Evaluation and Management of Polyarthralgia

Initial Clinical Assessment: Distinguish Arthralgia from Arthritis

The single most critical step is to determine whether objective joint swelling (synovitis) is present on physical examination, because this fundamentally separates true inflammatory arthritis from simple arthralgia and dictates urgency of referral. 1

Arthralgia is joint pain without visible or palpable swelling; arthritis is joint pain with objective synovitis (swelling you can see or feel). 1
Examine all peripheral joints systematically for tenderness, swelling, erythema, warmth, and range of motion; include the spine and perform an MCP squeeze test (pain with compression suggests inflammation). 2, 1
Morning stiffness lasting >30–60 minutes strongly indicates inflammatory arthritis rather than mechanical pain. 1, 3
A dramatic improvement within 24–48 hours after NSAIDs or corticosteroids (but not opioids) confirms an inflammatory process. 1

History: Key Features to Elicit

Duration: Symptoms persisting ≥6 weeks indicate persistent inflammatory arthritis and mandate rheumatologic work-up. 1
Pattern: Document whether pain is migratory vs. persistent, symmetric vs. asymmetric, and acute vs. chronic. 1
Number and type of joints: Small joints (MCP, PIP) vs. large joints (knees, ankles); symmetry suggests rheumatoid arthritis, asymmetry suggests spondyloarthritis or psoriatic arthritis. 1, 3
Systemic symptoms: Fever, weight loss, rash, dry eyes/mouth, urethritis, or recent infections point toward specific rheumatologic conditions. 1, 3
Medication history: Recent immune checkpoint inhibitors, statins, or other drugs can cause arthralgia. 3
Functional impact: Ask which specific activities the patient cannot perform (e.g., climbing stairs, opening jars) rather than relying solely on pain scores. 4

Laboratory Work-Up

Initial Panel for All Patients

ESR and CRP: Elevated in inflammatory arthritis, but normal values do not exclude inflammatory disease. 2, 1, 3
Complete blood count, urinalysis, basic metabolic panel (glucose, creatinine, liver enzymes) to identify systemic abnormalities. 1
Calcium and alkaline phosphatase (bone profile) to detect metabolic bone disease. 1

Targeted Autoimmune Serology (if symptoms persist >4 weeks)

Rheumatoid factor (RF) and anti-CCP antibodies when symmetrical polyarthritis resembling rheumatoid arthritis is suspected. 2, 1, 3
ANA when connective-tissue disease (e.g., lupus) is part of the differential. 2, 1
HLA-B27 for suspected spondyloarthritis (inflammatory back pain, sacroiliitis, asymmetric peripheral arthritis, enthesitis, dactylitis, uveitis). 2, 1
Creatine kinase (CK) to exclude myositis if proximal muscle pain or weakness is present; CK should be normal in polymyalgia-like syndromes. 2, 3

Additional Tests in Specific Contexts

Serum protein electrophoresis, TSH, vitamin D when endocrine or protein abnormalities are suspected. 1
ANCA and tuberculosis screening if vasculitic or infectious mimics are considered. 1
Viral hepatitis B, C, and latent TB testing before initiating DMARD or biologic therapy. 2

Imaging Studies

Plain radiographs of affected joints are the first-line imaging modality to detect erosions, osteophytes, or metastatic lesions. 2, 1
Radiographs of hands, wrists, and feet are advised because erosions on these studies predict rheumatoid arthritis development and disease persistence. 1
Repeat radiographs within 12 months to monitor disease progression or response to therapy. 1
MRI is preferred for detecting bone-marrow edema, early inflammatory changes, and diagnosing chronic non-bacterial osteitis (CNO), but lacks sufficient evidence for routine use in migratory arthralgia. 1
Musculoskeletal ultrasound can identify synovitis at the point of care and aid in early RA detection. 1

Differential Diagnosis: Inflammatory vs. Non-Inflammatory

Inflammatory Causes (Require Urgent Work-Up and Possible Rheumatology Referral)

