What are the steps involved in an autoimmune workup and subsequent treatment?

Autoimmune Workup: Diagnostic Approach and Treatment

Initial Clinical Assessment

Begin with a focused history targeting joint pain, skin manifestations, recent infections, and family history of autoimmune disorders, as these elements are essential for identifying autoimmune disease patterns. 1

• Perform physical examination specifically evaluating joint involvement, skin changes, and spleen size to detect characteristic autoimmune manifestations 1
• Document any recent viral illnesses or exposure to lymphocyte-depleting therapies (fludarabine, ATG, corticosteroids, cytotoxic chemotherapy) 2

Core Laboratory Investigations

The initial laboratory workup must include CBC with differential, inflammatory markers (ESR and CRP), comprehensive metabolic panel, and autoantibody screening to establish baseline organ function and identify immune dysregulation. 1, 3

Essential First-Line Tests:

• CBC with differential to detect cytopenias (anemia, thrombocytopenia, lymphopenia) common in autoimmune conditions 2, 1, 3
• ESR and CRP to quantify inflammatory activity and guide treatment intensity 2, 1, 3
• Comprehensive metabolic panel including liver enzymes (AST, ALT) and kidney function (creatinine, BUN) to assess organ involvement 1, 3
• ANA (antinuclear antibody) as the primary screening tool for systemic autoimmune diseases 1, 3
• Rheumatoid factor (RF) and anti-CCP antibodies if inflammatory arthritis is suspected 1, 3

Disease-Specific Autoantibody Panels

Once initial screening suggests autoimmune disease, proceed with targeted antibody testing based on clinical presentation:

For Suspected Systemic Lupus Erythematosus:

• Anti-dsDNA, anti-Smith, anti-RNP, anti-SSA, anti-SSB antibodies 3
• Complement levels (C3, C4, CH50) 3

For Suspected Inflammatory Myositis:

• CK, AST, ALT, LDH, and aldolase to detect muscle inflammation 2, 1, 3
• Troponin to evaluate myocardial involvement, which requires immediate treatment escalation 2, 1, 3
• Anti-Jo-1 and myositis-specific antibodies 3
• Consider EMG, MRI of proximal limbs, or muscle biopsy if diagnosis remains uncertain 2

For Suspected Autoimmune Hepatitis:

• Liver function tests, serum immunoglobulins, anti-smooth muscle antibodies, anti-liver kidney microsomal antibodies 1, 3
• Liver biopsy is required for definitive diagnosis 1

For Suspected Vasculitis:

• ANCA (antineutrophil cytoplasmic antibodies) 3
• Cryoglobulins and serum protein electrophoresis 3

For Suspected Autoimmune Encephalitis:

• CSF analysis including cell count, protein, glucose, IgG index, and oligoclonal bands 2, 3
• Neural-specific antibodies in both serum and CSF 2
• Brain MRI and EEG to identify focal or multifocal abnormalities 2
• Consider brain FDG-PET when clinical suspicion is high but other studies are uninformative 2

Additional Specialized Testing

• HLA-B27 for suspected spondyloarthropathies 3
• Thyroid function tests (TSH, free T4) and thyroid antibodies (anti-TPO, anti-thyroglobulin) for autoimmune thyroid disease 3
• Celiac antibodies (tissue transglutaminase, endomysial antibodies) in appropriate clinical settings 3
• Iron studies including ferritin and transferrin saturation to exclude hemochromatosis when liver enzymes are elevated 3

Imaging Studies

• Joint radiographs for suspected inflammatory arthritis 1
• Abdominal ultrasound or CT to evaluate organomegaly in systemic disease 1
• Muscle MRI for suspected inflammatory myopathies 2, 1
• Chest X-ray to evaluate for thymoma in patients with lymphopenia 2

Pre-Treatment Infectious Disease Screening

Before initiating any immunosuppressive therapy, screen for HIV, hepatitis B, hepatitis C, and latent tuberculosis to prevent reactivation during treatment. 2, 1, 3

• Test for HIV, hepatitis B virus, hepatitis C virus in all patients 2
• Perform tuberculosis testing (PPD or interferon-gamma release assay) 2
• Consider Helicobacter pylori testing in patients with immune thrombocytopenia 2

Treatment Initiation

Once infection is excluded and autoimmune disease is confirmed or highly suspected, initiate corticosteroids promptly—do not delay treatment while awaiting complete autoantibody results in severe presentations. 2, 1

Corticosteroid Dosing by Severity:

Mild to Moderate Disease (Grade 1-2):

• Prednisone 0.5-1 mg/kg/day orally 2, 1
• Continue monitoring with weekly laboratory assessments 2

Severe Disease (Grade 3-4):

• Prednisone 1-2 mg/kg/day or methylprednisolone IV for severe compromise (respiratory involvement, severe weakness, dysautonomia) 2
• Consider hospitalization for severe presentations 2

Alternative or Adjunctive First-Line Therapies:

IVIG (Intravenous Immunoglobulin):

• Use when corticosteroids are contraindicated (uncontrolled hypertension, uncontrolled diabetes, acute peptic ulcer, severe behavioral symptoms) 2
• Preferred in agitated patients and those with bleeding disorders 2
• Dose: 1 g/kg as one-time dose, may repeat if necessary 2

Plasma Exchange (PLEX):

• Preferred in patients with severe hyponatremia, high thromboembolic risk (cancer, smoking, hypertension, diabetes), or associated demyelination 2
• Consider for refractory cases 2

Combination Therapy:

For severe initial presentations (severe NMDAR-antibody encephalitis, new-onset refractory status epilepticus, severe dysautonomia), start combination therapy with steroids plus IVIG or steroids plus PLEX from the beginning rather than sequentially. 2

Specialist Referral

Early referral to rheumatology, neurology, or appropriate subspecialty is essential and should occur within days of suspected diagnosis, not after completing the entire workup. 2, 1

• Urgent referral for Grade 3-4 toxicities 2
• Early referral for Grade 2 symptoms with objective findings 2

Monitoring During Treatment

• Serial ESR and CRP to assess treatment response 1, 3
• CBC weekly during active treatment to monitor for treatment-related cytopenias 2
• CK levels in myositis patients to guide corticosteroid tapering 2
• Periodic organ function assessment based on systems involved 1

Second-Line Immunosuppression

If no improvement after 2-4 weeks of first-line therapy or if symptoms worsen:

• Rituximab for refractory cases 2
• Methotrexate, azathioprine, or mycophenolate mofetil if symptoms persist after 4-6 weeks 2
• Thrombopoietin receptor agonists for refractory immune thrombocytopenia 2
• Consider experimental therapies like IL-6 inhibitors or bortezomib for severe refractory autoimmune encephalitis 2

Critical Pitfalls to Avoid

Never rely solely on autoantibody results without clinical correlation—positive autoantibodies in asymptomatic patients have poor predictive value and should not drive treatment decisions. 1, 4

• Do not delay treatment in severe presentations while awaiting complete diagnostic workup 1
• Do not start immunosuppressive therapy without screening for HIV, hepatitis, and tuberculosis 2, 1
• Do not use irradiated and filtered blood products in patients with severe aplastic anemia (Grade 3-4) 2
• Recognize that different testing methodologies (indirect immunofluorescence vs. multiplex bead assay) may yield different results for the same antibody 4
• Initiate Pneumocystis jirovecii and Mycobacterium avium complex prophylaxis when lymphocyte count falls below 250/μL 2