Systemic Lupus Erythematous (SLE)

Lale Ertuglu

Background

  • Multisystemic autoimmune disease characterized by loss of immune tolerance, resulting in autoantibody formation to nuclear material and immune complex deposition
  • Incidence: typical onset at 16-35y but juvenile and late-onset forms exist
  • Prevalence: More common in women (~9:1). Affects 1:1000 in the US; more common in Black, Hispanic, Asian, and indigenous populations
  • Etiology: genetic predisposition (HLA-DR2/ DR3 variants, as well as non-HLA genes including those involved in complement and cytokines) + environmental factors (estrogen, infection, UV light, viruses, medication, heavy metals) result in break in immune tolerance with auto-reactive antibodies and T-cells targeting antinuclear antigens, subsequently with abnormal cytokine inflammatory cascades and immune complex formation

Presentation

  • Constitutional: fatigue (most common complaint), fevers, myalgia, weight loss
  • MSK: arthralgias and arthritis (usually polyarticular, symmetric, migratory and non-erosive) often involving MCPs/PIPs/knees/MTPs, Raynaud’s.
  • Mucocutaneous: malar rash, discoid skin lesions, photosensitivity, painless oral (usually palatal) ulcers, nasal ulcers, scarring alopecia from discoid lupus is specific (vs non-scarring diffuse alopecia which is common)
  • Cardiac: pericarditis (~25% of pts will develop at some point in disease course), verrucous (Libman-sacks) endocarditis, myocarditis, increased risk CAD
  • Hematologic: anemia of chronic disease (most common), leukopenia, ITP, AIHA
  • Renal: Lupus nephritis is the most common organ-threatening manifestation, can be refractory to therapy. Diagnosed and classified with renal biopsy.
    • Renal biopsy indicated if idiopathic AKI or progression of CKD, or if persistent proteinuria or hematuria
    • Class I and II are usually clinically silent. Class III and IV typically present as nephritic syndrome, class V mostly presents as nephrotic syndrome. Most patients present as an overlap (such as III + V or IV +V)
  • Pulmonary: pleuritis (if chronic may be complicated by shrinking lung syndrome), pleural effusion, ILD, pHTN
  • Neurologic: stroke, cerebritis, psychosis, mononeuritis multiplex
  • Ophtho: keratoconjunctivitis sicca (2/2 Sjogren’s syndrome)
  • GI: dysphagia due to esophageal dysmotility, intestinal pseudo-obstruction, elevation of LFTs (significant liver disease is rare)

Evaluation

  • Serologic workup: CBC, BMP, UA with sediment and Ur Pr:Cr ratio (screen for nephritis), ESR/CRP (nonspecific), ANA (sensitivity >98%) with reflex (including highly specific antidsDNA and anti-Smith), complement levels (C3 & C4 usually low in active disease);
  • Additional workup: if history of DVT or recurrent pregnancy loss, consider APLS antiphospholipid antibody testing (lupus anticoagulant, anti-cardiolipin, anti- β2 glycoprotein); if concern for myositis overlap, consider CK
  • 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

  • Treatment goal: control flares and prevent end-organ damage
  • Acute flare: often will require steroids; aim for lowest dose for shortest possible period
    • Mild disease: prednisone ≤ 10mg/ daily
    • Severe/ organ-threatening: steroid pulses (e.g., methylprednisolone 500–1000 mg IV x 3 days) + biologic (e.g. MMF or cyclophosphamide in lupus nephritis) with subsequent steroid taper
    • Maintenance therapy should be changed if regular flares occur
  • Maintenance:
    • 1st line: HCQ 200-400mg/day (5mg/kg)
    • Requires retinal screening at baseline and annually after 5 years of therapy
    • Not immunosuppressive
    • Safe in pregnancy with improved pregnancy outcomes and reduced neonatal lupus
    • 2nd line: highly dependent on organ involvement; consider MTX, azathioprine, MMF, belimumab, anifrolumab, rituximab
    • Lupus nephritis: increasing emphasis on upfront combination therapies with mycophenolate mofetil combined with either belimumab or voclosporin
  • Monitoring: usual biologic toxicity monitoring. Additionally, at least semiannual UA, UPCR, and creatinine to evaluate for lupus nephritis, even if asymptomatic. Trending rising dsDNA and low complements can predict flare.
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