What is required to diagnose Systemic Lupus Erythematosus (SLE)?

Diagnosing Systemic Lupus Erythematosus (SLE)

The diagnosis of SLE requires meeting at least 4 of 11 clinical and laboratory criteria established by the American College of Rheumatology, with antinuclear antibody (ANA) testing being the primary laboratory test used for diagnosis. 1

Diagnostic Approach

Clinical Manifestations to Evaluate

1. Mucocutaneous manifestations:

   • Lupus-specific skin lesions (acute, subacute, chronic, or intermittent cutaneous LE)
   • Non-specific skin lesions
   • Oral ulcers
   • Alopecia
   • Skin biopsy may be required for definitive diagnosis 2

2. Musculoskeletal involvement:

   • Arthritis
   • Myalgia/myositis

3. Serositis:

   • Pleuritis
   • Pericarditis

4. Neuropsychiatric manifestations:

   • Seizures
   • Psychosis
   • Headache
   • Cognitive impairment
   • Peripheral neuropathy 2

5. Renal involvement:

   • Proteinuria
   • Hematuria
   • Cellular casts
   • Elevated serum creatinine 2

Laboratory Testing Algorithm

Step 1: Initial Screening

• ANA testing - should be performed only in patients with unexplained involvement of two or more organ systems 1
  • ANA titer ≥1:40 with characteristic multiorgan involvement: proceed with diagnosis
  • ANA titer ≥1:40 without meeting full clinical criteria: proceed to additional testing
  • ANA titer <1:40: SLE usually ruled out (rare cases of ANA-negative lupus may occur)

Step 2: Confirmatory Testing

• Anti-dsDNA antibodies - high specificity for SLE
• Anti-Sm (Smith) antibodies - highly specific for SLE
• Complement levels (C3, C4) - often decreased in active disease
• Complete blood count - check for cytopenias (anemia, leukopenia, thrombocytopenia)
• Urinalysis and urine protein/creatinine ratio - for renal involvement assessment 2

Step 3: Additional Testing (as indicated)

• Antiphospholipid antibodies (anticardiolipin, lupus anticoagulant, anti-β2 glycoprotein)
• Anti-Ro/SSA and Anti-La/SSB antibodies
• Anti-RNP antibodies
• Anti-C1q antibodies 2
• Renal biopsy - for suspected lupus nephritis
• Brain MRI - for neuropsychiatric manifestations 2

Diagnostic Pitfalls and Caveats

1. Low predictive value of ANA in primary care:

   • ANA has low predictive value in patients without typical clinical symptoms due to low disease prevalence
   • Only order ANA in patients with unexplained involvement of two or more organ systems 1

2. SLE mimickers:

   • Common conditions like rosacea can mimic the butterfly rash
   • Rare conditions including Kikuchi disease, type-1 interferonopathies, and Castleman's disease can mimic SLE 3
   • Proper diagnosis must be based on complete medical history and appropriate constellation of findings

3. Renal involvement assessment:

   • Kidney involvement is a major cause of morbidity
   • Renal biopsy is essential to differentiate lupus nephritis from other glomerular diseases that may coexist with SLE 4
   • Monitor serum creatinine, urinalysis, proteinuria, and blood pressure 2

4. Neuropsychiatric manifestations:

   • Diagnostic work-up should be similar to that in the general population presenting with the same neuropsychiatric manifestations
   • Cognitive impairment should be assessed by evaluating memory, attention, concentration, and word-finding difficulties 2

5. Disease activity monitoring:

   • Regular assessment of clinical manifestations and laboratory parameters is essential
   • Use validated global activity indices to monitor disease activity and flares 2

By following this structured approach to diagnosis, clinicians can identify SLE early and initiate appropriate management to improve patient outcomes in terms of morbidity, mortality, and quality of life.