What step‑by‑step algorithm should I use to evaluate an adult with joint pain, swelling, stiffness or functional limitation, using the number of joints involved to guide the differential diagnosis and work‑up?

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Algorithm for Assessing Arthritis Based on Number of Joints Involved

Step 1: Confirm True Articular Pain vs. Periarticular Disease

Palpate for synovitis (soft, boggy joint swelling) rather than bony enlargement or periarticular tenderness. 1, 2 A positive "squeeze test" (pain with compression of metacarpophalangeal or metatarsophalangeal joints) indicates true joint inflammation. 1


Step 2: Classify as Inflammatory vs. Non-Inflammatory

Inflammatory Arthritis Features:

  • Morning stiffness ≥30 minutes (ideally ≥1 hour) 1, 3, 4
  • Warm, swollen joints with palpable synovitis 1, 2
  • Improvement with activity 2, 5
  • Systemic symptoms (fatigue, fever, weight loss) 4, 6

Non-Inflammatory Arthritis Features:

  • Morning stiffness <30 minutes 1, 2
  • Bony hypertrophy and crepitus 2, 6
  • Pain worsens with activity, improves with rest 2, 5
  • No systemic symptoms 5

Step 3: Categorize by Number of Joints Involved

Monoarticular (1 joint):

  • First priority: Rule out septic arthritis and crystal arthropathy 1
  • Perform joint aspiration with synovial fluid analysis (cell count, Gram stain, culture, crystal analysis) 1

Oligoarticular (2-4 joints):

  • Consider spondyloarthropathies (psoriatic arthritis, reactive arthritis, ankylosing spondylitis) 1, 2
  • Look for asymmetric distribution, DIP involvement, dactylitis, or axial symptoms 1
  • Order HLA-B27 if axial pain, enthesitis, or reactive arthritis suspected 1, 3

Polyarticular (≥5 joints):

  • Proceed to Step 4 for detailed differential diagnosis algorithm

Step 4: Polyarticular Inflammatory Arthritis—Apply Joint Distribution Pattern

A. Symmetric Small Joint Involvement (MCPs, PIPs, wrists, MTPs):

Most likely diagnosis: Rheumatoid Arthritis 1, 3, 4

Immediate workup:

  • Serology: RF and anti-CCP antibodies (order simultaneously) 1, 3
    • Anti-CCP: 90% specificity, 60% sensitivity 1, 3
    • RF: 70% specificity, 60% sensitivity 1, 3
    • Note: Seronegative RA accounts for 20-30% of cases—negative serology does NOT exclude RA 3, 2
  • Inflammatory markers: ESR and CRP (CRP preferred for monitoring) 1, 3, 2
  • Baseline labs: CBC with differential, comprehensive metabolic panel, urinalysis 1, 3
  • Imaging: Bilateral hand, wrist, and foot X-rays to assess for erosions 1, 3, 2
    • Erosions on baseline films predict persistent disease 1, 3

Apply 2010 ACR/EULAR Classification Criteria (score ≥6/10 = definite RA): 3, 2

Domain Scoring
Joint involvement 1 large joint = 0 pts; 2-10 large = 1 pt; 1-3 small = 2 pts; 4-10 small = 3 pts; >10 joints = 5 pts [3,2]
Serology Negative RF & anti-CCP = 0 pts; Low positive = 2 pts; High positive = 3 pts [3,2]
Acute phase reactants Normal CRP & ESR = 0 pts; Abnormal = 1 pt [3,2]
Symptom duration <6 weeks = 0 pts; ≥6 weeks = 1 pt [3,2]

Refer to rheumatology within 6 weeks of symptom onset if score ≥6 or high clinical suspicion. 1, 3 Early treatment prevents irreversible joint damage. 1, 3


B. Asymmetric Oligoarthritis with DIP Involvement, Dactylitis, or Nail Changes:

Most likely diagnosis: Psoriatic Arthritis 1, 2

Key distinguishing features:

  • DIP joint involvement (RA typically spares DIPs) 1, 3
  • Dactylitis ("sausage digits") 1
  • Nail pitting, onycholysis 1, 2
  • Psoriatic skin plaques 1, 2
  • Typically anti-CCP negative 1, 3

Workup:

  • RF and anti-CCP (usually negative) 1
  • ESR/CRP (may be elevated) 1, 2
  • HLA-B27 if axial involvement 1
  • X-rays of affected joints 2
  • Skin and nail examination mandatory 1, 2

C. Axial Pain + Peripheral Arthritis (Especially Lower Extremity):

Consider: Spondyloarthropathies (Ankylosing Spondylitis, Reactive Arthritis) 1, 2

Red flags for axial spondyloarthropathy:

