BACKGROUND: Select patients are diagnosed with both, psoriasis (PSO) and hidradenitis suppurativa (HS), leading to a unique disease pattern. Genetic risk factors remain unidentified. METHODS: The study harnessed an international collection of patients with psoriasis and HS (PSO-SH). Clinical and genetic data was collected and analyzed. RESULTS: 87 PSO-SH patients (70% female) were identified. They had a high number of comorbidities (89%), and worse general physical health compared to PSO-only (OR 3.09 95%CI 1.56-6.12) or HS-only (OR 2.5, 95%CI 1.23-5.00) patients. PSO-SH patients were at significantly higher risk of having Crohn's disease (OR 4.6-11.9
95% CI). Data revealed the highest overall genetic risk score for PSO-SH patients (PSO-PRS
108.22), followed by PSO (101.18), HS (99.84), and healthy controls (98.58). High non-HLA scores were associated with an increased risk for developing both psoriasis and HS, indicating a distinct biological profile compared to HS-only and PSO-only individuals. LIMITATIONS: Some clinical information was collected retrospectively. CONCLUSIONS: This study highlights a shared genetic susceptibility of HS and psoriasis at non-HLA loci. Recognizing PSO-SH patients as a distinct patient group with high morbidity and increased risk for developing Crohn's disease will help to improve patient management.