Still's disease and malignancies: insights into the balance between inflammatory enhancement and immune control. Data from the International AIDA Network Still's Disease Registry

Still's disease is an autoinflammatory condition marked by excessive activation of the innate immune system, resulting in intense and persistent systemic inflammation if left untreated. Chronic inflammation is recognized as both an initiator and promoter of carcinogenesis, although growing evidence suggests it may act against cancer development. Therefore, this study aimed to evaluate the cancer risk in patients with Still's disease. Data were obtained from the international Autoinflammatory Diseases Alliance (AIDA) Network registry for Still's disease. Statistical analysis included a machine learning-based approach to evaluate associations between independent variables and malignancy. A total of 626 patients with Still's disease were included, of whom 14 (2.2%) developed 15 malignant neoplasms. Patients with malignancy history exhibited higher age at disease onset and diagnosis, as well as longer duration of fever during flares. Machine learning-based analysis, including Elastic Net and Firth's penalized likelihood logistic regression, identified an association between cancer development and fever duration (relative risk = 1.002, 95% confidence interval 1.000-1.004, p = 0.01). Despite being a severe systemic inflammatory condition, Still's disease appears to be associated with a relatively modest prevalence of cancer. However, uncontrolled systemic inflammation, as reflected by prolonged fever duration, may contribute to carcinogenesis in these patients.