What is the diagnostic workup and treatment for polyarthralgia?

Diagnostic Workup for Polyarthralgia

Begin with a complete rheumatologic examination of all peripheral joints assessing for tenderness, swelling, and range of motion, along with spine examination, followed by targeted laboratory testing including inflammatory markers (ESR, CRP), autoimmune panel (ANA, RF, anti-CCP), and imaging when clinically indicated. 1

Initial Clinical Assessment

History and Physical Examination

• Document symptom onset, duration, and pattern (migratory vs. persistent, symmetric vs. asymmetric) to differentiate inflammatory from non-inflammatory causes 1
• Examine all peripheral joints systematically for tenderness, swelling, erythema, warmth, and range of motion limitations 1
• Assess for true weakness versus pain - muscle weakness suggests myositis rather than isolated arthralgia 1
• Evaluate spine involvement including range of motion and tenderness 1
• Screen for systemic symptoms: fever, weight loss, rash, recent infections, or travel history to endemic areas for arboviral infections 2
• Review medication history including recent use of NSAIDs or salicylates that may mask inflammatory arthritis 1

Critical Differential Diagnoses to Exclude

High-priority conditions requiring immediate evaluation:

• Septic arthritis - requires urgent arthrocentesis if suspected 1
• Acute rheumatic fever in moderate-to-high risk populations with preceding streptococcal infection 1
• Arboviral infections (chikungunya, dengue) in patients with travel history presenting with severe polyarthralgia 2
• Myositis with myocardial involvement - check troponin if muscle weakness present 1

Laboratory Workup

First-Line Testing (All Patients)

• Inflammatory markers: ESR and CRP 1

  • Note: ESR ≥60 mm/hr and/or CRP ≥3.0 mg/dL suggests significant inflammation in low-risk populations 1
  • Caveat: Normal ESR and CRP do not exclude inflammatory disease; consider serum amyloid A (SAA) if clinical suspicion remains high 3

• Autoimmune panel: 1

  • Antinuclear antibody (ANA)
  • Rheumatoid factor (RF)
  • Anti-citrullinated protein antibody (anti-CCP)

• Additional testing based on clinical presentation: 1

  • HLA-B27 if reactive arthritis or axial symptoms present
  • Creatine kinase (CK) to differentiate from myositis 1

Endocrine Screening (When Indicated)

• Thyroid function tests (TSH, free T4) and antithyroid antibodies in patients with unexplained polyarthralgia, particularly with fatigue and weight changes 4
• ACTH and cortisol levels if hyponatremia, hypoglycemia, or refractory symptoms with elevated inflammatory markers 5

Metabolic Evaluation (When Indicated)

• Serum calcium, phosphate, potassium, and alkaline phosphatase if bone pain or fractures present to exclude Fanconi syndrome 6
• Urinalysis for aminoaciduria and phosphaturia if metabolic bone disease suspected 6

Imaging Studies

Plain Radiography

• Obtain X-rays of affected joints to evaluate for erosions, joint damage, or metastatic lesions when symptoms persist 1
• Consider spine and pelvic imaging if axial symptoms or metabolic bone disease suspected 6

Advanced Imaging (Grade 2 or Higher Symptoms)

• Ultrasound of affected joints is highly valuable for detecting subclinical synovitis and predicting progression to rheumatoid arthritis, even in ACPA-negative patients 1, 7

  • Presence of ultrasound synovitis increases risk of RA development 7-fold 7

• MRI of affected joints when: 1

  • Persistent arthritis unresponsive to treatment
  • Suspicion for metastatic lesions
  • Evaluation of soft tissue involvement

Arthrocentesis

• Perform joint aspiration if septic arthritis or crystal-induced arthritis suspected 1

Monitoring Strategy

Serial Assessments

• Repeat rheumatologic examinations and inflammatory markers every 4-6 weeks after treatment initiation 1
• Monitor CK, ESR, and CRP if myositis in differential 1

Rheumatology Referral Indications

• Early referral (Grade 2): Joint swelling (synovitis) present or symptoms persist despite initial management 1
• Urgent referral (Grade 3-4): Severe pain with signs of inflammation, irreversible joint damage, or disabling symptoms 1

Special Considerations

Immune Checkpoint Inhibitor Context

If patient receiving immunotherapy, additional workup includes: 1

• Troponin and ECG to evaluate myocardial involvement
• EMG and muscle MRI if weakness present
• Paraneoplastic autoantibody panel for myositis
• Screen for viral hepatitis B, C, and tuberculosis before DMARD treatment 1

Common Pitfalls to Avoid

• Do not dismiss normal inflammatory markers - 14% of polymyalgia rheumatica patients have normal ESR and CRP at diagnosis; consider SAA testing 3
• Recognize that prior NSAID use may mask classic migratory polyarthritis pattern 1
• Ultrasound provides superior sensitivity over clinical examination for detecting synovitis and predicting RA development 7
• Polyarthralgia in moderate-to-high risk populations warrants more aggressive workup for acute rheumatic fever 1