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Systemic Lupus Erythematosus (SLE, lupus)

 

Definition of SLE

  • An inflammatory, multi-system autoimmune disease with a relapsing-remitting course with a wide spectrum of severity of disease

 

 Epidemiology of SLE

  • Incidence of SLE is 5/100,000 in the U.S.
  • Ethnic incidence: Afro-Caribbean>Asian>Caucasian
  • Peak age of onset of SLE 20-40 years old
  • Females:Males = 9:1

 

Aetiology of SLE (lupus)

  • Genetics
    • Monozygotic twins 25% vs dizygotic 3%
    • Multiple genes found to be more common in patients with SLE
  • Hormonal influence
    • Disparity in incidence between men and women is reduced post-menopause age
    • Potentially an infectious trigger but uncertain
  • Anti-TNF therapy can induce lupus
  • Some drugs can induce a lupus-like syndrome
    • E.g. Hydralazine, methyldopa, penicillamine, minocycline
    • Drug induced SLE is associated with HLA DR-4

 

Pathophysiology of SLE (lupus)

  • Possibly a defect in apoptosis that upsets immune tolerance mechanisms
  • T-cell abnormalities
  • Circulating immune complexes

 

Presentation of SLE (lupus)

  • Systemic – fatigue often a prominent feature
  • Arthritis – usually affecting small joints, may be asymmetrical and pain often out of proportion to swelling
    • Jaccoud’s arthropathy: A deforming non-erosive polyarthropathy with ulnar deviation and MCP subluxation, deformities can be reduced
  • Renal disorder (lupus nephritis) – presents with proteinuria, haematuria, ARF, CKD, hypertension, nephrotic syndrome
    • 1 = sedimented
    • 2 = mesangial
    • 3 = proliferative <50%
    • 4 = proliferative >50% (most are in this category)
    • 5 = membranous
    • 6 = sclerosed
  • Serositis
    • Pleuritis – pleuritic chest pain
    • Pericarditis – often asymptomatic
    • Peritonitis – recurrent episodes of diarrhoea and abdominal pain
  • Mucocutaneous
    • Photosensitivity
    • Malar rash – fixed erythema over the malar eminences
    • Oral ulcers
    • Discoid rash – erythematous, raised patches of keratotic scale, which progress to atrophic, depressed lesions. Affects ears, cheeks, scalp, chest, forehead
    • Raynaud’s phenomenon
    • Livedo reticularis
  • Pulmonary
    • Pneumonitis
    • Interstitial lung disease
    • PE
  • Cardiac
    • Myocarditis
    • Libman-Sachs endocarditis – atypical sterile clusters of vegetations on posterior mitral valve leaflet
  • Neurological disorder
    • Seizures
    • Psychosis
    • Psychiatric symptoms e.g. depression anxiety very common and often under-recognised
    • Headache
    • Aseptic meningitis

 

Investigations in SLE (lupus)

  • FBC
    • Anaemia, leukopenia, lymphopenia, thrombocytopenia
  • ESR and CRP
    • ESR often raised disproportionate to CRP (which is usually relatively normal)
  • Complement
    • Low in disease flares
    • Rising complement implies response to treatment
  • Immunology
    • ANA +ve in 99% (some controversy over whether ANA negative SLE really exists)
    • Anti-Sm (pathognomonic but poor sensitivity)
    • Anti-dsDNA
      • Sensitivity 70%
    • Anti-Ro and anti-La antibodies in about 15% (And increase the risk of neonatal heart block)
    • Anti-histone Ab in drug induced lupus
    • Rheumatoid factor – positive in 25%
    • Anti-cardiolipin/lupus anticoagulant/anti B2 glycoprotein
  • Biopsy
    • Renal
    • Skin  – often shows complement and immunoglobulin deposits at dermo-epidermal junction
  • Imaging dependant on organ involvement
    • CXR, CT, echo, renal US, MRI can all be appropriate

 

Treatment of SLE (lupus)

  • Lifestyle and multidisciplinary approach
    • Patient education
    • UV protection
    • Minimise cardiovascular risk factors
  • Hydroxychloroquine – cornerstone of treatment
    • Reduces flares and improves fatigue
    • Prolongs life
    • May be sufficient treatment for mild disease e.g. skin or musculoskeletal
  • Paracetamol and NSAIDs for analgesia
  • Steroids
    • Short term courses for flares
  • DMARDS (disease modifying anti-rheumatic agents)
    • Dependant on disease manifestations
    • Consider methotrexate for chronic arthritis
    • Azathioprine or mycophenolate in moderate disease
    • CNS or renal involvement requires aggressive treatment
      • High doses steroids
      • Azathioprine or mycophenolate
      • Cyclophosphamide (remember many patients are women of child-bearing age so can be difficult)
      • Ciclosporin
      • May require multiple agents
  • Biologics
    • Used in refractory disease
    • Rituximab (anti-CD20)
    • Belimumab (blocks B lymphocyte stimulator)

 

 Complications of SLE (lupus)

  • Cardiovascular disease (x5)
  • Infection
  • Antiphospholipid syndrome (APLS)
  • Osteoporosis

 

Prognosis in SLE (lupus)

  • 5-year survival is 95%
  • Infection and cardiovascular disease key causes of mortality
  • Prognostically poor features in SLE:
    • Multi-system disease
    • Lupus nephritis
    • Men
  • Drug-induced lupus  improves once drug stopped