Systemic Lupus Erythematosus

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Systemic Lupus Erythematosus

• Justin A. Crocker
• AM Report 12/2/09

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SLE

• Autoimmune disease that affects multisystems
• 1.5 million cases of lupus
• Prevalence of 17 to 48 per 100,000 population
• Women gt Men - 91 ratio
• 90 cases are women
• African Americans gt Whites
• Onset usually between ages of 15 and 45 years,
  but
• Can occur in childhood or later in life

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Clinical Manifestations

• For the purpose of identifying patients in
  clinical studies, a person has SLE if 4 or more
  of the 11 criteria are present, serially or
  simultaneously, during any interval of
  observation. (specificity 95, sensitivity 75)
• It is important to remember that a patient may
  have SLE and not have 4 criteria.

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Criteria

• Butterfly rash
• Discoid lupus
• Photosensitivity
• Oral ulcers
• Arthritis
• Serositis

• 7. Neurologic d/o
• 8. Hematologic d/o
• 9. Renal d/o
• 10.Immunologic anti-DNA, anti-Sm, false pos STS
• 11.Anti-nuclear antibody

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Cutaneous

• Most common rash is photosensitive, raised
  erythematous malar rash. 55-85 develop at some
  point in disease
• Discoid Lupus Erythematosus (DLE) 15-30
  circular, scaly hyperpimented lesions with
  erythematous rim, atrophic centercan be
  disfiguring
• Mouth/vaginal/nasal ulcers
• Alopecia may be diffuse or patchy. Occurs 50

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Malar Rash
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Discoid Rash
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Oral Ulcers
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MSK

• Polyarthritis, mild to disabling, occurs most
  frequently in hands, wrists, knees. Occurs 90
• Joint deformities occur in only 10
• Arthritis of SLE tends to be transitory
• If single joint has persistent pain, consider
  osteonecrosis (prevalence increased in SLE over
  general population, especially if on steroids.)
• Myositis with elevated CK and weakness rarely
  occurs

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Arthritis
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Serositis - Pulmonary

• Pleuritis with or without effusion
• - if case is mild, tx NSAIDS
• - if case is severe, tx steroids
• Life-threatening manifestations interstitial
  inflammation which can lead to fibrosis and
  intra-alveolar hemorrhage.
• Also pneumothorax and pulmonary HTN can occur

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Serositis Cardiac

• Pericarditis most common cardiac manifestation
  and usually responds to NSAIDs.
• Myocarditis (rare) and fibrinous endocarditis
  (Libman-Sacks) may occur. Steroids plus treatment
  for CHF/arrhythmia or embolic events.
• MI due to atherosclerosis can occur in lt35 y/o

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Neuro

• Cranial or peripheral neuropathy occurs in
  10-15, it is probably secondary to vasculitis in
  small arteries supplying nerves.
• Diffuse CNS dysfunction memory and reasoning
  difficulty
• Headache if excruciating, often indicate acute
  flare
• Seizures of any type
• Psychosis must distinguish from steroid-induced
  psychosis (occurs in 1st weeks of tx at doses
  40mg prednisone and resolves after several days
  of reducing or stopping tx)

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Cont.

• TIA, Stroke mostly increased among patients that
  are APLA positive
• 50-fold increase in risk of vascular events in
  women under 45 compared to healthy women
• Treatment for clotting event is long-term
  anticoagulation

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Heme

• Anemia usually Normochromic, normocytic
• Leukopenia almost always consists of
  lymphopenia, not granulocytopenia
• Thrombocytopenia

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Renal

• Nephritis usually asymptomatic, so always check
  UA if patient has known or suspected SLE
• Occurs early in course of disease-if not present
  w/in 1 yr, probably will not occur.
• Histologic classification by renal biopsy is
  useful to plan therapy

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Histologic Classifications

• Class I is minimal mesangial glomerulonephritis
  which is histologically normal on light
  microscopy but with mesangial deposits on
  electron microscopy.
• Class II is based on a finding of mesangial
  proliferative lupus nephritis. This form
  typically responds completely to treatment with
  corticosteroids.
• Class III is focal proliferative nephritis and
  often successfully responds to treatment with
  high doses of corticosteroids.
• Class IV is diffuse proliferative nephritis. This
  form is mainly treated with corticosteroids and
  immunosuppressant drugs.
• Class V is membranous nephritis and is
  characterized by extreme edema and protein loss.
• Class VI Glomerulosclerosis

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Immunoglobulins

• Anti-dsDNA IgG very specific, may correlate with
  disease activity
• Anti-Sm specific, but only present in 25 of
  cases, does not correlate with activity
• APLA not specific. Used to identify patients at
  increased risk for clots, thrombocytopenia and
  fetal loss

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ANA

• ANA positive in 95 of cases. Pretest
  probability affects interpretation. In PCP
  setting, 2 for SLE. In rheum 30
• Low Positive (1160 or lower) SLE likelihood lt2
  (lt26 for rheumatologists)
• High Positive (1320 or higher) SLE likelihood
  2-17 (32-81 for rheumatologists)
• SLE specific patterns Rim and Homogenous

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Additional work-up

• Serum cr. and albumin
• CBC w/ diff
• U/A
• ESR
• Complement levels
• Renal bx if warranted

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Treatment

• Treatment plans are based on patient age, sex,
  health, symptoms, and lifestyle
• Goals of treatment are to
• -prevent flares
• -treat flares when they occur
• -minimize organ damage and complications

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Conservative management

• For those w/out major organ involvement.
• NSAIDs to control pain, swelling, and fever
• Caution w/ NSAIDS though. SLE pts are at
  increased risk for aseptic meningitis
• Antimalarials Generally to treat fatigue joint
  pain, skin rashes, and inflammation of the lungs
• Commonly used Hydroxycholorquine
• Used alone or in combination with other drugs

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Cont.

• Corticosteroids (Mainstay of SLE treatment)
• To rapidly suppress inflammation
• Usually start with high-dose IV pulse and convert
  to PO steroids with goal of tapering and
  converting to something else.
• Commonly used prednisone, hydrocortisone,
  methylprednisolone, and dexamethasone

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Immunosuppressives

• Primarily for CNS/renal involvement
• Mycophenolate mofetil (cellcept)
• Azathioprine (imuran) requires several months to
  be effective, effective in smaller percentage of
  patients
• MTX for treatment of dermatitis and arthritis,
  not life-threatening disease
• Cyclosporine used in steroid-resistant SLE, risk
  of nephrotoxicity
• Cyclophosphamide (cytoxan) Almost all trials
  performed on patients with nephritis