Fever of Unknown Origin Criteria:

• Fever > 38.3 on several occasions
• Duration of fever > 3 weeks
• Uncertain diagnosis after 1 week of inpatient investigation

5 Main Etiologies for FUO:

• Infection
• Malignancy
• Connective tissue disease
• Other
• No diagnosis

Adult Onset Still’s Disease (AOSD):

• Very uncommon – estimated annual incidence of 0.16 cases per 100,000 people
• Equal distribution between the sexes
• Bimodal age distribution: one peak between 15-25 and the other between 36-46 years old
• Diagnosis of exclusion, must exclude infection, malignancy, or other rheumatologic disease.

AOSD is multisystem inflammatory disease characterized by 4 major findings:

1. High spiking fevers
2. Salmon-color rash
3. Arthritis
4. High neutrophil counts

AOSD Laboratory Findings:

• Elevated ESR / CRP (99%)
• Elevated Ferritin (~75%)
• Leukocytosis > 10,000/mm3 (92%), >15,000/mm3 (81%) with neutrophil predominance (>80%)
• Abnormal LFTs (~ 75%)
• Negative ANA (92%)
• Negative RF (93%)

Yamaguchi Criteria for AOSD:

• Diagnosis requires 5 criteria total – with at least 2 major criteria

AOSD Treatment:

Initial therapeutic decisions should be based on the degree of disease activity:

• Mild disease: fevers, rash, and/or mild arthritis
• Moderate disease: high fevers, debilitating joint symptoms, evidence of internal organ involvement that is not life-threating or severe
• Severe disease: presence of life-threating organ involvement

Treatment options:

• NSAIDS – effective alone for 20% of mild patients
• Glucocorticoids – should be started in all patients meeting moderate disease criteria
• Methotrexate – used in patient’s who fail to improve with steroids
• Can also consider other DMARDs – will not be discussed here!