Comprehensive Autoimmune Disease Workup
A full workup of autoimmune disease should include complete blood count with differential, comprehensive metabolic panel, inflammatory markers (ESR, CRP), antinuclear antibody (ANA) testing, and disease-specific autoantibody panels based on clinical presentation, with additional organ-specific testing as indicated by symptoms. 1
Initial Laboratory Evaluation
Complete Blood Count (CBC) with differential
- Evaluate for cytopenias, lymphopenia, neutrophilia
- Assess for anemia of chronic disease
Comprehensive Metabolic Panel
- Liver function: AST, ALT, alkaline phosphatase, bilirubin
- Renal function: BUN, creatinine
- Electrolytes and protein levels
- Albumin/globulin ratio
Inflammatory Markers
- Erythrocyte sedimentation rate (ESR)
- C-reactive protein (CRP)
Core Autoantibody Testing
- Antinuclear antibody (ANA) by immunofluorescence (IFL) - preferred over ELISA 1
- Total IgE and IgG levels
- Rheumatoid factor (RF)
- Anti-citrullinated protein antibodies (ACPA)
Organ-Specific Testing
Rheumatologic Evaluation
- Anti-dsDNA, anti-Smith (SLE)
- Anti-Scl-70, anti-centromere (Scleroderma)
- Anti-RNP, anti-SSA, anti-SSB (Sjögren's, SLE)
- Joint imaging: X-rays, ultrasound, or MRI of affected joints
- Synovial fluid analysis if effusion present 1
Hepatic Evaluation
- Anti-smooth muscle antibodies (SMA)
- Anti-liver kidney microsomal type 1 (LKM1) antibodies
- Anti-liver cytosol type 1 (LC1) antibodies
- IgG–anti-thyroid peroxidase (TPO)
- Liver biopsy - considered prerequisite for autoimmune hepatitis diagnosis 2
Dermatologic Evaluation
- Skin biopsy for histopathology and immunofluorescence
- Evaluation of rashes, purpura, urticaria 1
Pulmonary Evaluation
- Pulmonary function tests
- Non-contrast CT scan of chest or CT angiogram
- V/Q scan if thromboembolic disease suspected
- Echocardiogram with RVSP assessment (if RVSP > 45 mmHg, further workup indicated) 2
Renal Evaluation
- Urinalysis with microscopy
- Urine protein-to-creatinine ratio
- Renal biopsy for definitive diagnosis of renal involvement 1
Neurologic Evaluation
- Cerebrospinal fluid analysis for oligoclonal bands and IgG index
- Testing for neuronal autoantibodies in serum and CSF
- EMG, MRI for neuromuscular symptoms 2
Specialized Testing Based on Clinical Presentation
For Suspected Immune Checkpoint Inhibitor-Related Autoimmunity
- CK, transaminases (AST, ALT), LDH, and aldolase for myositis
- Troponin to evaluate myocardial involvement
- Consider paraneoplastic autoantibody testing 2
For Suspected Chronic Urticaria
- Differential blood count
- C-reactive protein level/ESR
- IgG–anti-TPO level and total IgE level
- CU index for patients not responsive to H1 antihistamines 2
Important Considerations
Timing of testing: Autoantibody titers and specificity may vary during disease course; seronegative individuals at diagnosis may express conventional autoantibodies later 2
Repeat testing: May be necessary if clinical suspicion remains high despite initial negative results 1
Laboratory selection: Complete autoimmune serology workup is not available in all laboratories; identify reference laboratories for full evaluation, especially in cases of diagnostic uncertainty 2
Interpretation: Test results must be interpreted within the specific clinical context; false positives can occur, especially with low-titer ANA 1
Monitoring: In adults, autoantibody titers correlate only roughly with disease activity and don't need regular monitoring unless clinical phenotype changes; in pediatric patients, titers may be useful biomarkers of disease activity 2
By following this comprehensive approach to autoimmune disease workup, clinicians can effectively diagnose, monitor, and manage these complex conditions, ultimately improving patient outcomes in terms of morbidity, mortality, and quality of life.