What is the recommended workup for evaluating suspected systemic lupus erythematosus?

Lupus Workup

Begin with ANA testing at 1:160 dilution as the initial screening test; if positive, proceed immediately with comprehensive autoantibody panel, complement levels, and multi-system clinical and laboratory evaluation to confirm systemic lupus erythematosus using the EULAR/ACR 2019 criteria. 1

Initial Screening Strategy

• Screen with ANA testing using 1:160 dilution cutoff to avoid false positives in unselected populations 1
• If ANA is negative, SLE is highly unlikely and alternative diagnoses should be pursued 1
• ANA positivity alone is insufficient for diagnosis, as it occurs in other conditions 2

Confirmatory Autoantibody Testing (When ANA Positive)

Proceed with comprehensive autoantibody panel including:

• Anti-dsDNA antibodies using double-screening strategy: perform last-generation solid phase assay first, then confirm with Crithidia luciliae immunofluorescence test 1
• Anti-Ro/SSA and anti-La/SSB antibodies (particularly important as anti-Ro/SSA associates with subacute cutaneous lupus and photosensitivity) 2
• Anti-Sm antibodies (highly specific for SLE) 2, 3
• Anti-RNP antibodies 2
• Anti-phospholipid antibodies (anticardiolipin, anti-β2-glycoprotein I, lupus anticoagulant) 2
• Anti-C1q antibodies have nearly 100% prevalence during active lupus nephritis with critical negative predictive value 1

Complement and Inflammatory Markers

• Measure C3 and C4 complement levels at baseline, as low complement combined with positive anti-dsDNA strongly supports active SLE 1
• Erythrocyte sedimentation rate (ESR) 2, 1
• C-reactive protein (CRP): note that CRP >50 mg/L suggests superimposed infection rather than lupus flare alone 4

Essential Baseline Laboratory Tests

• Complete blood count (CBC) to detect cytopenias (anemia, leukopenia, lymphopenia, thrombocytopenia) 2, 1
• Serum creatinine and serum albumin for renal function assessment 2, 1
• Urinalysis with microscopy to detect proteinuria, hematuria, cellular casts 2, 1
• Urine protein-to-creatinine ratio if urinalysis is abnormal 2, 1

Multi-System Clinical Evaluation

Assess for involvement across organ systems, as SLE diagnosis requires at least two organ systems to be affected 1:

Mucocutaneous Manifestations

• Malar rash (present in 37.69% at initial presentation) 5
• Photosensitivity (79.4% report as early symptom) 6
• Discoid lupus lesions 2, 5
• Oral or nasal ulcers 5
• Alopecia (39.29% at presentation) 5
• Perform skin biopsy for histological confirmation when cutaneous lesions are present 2, 1

Musculoskeletal Manifestations

• Arthralgia (86.7% report as early symptom, 68.75% at presentation) 6, 5
• Arthritis (48.31% at presentation) 5
• Myalgia (76.1% report as early symptom, 55.65% at presentation) 6, 5

Constitutional Symptoms

• Fatigue (89.4% report as early symptom) 6
• Fever (53.7% report as early symptom—notably high percentage) 6
• Weight changes (13.43% at presentation) 5

Renal Manifestations

• For patients with abnormal urinalysis or elevated creatinine, obtain urine protein-to-creatinine ratio, perform urine microscopy, order renal ultrasound 2
• Perform renal biopsy when lupus nephritis is suspected to confirm diagnosis, assess disease activity versus chronicity, and guide immunosuppressive therapy 1

Neuropsychiatric Manifestations

• Monitor for seizures, paresthesiae, numbness, weakness, headache, depression, and cognitive impairment 2
• Diagnostic workup (clinical, laboratory, neuropsychological, and imaging tests) should be similar to that in the general population presenting with the same neuropsychiatric manifestations 7

Hematologic Manifestations

• Assess CBC for hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia 2, 1

Diagnostic Confirmation

• Apply EULAR/ACR 2019 criteria as the standard for classification 1
• Diagnosis requires positive ANA, involvement of at least two organ systems, and fulfillment of the EULAR/ACR 2019 criteria 1
• Use validated activity indices (SLEDAI, BILAG, or SLE-DAS) to monitor lupus activity and detect flares 1, 4

Critical Pitfalls to Avoid

• Do not rely solely on ANA testing for diagnosis, as it can be positive in other conditions 2
• Do not rely on serological activity alone without clinical correlation, as this risks overtreatment 4
• Recognize that CRP elevation >50 mg/L warrants infection workup rather than assuming lupus flare alone 4
• Repeat anti-dsDNA and complement levels at follow-up visits even if previously negative/normal, as these can become positive later 1
• Re-evaluate anti-Ro/SSA and anti-La/SSB antibodies before pregnancy due to risk of neonatal lupus and congenital heart block 2

Special Populations

Cutaneous Lupus Patients

• Use the Cutaneous Lupus Disease Area and Severity Index (CLASI) to quantify disease activity and damage 2, 4
• Monitor for progression to systemic lupus, which occurs in 0-42% of adult patients with cutaneous lupus 8
• Risk factors for progression include positive ANA, hematologic abnormalities, and higher number of lupus classification criteria at baseline 8

Pregnancy Considerations

• Screen for anti-Ro/SSA, anti-La/SSB, and antiphospholipid antibodies before pregnancy due to risks of congenital heart block, miscarriage, and thrombosis 7, 2

Ongoing Monitoring After Diagnosis

• Monitor every 6-12 months with CBC, ESR, CRP, serum albumin, creatinine, urinalysis, anti-dsDNA, C3, and C4 levels 2, 1, 4
• Persistent anti-dsDNA antibodies and hypocomplementemia after treatment indicate high risk for renal relapse 1