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Treatment of Systemic Lupus
Treatment for systemic lupus erythematosus (SLE) should be tailored to each patient based on an assessment of disease activity, damage, and comorbidities. Lupus nephritis, a form of kidney involvement, affects about 1/3 of SLE patients and can lead to end-stage renal disease if not properly treated. Treatment involves immunosuppressive drugs like corticosteroids, cyclophosphamide, mycophenolate, and azathioprine to induce remission based on the class of lupus nephritis determined by renal biopsy. Prognosis is generally good if treatment can normalize kidney function and blood pressure.
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Treatment of Systemic Lupus
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- 2. Treatment Decisions inSLE Ahmed Elshebiny University of Menoufyia
- 3. General Principles Treatmentshould be tailored to every patient Risk benefit evaluation Timing of treatment changes Treatment Precautions Monitoring response and side effects General measures Cardiovascular risk correction Cancer screening
- 4. Treatment Plan Generalmeasures
- 5. Assessment of diseaseactivity Various global or individual organ scoring systems( SLEDAI, SLAM, BILAG, ECLAM, LAI..) SLICC /ACR damage index Practice points : assess Disease activity Disease damage Co morbidities especially infection Drug side effects Quality of life
- 6. Causes of mortalityEarly in the first years Infection Flares Late Atherosclerosis and cardiovascular disease In 1950, 5 year survival in patients with nephritis was nearly zero, recently it is 85%
- 7. Lupus Nephritis 1/3of patients with lupus develop overt renal disease , of them nearly 25 % reach ESRD by 10 years. Histologically almost all patients will have changes Renal biopsy …..modified (ISN/Renal pathological Society) classification 6 classes of lupus nephritis
- 8. Lupus Nephritis (pathophsiology)Immune complexes Glomerular Thrombosis (associated with antiphospholipid syndrome)
- 9. Modified Classification ofLN (Kumar and Clarks’s , Clinical Medicine 2009) Progressive renal failure Advanced sclerosing VI 10-20% of cases Good prognosis Membranous V Progression to NS, HTN, and Renal imp. Most common and most severe Diffuse LN IV 10-20% of cases Hematuria and proteinuria Focal LN III Mild renal disease Mesangial proliferative LN II A symptomatic Minimal mesangial LN I Clinical Histological Class
- 10. Lupus nephritis (CLINICALLY) Indicators of activity Clinically relevant lupus nephritis Anti C1q Biopsy Heavy proteinuria and edema are common with diffuse proliferative and membranous HTN with diffuse proliferative Systemic manifestations, CNS, serositis are associated with focal and diffuse proliferative Asymptomatic may or insidious finding with mesangial and membranous
- 11. Renal biopsy Shouldbe considered especially in the first attack of nephritis May be useful in recurrent nephritis Biopsy gives idea about prognosis and outcome of nephritis and can alter management Clinical situation can predict biopsy findings in 75% of cases , Always perform biopsy if its findings will alter the ttt Interpret biopsy with the clinical Biopsy may depend on the pathologist (E- Medicine, Rheumatology, Nephritis, Lupus,2009)
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- 14. Activity and Chronicityin Renal biopsy Glomerular sclerosis, segmental or global Fibrous adhesion Fibrous crescents Endocapillary hypercellularity with or without leucocyte infiltration ; luminal reduction Karyorrhexis Fibrinoid necrosis Rupture of GBM Cellular or Fibrocellular Crescents Subendothelial deposits on LM Intraluminal Immune aggregates Chronicity Index Activity index
- 15. Treatment of Lupusnephritis When to give steroids? When to add cyclophosphamide? Aggressive disease, inadequate response, sensitivity to steroids How to treat HTN and proteinuria? Nutrition ( fat and protein) Statins? Active lupus nephritis should avoid pregnancy? How?
