What are the diagnostic criteria and treatment options for a patient suspected of having systemic lupus erythematosus (SLE)?

Diagnosing Systemic Lupus Erythematosus

Diagnose SLE using the 2019 EULAR/ACR classification criteria, which require a positive ANA (≥1:80 titer) as an entry criterion, followed by weighted scoring of clinical and immunologic domains totaling ≥10 points, achieving 96.1% sensitivity and 93.4% specificity. 1

Essential Serological Testing at Initial Evaluation

When SLE is suspected, order the following laboratory tests immediately:

• Antinuclear antibodies (ANA) - mandatory entry criterion; positive at ≥1:80 titer required for classification 2, 1
• Anti-double-stranded DNA (anti-dsDNA) - highly specific for SLE and correlates with disease activity 3, 2
• Anti-Smith antibodies - highly specific for SLE 2
• Complement levels (C3, C4) - hypocomplementemia indicates active disease and immune complex consumption 3, 2
• Complete blood count - detects cytopenias (thrombocytopenia, leukopenia, autoimmune hemolytic anemia) 3, 2
• Comprehensive metabolic panel including creatinine - assesses renal involvement 2
• Urinalysis with microscopy - identifies proteinuria and cellular casts indicating lupus nephritis 2
• Antiphospholipid antibody panel (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) - associated with thrombotic manifestations and pregnancy complications 3, 2

Additional Immunologic Markers with Prognostic Value

• Anti-Ro/SSA and anti-La/SSB antibodies - associated with neonatal lupus risk and specific organ involvement 3
• Anti-RNP antibodies - may have prognostic value 3
• Serum albumin - provides information on renal involvement prognosis 3
• Urine protein/creatinine ratio - quantifies proteinuria severity 3

Critical Pitfall: CRP Interpretation

Patients with SLE rarely have elevated CRP levels; if CRP is significantly elevated (>50 mg/L) with clinical suspicion, aggressively exclude superimposed infection before attributing symptoms to lupus activity alone. 3

Organ-Specific Diagnostic Workup

Renal Involvement

• Kidney biopsy is essential when lupus nephritis is suspected, as histological classification (Class III, IV, V) determines treatment selection and prognosis 2, 4
• Monitor serum creatinine, urine sediment, proteinuria, and blood pressure - these have predictive value for renal outcomes 3

Cutaneous Manifestations

• Skin biopsy for histological analysis when cutaneous lupus is difficult to distinguish from mimicking conditions 3
• Repeat biopsy if lesion morphology changes or treatment fails 3

Neuropsychiatric Involvement

• MRI and EEG to exclude structural brain disease when patients present with headache, seizures, psychosis, or cognitive dysfunction 2
• Aggressively exclude infection in immunosuppressed patients before attributing neuropsychiatric symptoms to SLE 2, 4
• Assess cognitive impairment by evaluating memory, attention, concentration, and word-finding difficulties 3

Pulmonary Involvement (Acute Lupus Pneumonitis)

• High-resolution CT (HRCT) is essential for confirming diagnosis, classifying disease patterns, and excluding alternative diagnoses 5
• Elevated CRP supports active inflammation in this context 5

Monitoring Disease Activity After Diagnosis

Use validated disease activity indices (SLEDAI or BILAG) at each visit to objectively track disease progression and treatment response 3, 2, 4

At each follow-up visit, monitor:

• Anti-dsDNA, C3, C4 levels 2, 4
• Complete blood count 2, 4
• Serum creatinine 2, 4
• Proteinuria and urine sediment 2, 4
• Blood pressure 3
• Patient global assessment using 0-10 visual analog scale 3

High-risk patients (males, juvenile onset, serologically active including anti-C1q antibodies) require monitoring every 3 months to detect early organ involvement 2

Assessment of Organ Damage and Comorbidities

• Assess organ damage annually using standardized damage indices 3
• Screen cardiovascular risk factors at baseline and annually: smoking status, vascular events, physical activity, blood cholesterol, glucose, blood pressure, body mass index 3
• Osteoporosis screening according to existing guidelines for postmenopausal women and patients on steroids 3
• Cancer screening per general population guidelines, including cervical smear tests 3
• Infection screening based on patient risk, including HIV 3

Treatment Initiation After Diagnosis

Foundation Therapy for All Patients

Hydroxychloroquine at ≤5 mg/kg real body weight is mandatory for all SLE patients unless contraindicated, as it reduces disease activity, prevents flares, and improves survival. 2, 4, 1

• Ophthalmological screening required: baseline examination, repeat after 5 years, then yearly using visual fields and/or spectral domain-optical coherence tomography 2, 4
• Retinal toxicity risk exceeds 10% after 20 years of continuous use 2

Glucocorticoid Management

• IV methylprednisolone pulse therapy (250-1000 mg daily for 1-3 days) for acute flares provides immediate effect and enables lower oral glucocorticoid starting doses 2, 4
• Minimize chronic glucocorticoids to <7.5 mg/day prednisone equivalent and withdraw when possible to prevent organ damage 2, 4

Immunosuppressive Agent Selection by Disease Severity

Mild disease (skin and joint manifestations):

• Add methotrexate if hydroxychloroquine and low-dose glucocorticoids are insufficient 2, 4

Moderate disease requiring glucocorticoid-sparing:

• Azathioprine (particularly suitable for women contemplating pregnancy) 2, 4
• Mycophenolate mofetil for renal and non-renal manifestations 2, 4

Severe organ-threatening disease (lupus nephritis, cardiopulmonary, neuropsychiatric):

• Induction therapy: Mycophenolate mofetil or low-dose cyclophosphamide (Euro-Lupus regimen) 2, 4
• Maintenance therapy: Mycophenolate mofetil or azathioprine 2, 4
• Treatment goal: ≥50% reduction in proteinuria to subnephrotic levels and serum creatinine within 10% of baseline by 6-12 months 2

Biologic Therapies for Refractory Disease

• Belimumab (anti-BAFF antibody) is FDA-approved as add-on treatment for active extrarenal SLE and lupus nephritis when standard therapy is insufficient 2, 6
• Rituximab for organ-threatening disease refractory to standard immunosuppressive agents, particularly hematological manifestations 2, 4
• Anifrolumab (anti-type 1 interferon receptor) approved for moderate-to-severe extrarenal SLE 2, 1

Adjunctive Therapies

• Low-dose aspirin for patients with antiphospholipid antibodies, those receiving corticosteroids, or those with cardiovascular risk factors 2, 4
• Calcium and vitamin D supplementation for all patients on long-term glucocorticoids 2, 4
• Photoprotection with sunscreens to prevent cutaneous flares 2, 4

Critical Pitfalls to Avoid

Do not delay kidney biopsy in suspected lupus nephritis - histological classification is essential for treatment selection and prognosis 2

Do not use mycophenolate mofetil, cyclophosphamide, or methotrexate in women who are pregnant or contemplating pregnancy; azathioprine, hydroxychloroquine, and prednisolone are safe alternatives 2, 4

Do not overlook antiphospholipid antibody syndrome, which requires anticoagulation (warfarin with target INR 2.0-3.0 for first venous thrombosis, 3.0-4.0 for arterial or recurrent thrombosis) in addition to immunosuppression 2, 4

SLE patients have 5-fold increased mortality risk - screen regularly for infections, cardiovascular disease, hypertension, diabetes, dyslipidemia, osteoporosis, and malignancies (especially non-Hodgkin lymphoma) 2, 4