What are the initial steps for an inflammatory/autoimmune (inflammation of the body's immune system) lab workup?

Initial Laboratory Workup for Inflammatory/Autoimmune Conditions

The initial laboratory workup for inflammatory/autoimmune conditions should include inflammatory markers (ESR and CRP), complete blood count with differential, comprehensive metabolic panel, and autoantibody testing based on clinical presentation. 1

Core Laboratory Tests

• Inflammatory Markers: Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are essential first-line tests to assess systemic inflammation 1, 2
• Complete Blood Count (CBC) with differential: Necessary to evaluate for cytopenias and other hematologic abnormalities that may indicate autoimmune disease 1, 3
• Comprehensive Metabolic Panel: Essential to assess liver and kidney function, which may be affected by autoimmune processes or needed for baseline values before treatment 1
• Autoantibody Testing: Antinuclear antibodies (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies should be included in the initial workup 1, 4

Disease-Specific Laboratory Tests

• For Inflammatory Arthritis: Consider plain radiographs of affected joints, ultrasound or MRI if clinically indicated, and specific autoantibodies (RF, anti-CCP) 4
• For Myositis/Myopathy: Test creatine kinase (CK), transaminases (AST, ALT), lactate dehydrogenase (LDH), and aldolase; consider troponin to evaluate for myocardial involvement 4
• For Autoinflammatory Syndromes: Consider genetic testing using next-generation sequencing (NGS) platforms for suspected monogenic disorders 4
• For Suspected Immune Checkpoint Inhibitor-Related Adverse Events: Include thyroid function tests and specific autoantibody panels based on organ involvement 4

Additional Considerations

• Serum Amyloid A (SAA) and S100 proteins may be assessed if available, especially for monitoring chronic inflammation 4
• Complement Levels (C3, C4): Particularly useful for suspected systemic lupus erythematosus 1, 3
• Screening for Infections: Test for viral hepatitis B, C, and latent/active tuberculosis before initiating immunosuppressive therapy 4
• Specialized Tests: Consider disease-specific tests such as mevalonic acid in urine for mevalonate kinase deficiency or specific genetic tests for hereditary periodic fever syndromes 4, 5

Algorithmic Approach

1. First-line tests (for all patients with suspected inflammatory/autoimmune disease):

   • ESR and CRP 1, 2
   • CBC with differential 1
   • Comprehensive metabolic panel 1
   • ANA testing 1

2. Second-line tests (based on clinical presentation):

   • Joint symptoms: RF, anti-CCP, joint imaging 4
   • Muscle weakness/pain: CK, LDH, aldolase, transaminases, troponin 4
   • Skin manifestations: Consider skin biopsy and specific antibody panels 1
   • Fever of unknown origin: Consider genetic testing for autoinflammatory syndromes 4

3. Monitoring tests (after diagnosis):

   • Regular assessment of inflammatory markers (ESR, CRP) 4, 1
   • Disease-specific monitoring based on organ involvement 1
   • Medication-specific monitoring (e.g., CBC, liver function for immunosuppressants) 6

Common Pitfalls to Avoid

• Overreliance on autoantibody testing: A negative ANA does not rule out autoimmune disease; clinical correlation is essential 1
• Delaying treatment while awaiting complete diagnostic workup in severe presentations 1
• Not screening for infections before starting immunosuppressive therapy 4
• Misinterpreting discordant ESR and CRP results: These can occur in various conditions and during resolution of inflammation 2
• Failure to consider autoinflammatory diseases in the differential diagnosis of inflammatory conditions, especially in pediatric patients 3, 7

Special Considerations

• Chronic inflammation may bridge the gap between autoinflammatory and autoimmune diseases, requiring comprehensive testing 5, 7
• Consider the possibility of post-infectious autoimmunity, including post-COVID autoimmune manifestations in patients with relevant history 8
• Early referral to rheumatology is recommended for patients with suspected autoimmune disease for further specialized testing and management 4, 1