Review symptoms and medical history (rash, joint pain/swelling, fevers, fatigue, chest pain, mouth ulcers, hair loss, photosensitivity, Raynaud’s)
Physical exam (skin, joints, lungs, kidneys, nervous system)
Order ANA test (antinuclear antibody)
If ANA is positive or suspicion remains high, order anti–double-stranded DNA (anti-dsDNA)
Order anti-Smith (anti-Sm)
Order complement levels C3 and C4
Order CBC with differential (anemia, leukopenia, thrombocytopenia)
Order urinalysis (protein, blood, casts)
Order urine protein/creatinine ratio or 24-hour urine protein
Order serum creatinine and eGFR
Order ESR and/or CRP (inflammation markers)
Check for antiphospholipid antibodies: lupus anticoagulant, anticardiolipin IgG/IgM, anti–β2 glycoprotein I IgG/IgM
Test for specific organ involvement as indicated:
Chest imaging (chest X-ray or CT) for pleuritis/pericarditis symptoms
Echocardiogram for suspected pericardial involvement
Kidney evaluation (referral to nephrology)
Consider kidney biopsy if significant nephritis is suspected/confirmed
Additional labs for neurologic involvement as directed
Rule out related or mimicking conditions with targeted testing as directed (e.g., infections, rheumatoid arthritis, other autoimmune diseases)
Repeat monitoring labs if diagnosed or if symptoms persist/worsen (CBC, CMP/creatinine, urinalysis/protein, complements, anti-dsDNA, antiphospholipid panel when relevant)
Use a rheumatologist evaluation and classification criteria (e.g., ACR/EULAR) alongside lab and clinical findings