What is the initial approach to an autoimmune workup?

Initial Approach to an Autoimmune Workup

The initial autoimmune workup should include complete blood count with differential, comprehensive metabolic panel, inflammatory markers (ESR, CRP), antinuclear antibody (ANA), and specific autoantibody testing based on clinical presentation and suspected disease. 1

Basic Laboratory Evaluation

First-Line Testing

• Complete blood count (CBC) with differential

  • Look for cytopenias (anemia, leukopenia, thrombocytopenia)
  • Evaluate for lymphopenia which may suggest systemic lupus erythematosus
  • Check for neutrophilia which may indicate active inflammation

• Comprehensive metabolic panel

  • Assess liver function (AST, ALT, alkaline phosphatase, bilirubin)
  • Evaluate renal function (BUN, creatinine)
  • Check electrolytes and protein levels

• Inflammatory markers

  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)
  • Serum amyloid A (SAA) if available 1

Autoantibody Testing

• Antinuclear antibody (ANA) - primary screening test for many autoimmune diseases

  • Immunofluorescence (IFL) is the preferred method over ELISA
  • Positive results should be followed by specific antibody testing 1

• Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) - for suspected rheumatoid arthritis

• Disease-specific autoantibodies based on clinical presentation:

  • Anti-dsDNA, anti-Smith for SLE
  • Anti-Scl-70, anti-centromere for systemic sclerosis
  • Anti-Jo-1 for inflammatory myopathies
  • Anti-SSA/Ro, anti-SSB/La for Sjögren's syndrome 1

Specialized Testing Based on Clinical Presentation

For Suspected Autoimmune Hepatitis

• Anti-smooth muscle antibodies (SMA)
• Anti-liver kidney microsomal type 1 (LKM1) antibodies
• Anti-liver cytosol type 1 (LC1) antibodies
• Liver biopsy is considered prerequisite for diagnosis 1

For Suspected Autoimmune Neurological Disease

• Cerebrospinal fluid analysis for oligoclonal bands, IgG index
• Neuronal autoantibodies in serum and CSF
• Brain MRI with and without contrast
• EEG if encephalopathy is suspected 1

For Suspected Autoinflammatory Syndromes

• Genetic testing for specific mutations based on clinical presentation:
  • NLRP3 for cryopyrin-associated periodic syndromes
  • TNFRSF1A for tumor necrosis factor receptor-associated periodic syndrome
  • MVK for mevalonate kinase deficiency 1

For Suspected Pulmonary Arterial Hypertension with Autoimmune Features

• Echocardiogram with RVSP assessment
• If RVSP > 45 mmHg, proceed with:
  • Pulmonary function tests
  • CT scan of chest or CT angiogram
  • V/Q scan
  • Right heart catheterization 1

Diagnostic Approach by Organ System Involvement

Skin Manifestations

• Skin biopsy for histopathology and immunofluorescence
• Evaluate for rashes, purpura, urticaria, or psoriasis-like lesions 1

Joint Involvement

• X-rays of affected joints
• Ultrasound or MRI for detailed evaluation
• Synovial fluid analysis if effusion is present 1

Renal Involvement

• Urinalysis with microscopy
• Urine protein-to-creatinine ratio
• Consider renal biopsy for definitive diagnosis 1

Important Considerations and Pitfalls

1. Timing of autoantibody testing is crucial

   • Autoantibody titers and specificity may vary during disease course
   • Seronegative individuals at diagnosis may express conventional autoantibodies later 1
   • Repeated testing may be necessary if clinical suspicion remains high

2. Interpretation challenges

   • False positives can occur, especially with low-titer ANA
   • Different testing methodologies may yield different results
   • Tests should only be ordered based on clinical presentation 2

3. Quality of testing matters

   • Send samples to reference laboratories for full evaluation in cases of diagnostic uncertainty 1
   • Be aware of the methodology used for testing (IFL vs. ELISA)

4. Consider infection as a trigger

   • Test for viral infections (HIV, hepatitis B/C, CMV, EBV, parvovirus)
   • Bacterial cultures and evaluation for infection should be performed 1

5. Medication-induced autoimmunity

   • Review medication history for drugs associated with autoimmune manifestations
   • Consider immune checkpoint inhibitor-related adverse events in patients on cancer immunotherapy 1

By following this systematic approach to autoimmune workup, clinicians can efficiently identify the underlying autoimmune condition and initiate appropriate management to improve patient outcomes.