What tests and treatments are recommended for patients suspected of having an autoimmune disease?

Comprehensive Autoimmune Disease Testing and Treatment Protocol

For patients with suspected autoimmune disease, a systematic laboratory evaluation including complete blood count with differential, comprehensive metabolic panel, inflammatory markers, and disease-specific autoantibodies is essential for diagnosis, with treatment tailored to the specific condition identified. 1

Initial Diagnostic Evaluation

Core Laboratory Tests

• Complete blood count with differential
• Comprehensive metabolic panel
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP)
• Serum immunoglobulin levels (IgG, IgA, IgM)
• Urinalysis with protein/creatinine ratio 1, 2

First-Line Autoantibody Testing

• Antinuclear antibodies (ANA)
• Smooth muscle antibodies (SMA)
• Anti-liver/kidney microsome type 1 (LKM-1)
• Antimitochondrial antibodies (AMA) 1

Second-Line Testing (Based on Clinical Suspicion)

• Rheumatoid factor (RF)
• Anti-cyclic citrullinated peptide (anti-CCP)
• HLA-B27 (if autoimmune disease suspected)
• ALPS panel (if autoimmune lymphoproliferative syndrome suspected)
• Anti-double-stranded DNA (anti-dsDNA)
• Antiphospholipid antibodies
• Complement levels (C3, C4) 1

Organ-Specific Testing

• Liver: Anti-F-actin, anti-SLA/LP (soluble liver antigen/liver pancreas), anti-LC1 (liver cytosol type 1) 1
• Neurological: CSF analysis, oligoclonal bands, anti-NMDA receptor antibodies, MOG-IgG 1
• Pulmonary: GM-CSF antibody testing (for autoimmune pulmonary alveolar proteinosis) 1

Imaging Studies

Initial Imaging

• Chest X-ray
• Ultrasound of affected areas (abdomen, joints, thyroid as indicated)
• Consider whole-body MRI in selected patients 1

Advanced Imaging (Based on Symptoms)

• PET/CT scan (judicious use recommended, especially in children)
• MRI with contrast for neurological symptoms
• High-resolution CT chest for pulmonary symptoms
• Dedicated organ-specific imaging as needed 1

Tissue Sampling

• Biopsy of affected organs may be necessary for definitive diagnosis
• For autoimmune hepatitis: liver biopsy shows characteristic interface hepatitis with plasma cell-rich infiltrates 1
• For neurological autoimmune conditions: CSF analysis and sometimes brain biopsy 1
• Ensure sufficient tissue is acquired and reviewed by a pathologist familiar with autoimmune conditions 1

Treatment Approach

First-Line Therapy

• Corticosteroids: Often the initial treatment for acute flares
  • Prednisone (40-70 mg per day) for most autoimmune conditions
  • Higher doses (>0.5 mg/kg per day) often needed compared to other immune diseases
  • Treat to best observed response, then slow taper 1

Disease-Modifying Agents

• Conventional immunosuppressants:
  • Methotrexate
  • Azathioprine
  • 6-Mercaptopurine (6-MP)
  • Mycophenolate mofetil 1, 2

Biologic Therapies

• TNF inhibitors for appropriate conditions:
  • Adalimumab: For rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, and uveitis 3
  • Etanercept: For rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis 4
• Rituximab: For refractory cases of certain autoimmune conditions 1
• Plasmapheresis: For severe, treatment-resistant cases 1

Preventive Care and Monitoring

Vaccination

• Complete all appropriate vaccinations before starting immunosuppression:
  • Influenza
  • Pneumococcal
  • Herpes zoster
  • Avoid live vaccines while on immunosuppression 2, 4

Monitoring

• Regular laboratory assessment of organ function
• Monitor for medication side effects
• Screen for skin and non-skin cancers
• Assess bone health and fracture risk 2

Common Pitfalls and Caveats

1. False positives: Low-titer autoantibodies can occur in healthy individuals; clinical correlation is essential 5

2. Seronegative cases: Some patients with autoimmune disease may initially test negative for conventional autoantibodies; consider repeated testing or testing for less common antibodies 1

3. Overlap syndromes: Multiple autoimmune conditions can coexist in the same patient; comprehensive testing is important 1

4. Drug-induced autoimmunity: Some medications can induce autoantibody formation without clinical disease; etanercept has been associated with development of ANA and anti-dsDNA antibodies 4

5. Interpretation challenges: Autoantibody patterns and titers require expert interpretation; send samples to reference laboratories when needed 1

By following this systematic approach to diagnosis and treatment, clinicians can effectively identify and manage autoimmune diseases, improving patient outcomes and quality of life.