Systemic Lupus Erythematosus (SLE)

Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune, multi-systemic syndrome. It presents with the classic triad of fever, arthralgia and rash (malar, discoid or photosensitive).

Black, Hispanic, and Asian people are affected at higher rates than white people. Women of childbearing age are affected more than men (11:1 ratio). The risk, however, decreases after menopause in women, although it is still twice as common as in men.

“Lupus” is Latin for ‘wolf’ – the malar rash resembles a wolf’s bite.

Systemic manifestations of SLE

System	Manifestations
Consitutional	Fatigue, unexplained fever, weight loss
Musculoskeletal	Arthralgia, symmetric arthritis, myalgia, avascular necrosis
Dermatologic	Malar rash, discoid rash, photosensitive rash (maculopapular), oral ulcers, Raynaud phenomenon
Renal	Acute Kidney Injury, Glomerulonephritis
Neuropsychiatric	Confusion, seizure, psychosis
Pulmonary	Pleuritis, pleural effusion, ILD
Cardiac	Pericarditis, myocarditis, endocarditis (Libman-Sacks syndrome)
Haematologic	Deficiency in any cell line
Obstetric	Spontaneous abortions

Diagnostic criteria for SLE (SOAP BRAIN MD) – Meeting 4 of the criteria is 95% specific and 85% sensitive for lupus.

• Serositis
• Oral or nasopharyngeal ulcers
• Arthritis (non-erosive involving 2+ peripheral joints)
• Photosensitivity
• Blood disorder (in any cell line)
• Renal dysfunction
• ANA positive (sensitive)
• Immunologic phenomenon (anti-Smith, anti-dsDNA, antiphospholipid antibodies)
• Neurologic signs and symptoms not explained otherwise
• Malar rash
• Discoid rash

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• Associated conditions
  • Anti-phospholipid syndrome (20 – 30%)
  • Sjogren’s disease (17.5 %)
  • Autoimmune thyroid disease (7.5%)
• Risk factors
  • HLA-DR2 and HLA-DR
  • UV light exposure triggers or exacerbates the disease
  • Infections (e.g. EBV) can trigger or exacerbate the disease – potentially through molecular mimicry
  • Drugs (e.g. hydralazine, procainamide, isoniazide) can trigger the disease
  • Hormonal factors
    • Oestrogen influences disease activity by modulating the immune response
    • Women are at ten times the risk of developing SLE than men
    • Individuals with Klinefelter syndrome are at 14 times more risk of developing SLE
    • Oestrogen-containing contraceptives and postmenopausal hormone replacement therapy can cause flares in patients with SLE
  • Autoimmunity
  • Family history of SLE: concordant rates for identical twins have been reported as high as 50%.
  • Pregnancy – first presentation or flares
  • Vitamin D deficiency – linked to autoimmunity
  • Cigarette smoking
  • Silica dust exposure
  • Early-life risk factors
    • Low birthweight (< 2500 g)
    • Preterm birth (≥1 month early)
    • Childhood exposure to agricultural pesticides
• Pathophysiology
  • Defects in apoptosis or in the clearance of apoptotic cells → inappropriate exposure of intracellular antigens → polyclonal B- and T-cell activation → autoantibody production against dsDNA, Sm nuclear antigen and phospholipids → formation and deposition of immune complexes → inflammation and organ damage
• Signs and symptoms
  • Remitting and relapsing
  • Malar or butterfly rash
    • Fixed erythematous rash on the zygomatic process
    • Spares the nasolabial folds
  • Photosensitivity
  • Arthralgia
  • Fever
  • Weight loss
  • Malaise
  • Arthritis
  • Mouth ulcers
  • Non-scarring alopecia
  • Discoid erythematosus
    • Erythematous raised patches with scaling and follicular plugging
  • Lymphadenopathy
  • Livedo reticularis
    • Mottled reticular patterned skin rash of purple discolouration
• Differentials
  • Rheumatoid arthritis
  • Mixed connective tissue disease
  • Sjogren’s syndrome
• Investigations
  • Complete blood count: haematological abnormalities are part of the diagnostic criteria
    • Normochromic normocytic anaemia
    • Leucopaenia
    • Thrombocytopaenia
  • Raised ESR
  • Normal CRP
  • Anti-nuclear antibody (ANA): 95% sensitive but non-specific without clinical features
    • Positive
  • Anti-dsDNA: highly specific
    • Positive (70%)
  • Anti-Smith antibody: most specific. Its presence is diagnostic
    • Positive (30 – 40%)
  • C3 and C4 complement
    • Decreased during active disease
  • Urea and electrolytes: deranged in lupus nephritis
    • Proteinuria
    • Haematuria
• Treatment
  • High-factor sunscreen and sun avoidance
  • Immunisation
  • Screening for complications
  • Smoking cessation
  • Optimise nutrition and exercise
  • Hydroxychloroquine for all patients with SLE unless contraindicated
  • NSAIDs, unless there is renal disease
  • Corticoteroids e.g. prednisolone
  • DMARDs (methotrexate, mycophenolate or cyclophosphamide) and biological therapies (rituximab or belimumab) for resistant or severe diseases
• Prognosis
  • ~ 80% survival at 15 years
  • Increases the long-term risk of cardiovascular disease and osteoporosis

Treatment of SLE flares

Acute flare	Treatment
Mild flares (no serious organ damage)	Hydroxychloroquine or low-dose corticosteroids
Moderate flares (organ damage)	DMARDs
Severe flares (life- or organ-threatening)	High-dose steroids, DMARDs or biological therapy.