What is the guideline-supported work-up for autoimmune diseases?

Guideline-Supported Diagnostic Work-up for Autoimmune Diseases

The diagnostic work-up for autoimmune diseases should include a comprehensive panel of laboratory tests, imaging studies, and specialty consultations based on the suspected condition, with early rheumatology referral for all cases with moderate to severe presentations.

Initial Evaluation

• Complete history focusing on symptoms of joint pain, infections, and family history of autoimmune disorders 1
• Physical examination with special attention to joint involvement, skin manifestations, and spleen size 1
• Laboratory evaluation of inflammatory markers: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) 1

Laboratory Investigations

Basic Autoimmune Panel

• Complete blood count (CBC) with differential to assess for cytopenias 2
• Comprehensive metabolic panel including liver and kidney function tests 2
• Antinuclear antibodies (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies 2, 1
• Inflammatory markers (ESR, CRP) 2, 1

Disease-Specific Testing

• For suspected autoimmune hepatitis:

  • Liver function tests (AST, ALT, alkaline phosphatase, bilirubin) 2
  • Serum immunoglobulins 2
  • Liver-specific autoantibodies (anti-smooth muscle, anti-liver/kidney microsomal type 1) 2
  • Liver biopsy is considered a prerequisite for diagnosis 2

• For suspected inflammatory myositis:

  • Creatine kinase (CK), transaminases, lactate dehydrogenase (LDH), and aldolase 2
  • Troponin to evaluate for myocardial involvement 2
  • Consider electromyography (EMG), MRI of affected muscles, and/or muscle biopsy when diagnosis is uncertain 2

• For suspected immune thrombocytopenia:

  • Peripheral blood smear and reticulocyte count 2
  • Direct antiglobulin test to rule out Evans syndrome 2
  • Bone marrow evaluation if other cell lines are affected 2

• For suspected lymphopenia:

  • Evaluation for lymphocyte-depleting therapy history 2
  • Screening for infections (CMV, HIV, hepatitis) 2
  • Chest X-ray to evaluate for thymoma 2

Imaging Studies

• Joint radiographs for suspected inflammatory arthritis 1
• Abdominal ultrasound or CT scan to evaluate for organomegaly in suspected systemic disease 1
• Muscle MRI for suspected inflammatory myopathies 2

Special Considerations

Autoantibody Testing

• Indirect immunofluorescence (IFL) is the gold standard for initial autoantibody screening 2
• ELISA methods should not be used as the sole primary screening test for autoimmune hepatitis-related autoantibodies 2
• Consider repeated autoantibody testing in initially seronegative patients as autoantibody titers may vary during disease course 2
• Send patient sera to reference laboratories for full evaluation in cases of diagnostic uncertainty 2

Histopathological Evaluation

• Liver biopsy is essential for autoimmune hepatitis diagnosis 2
• Consider transjugular approach when severe coagulopathy is present 2
• Muscle biopsy may be necessary when inflammatory myopathy diagnosis is uncertain 2
• Temporal artery biopsy if temporal arteritis is suspected 2

Management Approach

• Early referral to rheumatology for suspected autoimmune disease 2, 1
• Initial treatment with corticosteroids (prednisone) at appropriate doses based on disease severity 2, 1
• Consider steroid-sparing agents such as methotrexate for long-term management 3
• Methotrexate dosing typically starts at 10-25 mg weekly for rheumatoid arthritis 3

Monitoring and Follow-up

• Regular monitoring of disease activity through clinical assessment and laboratory markers 1
• Periodic assessment of organ function based on systems involved 2, 1
• Monitoring for medication side effects, particularly with immunosuppressive therapy 3

Common Pitfalls to Avoid

• Failure to consider seronegative autoimmune disease when clinical suspicion is high 4
• Relying solely on autoantibody testing without clinical correlation 2
• Delaying treatment while awaiting complete diagnostic work-up in severe presentations 2
• Not screening for infectious diseases (HIV, hepatitis, tuberculosis) before starting immunosuppressive therapy 2