Systemic Lupus

Erythematosus
Justin A. Crocker
AM Report 12/2/09
SLE
 Autoimmune disease that affects multisystems
 1.5 million cases of lupus
 Prevalence of 17 to 48 per 100,000 population
 Women > Men - 9:1 ratio
 90% cases are women
 African Americans > Whites
 Onset usually between ages of 15 and 45 years,
but
 Can occur in childhood or later in life
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.
Criteria
1. Butterfly rash 7. Neurologic d/o
2. Discoid lupus 8. Hematologic d/o
3. Photosensitivity 9. Renal d/o
4. Oral ulcers 10.Immunologic: anti-
5. Arthritis DNA, anti-Sm, false
6. Serositis pos STS
11.Anti-nuclear antibody
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 center—can be
disfiguring
 Mouth/vaginal/nasal ulcers
 Alopecia: may be diffuse or patchy. Occurs 50%
Malar Rash
Discoid Rash
Oral Ulcers
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
Arthritis
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
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 <35 y/o
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)
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
Heme
 Anemia: usually Normochromic,
normocytic
 Leukopenia: almost always consists of
lymphopenia, not granulocytopenia
 Thrombocytopenia
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
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
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
ANA
 ANA: positive in 95% of cases. Pretest
probability affects interpretation. In PCP setting,
2% for SLE. In rheum: 30%
 Low Positive (1:160 or lower): SLE likelihood
<2% (<26% for rheumatologists)
 High Positive (1:320 or higher): SLE likelihood:
2-17% (32-81% for rheumatologists)
 SLE specific patterns: Rim and Homogenous
Additional work-up
- Serum cr. and albumin
- CBC w/ diff
- U/A
- ESR
- Complement levels
- Renal bx if warranted
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
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
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
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