Infectious

Septic arthritis: Fever, chills, markedly elevated CRP/ESR, possible bacteremia; requires urgent joint aspiration. 1
Acute rheumatic fever: Migratory polyarthritis following group A streptococcal infection; rapid response to salicylates/NSAIDs within 24–48 hours. 1
Lyme disease: History of tick exposure in northeastern or upper-midwestern United States; erythema migrans precedes arthritis in 60–80% of cases; treat early disease with oral doxycycline, neurologic involvement or treatment failure with IV ceftriaxone. 1
Reactive arthropathies: Consider only after exclusion of autoimmune and viral causes. 1

Autoimmune/Inflammatory Arthritides

Rheumatoid arthritis: Symmetrical polyarthritis of small joints (MCP, PIP), characteristic erosions on imaging, anti-CCP or RF positivity, elevated inflammatory markers. 1
Psoriatic arthritis: Presence of psoriasis (current, past, or family history), inflammatory arthritis, nail dystrophy, dactylitis, juxta-articular new bone formation, DIP joint involvement. 1
Axial spondyloarthritis: Inflammatory back pain, sacroiliitis, asymmetric peripheral arthritis, enthesitis, dactylitis, uveitis, HLA-B27 positivity, good response to NSAIDs. 1
Systemic lupus erythematosus: Systemic features (e.g., rash, serositis) accompany joint symptoms. 1
Adult-Onset Still's Disease (AOSD): Quotidian fever >39°C, leukocytosis >10,000/µL with >80% neutrophils. 1
Polymyalgia rheumatica: Pain but not true weakness; RF and anti-CCP negative; inflammatory markers highly elevated; CK normal; MRI and EMG show no myopathy. 2

Crystal-Induced

Gout: May coexist with pre-existing osteoarthritis; presents with acute mono- or oligo-arthritis. 1

Non-Inflammatory Causes

Degenerative

Osteoarthritis: Common in older adults with history of joint strain; imaging shows subchondral sclerosis, cysts, osteophytes, joint-space narrowing. 1
Hand osteoarthritis: Pain on use, mild morning stiffness (<30 min), involvement of DIP, PIP, and thumb base joints, Heberden/Bouchard nodes in adults >40 years. 1

Metabolic/Systemic

Paget's disease: Familial predisposition, pelvic/skull involvement, elevated alkaline phosphatase, age >50 years, mixed lytic/sclerotic lesions on imaging. 1
Osteomalacia: Generalized bone pain, muscle weakness, low serum phosphate, elevated alkaline phosphatase, vitamin D deficiency. 1
Hereditary hemochromatosis: Preferential involvement of MCP joints and wrists. 1

Other

Chronic non-bacterial osteitis (CNO): Bone-marrow edema on MRI affecting anterior chest wall, spine, mandible. 1
Fibromyalgia: Widespread pain without objective synovitis; normal inflammatory markers. 2
Statin-induced myopathy: Proximal muscle pain; elevated CK. 2

Treatment Algorithm

Step 1: Mild-to-Moderate Symptoms (No Objective Synovitis)

Initiate NSAIDs (e.g., naproxen 500 mg twice daily) or acetaminophen as first-line therapy for pain control. 2, 1, 3
For isolated mono- or oligo-arthritis, consider a single intra-articular glucocorticoid injection (e.g., triamcinolone hexacetonide) to achieve rapid symptom relief. 1, 3
Expect anti-inflammatory benefit within several hours to a few days after NSAID or intra-articular steroid administration. 1

Step 2: Inflammatory Arthritis (Objective Synovitis Present)

Add systemic glucocorticoids when symptomatic treatment is insufficient and objective inflammation persists. 1
Start prednisone at approximately 20 mg/day, adjusting based on response. 1, 3
Once clinical improvement is achieved, taper glucocorticoids to the lowest effective dose to minimize long-term adverse effects. 1
Avoid chronic oral corticosteroids due to long-term harm. 3

Step 3: Non-Pharmacologic Interventions (For All Patients)

Structured physical activity and exercise programs consistently demonstrate the most uniform positive impact on pain. 1, 3
Cognitive-behavioral therapy yields uniformly positive effects on pain perception and coping. 1, 3
Disease-specific education, orthotic devices, and weight-management counseling address modifiable contributors to joint stress. 1, 3
Physical and occupational therapy, including strengthening exercises, joint protection techniques, and ergonomic adaptations, help preserve joint mobility and reduce disability. 3

