Polyarthralgia: Pain In More Than Four Joints

Introduction

Polyarthralgia refers to joint pain affecting five or more joints. Distinguishing between polyarthralgia (pain without objective inflammation) and polyarthritis (pain with objective signs of inflammation like swelling, warmth, or erythema) is a critical skill for the MCCQE1 and constitutes a core competency under the CanMEDS Medical Expert role.

For Canadian medical students and international graduates, mastering the approach to polyarticular joint pain is essential. The differential diagnosis is broad, ranging from self-limiting viral infections to chronic autoimmune conditions like Rheumatoid Arthritis (RA) or Systemic Lupus Erythematosus (SLE).

Clinical Approach to Polyarthralgia

The primary goal in the clinical assessment is to categorize the presentation into Inflammatory vs. Non-inflammatory (Mechanical) and Acute (<6 weeks) vs. Chronic (≥6 weeks).

Differential Diagnosis

The differential for polyarthralgia is extensive. For MCCQE1 preparation, organize your thinking by duration.

Investigations

Investigations should be guided by the clinical picture (“Choosing Wisely Canada”). Do not order a “Rheumatology Panel” indiscriminately.

Laboratory Studies

1. Acute Phase Reactants:
   • ESR & CRP: Elevated in inflammatory conditions. Normal in OA and Fibromyalgia.
2. Serology (If inflammatory suspected):
   • Rheumatoid Factor (RF): Sensitive but not specific (positive in Hep C, endocarditis, age).
   • Anti-CCP (Cyclic Citrullinated Peptide): Highly specific (>95%) for RA. MCCQE1 High Yield.
   • ANA (Antinuclear Antibody): High sensitivity for SLE (99%), low specificity. Only order if SLE features are present.
3. Other:
   • CBC: Anemia of chronic disease, leukopenia (SLE), thrombocytosis (active inflammation).
   • Urinalysis: Check for proteinuria/casts (Lupus Nephritis).
   • Viral Serology: Parvovirus B19 IgM, Hep B/C if indicated.

Imaging

• X-rays:
  • Early RA: Periarticular osteopenia, soft tissue swelling.
  • Late RA: Marginal erosions, joint space narrowing.
  • OA: Osteophytes, subchondral sclerosis, asymmetric joint space narrowing.

Canadian Guidelines & Management

Management depends on the etiology. The goal is to suppress inflammation, preserve function, and prevent deformity.

Rheumatoid Arthritis (CRA Guidelines)

• Early Referral: Patients with suspected RA should be seen by a rheumatologist within 4 weeks.
• Treat to Target: Aim for remission or low disease activity.
• Pharmacotherapy:
  1. DMARDs (Disease-Modifying Antirheumatic Drugs): Methotrexate is the anchor drug (Gold standard).
  2. Adjuncts: NSAIDs or low-dose prednisone for bridging therapy.
  3. Biologics: TNF inhibitors (e.g., Adalimumab, Etanercept) if Methotrexate fails.

Osteoarthritis (Osteoarthritis Research Society International - OARSI)

• Non-pharmacological (First Line): Weight loss, exercise, physiotherapy.
• Pharmacological: Topical NSAIDs (knee/hand), Oral NSAIDs (if no contraindications), Acetaminophen (conditional recommendation due to low efficacy). Intra-articular steroid injections.

Viral Arthritis

• Management: Symptomatic treatment (NSAIDs). Usually resolves in weeks.

Key Points to Remember for MCCQE1

• Symmetry matters: Symmetric small joint polyarthritis is RA until proven otherwise.
• Duration cutoff: Chronic arthritis is defined as symptoms persisting for ≥ 6 weeks.
• Serology: Anti-CCP is more specific than RF for Rheumatoid Arthritis.
• Red Flags: Always rule out septic arthritis (even in polyarticular presentations) and systemic vasculitis.
• Viral Mimics: Parvovirus B19 infection in adults looks exactly like acute RA.
• Spine Involvement: RA affects the C-spine (C1-C2 subluxation) but spares the thoracic and lumbar spine. OA and Spondyloarthropathies affect the lumbar spine.

# Mnemonics for MCCQE1
 
**SERIOUS** (Features suggesting Inflammatory Arthritis)
**S** - Swelling in joints
**E** - Early morning stiffness > 1 hr
**R** - Recurrent pain
**I** - Inability to move joint (Loss of function)
**O** - Obvious redness/warmth
**U** - Unexplained weight loss/fever
**S** - Symmetric symptoms

Sample Question

Clinical Scenario

A 42-year-old female presents to her family physician with a 2-month history of pain and stiffness in her hands and feet. She reports that the stiffness is worst in the morning and lasts for about 2 hours, improving as the day progresses. She also reports feeling generally fatigued. On physical examination, there is boggy swelling and tenderness of the second and third metacarpophalangeal (MCP) joints and proximal interphalangeal (PIP) joints bilaterally. The distal interphalangeal (DIP) joints are spared.

Which one of the following investigations is the most specific for confirming the likely diagnosis?

• A. Erythrocyte Sedimentation Rate (ESR)
• B. Rheumatoid Factor (RF)
• C. Anti-cyclic citrullinated peptide (Anti-CCP)
• D. Antinuclear Antibody (ANA)
• E. Hand X-rays

Explanation

The correct answer is:

• C. Anti-cyclic citrullinated peptide (Anti-CCP)

Detailed Explanation:

The clinical presentation is classic for Rheumatoid Arthritis (RA):

1. Demographics: Female, middle-aged.
2. Chronicity: > 6 weeks (2 months).
3. Inflammatory nature: Morning stiffness > 1 hour, fatigue, “boggy” swelling (synovitis).
4. Distribution: Symmetric, small joints (MCPs, PIPs), sparing the DIPs (DIP involvement suggests OA or Psoriatic Arthritis).

Why C is correct: Anti-CCP antibodies are highly specific (>95%) for RA. While their sensitivity is comparable to Rheumatoid Factor, their high specificity makes them the best confirmatory test, especially in early disease. This aligns with MCCQE1 objectives on selecting specific diagnostic tests.

• Option A (ESR): Sensitive for inflammation but completely non-specific. Elevated in infection, malignancy, and other autoimmune diseases.
• Option B (RF): Sensitive (~70-80%) but non-specific. It can be positive in Hepatitis C, Sjogren’s, Endocarditis, and even in healthy elderly individuals.
• Option D (ANA): Sensitive for SLE, but not specific for RA. While some RA patients are ANA positive, it is not the diagnostic test of choice.
• Option E (Hand X-rays): While useful for baseline and monitoring damage (erosions), early RA X-rays often only show soft tissue swelling or periarticular osteopenia. Anti-CCP is better for confirmation of diagnosis at this stage.

References

1. Medical Council of Canada. MCCQE Part I Clinical Decision-Making and Multiple-Choice Questions Objectives.
2. Canadian Rheumatology Association (CRA). Guidelines for the Management of Rheumatoid Arthritis. rheum.ca 
3. Choosing Wisely Canada. Rheumatology: Five Things Physicians and Patients Should Question. choosingwiselycanada.org 
4. Toronto Notes. Rheumatology Chapter. 2023 Edition.
5. Uptodate. Evaluation of the adult with polyarticular pain. Accessed 2023.