What laboratory tests should be ordered for a patient with new‑onset joint pain and skin discomfort?

Laboratory Workup for New-Onset Joint Pain with Skin Discomfort

Order an autoimmune panel including RF, anti-CCP antibodies, ANA, ESR, and CRP immediately, along with a complete blood count with differential, comprehensive metabolic panel, and urinalysis to distinguish inflammatory from non-inflammatory causes and identify systemic disease. 1, 2

Essential First-Line Laboratory Tests

Inflammatory Markers

• ESR and CRP should be performed at baseline for both diagnostic and prognostic purposes, with CRP preferred for ongoing monitoring as it is more reliable and not age-dependent 1, 2
• Markedly elevated inflammatory markers (CRP >10 mg/L, ESR >30 mm/hr) strongly suggest inflammatory arthritis, though normal values do not exclude it 2
• Repeat ESR and CRP when clinically relevant to monitor disease activity and treatment response 1, 2

Autoimmune Serology

• RF and anti-CCP antibodies are predictive of rheumatoid arthritis diagnosis and prognosis; negative tests do not exclude progression to RA 1, 2
• Anti-CCP has high specificity (90%) with moderate sensitivity (60%), while RF has lower specificity (70%) with similar sensitivity 2
• Both tests should be ordered simultaneously at initial presentation as cornerstone autoantibody tests 2

Additional Autoantibodies (When Indicated)

• ANA testing should be considered if a connective tissue disease or systemic inflammatory disorder is suspected, or if diagnosis remains uncertain 1, 2
• If ANA is positive, order anti-dsDNA and extractable nuclear antigen (ENA) panels to exclude systemic lupus erythematosus 2
• HLA-B27 testing may be helpful if symptoms suggest reactive arthritis, affect the spine, or if spondyloarthropathy is suspected (particularly in RF- and anti-CCP-negative patients) 1, 2

Baseline Organ Function Assessment

Metabolic and Hematologic Evaluation

• Complete blood count with differential to assess for cytopenias before starting treatment and calculate neutrophil-to-lymphocyte ratio 2, 3
• Comprehensive metabolic panel including liver function tests, renal function, glucose, and urate levels for baseline assessment and to identify contraindications to disease-modifying therapy 1, 2
• Urinalysis as part of the standard initial workup 1, 2

Pre-Treatment Infectious Disease Screening (If Immunosuppression Anticipated)

• Screen for hepatitis B, hepatitis C, and tuberculosis before starting any biologic therapy or disease-modifying antirheumatic drugs 2, 3

Algorithmic Approach Based on Clinical Presentation

If Morning Stiffness >30 Minutes + Multiple Small Joints Involved

1. Order RF, anti-CCP, ESR, CRP, CBC, CMP, urinalysis immediately 1, 2
2. Obtain bilateral hand, wrist, and foot X-rays to assess for erosions 1, 2
3. Refer to rheumatology within 6 weeks if inflammatory arthritis suspected 2

If Skin Involvement Prominent (Rash, Plaques, Nodules)

1. Add ANA to the autoimmune panel 1, 4
2. Perform thorough skin examination documenting distribution and morphology 4
3. Consider skin biopsy if vasculitic lesions or atypical rash present 4

If Axial or Entheseal Symptoms Present

1. Add HLA-B27 testing to the initial panel 1
2. Consider pelvic/sacroiliac joint X-rays 1

If Monoarticular Presentation with Fever

1. Perform arthrocentesis for cell count, Gram stain, culture, and crystal analysis to exclude septic arthritis before ordering serologic tests 4, 5
2. Treat as septic arthritis until proven otherwise 6

Critical Pitfalls to Avoid

• Do not delay treatment waiting for positive serology: Seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease 2
• Do not dismiss the diagnosis based on normal ESR/CRP: Acute phase reactants are poor predictors and can be normal even in active inflammatory disease 2
• Do not rely on autoantibody positivity alone: Clinical context with definite synovitis takes precedence over serologic findings 2, 4
• Do not order genetic testing routinely: There is no genetic test that can be routinely recommended, except HLA-B27 in specific clinical settings 1

Monitoring After Initial Workup

• Serial rheumatologic examinations with inflammatory markers should be conducted every 4-6 weeks after treatment is instituted 1, 4
• Repeat X-rays within 6-12 months to monitor for radiographic progression if inflammatory arthritis is confirmed 2