What labs and workup are recommended for a patient with joint pain, arthritis, and generalized pain, considering age, sex, and medical history?

Laboratory Workup for Joint Pain, Arthritis, and Generalized Pain

Order a complete blood count (CBC), urinalysis, transaminases, antinuclear antibodies (ANA), erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies as your initial laboratory panel for new onset polyarticular joint pain. 1

Essential First-Line Laboratory Tests

Core inflammatory and autoimmune panel:

• CBC, urinalysis, and transaminases are required to exclude non-rheumatologic diseases (infections, malignancy, liver disease) and assess for systemic involvement 1, 2
• ESR or CRP quantifies the degree of inflammation and predicts persistent/erosive disease 1, 2
• Rheumatoid factor (RF) should be interpreted as negative (≤14-15 IU/mL), low positive (>ULN but ≤3× ULN), or high positive (>3× ULN) 1
• Anti-CCP antibodies are critical as both RF and anti-CCP positivity predict severe disease and poor prognosis 1, 2
• ANA testing helps identify systemic lupus erythematosus and other connective tissue diseases 1, 2

Clinical Context That Guides Laboratory Interpretation

Key physical examination findings that indicate inflammatory arthritis:

• Palpable synovitis (warm, swollen joints with effusion) indicates true inflammation rather than mechanical pain 1
• Positive "squeeze test" (pain with compression of metacarpophalangeal or metatarsophalangeal joints) strongly suggests inflammatory arthritis 1
• Morning stiffness >30 minutes supports inflammatory rather than mechanical causes 1, 3
• Swelling involving metacarpophalangeal (MCP) or metatarsophalangeal (MTP) joints strongly suggests inflammatory arthritis 1

Complete rheumatologic examination should assess:

• All peripheral joints for tenderness, swelling, and range of motion 4, 2
• Spine examination for axial involvement 4, 2
• Age, gender, geographical area, functional status, duration of symptoms, number and pattern of tender/swollen joints, and extra-articular/systemic features 2

Additional Testing Based on Clinical Suspicion

When to add specific tests:

• HLA B27 testing if symptoms suggest reactive arthritis or affect the spine (seronegative spondyloarthropathy) 4
• Joint aspiration with synovial fluid analysis (cell count, Gram stain, culture, crystal analysis) if septic arthritis or crystal-induced arthritis (gout, pseudogout) is suspected 4, 2
• Blood cultures if fever is present, symptoms have acute onset, or bloodstream infection is suspected 2
• Creatine kinase (CK) levels should be checked if there is true weakness (not just pain) to differentiate polymyalgia-like syndrome from myositis 4

Imaging Studies

Plain radiographs are the initial imaging method:

• X-rays of affected joints should be obtained at baseline to evaluate joint damage, erosions, and exclude alternative diagnoses like metastases 4, 2
• Ultrasound with power Doppler or MRI complements radiographs when clinical examination is equivocal, to detect early synovitis not visible on plain films, or if symptoms persist unresponsive to treatment 4, 2
• Ultrasound detects synovitis 2.18-fold more frequently than clinical examination, and MRI detects synovitis 2.20-fold more frequently 2

Critical Pitfalls to Avoid

False positive rheumatoid factor can occur with:

• Infections (mononucleosis, cytomegalovirus, parvovirus) 1
• Other autoimmune diseases (Sjögren's syndrome, systemic lupus, systemic sclerosis) 1
• Vasculitis of various vessel sizes 1
• Always interpret RF in conjunction with anti-CCP and clinical findings 1

Laboratory limitations:

• More than 30-40% of patients with rheumatoid arthritis have negative tests for RF or anti-CCP antibodies, and 40% have normal ESR or CRP 5
• Laboratory tests lack sensitivity and specificity to serve as screening tools; they are most valuable when used selectively in patients with clinically significant likelihood of disease 6
• A single test used to rule in or rule out the most likely joint disease is more helpful than a panel of tests used indiscriminately 6

Timing of Rheumatology Referral

Refer to rheumatology within 6 weeks of symptom onset if:

• Arthritis involves more than one joint with swelling not caused by trauma or bony enlargement 1
• There is joint swelling (synovitis) or if symptoms persist despite initial management 4
• Earlier treatment initiation improves outcomes in inflammatory arthritis 1

Monitoring After Diagnosis

Serial follow-up assessments:

• Patients with inflammatory arthritis should be monitored with serial rheumatologic examinations and inflammatory markers every 4-6 weeks after treatment initiation 4, 2
• Test for viral hepatitis B, C, and latent or active tuberculosis before starting DMARD or biologic treatment 4, 2
• Repeated screening labs annually in patients who require biologic treatment for 1 year until treatment is completed 4

Initial Symptomatic Management While Awaiting Workup

Conservative management before specialist evaluation:

• Consider NSAIDs (such as naproxen 500 mg twice daily) after evaluating gastrointestinal, renal, and cardiovascular status 1
• Avoid starting DMARDs (like methotrexate) until rheumatology consultation, as these require specific monitoring protocols and should be initiated by specialists 1