What is the definition of Adult-Onset Still's Disease (AOSD)?

From the Guidelines

Adult-onset Still's disease (AOSD) is a rare inflammatory disorder characterized by high spiking fevers, salmon-pink rash, joint pain, and elevated inflammatory markers, diagnosed through a combination of clinical symptoms and laboratory findings, with key features including daily fevers exceeding 39°C, arthritis or joint pain, and highly elevated acute phase reactants, such as CRP, ferritin, and neutrophil count 1.

Key Features of AOSD

• High spiking fevers, typically exceeding 39°C, lasting for at least 7 days 1
• Transient salmon-pink rash, often coinciding with fever spikes, preferentially involving the trunk 1
• Musculoskeletal involvement, usually present with arthralgia or myalgia, with overt arthritis being supportive but not necessary for diagnosis 1
• Highly elevated acute phase reactants, such as CRP, ferritin, and neutrophil count 1

Diagnosis and Management

• Diagnosis is based on operational definitions, including fever, rash, musculoskeletal involvement, and high levels of inflammation 1
• Treatment usually begins with NSAIDs for mild cases, but most patients require corticosteroids like prednisone 1
• For steroid-resistant cases or to reduce steroid dependency, disease-modifying antirheumatic drugs (DMARDs) like methotrexate may be used 1
• Biologic agents targeting IL-1 (anakinra, canakinumab) or IL-6 (tocilizumab) have shown effectiveness for refractory cases 1

Disease Course and Prognosis

• The disease course varies, with some patients experiencing a single episode while others develop chronic arthritis or recurrent flares requiring long-term management 1
• Patients who have the chronic articular disease pattern often present with joint erosions, and may require total hip replacement in severe cases 1

From the Research

Definition of Adult Still's Disease

• Adult-onset Still's disease (AOSD) is a rare systemic inflammatory condition characterized by a clinical triad of high spiking fever, arthralgia (± arthritis), and evanescent skin rash 2.
• AOSD is a multisystemic complex disorder clinically characterized by episodes of spiking fever, evanescent rash, polyarthritis or diffuse arthralgias; multiorgan involvement may develop according to the hyper-inflammatory extent 3.
• The disease is at the crossroad of auto-inflammatory syndromes and autoimmune diseases, with pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-18, and IFN-γ playing a major role in its pathogenesis 4.

Clinical Manifestations

• The clinical presentation of AOSD is highly variable, accompanied by a broad spectrum of disease manifestations 2.
• AOSD patients may experience various life-threatening complications, such as macrophage activation syndrome, which is reported in as high as 23% of AOSD patients and is considered the most severe complication with a high mortality rate 2.
• The disease course can be classified into two distinct categories: "systemic" and "articular" 2.

Diagnosis

• The diagnosis of AOSD is difficult due to the ambiguity in presentation and the lack of serologic markers, often leading to a delay in diagnosis 2.
• The Yamaguchi and Fautrel criteria are the most widely used diagnostic tools in clinical practice 2.
• A clinical diagnosis of AOSD is generally reached by exclusion while investigating a patient with fever of unknown origin 2.

Treatment

• The current treatment paradigm for AOSD includes non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids initially, conventional synthetic disease-modifying anti-rheumatic drugs in steroid-refractory patients, and biologics in those resistant to conventional treatment 2.
• Biologic agents such as IL-1 and IL-6 blockers have been shown to be effective in treating systemic and articular inflammation of AOSD patients 5, 3.
• Canakinumab is the only FDA-approved biologic for the treatment of AOSD 2.