Supplementary Material for: Bridging the Gap: Characterizing Complex Immune-Mediated Inflammatory Diseases with Cutaneous Manifestations

Background: The coexistence of multiple immune-mediated inflammatory diseases (IMIDs) in a single patient represents a growing clinical challenge, yet comprehensive data on patients with more than two IMIDs remain limited.
Objective: To characterize the clinical profiles, therapeutic responses, and quality of life outcomes in patients presenting with complex IMID associations involving cutaneous manifestations.
Methods: We established the CIMID-Skin registry, a prospective observational study enrolling adult patients with multiple IMIDs including at least one dermatological condition. Patients were stratified into control (2 IMIDs) and complex (≥3 IMIDs) groups. Clinical data validated severity scores, and patient-reported outcomes were systematically collected.
Results: The cohort (n=54) was predominantly female (77.8%), with a mean age of 45.4 years and overweight range BMI (27.4 kg/m²). Patients frequently presented with multiple IMIDs, with 59.3% having ≥3 conditions. The most common diseases were psoriasis and hidradenitis suppurativa (42.6% each) and psoriatic arthritis (40.7%). Paradoxical reactions were observed in a significant proportion of patients, with paradoxical psoriasis reported in 24.1% of the cohort. Quality of life was markedly impaired, with 65.2% showing moderate-to-extreme DLQI impact, and 24.1% reaching the WHO-5 depression threshold.
Conclusions: Patients with complex IMID associations demonstrate distinct clinical patterns and therapeutic challenges. The high prevalence of paradoxical reactions and the specific clustering of certain IMIDs suggest shared pathophysiological mechanisms that warrant further investigation.