Systemic Lupus Erythematous (SLE)

Van Jones

Background

  • Multisystemic autoimmune disease caused by autoantibody formation to nuclear material (ANA) and immune complex deposition.
  • Incidence: 16-35y, but juvenile & late-onset forms exist.
  • Prevalence: F>M (~9:1). 1:1000 in the US. More common in Black, Hispanic, Asian, and indigenous populations.
  • Etiologic factors: genetics (HLA-DR2/DR3 variants) + environment (estrogens [endogenous and exogenous], infection [EBV], UV light, tobacco smoking, crystalline silica).

Presentation

  • Constitutional: fatigue, malaise, fever, weight loss.
  • MSK: arthralgias, myalgias, non-erosive polyarthritis.
  • Mucocutaneous: photosensitivity, malar rash, discoid skin lesions, scarring alopecia (specific for discoid lupus).
  • ENT: oral/nasal ulcers (± pain).
  • Heme: cytopenias, AIHA.
  • Neuro: cognitive dysfunction, HA, mononeuritis multiplex, stroke/TIA.
  • Cardiac: pericarditis, Libman-Sacks endocarditis, myocarditis, ↑ CAD risk.
  • Pulmonary: pleuritis ± effusion, DAH, ILD, pHTN, shrinking lung syndrome.
  • Renal: lupus nephritis (most serious manifestation - most patients present as an overlap of class III/IV +/- V).
    • Class I: minimal mesangial → clinically silent.
    • Class II: mesangial prolif. → clinically silent (usually).
    • Class III: focal prolif. → nephritic.
    • Class IV: diffuse prolif. → nephritic.
    • Class V: membranous → nephrotic.
    • Class VI: advanced sclerotic → ESRD.
  • Ophtho: sicca syndrome (2/2 Sjogren’s syndrome), conjunctivitis, episcleritis. 
  • GI: GI upset, intestinal ischemia 2/2 vasculitis, LFT elevation.

Evaluation

  • CBC, BMP, UA with sediment, UPCR, ESR/CRP, ANA (>98% sensitive) with reflex (anti-dsDNA [parallels active disease & lupus nephritis] & anti-Smith highly specific), C3/C4 (low in active disease).
  • APLS ab testing (lupus anticoagulant, anti-cardiolipin, anti-β2 glycoprotein).
  • Can use 2019 ACR/EULAR classification criteria to guide diagnosis: (requires positive ANA ≥1:80 as entry criterion; then score ≥10 points across domains meets criteria).

Clinical Criteria

Weight

Laboratory Criteria

Weight
Constitutional
Fever		 2 Antiphospholipid
antibodies
Lupus AC, CL, b2GP1		 2
Hematologic
Leukopenia
Thrombocytopenia
Autoimmune hemolysis

3
4
4 		Complement proteins
Low C3 OR C4
Low C3 AND C4

3
4
Neuropsychiatric
Delirium
Psychosis
Seizure

2
3
4 		SLE-specific antibodies
Anti-dsDNA OR
Anti-Smith

6
Mucocutaneous
Non-scarring alopecia
Oral ulcers
Subacute cutaneous OR discoid lupus
Acute cutaneous lupus

2
2
4
6
Serosal
Pleural or pericardial effusion
Acute pericarditis

5
6
Musculoskeletal
Joint involvement (2+ joints)

6
Renal
Proteinuria (>0.5g/24h)
Renal Bx Class II or V lupus nephritis
Renal Bx Class III or IV lupus nephritis

4
8
10

Management

Maintenance: HCQ (lowers flares & mortality - requires annual retinal screening).

LN:

  • Class III/IV: high-dose prednisone + MMF + one additional agent (belimumab,
    obinutuzumab, or calcineurin inhibitor).
  • Class V: high-dose prednisone + MMF + calcineurin inhibitor. Add ACEi.

Acute flare: steroids - aim for lowest dose for shortest possible period.

  • Mild disease: low-dose prednisone (up to 10mg/d) with taper.
  • Severe/organ-threatening: steroid pulses (e.g., methylprednisolone 500–1000 mg IV x 3 days) with taper.
  • Organ-specific therapy add-on if refractory to pulse steroids.
  • Mucocutaneous: MTX, anifrolumab, belimumab, lenalidomide.
  • Arthritis: AZA, MTX.
  • Pericarditis/pleuritis: MMF, AZA, belimumab, colchicine.
  • Anemia/thrombocytopenia: RTX, IVIG.
  • Neuritis/myelitis: CYC, RTX.
  • Libman-Sacks endocarditis: anticoagulation.
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