What bloodwork should be ordered for a patient presenting with polyarticular pain?

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Bloodwork for Polyarticular Pain

Order inflammatory markers (ESR and CRP), complete blood count with differential, rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), and antinuclear antibody (ANA) as your initial laboratory panel for polyarticular pain. 1, 2

First-Line Essential Laboratory Tests

Inflammatory Markers

  • ESR and CRP should be obtained immediately to assess for inflammation and help distinguish inflammatory from noninflammatory arthritis 1, 2, 3
  • Significantly elevated markers indicate inflammatory arthritis or infection, while normal or mildly elevated markers suggest non-inflammatory causes such as osteoarthritis 3
  • Important caveat: Anemia and azotemia can artificially elevate ESR independent of inflammatory activity 2
  • Normal ESR does not exclude inflammatory arthritis; CRP may be more sensitive in acute crystal arthropathy 2

Complete Blood Count with Differential

  • CBC with differential is mandatory to evaluate for infection, inflammation, or malignancy 1
  • Helps characterize anemia, which commonly accompanies rheumatoid arthritis as anemia of chronic disease and correlates with disease activity 2
  • Assesses for leukocytosis that may indicate infection 2

Autoimmune Serologic Testing

Rheumatoid Arthritis Markers

  • RF and ACPA should be tested immediately when inflammatory polyarthritis is suspected 1, 2
  • These antibodies are highly predictive of RA diagnosis and prognosis 2
  • Critical pitfall: Negative RF and ACPA do not exclude progression to RA 2

Connective Tissue Disease Screening

  • ANA testing should be performed if connective tissue disease is suspected based on clinical features 1

Additional Testing Based on Clinical Context

Metabolic Panel

  • Comprehensive metabolic panel (blood glucose, renal function, liver function) should be obtained 4
  • Blood glucose has the highest diagnostic yield among screening tests, as diabetes mellitus is the most common cause of polyneuropathy that may present with joint symptoms 4

Vitamin B12 Assessment

  • Serum B12 should be checked, as deficiency was found in approximately 3.6% of patients with polyneuropathy 4
  • Consider methylmalonic acid and homocysteine if B12 is in the low-normal range (200-500 pg/dL), as these metabolites detect deficiency in 5-10% of patients with normal-range B12 4

Infectious Disease Screening

  • Blood cultures should be performed if fever is present or if bloodstream infection is suspected 1
  • Consider testing for viral hepatitis B, C, and tuberculosis, especially before starting immunosuppressive therapy 1

When to Perform Joint Aspiration

Arthrocentesis must be performed urgently if septic arthritis or crystal-induced arthritis cannot be excluded clinically 1, 3

Synovial Fluid Analysis Should Include:

  • Total cell count and differential leukocyte count 1
  • Crystal analysis for gout or pseudogout 1
  • Gram stain and culture for infectious causes 1
  • Important: Withhold antimicrobials for at least 2 weeks prior to aspiration if the patient is medically stable, to increase organism recovery 3

Common Pitfalls to Avoid

  • Do not rely on serum uric acid during acute presentations, as it may be normal during acute gout flare 2
  • Do not assume normal inflammatory markers exclude inflammatory arthritis 2
  • Do not skip joint aspiration when septic arthritis is a consideration—this is a critical rule-out that requires urgent evaluation 2
  • Laboratory test results must be interpreted in the context of clinical information, as the etiologic yield of laboratory testing alone is limited by low specificity 4

References

Guideline

Diagnostic Approach for Severe Joint Pain

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Differential Diagnosis for Anemia and Joint Pain in Adults

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Diagnostic Approach to Periarthritis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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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