Adult-Onset Still’s Disease

Adult-onset Still’s disease (AoSD) is a rare but clinically well-known, polygenic, systemic autoinflammatory disease. It is typically characterized by four main (cardinal) symptoms: spiking fever ≥39 °C, arthralgia or arthritis, skin rash, and hyperleukocytosis (≥10,000 cells/mm(3)). However, many other clinical features are possible, and it can appear in all age groups with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications. Hence, it remains a diagnostic challenge, and the clinician should first rule out infectious, tumoral, or inflammatory differential diagnoses. Determination of the total and glycosylated ferritin levels, although not pathognomonic, can help in diagnosis. New biomarkers have recently been described, but they need to be validated. The disease evolution of AoSD can be monocyclic, polycyclic, or chronic. In chronic disease, a joint involvement is often predominant, and erosions are noted in one-third of patients. Many progresses have been made in the understanding of the pathogenesis over the last decades. This chapter provides a comprehensive insight into the complex and heterogeneous nature of AoSD describing the identified cytokine signaling pathways and biomarkers. It also discusses the current evidence for the usage of biologics in AoSD to provide guidance for treatment decisions, taking into account both the efficacy and the safety of the different therapeutic options.