1、Systemic Lupus ErythematosusSLEAutoimmune disease that affects multisystems1.5 million cases of lupusPrevalence of 17 to 48 per 100,000 populationWomen Men - 9:1 ratio90% cases are womenAfrican Americans WhitesOnset usually between ages of 15 and 45 years, butCan occur in childhood or later in lifeC
2、linical 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
3、and not have 4 criteria.Criteria1.Butterfly rash2.Discoid lupus3.Photosensitivity4.Oral ulcers5.Arthritis6.Serositis7. Neurologic d/o8. Hematologic d/o9. Renal d/o10.Immunologic: anti-DNA, anti-Sm, false pos STS11.Anti-nuclear antibodyCutaneousMost common rash is photosensitive, raised erythematous
4、malar rash. 55-85% develop at some point in diseaseDiscoid Lupus Erythematosus (DLE): 15-30% circular, scaly hyperpimented lesions with erythematous rim, atrophic centercan be disfiguringMouth/vaginal/nasal ulcersAlopecia: may be diffuse or patchy. Occurs 50%Malar RashDiscoid RashOral UlcersMSKPolya
5、rthritis, 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 steroid
6、s.)Myositis with elevated CK and weakness rarely occursArthritisSerositis - PulmonaryPleuritis with or without effusion- if case is mild, tx: NSAIDS- if case is severe, tx: steroidsLife-threatening manifestations: interstitial inflammation which can lead to fibrosis and intra-alveolar hemorrhage. Al
7、so pneumothorax and pulmonary HTN can occurSerositis CardiacPericarditis: 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
8、can occur in 35 y/oNeuroCranial or peripheral neuropathy occurs in 10-15%, it is probably secondary to vasculitis in small arteries supplying nerves. Diffuse CNS dysfunction: memory and reasoning difficultyHeadache: if excruciating, often indicate acute flareSeizures of any typePsychosis: must disti
9、nguish 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 positive50-fold increase in risk of vascular events in women under 45 compared to healt
10、hy womenTreatment for clotting event is long-term anticoagulationHemeAnemia: usually Normochromic, normocyticLeukopenia: almost always consists of lymphopenia, not granulocytopeniaThrombocytopenia RenalNephritis: usually asymptomatic, so always check UA if patient has known or suspected SLE Occurs e
11、arly 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 ClassificationsClass I is minimal mesangial glomerulonephritis which is histologically normal on light microscopy but with mesangial deposits on
12、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
13、 is diffuse proliferative nephritis. This form is mainly treated with cor ticosteroids and immunosuppressant drugs.Class V is membranous nephritis and is characterized by extreme edema and protein loss.Class VI GlomerulosclerosisImmunoglobulinsAnti-dsDNA IgG: very specific, may correlate with diseas
14、e activityAnti-Sm: specific, but only present in 25% of cases, does not correlate with activityAPLA: not specific. Used to identify patients at increased risk for clots, thrombocytopenia and fetal lossANAANA: positive in 95% of cases. Pretest probability affects interpretation. In PCP setting, 2% fo
15、r SLE. In rheum: 30%Low Positive (1:160 or lower): SLE likelihood 2% (26% for rheumatologists) High Positive (1:320 or higher): SLE l i k e l i h o o d : 2 - 1 7 % ( 3 2 - 8 1 % f o r rheumatologists)SLE specific patterns: Rim and HomogenousAdditional work-up-Serum cr. and albumin-CBC w/ diff-U/A-ES
16、R-Complement levels-Renal bx if warranted TreatmentTreatment plans are based on patient age, sex, health, symptoms, and lifestyleGoals of treatment are to: -prevent flares -treat flares when they occur -minimize organ damage and complicationsConservative managementFor those w/out major organ involve
17、ment. NSAIDs: to control pain, swelling, and feverCaution 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 lungsCommonly used: HydroxycholorquineUsed alone or in combination with other dr
18、ugsCont.Corticosteroids (Mainstay of SLE treatment)To rapidly suppress inflammationUsually 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 dexamethasoneImmunosuppressive
19、sPrimarily for CNS/renal involvementMycophenolate mofetil (cellcept)Azathioprine (imuran): requires several months to be effective, effective in smaller percentage of patientsMTX: for treatment of dermatitis and arthritis, not life-threatening diseaseCyclosporine: used in steroid-resistant SLE, risk of nephrotoxicityCyclophosphamide (cytoxan) Almost all trials performed on patients with nephritisThank you for your attetion!
