What are the symptoms and treatment options for Adult Onset Still's Disease (AOSD)?

Adult-Onset Still's Disease: Clinical Manifestations

Adult-Onset Still's Disease (AOSD) presents with a classic triad of high-spiking fevers (>39°C), evanescent salmon-pink rash, and arthritis/arthralgia, occurring in over 95% of patients for fever and 64-100% for joint involvement. 1

Core Clinical Features

Fever Pattern

• High-spiking fevers exceeding 39°C that are transient, lasting typically under 4 hours 1
• Quotidian or double quotidian pattern with highest temperatures in late afternoon or early evening 1
• Fever heralds the onset of other manifestations including serositis, sore throat, myalgias, and arthralgias 1
• Overall incidence across major studies: 95.7% 1

Characteristic Rash

• Evanescent, salmon-pink, maculopapular eruption predominantly on proximal limbs and trunk 1
• Rare involvement of face and distal limbs 1
• Often accompanied by fever and can be mildly pruritic, frequently confused with drug allergy 1
• Koebner phenomenon has been described 1
• Incidence ranges from 51% to 87%, with average of 72.7% 1

Articular Manifestations

• Arthralgia and arthritis occur in 64-100% of patients 1
• Most frequently affected joints: knees (69-82%), wrists (67-73%), and ankles (38-55%) 1
• Carpal and pericapitate abnormalities are typically higher than in rheumatoid arthritis, offering diagnostic differentiation 1
• Wrist changes typically present 6 months after disease onset, with progressive joint space narrowing in pericapitate or carpometacarpal distribution 1
• Ankylosis develops after 1.5-3 years 1
• Pattern is typically symmetric polyarthritis with joint pain associated with fever spikes 1

Additional Systemic Manifestations

Pharyngeal and Muscular

• Sore throat: 35-92% of patients across major series 1
• Myalgia: 56-84% incidence, generalized and appearing with fever exacerbations 1
• Inflammatory myopathy is rare, though muscle enzyme elevation has been reported 1

Lymphoreticular System

• Lymphadenopathy: 32-74% of patients 1
• Splenomegaly: 14-65% of patients 1

Serositis

• Pleuritis: 12-53% of patients 1
• Pericarditis: 10-37% of patients 1

Hepatic Involvement

• Hepatomegaly and liver biochemistry abnormalities present in approximately 50-75% of patients 1
• AOSD can present as pseudo-angiocholitis 1
• Jaundice and acute hepatitis leading to hepatic failure remain exceedingly rare 1

Laboratory Abnormalities

Inflammatory Markers

• ESR elevated in virtually all patients in major series 1
• CRP typically raised 1

Hematologic Abnormalities

• Leucocytosis with striking neutrophilia: 50% of patients have counts >15×10⁹ cells/L, 37% have WBC >20×10⁹ 1
• Anaemia of chronic disease seen with active disease, often normalizes with remission 1
• Reactive thrombocytosis is common 1
• Pancytopenia should alert to haemophagocytic syndrome, which requires prompt immunosuppressive treatment 1

Ferritin

• Very high ferritin levels ranging from 4,000-30,000 ng/mL are common, with extreme levels up to 250,000 ng/mL reported 1
• Serum ferritin correlates with disease activity and often normalizes with remission 1

Disease Patterns

AOSD follows three distinct clinical patterns, each affecting approximately one-third of patients 2:

• Self-limited/monocyclic: Systemic symptoms with remission within 1 year (median 9 months) 2
• Intermittent/polycyclic: Recurrent flares with complete remission between episodes 2
• Chronic articular: Dominated by joint manifestations that can lead to severe joint destruction 2

Critical Complications

Macrophage Activation Syndrome (MAS)

• Most life-threatening complication with high mortality rate 3
• Reported in up to 23% of AOSD patients 3
• Requires high-dose glucocorticoids and high-dose anakinra (>4 mg/kg/day in children or 100 mg twice daily in adults) 2
• Cyclosporine A and/or IFN-γ inhibitors may be considered 2

Coagulation Abnormalities

• Rare but include prolongations of PTT or PT 1
• Disseminated intravascular coagulation has been described and can be fatal 1
• Risk factors include severe disease activity, liver abnormalities, and particular drugs (salicylates, NSAIDs, some DMARDs) 4

Diagnostic Considerations

• AOSD is a diagnosis of exclusion requiring elimination of infectious, neoplastic, and other autoimmune diseases 5
• Yamaguchi criteria are most widely used, though Fautrel criteria offer benefit of adding ferritin and glycosylated ferritin values 6
• AOSD is responsible for a significant proportion of fever of unknown origin cases 5
• Differential diagnosis must exclude malignant hematological disorders, especially when lymphadenopathy, splenomegaly, fever, and leukocytosis dominate 4