What is the initial approach to an autoimmune workup?

Initial Autoimmune Workup

Begin with a focused clinical assessment followed by a standardized laboratory panel including CBC with differential, inflammatory markers (ESR and CRP), comprehensive metabolic panel, and ANA screening, with additional disease-specific testing guided by clinical presentation. 1, 2

Clinical Assessment

History and Physical Examination

• Obtain a detailed history focusing on joint pain patterns, skin manifestations (rashes, photosensitivity), recent viral infections, and family history of autoimmune disorders 1, 2
• Document any exposure to lymphocyte-depleting therapies such as fludarabine, ATG, corticosteroids, or cytotoxic chemotherapy 2
• Perform a physical examination evaluating joint involvement (swelling, tenderness, range of motion), skin changes (malar rash, discoid lesions, sclerodactyly), and spleen size 1, 2

Initial Laboratory Panel

Essential First-Line Tests

• Complete blood count (CBC) with differential to detect cytopenias (anemia, leukopenia, thrombocytopenia) common in autoimmune conditions 1, 2, 3
• Inflammatory markers: ESR and CRP to quantify inflammatory activity and establish baseline disease activity 1, 2, 3
• Comprehensive metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, bilirubin) and kidney function tests (creatinine, BUN) to assess organ involvement 1, 2, 3
• Antinuclear antibody (ANA) as the primary screening tool for systemic autoimmune diseases 1, 2, 3

Additional First-Line Autoantibodies

• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies for suspected inflammatory arthritis 1, 3

Disease-Specific Testing Based on Clinical Presentation

For Suspected Systemic Lupus Erythematosus

• Anti-dsDNA, anti-Smith, anti-RNP, anti-SSA (Ro), and anti-SSB (La) antibodies 2, 3
• Complement levels (C3, C4, CH50) to assess complement consumption 2, 3

For Suspected Inflammatory Myositis

• Creatine kinase (CK), AST, ALT, lactate dehydrogenase (LDH), and aldolase to detect muscle inflammation 1, 2, 3
• Troponin to evaluate for myocardial involvement 1, 2, 3
• Anti-Jo-1 and other myositis-specific antibodies 3

For Suspected Autoimmune Hepatitis

• Liver function tests, serum immunoglobulins, anti-smooth muscle antibodies, and anti-liver kidney microsomal antibodies 1, 3
• Hepatitis serologies to exclude viral causes 3
• Liver biopsy is considered a prerequisite for definitive diagnosis 1

For Suspected Systemic Sclerosis

• Anti-centromere, anti-Scl-70, and anti-RNA polymerase III antibodies 3

For Suspected Autoimmune Thyroid Disease

• Thyroid function tests (TSH, free T4) and thyroid antibodies (anti-TPO, anti-thyroglobulin) 3

For Suspected Autoimmune Neurological Conditions

• Cerebrospinal fluid analysis including cell count, protein, glucose, IgG index, and oligoclonal bands 2, 3
• Neural-specific antibodies in both serum and CSF 2, 3

For Suspected Spondyloarthropathies

• HLA-B27 typing 3

Imaging Studies

• Joint radiographs for suspected inflammatory arthritis 1
• Abdominal ultrasound or CT scan to evaluate for organomegaly in suspected systemic disease 1
• Muscle MRI for suspected inflammatory myopathies 1

Pre-Treatment Screening

Before initiating immunosuppressive therapy, screen for:

• Latent tuberculosis infection 2, 3
• Viral hepatitis (hepatitis B and C) 2, 3
• HIV 1

Critical Pitfalls to Avoid

• Do not rely solely on autoantibody testing without clinical correlation—autoantibodies can be present in healthy individuals and do not make a diagnosis in isolation 1, 4
• Do not delay treatment while awaiting complete diagnostic workup in severe presentations—initiate corticosteroids promptly in life-threatening cases 1, 2
• Do not fail to screen for infectious diseases before starting immunosuppressive therapy 1, 2
• Recognize that autoantibody negativity does not exclude autoimmune disease—clinical judgment remains paramount 4

Management Algorithm

Immediate Actions for Severe Presentations

• Initiate corticosteroids without delay: prednisone 1-2 mg/kg/day orally or methylprednisolone IV for severe disease 2
• Consider IVIG or plasma exchange in patients with contraindications to corticosteroids 2

Early Specialist Referral

• Refer to rheumatology, neurology, or appropriate subspecialty within days of suspected diagnosis 1, 2

Monitoring Treatment Response

• Serial ESR and CRP measurements to assess treatment response 1, 2, 3
• Periodic organ function assessment based on systems involved 1, 2
• Consider second-line immunosuppression (rituximab, methotrexate) if no improvement after 2-4 weeks of first-line therapy 2