What is the recommended diagnostic work‑up and treatment approach for a patient presenting with polyarthralgia?

Management of Polyarthralgia

Critical First Step: Distinguish Arthralgia from Arthritis

The single most important clinical determination is whether objective joint swelling (synovitis) is present on physical examination—this fundamentally changes your differential diagnosis and management approach. 1

• Arthralgia = joint pain WITHOUT visible or palpable swelling 1
• Arthritis = joint pain WITH objective synovitis (visible or palpable swelling) 1, 2
• Perform a metacarpophalangeal (MCP) squeeze test: pain or difficulty making a fist with compression indicates underlying inflammation 1, 2
• Morning stiffness lasting >30–60 minutes strongly suggests inflammatory arthritis rather than simple arthralgia 1, 2
• A dramatic improvement within 24–48 hours after NSAIDs or corticosteroids (but NOT opioids) indicates an inflammatory process 1, 2

Diagnostic Work-Up

History and Physical Examination

• Document onset, duration, and pattern: migratory vs. persistent, symmetric vs. asymmetric, acute vs. chronic 1, 3
• Chronicity ≥6 weeks raises suspicion for persistent inflammatory arthritis 1
• Assess morning stiffness duration (>30–60 min = inflammatory) 1, 3
• Evaluate medication response: NSAIDs/corticosteroids vs. opioids to differentiate inflammatory from non-inflammatory pain 1, 3
• Screen for systemic symptoms: fever, weight loss, rash, recent infections, travel to endemic regions for arboviral infections 1, 3
• Perform a complete rheumatologic examination of all peripheral joints for tenderness, swelling, erythema, warmth, and range of motion; include spine assessment 1, 3

Laboratory Testing

Obtain in all patients:

• Inflammatory markers: ESR and CRP (caveat: normal values do NOT exclude inflammatory disease) 1, 3
• Complete blood count, urinalysis, metabolic panel (glucose, creatinine, liver function tests) 4
• Bone profile (calcium, alkaline phosphatase) 4

If symptoms persist >4 weeks:

• Autoimmune serology: ANA, RF, and anti-CCP 1, 3
• HLA-B27 if spondyloarthritis suspected 1, 3
• Creatine kinase (CK) if myositis suspected; add troponin if muscle weakness suggests cardiac involvement 1, 3

Additional tests to consider based on clinical suspicion:

• Protein electrophoresis, TSH, vitamin D 4
• ANCA, tuberculosis testing if mimicking conditions suspected 4

Imaging Studies

• Plain radiography of affected joints as first-line imaging to detect erosions, osteophytes, or metastatic lesions 1, 3
• MRI is preferred for detecting bone-marrow edema, early inflammatory changes, and chronic non-bacterial osteitis 1
• Musculoskeletal ultrasound can identify synovitis at point-of-care and aid in early RA detection 1

High-Priority Conditions to Exclude Immediately

Septic Arthritis

• Requires urgent joint aspiration if suspected 1, 3
• Typical presentation: fever, chills, markedly elevated CRP/ESR, possible bacteremia 1

Acute Rheumatic Fever

• Migratory polyarthritis following group A streptococcal infection 1, 2
• Rapid response to salicylates/NSAIDs within 24–48 hours is characteristic 1, 2
• More aggressive workup warranted in moderate-to-high risk populations 3

Myositis with Cardiac Involvement

• Check troponin if muscle weakness is present 1, 3
• Monitor CK in addition to ESR and CRP 1, 3

Treatment Approach

For Mild-to-Moderate Symptoms (No Objective Synovitis)

Initial symptomatic treatment:

• NSAIDs and/or analgesics as first-line therapy 4
• Intra-articular glucocorticoids for monoarthritis or oligoarthritis 4
• Anti-inflammatory effect expected within several hours to a few days 4

For Inflammatory Arthritis (Objective Synovitis Present)

If symptomatic treatment insufficient and tissue inflammation persists:

• Systemic glucocorticoids should be considered for both immune-related rheumatic and systemic symptoms 4
• Typical dosing for arthritis: median 20 mg/day prednisone 4
• When improvement achieved, taper to lowest effective dose to control symptoms 4

Non-Pharmacologic Interventions

Evidence-based approaches with most uniform positive effects on pain:

• Physical activity and exercise interventions (most uniformly positive effects) 4
• Psychological interventions (most uniformly positive effects) 4
• Educational interventions, orthotics, weight management for particular disease groups 4
• Adopt a patient-centered framework within a biopsychosocial perspective 4

Indications for Rheumatology Referral

Refer immediately if:

• Presence of clinical synovitis (objective joint swelling) 1, 3, 2
• Persistent symptoms >4 weeks without a clear alternative diagnosis 1, 3, 2
• Severe pain with signs of inflammation despite initial management 1, 3
• Persistent monoarthritis requiring exclusion of septic arthritis, malignancy, or chronic infection 1
• Atypical presentation (peripheral inflammatory arthritis, systemic symptoms, low inflammatory markers, age <60 years) 4
• Experience of or high risk of therapy-related side effects 4

Critical Clinical Pitfalls

• Do NOT wait for chronicity before referring—early referral is warranted when synovitis is detected 1, 2
• Normal ESR/CRP does NOT rule out inflammatory arthritis 1, 3, 2
• Prior NSAID use can mask the migratory pattern of acute rheumatic fever, obscuring diagnosis 1
• In low-risk populations, polyarthralgia is rarely due to acute rheumatic fever—consider more common etiologies 1

Monitoring Strategy

• Perform serial rheumatologic examinations and repeat inflammatory markers (ESR, CRP) every 4–6 weeks after initiating therapy 1, 3
• If myositis is in the differential, monitor CK in addition to ESR and CRP 1, 3
• Treatment aims should be based on shared decision-making between patient and physician 4