What is the typical approach to an autoimmune workup?

Typical Autoimmune Workup

The typical autoimmune workup should include a complete blood count with differential, inflammatory markers (ESR and CRP), comprehensive metabolic panel, and autoantibody screening (ANA, RF, anti-CCP), with additional disease-specific testing guided by clinical presentation. 1, 2

Initial Clinical Assessment

History and Physical Examination

• Focus on joint pain patterns, duration, and morning stiffness to identify inflammatory arthritis 1, 3
• Document history of recurrent infections, which may suggest underlying immune dysregulation 4, 1
• Obtain family history of autoimmune disorders, as genetic predisposition is common 4, 1
• Examine all joints systematically for swelling, warmth, and range of motion limitations 1, 3
• Assess skin for rashes, photosensitivity, ulcers, or other manifestations of systemic disease 1, 5
• Evaluate spleen size, as splenomegaly may indicate systemic autoimmune involvement 4, 1

Core Laboratory Testing

Basic Blood Work

• Complete blood count with differential to identify cytopenias (anemia, leukopenia, thrombocytopenia) common in autoimmune conditions 1, 2, 6
• Inflammatory markers: ESR and CRP to assess disease activity and degree of systemic inflammation 4, 1, 2, 3
• Comprehensive metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, bilirubin) and kidney function (creatinine, BUN) to evaluate organ involvement 1, 2

Autoantibody Screening Panel

• Antinuclear antibodies (ANA) as the primary screening tool for systemic autoimmune diseases 1, 2, 6
• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies for suspected inflammatory arthritis 1, 2, 3
• Total IgE and IgG-anti-thyroid peroxidase (anti-TPO) levels, as low total IgE with elevated anti-TPO suggests autoimmune mechanisms 4

Disease-Specific Testing

When Systemic Lupus Erythematosus is Suspected

• Anti-dsDNA, anti-Smith, anti-RNP, anti-SSA (Ro), and anti-SSB (La) antibodies 2
• Complement levels (C3, C4, CH50) to assess complement consumption 2

When Systemic Sclerosis is Suspected

• Anti-centromere, anti-Scl-70 (topoisomerase), and anti-RNA polymerase III antibodies 2

When Autoimmune Hepatitis is Suspected

• Anti-smooth muscle antibodies, anti-liver kidney microsomal antibodies, and serum immunoglobulins (IgG, IgA, IgM) 1, 2
• Liver biopsy for definitive diagnosis 1

When Inflammatory Myositis is Suspected

• Muscle enzymes: creatine kinase (CK), AST, ALT, lactate dehydrogenase (LDH), and aldolase 4, 1, 2
• Troponin to evaluate for myocardial involvement 4, 1, 2
• Anti-Jo-1 and other myositis-specific antibodies 2
• Muscle MRI for localization of inflammation 1

When Autoimmune Thyroid Disease is Suspected

• Thyroid function tests (TSH, free T4) and thyroid antibodies (anti-TPO, anti-thyroglobulin) 2

When Spondyloarthropathy is Suspected

• HLA-B27 typing 2

Additional Considerations

Pre-Treatment Infectious Disease Screening

• HIV, hepatitis B, hepatitis C, and tuberculosis screening must be performed before initiating immunosuppressive therapy 4, 1, 2
• This prevents reactivation of latent infections during treatment 4, 1

Specialized Testing Based on Clinical Context

• Cryoglobulins and serum protein electrophoresis for suspected cryoglobulinemic vasculitis 2
• Iron studies (ferritin, transferrin saturation) to exclude hemochromatosis when liver enzymes are elevated 2
• Celiac disease antibodies (tissue transglutaminase, endomysial antibodies) in appropriate clinical settings 2

Imaging Studies

• Joint radiographs for suspected inflammatory arthritis to assess for erosive changes 1
• Abdominal ultrasound or CT scan to evaluate for organomegaly in suspected systemic disease 1
• Chest radiograph to evaluate for thymoma or pulmonary involvement 4

Critical Pitfalls to Avoid

• Never rely solely on autoantibody testing without clinical correlation, as positive results may occur in healthy individuals 1
• Do not delay treatment while awaiting complete diagnostic workup in severe presentations, as early intervention prevents irreversible organ damage 1, 3
• Always screen for infectious diseases before starting immunosuppression, as failure to do so risks life-threatening opportunistic infections 4, 1
• Perform autoantibody testing before initiating immunosuppressive therapy when possible, as treatment may affect results and complicate diagnosis 2

Management Pathway

• Early referral to rheumatology is essential for suspected autoimmune disease to ensure appropriate diagnosis and treatment 1, 3
• Initial corticosteroid therapy (prednisone 0.5-1 mg/kg for severe disease, 10-20 mg/day for moderate disease) should be initiated based on disease severity 1, 3
• Serial monitoring of inflammatory markers (ESR, CRP) and clinical symptoms is necessary to assess treatment response 2, 3