What is the approach to diagnosing and treating autoimmune diseases in patients?

Diagnostic and Treatment Approach to Autoimmune Diseases

Begin with a focused history targeting joint pain, skin manifestations, recent infections, and family history of autoimmune disorders, followed by physical examination evaluating joint involvement, skin changes, and splenomegaly. 1, 2

Initial Clinical Assessment

History and Physical Examination:

• Document specific symptoms including joint pain patterns, skin rashes, fatigue severity, fever, and recent viral illnesses 1, 2
• Inquire about exposure to lymphocyte-depleting therapies (fludarabine, ATG, corticosteroids, cytotoxic chemotherapy) 2
• Examine for joint swelling and deformities, skin manifestations (rashes, purpura, photosensitivity), and organomegaly 1, 2

Essential Laboratory Work-Up

First-Line Testing (Order Immediately):

• Complete blood count with differential to detect cytopenias (anemia, leukopenia, thrombocytopenia) 1, 2, 3
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to quantify inflammatory activity 1, 2
• Comprehensive metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, bilirubin) and kidney function (creatinine, BUN) 1, 2
• Antinuclear antibodies (ANA) as the primary screening tool for systemic autoimmune diseases 1, 2

Second-Line Autoantibody Panel (Based on Clinical Suspicion):

• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies for suspected rheumatoid arthritis 1
• Anti-dsDNA, anti-Smith, anti-RNP, anti-SSA, and anti-SSB antibodies for suspected systemic lupus erythematosus 2
• Complement levels (C3, C4, CH50) for suspected lupus or vasculitis 2

Disease-Specific Diagnostic Pathways

For Suspected Autoimmune Hepatitis:

• Measure serum immunoglobulins (particularly IgG elevation) and liver-specific autoantibodies (ANA, SMA, anti-LKM1, anti-LC1) 4, 1
• Liver biopsy is mandatory before initiating treatment unless contraindicated by severe coagulopathy or acute liver failure 4
• Use transjugular approach for biopsy when coagulopathy is present 4
• Look for interface hepatitis with plasma cell infiltration, hepatocellular rosette formation, and emperipolesis on histology 4

For Suspected Inflammatory Myositis:

• Measure creatine kinase (CK), AST, ALT, lactate dehydrogenase (LDH), and aldolase to detect muscle inflammation 1, 2
• Check troponin levels to evaluate for myocardial involvement 1, 2
• Perform muscle MRI to identify areas of inflammation 1

For Suspected Autoimmune Encephalitis:

• Perform lumbar puncture with CSF analysis including cell count, protein, glucose, IgG index, IgG synthesis rate, and oligoclonal bands 4
• Test neuronal autoantibodies in both serum and CSF 4, 2
• Consider brain FDG-PET when clinical suspicion is high but other studies are uninformative 4

Imaging Studies

Order Based on Clinical Presentation:

• Joint radiographs for suspected inflammatory arthritis 1
• Abdominal ultrasound or CT scan to evaluate for hepatosplenomegaly in systemic disease 1
• Muscle MRI for suspected inflammatory myopathies 1
• Brain MRI for suspected autoimmune encephalitis 4

Treatment Initiation

Corticosteroids as First-Line Therapy:

• For mild to moderate disease: Prednisone 0.5-1 mg/kg/day orally 2, 5
• For severe disease: Prednisone 1-2 mg/kg/day orally or methylprednisolone IV 2, 5
• In acute severe presentations (fulminant hepatitis, severe encephalitis, severe dysautonomia), initiate corticosteroids immediately without waiting for complete autoantibody results 4, 2

Alternative First-Line Options:

• IVIG (intravenous immunoglobulin) for agitated patients, those with bleeding disorders, or when steroids are contraindicated 4, 2
• Plasma exchange (5-10 sessions every other day) for severe hyponatremia, high thromboembolic risk, or associated demyelination 4, 2

Combined First-Line Therapy:

• Consider combination of corticosteroids plus IVIG or corticosteroids plus plasma exchange from the beginning in severe presentations (NMDAR-antibody encephalitis, new onset refractory status epilepticus, severe dysautonomia) 4

Specialist Referral

Early referral to appropriate subspecialty (rheumatology, neurology, hepatology) is mandatory and should occur within days of suspected diagnosis 1, 2

Monitoring and Follow-Up

Serial Laboratory Monitoring:

• Repeat ESR and CRP to assess treatment response 1, 2
• Monitor CBC for treatment-related cytopenias 2
• Assess organ function tests based on systems involved 1, 2

Treatment Escalation:

• If no improvement after 2-4 weeks of first-line therapy, add second-line immunosuppression (rituximab for antibody-mediated disease, cyclophosphamide for cell-mediated disease) 4, 2

Critical Pitfalls to Avoid

Common Diagnostic Errors:

• Never rely solely on autoantibody testing without clinical correlation—autoantibodies can be present in healthy individuals and absent in true disease 4
• Do not delay treatment while awaiting complete diagnostic work-up in severe presentations—initiate corticosteroids immediately 4, 2
• Autoantibody titers may vary during disease course; seronegative individuals at diagnosis may express autoantibodies later, so repeat testing if clinical suspicion remains high 4, 6

Pre-Treatment Requirements:

• Screen for infectious diseases (HIV, hepatitis B and C, tuberculosis) before starting immunosuppressive therapy 1, 2
• Send patient sera to reference laboratories for complete autoimmune serology when local facilities lack comprehensive testing capabilities 4, 6

Cancer Screening:

• Perform CT chest, abdomen, and pelvis with contrast in relevant cases (particularly in paraneoplastic syndromes and dermatomyositis) 4
• Consider mammogram, pelvic ultrasound, or whole body FDG-PET based on specific cancer risk factors 4