What is the appropriate workup and differential diagnosis for a patient presenting with bilateral hand and foot swelling?

Workup and Differential Diagnosis for Bilateral Hand and Foot Swelling

Initial Clinical Assessment

Begin by determining whether this represents inflammatory arthritis, which requires urgent rheumatology referral within 6 weeks to prevent irreversible joint damage. 1, 2

Key Historical Features to Elicit

• Morning stiffness duration: Stiffness lasting ≥30 minutes (ideally ≥1 hour) strongly suggests inflammatory arthritis such as rheumatoid arthritis (RA) or psoriatic arthritis, while stiffness <30 minutes points toward osteoarthritis 3, 4, 2
• Pattern of joint involvement: Symmetric involvement of metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, wrists, and metatarsophalangeal (MTP) joints characterizes RA, whereas distal interphalangeal (DIP) joint involvement suggests psoriatic arthritis or osteoarthritis 3, 4
• Skin manifestations: Psoriatic plaques, nail pitting, or onycholysis indicate psoriatic arthritis; salmon-pink evanescent rash with high fevers suggests adult-onset Still's disease 3, 4
• Systemic symptoms: Assess for fever, weight loss, dyspnea (heart failure), or recent viral illness 3, 5

Critical Physical Examination Maneuvers

• Squeeze test: Compress MCPs and MTPs bilaterally—pain indicates synovitis and inflammatory arthritis 4, 2
• Soft tissue vs. bony swelling: Soft, boggy swelling suggests inflammatory synovitis; hard, bony enlargement (Heberden/Bouchard nodes) indicates osteoarthritis 3, 4
• Dactylitis assessment: "Sausage digits" with entire digit swelling points to psoriatic arthritis 2
• Cardiovascular examination: Check for jugular venous distension, peripheral edema, and cardiac findings to exclude heart failure as a systemic cause 2, 5

Essential Initial Laboratory Workup

Order these tests immediately when inflammatory arthritis is suspected: 1, 3, 4

• Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA/anti-CCP): Both should be ordered simultaneously—ACPA has 90% specificity and 60% sensitivity for RA; negative tests do not exclude RA (20-30% of RA is seronegative) 1, 3, 4
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP): CRP is preferred for ongoing monitoring as it is more reliable and not age-dependent; markedly elevated levels (CRP >10 mg/L, ESR >30 mm/hr) strongly suggest inflammatory arthritis 1, 3, 4, 2
• Complete blood count with differential: Required to detect cytopenias before starting disease-modifying antirheumatic drugs (DMARDs) 3, 4
• Comprehensive metabolic panel: Including liver function tests, renal function, glucose, and urate levels—essential before methotrexate initiation 3, 4
• Urinalysis: Part of standard initial workup for inflammatory arthritis 1, 3, 4, 2

Conditional Laboratory Tests

• Antinuclear antibodies (ANA): Order if diagnosis remains uncertain to screen for systemic lupus erythematosus or other connective tissue diseases 1, 3, 4
• HLA-B27: Consider if axial symptoms, enthesitis, or spondyloarthropathy features are present 1, 3, 4, 2
• Hepatitis B, hepatitis C, and tuberculosis screening: Required before initiating any biologic therapy 4

Imaging Studies

Obtain bilateral hand, wrist, and foot radiographs (posteroanterior view) as first-line imaging for all suspected inflammatory arthropathies. 1, 3, 4

• Look for: Periarticular osteopenia, uniform joint space narrowing, and marginal erosions (inflammatory) versus asymmetric joint space narrowing with osteophytes and subchondral sclerosis (osteoarthritis) 3, 4
• Prognostic significance: Presence of erosions on baseline radiographs is highly predictive of RA diagnosis and persistent disease 1, 3, 4

Advanced Imaging (When Diagnosis Uncertain)

• Ultrasound with Power Doppler: Superior to clinical examination for detecting synovitis—increases detection of subclinical inflammation by approximately 75%; particularly useful when patients do not meet 2010 ACR/EULAR criteria but suspicion remains high 3, 4
• MRI with IV contrast: More sensitive than ultrasound in early disease; detects bone marrow edema (osteitis), which is the strongest single predictor of future radiographic progression and functional deterioration 3, 4

Differential Diagnosis Framework

Inflammatory Arthritis (Most Likely with Morning Stiffness >30 Minutes + Elevated CRP/ESR)

Seronegative Rheumatoid Arthritis 3, 4

• Bilateral symmetric small joint involvement (MCPs, PIPs, wrists, MTPs)
• Morning stiffness ≥1 hour
• Negative RF and ACPA (accounts for 20-30% of RA cases)
• Markedly elevated inflammatory markers

Psoriatic Arthritis 3, 4, 2

• DIP joint involvement or asymmetric pattern
• Dactylitis ("sausage digits")
• Psoriatic skin lesions or nail changes (pitting, onycholysis)
• Negative RF; elevated CRP

Adult-Onset Still's Disease 3, 4

• High-spiking fevers (>39°C) with quotidian pattern
• Salmon-pink evanescent rash
• Markedly elevated ferritin (>1,000 ng/mL)
• Polyarthritis including hands and feet

Reactive Arthritis 4

• Recent conjunctivitis, urethritis, or gastrointestinal/genitourinary infection
• Consider HLA-B27 testing
• Asymmetric oligoarthritis pattern

Non-Inflammatory Causes

Hand Osteoarthritis 3

• Morning stiffness <30 minutes
• DIP and PIP joint involvement with bony enlargement (Heberden/Bouchard nodes)
• Thumb base (carpometacarpal) involvement
• Normal or mildly elevated inflammatory markers

Systemic Edema 2, 5

• Heart failure: Assess for dyspnea, jugular venous distension, cardiac findings
• Renal disease: Check comprehensive metabolic panel, urinalysis
• Liver disease: Assess for ascites, jaundice
• Medication-induced: Review medications (calcium channel blockers, NSAIDs)

Viral Arthritis 4, 6

• Recent viral infection (parvovirus B19, hepatitis B/C, Epstein-Barr virus, enterovirus)
• Symptoms resolving within 6 weeks suggest viral etiology; persistence beyond 6 weeks supports true inflammatory arthritis

Urgent Rheumatology Referral Criteria

Refer to rheumatology within 6 weeks of symptom onset if: 1, 3, 4, 2

• ≥2 swollen joints with morning stiffness >30 minutes
• Positive squeeze test of MCPs/MTPs
• Elevated inflammatory markers (CRP/ESR)
• Any clinical synovitis not better explained by another diagnosis

Early treatment within this window prevents irreversible joint damage and improves long-term outcomes. 3, 4, 2

Critical Pitfalls to Avoid

• Do not dismiss bilateral morning swelling as "just aging" without excluding inflammatory arthritis through proper workup 2
• Do not delay treatment waiting for positive serology—seronegative RA is common (20-30%) and has similar prognosis to seropositive disease 3, 4
• Do not dismiss the diagnosis based on normal ESR/CRP—acute phase reactants can be normal even in active inflammatory arthritis 3, 4
• Do not wait for complete diagnostic criteria—refer to rheumatology with ≥2 swollen joints and morning stiffness >30 minutes 2
• Distinguish unilateral from bilateral distribution—unilateral suggests local causes (DVT, infection), bilateral suggests systemic or inflammatory causes 2, 5