Mechanisms, biomarkers and targets for adult-onset Still’s disease

Abstract

Adult-onset Still’s disease (AoSD) is a rare but clinically well-known, polygenic, systemic autoinflammatory disease. Owing to its sporadic appearance in all adult age groups with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications, AoSD is an unsolved challenge for clinicians with limited therapeutic options. This Review provides a comprehensive insight into the complex and heterogeneous nature of AoSD, describing biomarkers of the disease and its progression and the cytokine signalling pathways that contribute to disease. The efficacy and safety of biologic therapeutic options are also discussed, and guidance for treatment decisions is provided. Improving the approach to AoSD in the future will require much closer cooperation between paediatric and adult rheumatologists to establish common diagnostic strategies, treatment targets and goals.

Abstract

Adult-onset Still’s disease (AoSD) is not easily diagnosed, and treatment options are limited. This Review provides an overview of the disease and its pathogenesis, clinical trial results, therapeutic options and a plan to diagnose and clinically manage these patients.

Key points

• Similar to systemic-onset juvenile idiopathic arthritis, adult-onset Still’s disease (AoSD) is a rare systemic autoinflammatory disease with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications.

• AoSD should be considered in patients with persistent fever, and the diagnosis is based on the combination of clinical and laboratory findings as well as the exclusion of other inflammatory conditions.

• Central to the pathogenesis of AoSD is the intense activation of innate immune cells and overproduction of several pro-inflammatory cytokines including IL-1, IL-6 and IL-18.

• Two IL-1 antagonists have been approved for treatment of AoSD, and growing evidence suggests that other biologic agents are therapeutic options, such as anti-IL-6 and anti-IL-18 therapeutics.

• As a reliable prediction of response and outcome is not possible, therapeutic decisions have to be made on the basis of clinical, biological or imaging characteristics of disease.

• A close cooperation between paediatric and adult rheumatologists is required to establish common diagnostic strategies, treatment targets and goals.