hidradenitis Suppurativa: A Cross- Sectional Study with Mediation Analysis

Abstract Objectives To examine the associations between C-reactive protein (CRP), hepcidin, and haemoglobin in adults with hidradenitis suppurativa (HS), and to formally test the hypothesis that hepcidin mediates the effect of inflammation on anaemia. Methods We performed a secondary cross-sectional analysis of a public dataset of 88 HS patients. Anaemia was defined using World Health Organization criteria. We used Spearman's correlation, multivariable regression, and formal mediation analysis with bootstrapping to assess the relationships between CRP, hepcidin, and haemoglobin. Results Anaemia was present in 58.0% of patients (n = 51). CRP was moderately correlated with hepcidin (ρ = 0.431, p < 0.001) and inversely with haemoglobin (ρ=−0.382, p < 0.001). Formal mediation analysis revealed a significant indirect effect of CRP on haemoglobin through hepcidin (β=−0.124; 95% Bootstrap CI: −0.197 to − 0.065), accounting for 66.8% of the total effect. In the multivariable model adjusted for hepcidin, the direct effect of CRP became non-significant (p = 0.24). Conclusions Our findings provide strong statistical evidence that the association between systemic inflammation and anaemia severity in HS is substantially mediated by hepcidin, supporting its role as a potential therapeutic target.