In a 45-year-old man with symmetric small-joint arthritis of the hands, mild hyperuricemia (serum uric acid 7.2 mg/dL) and peripheral eosinophilia, what is the most likely diagnosis and the appropriate initial work-up and management?

Diagnostic Approach to Symmetric Small Hand Joint Arthritis with Eosinophilia and Mild Hyperuricemia

This clinical presentation—symmetric small hand joint involvement in a 45-year-old man with peripheral eosinophilia and mild hyperuricemia (7.2 mg/dL)—is most consistent with Adult-Onset Still's Disease (AOSD) rather than gout, and requires immediate work-up to exclude infection and confirm the diagnosis through characteristic clinical features, inflammatory markers, and exclusion of alternative diagnoses.

Why This Is Likely NOT Gout

Atypical Features Against Gout

• Gout characteristically presents with podagra (first metatarsophalangeal joint involvement) in 96% of cases, not symmetric small hand joint arthritis 1
• The pattern of symmetric polyarticular small joint involvement is inconsistent with typical gout presentation, which favors large weight-bearing joints (knees, ankles, wrists) and is typically asymmetric 1
• Peripheral eosinophilia is NOT a feature of gout—gout typically presents with neutrophilia, not eosinophilia 1
• The serum uric acid of 7.2 mg/dL is only mildly elevated and has limited diagnostic value; approximately 10% of patients with acute gout have normal uric acid levels during attacks, but conversely, only 22% of asymptomatic individuals with uric acid >9 mg/dL develop gout within 5 years 2
• Hyperuricemia alone cannot diagnose gout and has only 53-61% specificity 2

Why Adult-Onset Still's Disease Is the Leading Diagnosis

Classic AOSD Features Present

• Symmetric polyarthritis affecting small joints of the hands (including proximal and distal interphalangeal joints, metacarpophalangeal joints) occurs in 64-100% of AOSD patients 1
• Peripheral eosinophilia can occur in AOSD as part of the systemic inflammatory response, though the guidelines emphasize neutrophilia is more common 1
• The age (45 years) and male gender fit the typical AOSD demographic 1

Critical Missing Information to Assess

• Fever pattern: AOSD characteristically presents with high-spiking quotidian fevers (>39°C) occurring in late afternoon/evening in 95.7% of cases 1
• Rash: Evanescent salmon-pink maculopapular rash occurs in 72.7% of AOSD cases 1
• Sore throat: Present in 35-92% of AOSD patients 1
• Lymphadenopathy and hepatosplenomegaly: Common systemic features 1

Immediate Diagnostic Work-Up

Essential Laboratory Tests

• Complete blood count with differential: Look for marked leukocytosis (often >15,000 cells/μL with 50% having WBC >20,000), neutrophilia (not just eosinophilia), anemia of chronic disease, and thrombocytosis 1
• Inflammatory markers: ESR and CRP are elevated in virtually all AOSD patients 1
• Ferritin level: Markedly elevated ferritin (often >1000 ng/mL) with low glycosylated ferritin fraction is highly characteristic of AOSD 1
• Liver function tests: Transaminase elevations occur commonly in AOSD 1
• Rheumatoid factor and anti-CCP antibodies: Should be negative in AOSD (helps exclude rheumatoid arthritis) 1
• ANA and other autoantibodies: Typically negative in AOSD 1

Critical Exclusion Testing

• Blood cultures and infectious work-up: AOSD is a diagnosis of exclusion; infection must be ruled out first 1
• Joint aspiration with synovial fluid analysis: If feasible, perform to exclude septic arthritis and confirm inflammatory (not crystalline) arthritis—Gram stain and culture are mandatory even if crystals are seen, as gout and infection can coexist 2
• Serum uric acid: Already obtained (7.2 mg/dL), but this level does not establish gout diagnosis 2

Imaging Studies

• Plain radiographs of hands: Look for characteristic carpal and pericapitate abnormalities that develop after 6 months in AOSD, with progressive joint space narrowing and eventual ankylosis after 1.5-3 years 1
• Chest X-ray: Assess for pleuritis/pericarditis (present in 12-53% of AOSD) 1
• Ultrasound of hands: If gout remains in differential despite atypical features, ultrasound can detect the "double contour sign" (sensitivity 74%, specificity 88%) 2

Differential Diagnosis to Exclude

Rheumatoid Arthritis

• Symmetric small joint involvement is classic for RA, but eosinophilia is not typical 1
• Check RF and anti-CCP antibodies (should be negative in AOSD) 1
• Carpal and pericapitate abnormalities are more prominent in AOSD than RA, offering a distinguishing feature 1

Septic Arthritis

• Must be excluded first—fever, joint swelling, and elevated inflammatory markers can mimic infection 2
• Joint aspiration with Gram stain and culture is mandatory if infection cannot be clinically excluded 2

Psoriatic Arthritis

• Can present with polyarticular small joint involvement 1
• Look for skin psoriasis, nail changes, and dactylitis 1

Reactive Arthritis

• Typically asymmetric and follows genitourinary or gastrointestinal infection 1
• Less likely given symmetric presentation 1

Management Algorithm

Step 1: Rule Out Infection (Highest Priority)

• Obtain blood cultures, inflammatory markers (ESR, CRP), and complete blood count 1
• If fever or systemic signs present, consider joint aspiration with Gram stain and culture 2

Step 2: Confirm AOSD Diagnosis

• Check ferritin level (expect >1000 ng/mL with low glycosylated fraction) 1
• Assess for characteristic fever pattern, rash, sore throat, lymphadenopathy 1
• Exclude alternative diagnoses: RF, anti-CCP, ANA should be negative 1

Step 3: Assess Disease Severity

• Evaluate for systemic complications: hepatitis, serositis, coagulopathy 1
• Screen for macrophage activation syndrome/hemophagocytic syndrome (pancytopenia, DIC)—this is a medical emergency requiring prompt immunosuppression 1

Step 4: Initiate Treatment (Once Infection Excluded)

• NSAIDs are first-line for mild disease 1
• Corticosteroids for moderate-to-severe disease 1
• Disease-modifying agents (methotrexate, biologics) for refractory or chronic articular disease 1

Common Pitfalls to Avoid

• Do not diagnose gout based on mild hyperuricemia alone—only 57% of patients with uric acid >7 mg/dL in men have gout, and the clinical presentation here is atypical 1, 2
• Do not miss septic arthritis—AOSD can mimic infection, and joint aspiration is mandatory if infection cannot be excluded 2
• Do not overlook macrophage activation syndrome—pancytopenia in the setting of AOSD requires immediate immunosuppressive treatment 1
• Do not assume rheumatoid arthritis without checking RF/anti-CCP—AOSD can mimic RA but has distinct features (higher ferritin, fever, rash, negative serology) 1
• Eosinophilia is NOT a feature of gout—this should immediately broaden your differential beyond crystal arthropathy 1