Systemic%20lupus%20erythematosus Diagnosis

Diagnosis of systemic lupus erythematosus (SLE) is based on clinical symptoms and laboratory findings

• Antinuclear antibodies (ANAs) are present in approximately 95% of patients with SLE 
  • A negative test indicates a low clinical probability of SLE; a positive test alone has a poor diagnostic value without the clinical features of autoimmune rheumatic disease 
• Entry criterion: An ANA titer of ≥1:80 on HEp-2 cells or an equivalent positive test is measured at least once; it is recommended to test by immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance
  • If patient is ANA negative, an alternative entry criterion could be low complement levels and/or presence of antiphospholipid antibodies

2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria for SLE

• A criterion is not included if there is an explanation other than SLE
• It is sufficient for a criterion to occur on at least 1 occasion
• Criteria need not be present all at the same time
• Only the criterion with the highest weight within each domain will be counted
• Classify as SLE if total score is ≥10 with at least 1 clinical criterion and entry criterion is met
  • If the total score is <10, inclusion of ACR-97 photosensitivity or a combination of clinical and immunological features can be used to diagnose SLE

Clinical Domains and Criteria

• Constitutional
  • Fever (temperature >38.3°C) = 2
• Hematologic
  • Leukopenia (white blood cell count <4000/mm³) = 3
  • Autoimmune hemolysis [presence of elevated indirect bilirubin, elevated lactate dehydrogenase (LDH), low haptoglobin, reticulocytosis, AND positive Coombs’ (direct antiglobulin) test] = 4
  • Thrombocytopenia (platelet count <100,000/mm³) = 4
• Mucocutaneous
  • Non-scarring alopecia (observed by a clinician) = 2
  • Oral ulcers (observed by a clinician) = 2
  • Subacute cutaneous OR discoid lupus (observed by a clinician) = 4
  • Acute cutaneous lupus (malar or generalized maculopapular rash observed by a clinician) = 6
• Musculoskeletal
  • Joint involvement (either synovitis involving ≥2 joints OR tenderness in ≥2 joints and at least 30 minutes of morning stiffness) = 6
• Neuropsychiatric
  • Delirium (change in consciousness with decreased ability to focus; symptoms developing over hours to <2 days or fluctuating throughout the day; either acute/subacute change in cognition or change in behavior, mood, or affect) = 2
  • Psychosis (hallucinations and/or delusions without insight and no delirium) = 3
  • Seizure (primary generalized seizure or partial/focal seizure) = 5
• Renal
  • Proteinuria (>0.5 g/24 hr by 24-hour urine or equivalent spot urine protein-to-creatinine ratio) = 4
  • Class II or V lupus nephritis on renal biopsy = 8
  • Class III or IV lupus nephritis on renal biopsy = 10
• Serosal
  • Pleural or pericardial effusion (with imaging evidence) = 5
  • Acute pericarditis (≥2 of the following: Pericardial chest pain, pericardial rub, ECG with new widespread ST elevation or PR depression, or new or worsened pericardial effusion on imaging) = 6

Immunologic Domains and Criteria

• Antiphospholipid antibodies
  • Anti-cardiolipin antibodies (IgA, IgG, or IgM) at medium or high titer OR
  • Anti-beta-2 glycoprotein 1 antibodies (IgA, IgG, or IgM) OR
  • Lupus anticoagulant positive = 2
• Complement proteins
  • Low C3 OR low C4 = 3
  • Low C3 AND low C4 = 4
• SLE-specific antibodies
  • Anti-dsDNA antibody in an immunoassay with demonstrated ≥90% specificity for SLE versus relevant disease controls OR
  • Anti-Smith antibody = 6

• Several reliable and validated measuring tools are available for assessing disease activity in SLE 
  • SLEDAI and BILAG are the indices more commonly used and most completely validated 

Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)

• Global index for assessing disease activity in the preceding 10 days 
• Used in both clinical and research purposes 
• Consists of 24 items which include specific manifestations from 9 organ systems with a total score of 105 
• Other versions of this index include SELENA-SLEDAI, SLEDAI 2000 and Mex-SLEDAI   

British Isles Lupus Assessment Group (BILAG)

• Assesses 9 organ systems; also evaluates relapse occurrence 
• BILAG 2004 consists of several questions assessed on a 0-4 scale: 0 = not present, 1 = improving, 2 = same, 3 = worse, 4 = new event 
• Responses are then combined into 5 states of disease activity: 
  • A: Very active disease needing immunosuppressants, medium- or high-dose corticosteroids or high-dose anticoagulation
  • B: Moderate disease activity needing a lower dose of corticosteroid, antimalarials, or NSAIDs
  • C: Little disease activity needing only symptomatic treatment
  • D: No disease activity at the time but previously present
  • E: No current or previous disease activity

Physician Global Assessment (PGA)

• A visual analogue scale (VAS) reflecting the physician's judgment of the overall disease activity of SLE 
• Most common VAS tool ranges from 0-3 where 0 = none, 1 = mild, 2 = moderate, 3 = severe 
  • A flare is indicated by an increase in the score of ≥1 since the last patient visit 
• Reliability is affected by the scale used thus the need for standardization of scoring

European Consensus Lupus Activity Measurement (ECLAM)

• Measures disease activity in the previous month 
• Evaluates 10 organ systems and 2 lab values, eg erythrocyte sedimentation rate (ESR) and complement levels 
• Consists of 33 items evaluated from 0.5 to 2 based on the type of involvement, and a combined global score that ranges from 0 to 17.5 

Categories of Disease Activity in SLE

Mild

• Constitutional symptoms, fatigue, mouth ulcers, mild arthritis, rash ≤9% body surface area (BSA)
• Disease is clinically stable without life-threatening organ involvement
• Platelet count 50-100 x 10³/mm³
• SLEDAI ≤6
• BILAG C or ≤1 BILAG B manifestation

Moderate

• Rheumatoid arthritis-like arthritis, serositis, rash 9-18% BSA, cutaneous vasculitis ≤18% BSA
• Platelet count 20-50 x 10³/mm³
• SLEDAI 7-12
• ≥2 BILAG B manifestations

Severe

• Major organ- or life-threatening disease (eg cerebritis, mesenteric vasculitis, myelitis, nephritis, pneumonitis, pericarditis, thrombotic thrombocytopenic purpura-like disease, acute hemophagocytic syndrome)
• Platelet count <20 x 10³/mm³
• SLEDAI >12
• ≥1 BILAG A manifestations