Systemic lupus erythematosus (SLE)

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Systemic lupus erythematosus(SLE)

• ??? ???????????Dr. Ince ChanHope Medical
  GroupMacao, China

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Overview

• SLE is an inflammatory, multisystem disorder
  with arthralgia and rashes as the most common
  clinical features, and cerebral and renal disease
  as the most serious problems.

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Epidemiology

• World-wide
• Common in women (FM791) ?with a peak age of
  onset between 20 and 40 years.

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Aetiology

• The cause is unknown but there are several
  predisposing factors- Heredity
• - Genetics
• - Complement
• - Sex hormone status Premenopausal
  women are most frequently affected.
• - Immunological factors Loss of
  self-tolerance has several consequences
• - Environmental tiggers

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Immunological factors

• B cell activation results in increased
  autoantibody (mainly IgG) production to a variety
  (up to 2000) of antigens (nuclear, cytoplasmic
  and plasma menbrane), e.g. ANA, anti-dsDNA.
• Development of and failure to remove immune
  complexes from the circulation leads to
  deposition of complexes in the tissue, causing
  vasculitis and disease (e.g. glomerulonephritis).
  Immune complexes also from in situ, e.g. kidney
  glomerular basement membrane.
• There is impaired T cell regulation of the immune
  response.
• There is abnormal cytokine production (IL-1 and
  IL-2), although its exact role in the
  pathogenesis is unknown. IL-6 and IL-10 levels
  are often reised.
• TNF-a promoters have also been linked to SLE.

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Environmental triggers

• Drugs such as hydralazine, methyldopa, isoniazid,
  D-penicillamine and minocycline can induce lupus
  not associated with anti-dsDNA. Flare-ups can be
  induced by the contraceptive pill and hormone
  replacement therapy (HRT).
• Ultraviolet light is another well-recognized
  trigger.

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Pathogenesis

• Although much interest has been focused on
  immunological abnormalities in relation to lupus,
  there seems from most reports to be little wrong
  with the process itself but rather a failure to
  clear apoptotic material efficiently. Nuclear
  constituents, e.g. DNA and histones, are released
  from these cells and their inefficient removal
  may lead to their being present in excess and
  possibly in some altered form. The nuclear
  material is then taken up by antigen-presenting
  cells and presented to T cells which in turn
  stimulate B cells to produce antibodies directed
  against nuclear antigens, e.g. Ro, La. The
  formation of some of these autoantibodies is due
  to proteases such as granzyme B which are active
  during apoptosis. Different subsets of
  autoantibodies may be related to the different
  clinical patterns.

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pathology

• SLE is characterized by a widespread vasculitis
  affecting capillaries, arterioles and venules.
  Fibrinoid (an eosinophilic amorphous material) is
  found along blood vessels and tissue fibres. The
  synovium of joints may be oedematous and also
  contain fibrinoid deposits which contain immune
  complexes. Haematoxylin bodies (rounded blue
  homogeneous haematoxylin-stained deposits) are
  seen in inflammatory infiltrates and are thought
  to result from the interaction of antinuclear
  antibodies and cell nuclei.

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Clinical features

• General - Fever (50) - Depression
• Skin (75) - Photosensitivity - Butterfly
  rash - Vasculitis - Purpura - Urticaria
• Chest (50) - Pleurisy/effusion -
  Restrictive lung defect (rare)
• Raynauds phenomenon (20)

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Clinical features

• Joints (90) - Aseptic necrosis of hip (rare)
  - Arthritis in small joints
• Nervous system (60) - Fits - Hemiplegia
  - Ataxia - Polyneuropathy - Cranial nerve
  lesions - Psychosis
• Heart - Pericarditis - Endocarditis -
  Aortic valve lesions

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Clinical features

• Abdominal pain
• Renal disease (30) - Glomerulonephritis (all
  types)
• Myopathy (lt5)
• Blood (75) - Anaemia (normochromic normocytic
  or haemolytic Coombs positive) -
  Leucopenia/lymphopenia - Thrombocytopenia
• The eyes - Episcleritis - conjunctivitis
  - optic neuritis
• The gastrointestinal system - mouth ulcers

