Adult-Onset Still's Disease (AOSD)

Overview

Characteristic Fever Pattern

• Quotidian (daily) spiking fever - temperature rises to ≥39°C (102.2°F), typically once or twice daily, most characteristically in the late afternoon or early evening
• The fever spike is typically abrupt in onset and short-lived - it rises rapidly and then returns to normal or near-normal within hours
• This is called a "quotidian" or "double quotidian" pattern (one or two spikes per day)
• The salmon-pink rash classically accompanies the fever spike - appearing at the time of peak temperature and fading as the fever resolves
• The fever may be the only initial manifestation, making early diagnosis challenging

Clinical Features

Systemic Features

The Classic Rash

• Salmon-colored, macular or slightly papular (maculopapular)
• Evanescent - appears with fever spikes (late afternoon) and disappears as fever resolves
• Located on chest, abdomen, and extensor surfaces of arms
• Usually non-pruritic
• May show Koebner phenomenon
• Lesions are discrete, 5-10 mm pink-to-red macules or slightly edematous papules
• The rash and fever spike are temporally linked - this is pathognomonic

Laboratory Findings

The combination of very high ferritin + glycosylated ferritin ≤20% is a hallmark finding. In healthy individuals 50-80% of ferritin is glycosylated; in AOSD this drops below 20%.

Diagnostic Criteria

1. Yamaguchi Criteria (1992) - Most Widely Used

Major Criteria

1. Fever ≥39°C (102.2°F) lasting 1 week or more
2. Arthralgia lasting 2 weeks or more
3. Typical skin rash (maculopapular, non-pruritic, salmon-pink rash with concomitant fever spikes)
4. Leukocytosis ≥10,000/mm³ with polymorphonuclear count ≥80%

Minor Criteria

1. Pharyngitis or sore throat
2. Lymphadenopathy and/or splenomegaly
3. Liver enzyme abnormalities (aminotransferases)
4. Negative rheumatoid factor AND negative antinuclear antibodies

Exclusion Criteria

• Absence of infection (especially sepsis, EBV infection)
• Absence of malignancy (especially lymphoma)
• Absence of inflammatory disease (especially polyarteritis nodosa)

2. Fautrel Criteria (2002) - Alternative

Major Criteria

1. Spiking fever ≥39°C (102.2°F)
2. Arthralgia
3. Transient erythema
4. Pharyngitis
5. Polymorphonuclear count ≥80%
6. Glycosylated ferritin fraction ≤20% (specific to Fautrel)

Minor Criteria

1. Typical rash
2. Leukocytosis ≥10,000/mm³

Key difference: Fautrel criteria include glycosylated ferritin as a major criterion and do not require exclusion criteria, making them somewhat easier to apply. Glycosylated ferritin ≤20% is highly specific for AOSD.

Disease Course

1. Monocyclic - single episode with complete remission (best prognosis)
2. Polycyclic - recurrent episodic flares with remissions in between (~26-36% of patients)
3. Chronic articular - persistent active disease; more destructive joint involvement (~26-36%)

Life-Threatening Complications

• Macrophage activation syndrome (MAS) - most feared; ferritin dramatically elevated
• Myocarditis
• Acute respiratory distress syndrome (ARDS)
• Fulminant hepatitis
• Disseminated intravascular coagulation (DIC)
• Thrombotic microangiopathy

Key Differential Diagnoses to Exclude

• Infections: sepsis, EBV, CMV, TB
• Lymphoma / other malignancies
• Systemic lupus erythematosus
• Reactive arthritis
• Polyarteritis nodosa
• Viral arthritis

• Fitzpatrick's Dermatology, 9th ed., Chapter 66 (Adult-Onset Still Disease), pp. 1184-1185
• Firestein & Kelley's Textbook of Rheumatology, Chapter discussing elevated ferritin in rheumatic diseases, pp. ~1441-1474
• Firestein & Kelley's Textbook of Rheumatology, Chapter 99 (sJIA/AOSD), pp. 2154-2155
• Yamaguchi M, et al. Preliminary criteria for classification of adult Still's disease. J Rheumatol. 1992;19:424-430
• Fautrel B, et al. Proposal for new set of classification criteria for adult-onset Still disease. Medicine (Baltimore). 2002;81(3):194-200