  • Age <45 years with low back pain >3 months 7
  • Pain worse in latter part of night 7
  • Morning stiffness >30 minutes 7
  • Improves with exercise, not relieved by rest 7

Workup:

  • HLA-B27 testing 1, 3
  • MRI of spine (sagittal T1 and STIR images) and sacroiliac joints (coronal/oblique T1 and STIR) 7
    • Plain radiographs miss most early disease 7
  • ESR/CRP 1, 2
  • History of recent GI/GU infection or uveitis 1

Refer to rheumatology early—sulfasalazine and methotrexate are NOT effective for axial disease; anti-TNF agents often required. 7


D. Polyarticular Arthritis with Systemic Features (Fever, Rash, Serositis):

Consider: Systemic Lupus Erythematosus, Adult-Onset Still's Disease, Viral Arthritis 3, 6

Workup:

  • ANA with reflex to anti-dsDNA and ENA panel if positive 1, 3
    • Note: Symmetric polyarthritis with elevated CRP is more typical of RA than SLE 3
  • Serum ferritin (>1,000 ng/mL suggests Adult-Onset Still's Disease) 3
  • Viral serologies (parvovirus B19, hepatitis B/C, EBV) if acute onset 3
    • Viral arthritis typically resolves within 6 weeks 3
  • CBC, urinalysis, comprehensive metabolic panel 1, 3

Step 5: Advanced Imaging When Diagnosis Uncertain

If clinical examination is equivocal but suspicion for inflammatory arthritis remains high: 1, 3

  • Ultrasound with Power Doppler: Detects subclinical synovitis; 75% more accurate than physical examination alone 1, 3
  • MRI with IV contrast: Most sensitive for early disease; detects bone marrow edema (osteitis), the strongest predictor of future erosive progression 1, 3

Step 6: Exclude Mimics and Non-Rheumatologic Causes

Common Pitfalls:

  • Infections causing false-positive RF: Mononucleosis, CMV, parvovirus, hepatitis B/C 1
  • Other autoimmune diseases with positive RF: Sjögren's syndrome, SLE, systemic sclerosis, vasculitis 1
  • Polymyalgia rheumatica: Proximal muscle pain without true weakness, normal CK, no definite synovitis 3
  • Osteoarthritis: Can coexist with inflammatory arthritis; look for bony enlargement vs. soft tissue swelling 1, 2

Always interpret RF and anti-CCP in conjunction with clinical findings—do not rely on serology alone. 1, 3


Step 7: Initial Management While Awaiting Rheumatology Referral

Symptomatic Treatment:

  • NSAIDs (e.g., naproxen 500 mg twice daily) after evaluating GI, renal, and cardiovascular status 1
  • Avoid starting DMARDs (methotrexate) until rheumatology consultation 1

Pre-DMARD Screening (if RA confirmed):

  • Hepatitis B, hepatitis C, tuberculosis screening before biologic therapy 1, 3
  • Baseline CBC, comprehensive metabolic panel, urinalysis 1, 3

Summary Algorithm Flowchart

Joint Pain → Confirm True Articular Pain (palpate for synovitis)
    ↓
Inflammatory Features? (morning stiffness ≥30 min, warm/swollen joints)
    ↓
YES → Count Joints Involved
    ↓
1 joint → Aspirate (rule out septic/crystal arthritis)
2-4 joints → Consider spondyloarthropathies (check HLA-B27, skin/nail exam)
≥5 joints → Assess Distribution Pattern:
    ↓
Symmetric small joints (MCPs, PIPs, wrists, MTPs)
    → Order RF, anti-CCP, ESR/CRP, X-rays
    → Apply 2010 ACR/EULAR criteria
    → Refer rheumatology within 6 weeks if score ≥6
    ↓
Asymmetric + DIP/dactylitis/nail changes
    → Psoriatic arthritis (skin exam, HLA-B27 if axial)
    ↓
Axial pain + peripheral arthritis
    → Spondyloarthropathy (HLA-B27, MRI spine/SI joints)
    ↓
Systemic features (fever, rash)
    → ANA, ferritin, viral serologies

Critical pearl: Do NOT delay treatment waiting for positive serology—seronegative RA is common and has similar prognosis. 3 Do NOT dismiss diagnosis based on normal ESR/CRP—acute phase reactants can be normal even in active inflammatory arthritis. 3

References

Guideline

Initial Laboratory Workup for Polyarticular Joint Pain

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Differentiating Types of Arthritis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Rheumatoid Arthritis Diagnosis and Treatment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

The clinical features of rheumatoid arthritis.

European journal of radiology, 1998

Research

Differential Diagnosis of Polyarticular Arthritis.

American family physician, 2015

Research

Diagnostic approach to polyarticular joint pain.

American family physician, 2003

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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