What is the approach to an autoimmune workup and subsequent treatment?

Autoimmune Disease Workup and Treatment Approach

The initial autoimmune workup should include antinuclear antibody (ANA) testing by immunofluorescence assay as the primary screening test, along with complete blood count, comprehensive metabolic panel, inflammatory markers (ESR and CRP), and disease-specific autoantibodies based on clinical presentation. 1

Initial Laboratory Evaluation

First-line Testing

• Complete blood count (CBC) with differential
  • Look for cytopenias, lymphopenia, neutrophilia 1
• Comprehensive metabolic panel
  • Assess liver and renal function, electrolytes, protein levels 1
• Inflammatory markers
  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP) 1
• Antinuclear antibody (ANA) by immunofluorescence assay
  • Primary screening test for many autoimmune conditions 1
  • Note: Up to 25% of healthy individuals can be ANA positive, so interpretation requires clinical context 1

Disease-Specific Autoantibodies

Based on clinical presentation, order targeted antibody panels:

• Systemic lupus erythematosus (SLE):

  • Anti-double-stranded DNA (anti-dsDNA)
  • Anti-Smith (anti-Sm)
  • Complement levels (C3, C4) 1

• Sjögren's syndrome:

  • Anti-Ro/SSA
  • Anti-La/SSB 1

• Rheumatoid arthritis:

  • Rheumatoid factor (RF)
  • Anti-citrullinated protein antibodies (ACPA) 1

• Autoimmune hepatitis:

  • Anti-smooth muscle antibodies (SMA)
  • Anti-liver kidney microsomal type 1 (LKM1) antibodies
  • Immunoglobulin G (IgG) levels 1

• Suspected neurological involvement:

  • Cerebrospinal fluid analysis for oligoclonal bands
  • IgG index
  • Neuronal autoantibodies in serum and CSF 1, 2

Specialized Testing Based on Organ Involvement

• Musculoskeletal:

  • Creatine kinase (CK), aldolase for myopathy
  • X-rays of affected joints
  • Ultrasound or MRI for detailed evaluation 1

• Cardiac:

  • Troponin
  • Echocardiogram 1

• Pulmonary:

  • Pulmonary function tests
  • Non-contrast CT scan of chest or CT angiogram 1

• Renal:

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

• Dermatologic:

  • Skin biopsy for histopathology and immunofluorescence 1

Cancer Screening in Suspected Autoimmune Conditions

• Perform cancer screening with CT chest, abdomen, and pelvis with contrast in relevant cases
• If negative, consider further testing with:
  • Mammogram/breast MRI
  • Pelvic ultrasound
  • Whole body FDG-PET guided by clinical presentation 3

Treatment Approach for Autoimmune Conditions

General Treatment Principles

The primary goal of treatment is to decrease inflammation, minimize symptoms, and lessen the potential for relapse 4. Treatment should be tailored to the specific autoimmune condition and its severity.

Treatment Algorithm for Autoimmune Encephalitis (Example)

For autoimmune encephalitis, a stepwise approach is recommended:

1. First-line therapy:

   • High-dose corticosteroids (IV methylprednisolone)
   • If contraindicated: IVIG or plasma exchange (PLEX) 3

2. If no improvement after initial treatment:

   • Add IVIG or PLEX
   • Consider IVIG first in agitated patients and those with bleeding disorders
   • Consider PLEX first in patients with severe hyponatremia or high thromboembolic risk 3

3. For severe presentations:

   • Consider combination therapy (steroids/IVIG or steroids/PLEX) from the beginning 3

4. For refractory cases:

   • Consider rituximab
   • For non-responders, consider experimental therapies like IL-6 inhibitors 3

Monitoring and Follow-up

• For patients with inactive disease and no comorbidities: laboratory assessments every 6-12 months
• For patients with active disease or on immunosuppressive therapy: more frequent monitoring 1
• Autoantibody titers may vary during disease course; seronegative patients at diagnosis may express autoantibodies later 1

Important Caveats

• Test results must be interpreted within the specific clinical context, as false positives can occur, especially with low-titer ANA 1
• Different testing methodologies for the same antibody may yield different results (e.g., indirect immunofluorescence vs. multiplex bead assay for ANA) 5
• Autoantibody testing should only be performed in patients with a reasonable clinical likelihood of having the suspected disease to ensure adequate positive predictive value 5
• Timing of autoantibody testing is crucial, and repeated testing may be necessary if clinical suspicion remains high 1
• Patients may express autoantibodies years before clinical manifestations appear (pre-clinical autoimmunity) 6