What tests should be ordered for a rheumatology workup?

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Last updated: October 17, 2025View editorial policy

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Standard Rheumatology Workup Tests

A comprehensive rheumatology workup should include acute phase reactants, autoantibody testing, and appropriate imaging studies to accurately diagnose and monitor rheumatic diseases. 1

Core Laboratory Tests

  • Complete Blood Count (CBC) with differential - Essential for detecting cytopenia, anemia, and neutropenia which can be present in various rheumatic diseases 1, 2

  • Acute Phase Reactants:

    • C-reactive protein (CRP) - Preferred over ESR as it's more reliable, not age-dependent, and correlates more closely with clinical and radiographic parameters of inflammation 1, 3
    • Erythrocyte sedimentation rate (ESR) - Useful for assessing inflammation in rheumatoid arthritis, polymyalgia rheumatica, and temporal arteritis 1, 3
  • Autoantibody Testing:

    • Rheumatoid Factor (RF) - Important for RA diagnosis, though 30-40% of RA patients may be seronegative 4, 3
    • Anti-citrullinated protein antibodies (ACPA) - High specificity for RA diagnosis and prognosis; negative tests don't exclude progression to RA 1, 4
    • Antinuclear antibodies (ANA) - Screening test for systemic lupus erythematosus and other connective tissue diseases 1, 5
  • Additional Autoantibody Tests (when clinically indicated):

    • Antibodies to extractable nuclear antigens - Helpful for specific connective tissue disease diagnosis 1, 2
    • Anti-double-stranded DNA antibodies - Specific for SLE 1, 3
    • Anti-neutrophil cytoplasmic antibodies (ANCA) - Essential for diagnosing Wegener's granulomatosis 3, 2
  • Other Laboratory Tests:

    • Biochemistry panel - Liver function tests, glucose, urate, and renal function 1, 5
    • Complement levels (C3, C4) - Useful for monitoring SLE activity 1, 2
    • Immunoglobulins - May be elevated in certain inflammatory conditions 1

Imaging Studies

  • X-rays of affected joints - Should be performed at baseline, particularly hands, wrists, and feet to detect erosions which predict RA development and disease persistence 1

  • Musculoskeletal ultrasound - Valuable for detecting early inflammatory changes in joints, tendons, and bursae; particularly useful for shoulder, elbow, wrist, and hand examinations 1

Disease-Specific Testing

  • For suspected autoinflammatory diseases:

    • Genetic testing using next-generation sequencing (NGS) platforms for CAPS, TRAPS, MKD, and DIRA 1
    • Mevalonic acid in urine for suspected MKD 1
  • For suspected Felty's syndrome:

    • Abdominal ultrasound or CT scan to confirm splenomegaly 5

Important Considerations

  • Laboratory tests should support clinical findings from history and physical examination, not replace them 4, 6

  • More than 30-40% of RA patients may have negative RF or ACPA tests or normal ESR/CRP, highlighting the limitations of laboratory testing 4

  • When ordering autoantibody tests, consider the pretest probability of rheumatic disease to avoid misinterpretation of false positives 6, 7

  • Repeat laboratory tests when clinically relevant to monitor disease activity and treatment response 1

  • For undifferentiated peripheral inflammatory arthritis, X-rays of hands, wrists, and feet should be repeated within 1 year to assess for development of erosions 1

Common Pitfalls to Avoid

  • Over-reliance on laboratory tests - No single test is diagnostic of any rheumatic disease; clinical correlation is essential 4, 6

  • Failure to repeat testing - Single measurements may not reflect disease activity; serial testing is often necessary 1

  • Inappropriate test ordering - Order tests based on specific clinical suspicion rather than as a general panel 6, 7

  • Misinterpreting normal results - Normal laboratory values don't exclude rheumatic disease 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Selection and use of laboratory tests in the rheumatic diseases.

The American journal of medicine, 1996

Guideline

Diagnostic Approach to Felty's Syndrome

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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