What is the initial workup and treatment for autoimmune diseases?

Initial Workup for Autoimmune Diseases

Begin with a complete blood count with differential, inflammatory markers (ESR and CRP), comprehensive metabolic panel, and antinuclear antibodies (ANA) as your first-line laboratory panel, while simultaneously obtaining a focused history on joint pain, recent infections, family history of autoimmune disorders, and examining for joint involvement, skin manifestations, and splenomegaly. 1, 2

History and Physical Examination

Critical Historical Elements

• Joint pain patterns: duration, distribution, morning stiffness 1, 3
• Recent viral illnesses or infections: particularly relevant for triggering autoimmune responses 2
• Family history: specifically autoimmune disorders in first-degree relatives 1, 3
• Exposure to immunosuppressive agents: fludarabine, ATG, corticosteroids, or cytotoxic chemotherapy 2
• Symptoms of organ involvement: weakness (myositis), neurologic changes, or constitutional symptoms 4, 2

Physical Examination Focus

• Joint examination: assess for synovitis, deformities, and erosive changes 1, 3
• Skin evaluation: look for rashes, photosensitivity, or dermatomyositis-specific findings 4, 1
• Spleen size: palpate and percuss for splenomegaly 1, 3
• Muscle strength testing: proximal muscle groups for myositis 4

First-Line Laboratory Panel

Essential Initial Tests

• Complete blood count with differential: detect cytopenias (anemia, leukopenia, thrombocytopenia) and neutropenia 1, 2, 3
• Inflammatory markers: ESR and CRP to quantify inflammatory activity 1, 2, 3
• Comprehensive metabolic panel: assess liver function (AST, ALT), kidney function (creatinine, BUN), and electrolytes 1, 2
• Antinuclear antibodies (ANA): primary screening tool for systemic autoimmune diseases 1, 2

Additional First-Line Autoantibodies

• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP): for suspected rheumatoid arthritis 1
• Autoimmune panel: consider broader screening if ANA is positive 3

Disease-Specific Testing Based on Clinical Presentation

For Suspected Inflammatory Myositis

• Creatine kinase (CK): most sensitive marker for muscle inflammation 4, 2
• Aldolase: additional muscle enzyme 4, 2
• Transaminases (AST, ALT) and LDH: can be elevated in myositis 4, 2
• Troponin: mandatory to evaluate myocardial involvement 4, 2
• ECG and echocardiogram: assess cardiac complications 4
• Myositis-specific autoantibodies: anti-TIF1γ, anti-NXP2 if paraneoplastic syndrome suspected 4
• Urinalysis: screen for rhabdomyolysis 4

For Suspected Systemic Lupus Erythematosus

• Anti-dsDNA, anti-Smith, anti-RNP, anti-SSA, anti-SSB antibodies: targeted testing after positive ANA 2
• Complement levels (C3, C4, CH50): assess disease activity 2

For Suspected Autoimmune Hepatitis

• Liver function tests: AST, ALT, alkaline phosphatase, bilirubin 1
• Serum immunoglobulins: typically elevated IgG 1
• Liver-specific autoantibodies: anti-smooth muscle, anti-LKM1 1
• Liver biopsy: considered prerequisite for definitive diagnosis 1

Imaging Studies

Initial Imaging Based on Presentation

• Joint radiographs: for suspected inflammatory arthritis to assess erosive changes 1, 3
• Abdominal ultrasound or CT scan: evaluate splenomegaly and other organomegaly in systemic disease 1, 3
• Muscle MRI: for suspected inflammatory myopathies when diagnosis uncertain 4, 1
• EMG: consider when overlap with neurologic syndromes suspected 4

Immediate Management Considerations

When to Initiate Treatment Before Complete Workup

In severe presentations with significant organ involvement or life-threatening manifestations, initiate corticosteroids immediately without waiting for complete autoantibody results. 2

Corticosteroid Dosing by Severity

• Mild to moderate disease: prednisone 0.5-1 mg/kg/day orally 4, 2, 5
• Severe disease: prednisone 1-2 mg/kg/day or methylprednisolone IV 4, 2
• Grade 1 myositis with elevated CK: prednisone 0.5 mg/kg/day 4
• Grade 3-4 myositis: methylprednisolone 1-2 mg/kg IV or higher dose bolus 4

Alternative First-Line Therapies

• IVIG or plasmapheresis: consider in patients with contraindications to corticosteroids or severe disease 2
• Note: plasmapheresis immediately after IVIG will remove immunoglobulin 4

Specialist Referral

Refer to rheumatology within days of suspected diagnosis, not weeks—early specialist involvement is essential for optimal outcomes. 1, 2

Urgent Referral Indications

• Grade 2 or higher myositis 4
• Severe weakness limiting mobility 4
• Respiratory involvement or dysphagia 4
• Rhabdomyolysis 4
• Any severe systemic manifestations 2

Monitoring and Follow-Up

Serial Laboratory Monitoring

• Disease activity markers: repeat ESR and CRP to assess treatment response 1, 2
• CBC monitoring: particularly in patients on immunosuppression 2
• CK levels: for myositis patients until normalization 4, 2
• Organ function tests: based on systems involved 1, 2

Second-Line Immunosuppression Criteria

Consider rituximab, methotrexate, azathioprine, or mycophenolate mofetil if: 4, 2

• No improvement after 2-4 weeks of first-line therapy
• Symptoms worsen despite adequate corticosteroid dosing
• Need for steroid-sparing agents due to prolonged treatment requirements

Critical Pitfalls to Avoid

Common Diagnostic Errors

• Do not rely solely on autoantibody testing without clinical correlation—autoantibodies can be present in healthy individuals and false positives lead to unnecessary treatment and patient anxiety 1, 6, 7
• Do not delay treatment in severe presentations while awaiting complete diagnostic workup—mortality increases with delayed immunosuppression 1, 2
• Do not fail to screen for infectious diseases (HIV, hepatitis B and C, tuberculosis) before starting immunosuppressive therapy—hepatitis B reactivation with TNF-blockers can be fatal 1, 8

Autoantibody Interpretation Caveats

• Autoantibody positivity alone does not establish diagnosis 6, 7
• Absence of autoantibodies does not exclude diagnosis 6
• Different testing methodologies (indirect immunofluorescence vs. multiplex bead assay) can yield different results 7
• Only order autoantibody testing when clinical suspicion is reasonable—otherwise predictive value of positive tests is too low 7

Treatment-Related Warnings

• Monitor for neutropenia when using TNF-blockers, particularly with combination immunosuppression 8
• Avoid live vaccines during immunosuppressive therapy 8
• Do not combine etanercept with anakinra or abatacept—increased infection risk without improved outcomes 8
• Screen for tuberculosis before initiating TNF-blocker therapy 8