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investigations

• Blood - CBC - ESR - ANA (50) -
  Rheumatoid factor (25) - Serum complement
  levels are reduced during active disease
  - Anticardiolipin antibodies (35-45) -
  Serological tests for syphilis (30) -
  Immunoglobulins are raised (usually IgG and IgM)
  - Creatinine and BUN

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Investigations

• Histology Characteristic histological and
  immunofluorescent abnormalities are seen in
  biopsies from, e.g., the kidney and skin.
• Diagnostic imaging CT scans of the brain
  sometimes show infarcts or haemorrhage with
  evidence of cerebral atrophy. MR can detect
  lesions in white matter which are not seen on
  CT. However, it can be very difficult to
  distinguish true vasculitis from small thrombi.

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Management

• The disease and its management should be
  discussed, pointing out that the prognosis is
  much improved though patients are advised to
  avoid excessive exposure to sunlight and should
  reduce cardiovascular risk factors.

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Management

• Drug therapy should be used for active disease.
  There is no evidence that treatment in remission
  alters the progression of the disease.
• - Arthralgia, arthritis, fever and
  serositis all respond well to standard
  doses of NSAIDs. - Antimalarial drugs
  (chloroquine or hydroxychloroquine) help mild
  skin disease, fatigue and arthralgias that
  cannot be controlled with NSAIDs.
• - Corticosteroids orally or as high-dose
  intravenous boluses and/or
  immunosuppressive drugs such as azathioprine or
  cyclophosphamide are essential for more
  severe disease (glomerulonephritis, vasculitis,
  cerebral disease or blood dyscrasias) and
  when the symptoms are poorly controlled.
• - Newer therapies include anti-CD40
  ligand monoclonal antibodies which are
  undergoing clinical trials.

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Course and prognosis

• An episodic course is characteristic, with
  exacerbations and complete remissions that may
  last for long periods. These remissions may occur
  even in patients with renal disease.
• A chronic course is occasionally seen. Earlier
  estimates of the mortality in SLE were
  exaggerated 10-year survival rate is about 90.
  In most cases the pattern of the disease becomes
  established in the first 10 years if serious
  problems have not developed in this time, they
  are unlikely to do so. The arthritis is usually
  intermittent. Chronic progressive destruction of
  joints as seen in RA and OA occurs rarely, but a
  few patients develop deformities such as ulnar
  deviation.

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Pregnancy and SLE

• Fertility is usually normal except in severe
  disease and there is no major contraindication to
  pregnancy. Barrier methods of contraception
  rather than the pill are advisable. Recurrent
  miscarriages occur and these may be associated
  with antiphospholipid (???) antibodies. Remission
  and exacerbations can occur during pregnancy with
  frequent exacerbations of the disease postpartum.
  The patient's usual treatment should be continued
  during pregnancy. Hypertension must be
  controlled. With severe renal disease and high
  antiphospholipid antibodies, fetal mortality is
  high (gt 25).

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Patient Education

• Patient education should stress the importance of
  taking medications as prescribed keeping
  follow-up appointments. Because the medica-tions
  used to treat SLE can have serious side effects,
  frequent monitoring is necessary so that the
  lowest doses needed to control the disease can be
  used.
• The patient should be informed that the
  com-plications of SLE may be silent, and regular
  evaluations may be the only way to detect them
  early.
• Smoking cessation is also important.

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Summary - Key symptoms

• Arthralgia
• Alopecia
• Discoid lesions
• Fever
• Malar rash
• Oral ulcer
• Photosensitivity
• Weight loss

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Summary - Key signs

• A patient must have 4 or more of the following 11
  criteria to be classified as having SLE -
  Malar rash - Discoid rash -
  Photosensitivity - Oral ulcer - Arthritis
  - Serositis - Renal disease - Neurologic
  disease - Hematologic disorders -
  Immunologic abnormalities - Positive
  antinuclear antibodies (ANA)

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Summary - Key tests

• ANA
• Anti-dsDNA
• Anti-Sm
• Complement levels (especially C3)
• False-positive test for syphilis

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Summary Key treatment

• NSAIDs
• Antimalariais hydroxychloroquine
• Corticosteroids Solu-Medrol, prednisone
• Immunosuppressive drugs methotrexate (MTX),
  azathioprine

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