Adult-onset Still's disease

Definition

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease of unknown cause. It is characterized by the classic triad of arthralgia or arthritis, daily (quotidian) fever spikes, and an evanescent salmon-colored rash. Systemic juvenile idiopathic arthritis is considered the same disease with onset in childhood (Still's disease continuum).

Classification

Yamaguchi criteria (at least 5 criteria, including at least 2 major criteria, after exclusion of infections, malignancies, and other rheumatic diseases):

• Major criteria: fever ≥ 39 °C for at least 1 week; arthralgia for at least 2 weeks; typical rash; leukocytosis ≥ 10,000/µL with at least 80 % granulocytes
• Minor criteria: sore throat; lymphadenopathy and/or splenomegaly; liver dysfunction; negative rheumatoid factor and negative ANA

The Fautrel criteria additionally include the fraction of glycosylated ferritin.

Occurrence & epidemiology

The annual incidence is about 0.16 per 100,000. Young adults between 17 and 35 years are typically affected. Unlike the systemic juvenile form, women are affected more often (about 70 %).

Aetiopathogenesis

The cause is unknown. Central is an overactivation of the innate immune system with increased production of proinflammatory cytokines, mainly interleukin-1β, interleukin-18, and interleukin-6. Gene expression patterns and genetic profiles resemble those of systemic juvenile idiopathic arthritis.

Clinical features

• Fever with daily spikes above 39 °C.
• Rash: evanescent, salmon-colored, maculopapular.
• Arthralgia or arthritis; myalgia.
• Sore throat, frequently as a prodromal symptom.
• Lymphadenopathy, splenomegaly, liver involvement, serositis.
• Macrophage activation syndrome (MAS) as the most dangerous complication.
• Adult-onset Still's disease accounts for 15–20 % of all cases of fever of unknown origin.

Diagnosis

• There is no confirmatory test; the diagnosis is clinical and a diagnosis of exclusion versus infections (especially sepsis and infectious mononucleosis), malignancies (especially malignant lymphoma), and other rheumatic diseases.
• Laboratory tests: leukocytosis with neutrophilia, markedly elevated ferritin, elevated inflammatory markers and liver enzymes; rheumatoid factor and ANA negative. A simplified approach in fever of unknown origin combines arthralgia, sore throat, neutrophilia, and ferritin ≥ 5 times normal.
• Biomarkers such as interleukin-18 reflect disease activity; very high ferritin may indicate MAS.

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Further reading (open access)

1. Mediterr J Rheumatol 2024: Systemic JIA and Adult-Onset Still's Disease as Part of the Still's Disease Continuum (PMC-Volltext)

Cross-references