Fever is a cardinal but nonspecific feature of systemic inflammation. More than 200 disorders are characterized by uncontrolled systemic inflammation, making it challenging to manage individual patients. Disorders encompass different entities such as autoimmune diseases, autoinflammatory disorders, or hyperinflammatory conditions. Despite some clinical similarities, these disorders comprise distinct pathophysiology and management strategies.

Distinguishing these diseases from benign causes of fever is pivotal, as early diagnosis and treatment results in decreased morbidity, mortality and health care costs. In these disorders, targeted treatment with biologicals has expanded during the previous years. Nevertheless, multiple caveats persist, such as toxicity, strict reimbursement criteria, and expensive drug development. Consequently, it is crucial that biological treatment is directed to patients with best benefit and is monitored by relevant biomarkers. Currently, a specific and rapid test to stratify patients and monitor response is lacking. Notably, reimbursement criteria for biological therapy rely on clinical suspicion or a proven genetic diagnosis, but so far, discriminatory lab abnormalities are not implemented.

With the multi-centre Flemish Joint Effort for Biomarker pRofiling in Inflammatory Systemic diseases (FEBRIS), we will integrate cytokine profiles by multiplex immunoassay (MIA) into the diagnostic workup and management of pediatric and adult patients with inflammatory syndromes of unknown origins and/or with insufficient response to first line therapy. In parallel with recent literature, we characterized specific cytokine profiles differentiating different diseases, allowing to implement it as a generic test that copes with the wide variety of diseases in the target group. The validation of our assay in larger cohorts with proven or suspected inflammatory disorders will guide time-, resource- and cost-efficient workup and personalized management.