- 16. Treatment of LupusNephritis base on biopsy Class Prepare for hemo which is better than peritoneal Arrange for renal Tx, treat extra-renal lupus VI Prednisone for 1-3 months followed by low dose for 1-2 years Azathioprin , chlorambucil, cyclophosphamide or MMF may decrease proteinuria V IV Prednisolone 1mg/kg/d for 1 month then taper depending on the clinical response to 5-10 mg for 2-2.5 years or Pulses for 3 days in severly ill add imunosupressive when indicated, adjust immunosupressine with cbc III 20-40 for 1 -3 months II Non specific I Treatment Clasas
- 17. Active Lupus Nephritis: Induction of remission Goal of therapy? Biopsy Extra-renal lupus AND OTHER GENERAL MEASURES Prospective controlled trials in active lupus nephritis show that administration of high doses of glucocorticoids (1000 mg of methylprednisolone daily for 3 days) by intravenous routes compared with daily oral routes shortens the time to maximal improvement by a few weeks but does not result in better renal function. It has become standard practice to initiate therapy for active, potentially life-threatening SLE with high-dose IV glucocorticoid pulses, based on studies in lupus nephritis. This approach must be tempered by safety considerations, such as the presence of conditions adversely affected by glucocorticoids (infection, hyperglycemia, hypertension, osteoporosis, etc .). (Harrison online 2008)
- 18. Prognosis of Lupusglomerulonephritis Treatment leading to normalization of proteinuria, HTN and renal dysfunction indicate a good prognosis. Glomerulosclerosis usually predicts ESRD (Kumar and Clarks’s , Clinical Medicine 2009)
- 19. Lupus cerebritis Isit lupus, the responsible? Stroke? Is it a flare or athersclerosis or antiphospholipid Siezures? Antiepiliptic Headache Cognitive dysfunction Others
- 20. Hematological abnormalities (cytopenias)Aetiology can be multifactorial Are often mild. Treatment is not always necessary Granulocyte colony stimulating factor? Leucopenia Thrombocytopenia (as ITP) Anemia (hemolytic) Ciclosporin may be considered in steroid resistant cases with caution of potential nephrotoxcicity Current , Rheumatology)
- 21. Serositis NSAIDs Moderatesteroids Hydroxychloroquine Steroid sparing
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- 23. Uncommom features Pnemonitisand diffuse alveolar hage Mesentric vasculitis
- 24. Pregnancy and LupusFactors that influence pregnancy outcome in Women with lupus (activity, nephritis, antiphospholipid) Lowest doses of cortisone for shortest periods to give responses If antiphospholipid add heparin and aspirin If anti Ro monitor fetus and deliver as soon as possible
- 25. Lupus+ Antiphospholipid syndromeINR recommendations
- 26. Prednisolone Long termuse leads to osteoporsis, a vascular necrosis, HTN, diabetes,…etc cataracts, glucoma, weight gain, myopathy and skin changes, mood changes…….. Growth retardation in children.. Adrenal insufficiency if stopped abruptly Metabolism is increased by Liver enzyme inducers B- fetal risk Contraindications No absolute , however severe bacterial, viral or fungal, active peptic ulcer , diabetes should be considered
- 27. Methylprednisolone Less mineralocorticoideffect and should be considered in patients with edema Oral and IV Doses 10-40 mg/kg
- 28. Cyclophosphamide 500-1000 mg/month IV for 6 months Then every 2-3 month Adjust doses according to cbc, clinical response, toxcity, GFR Phenobarb increases its toxcicity Cyclophosphamime increases the effect of succynylcholine for up to 10 days with IV doses Side effects: Nausea, vomiting hagic cystitis, alopecia, cytopenias, infection, infertility, teratogenicity, malignancies…
- 29. MMF (Celcept) orMycophenolic acid(Myfortic) Start with 500 bid then increase over 2 months to 1000 bid of MMF Antacids reduce its absorption Avoid live attenuated vaccines with its use
- 30. Azathioprine 2-3 mg/kgday single or divided doses Start with 1 mg then increase With allopurinol decrease the dose by 65-75% May cause anemia nd leucopenia in combinartion with ACE May decrease anti coagulant effect of warfarin Contraindications; documented active infections, cytopenias, Abnormal liver function test results may occur
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- 33. Plasmaphresis If thereis TTP or HUS
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