Indications for Rheumatology Referral

Refer promptly when:

Presence of clinical synovitis (objective joint swelling). 2, 1
Persistent symptoms >4 weeks without a clear alternative diagnosis. 2, 1
Atypical presentation: Peripheral inflammatory arthritis with systemic symptoms, low inflammatory markers, or patient age <60 years. 2, 1
Severe pain with signs of inflammation despite initial management. 1
Persistent monoarthritis requiring exclusion of septic arthritis, malignancy, or chronic infection. 1
Experience of or high risk for therapy-related side effects. 2, 1
PMR refractory to glucocorticoid therapy and/or relapses/prolonged therapy. 2

Monitoring Strategy

Perform serial rheumatologic examinations and repeat inflammatory markers (ESR, CRP) every 4–6 weeks after initiating therapy. 2, 1
If myositis is in the differential, monitor CK in addition to ESR and CRP. 1
Base treatment goals on shared decision-making between clinician and patient, aligning therapeutic intensity with patient preferences and disease activity. 1

Critical Pitfalls to Avoid

Early referral is warranted when synovitis is detected; waiting for chronicity may delay diagnosis. 1
Normal ESR/CRP does not rule out inflammatory arthritis. 1
Never rely solely on pain intensity scores; pain is multidimensional and requires assessment of functional impact and patient goals. 4
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
Do not ignore underlying treatable causes; providing only opioids for conditions like impending spinal cord compression without addressing the underlying pathology is inappropriate. 4

Special Populations

Immune Checkpoint Inhibitor-Associated Arthritis

Musculoskeletal symptoms occur in up to 40% of patients on immune checkpoint inhibitors. 3
Inflammatory markers are typically very elevated. 3
Grade 1: Mild pain with inflammation; continue ICPi; initiate acetaminophen and/or NSAIDs. 2
Grade 2: Moderate pain limiting instrumental ADL; consider holding ICPi; escalate analgesia; if inadequately controlled, initiate prednisone 10–20 mg/day; if no improvement after 4 weeks, treat as Grade 3. 2
Grade 3–4: Seek rheumatologist advice; test for viral hepatitis B, C, and latent or active TB before DMARD treatment. 2

Polymyalgia Rheumatica

Use glucocorticoids instead of NSAIDs in patients with PMR, with the exception of possible short-term use of NSAIDs and/or analgesics for pain related to other conditions. 2
Use the minimum effective GC dose within a range of 12.5–25 mg prednisone equivalent daily as initial treatment. 2
Initial tapering: Taper dose to 10 mg/day prednisone equivalent within 4–8 weeks. 2
Relapse therapy: Increase oral prednisone to the pre-relapse dose and decrease it gradually (within 4–8 weeks) to the dose at which the relapse occurred. 2
Tapering once remission is achieved: Taper daily oral prednisone by 1 mg every 4 weeks until discontinuation given that remission is maintained. 2
Consider intramuscular methylprednisolone (starting dose 120 mg every 3 weeks) as an alternative to oral GCs. 2

Ulcerative Colitis-Associated Arthropathy

Type I peripheral arthritis (pauciarticular, large joints, acute, self-limiting) is associated with intestinal disease activity; treatment of the underlying UC is normally effective in relieving symptoms. 2
Type II peripheral arthritis (polyarticular, small joints) is independent of UC activity. 2
For persistent symptoms in the absence of active UC, use short-term NSAIDs (low dose, short duration to minimize UC aggravation risk). 2
Sulfasalazine has a role in persistent peripheral arthritis. 2
In axial arthropathy, intensive physiotherapy associated with NSAIDs is recommended, but long-term NSAIDs should be avoided if possible. 2
Anti-TNF therapy is well established for patients with ankylosing spondylitis and UC intolerant or refractory to NSAIDs. 2

How should I evaluate and manage a patient with polyarthralgia, including work‑up to distinguish inflammatory from non‑inflammatory causes and appropriate treatment options?

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