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Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
Treatment of Systemic Lupus
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Treatment of Systemic Lupus

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For Internists and Critical care physicians

For Internists and Critical care physicians

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  • 1.  
  • 2. Treatment Decisions in SLE Ahmed Elshebiny University of Menoufyia
  • 3. General Principles <ul><li>Treatment should be tailored to every patient </li></ul><ul><li>Risk benefit evaluation </li></ul><ul><li>Timing of treatment changes </li></ul><ul><li>Treatment Precautions </li></ul><ul><li>Monitoring response and side effects </li></ul><ul><li>General measures </li></ul><ul><li>Cardiovascular risk correction </li></ul><ul><li>Cancer screening </li></ul>
  • 4. Treatment Plan General measures
  • 5. Assessment of disease activity <ul><li>Various global or individual organ scoring systems( SLEDAI, SLAM, BILAG, ECLAM, LAI..) </li></ul><ul><li>SLICC /ACR damage index </li></ul><ul><li>Practice points : assess </li></ul><ul><li>Disease activity </li></ul><ul><li>Disease damage </li></ul><ul><li>Co morbidities especially infection </li></ul><ul><li>Drug side effects </li></ul><ul><li>Quality of life </li></ul>
  • 6. Causes of mortality <ul><li>Early in the first years </li></ul><ul><ul><ul><li>Infection </li></ul></ul></ul><ul><ul><ul><li>Flares </li></ul></ul></ul><ul><li>Late </li></ul><ul><ul><ul><li>Atherosclerosis and cardiovascular disease </li></ul></ul></ul><ul><li>In 1950, 5 year survival in patients with nephritis was nearly zero, recently it is 85% </li></ul>
  • 7. Lupus Nephritis <ul><li>1/3 of patients with lupus develop overt renal disease , of them nearly 25 % reach ESRD by 10 years. </li></ul><ul><li>Histologically almost all patients will have changes </li></ul><ul><li>Renal biopsy …..modified (ISN/Renal pathological Society) classification </li></ul><ul><li>6 classes of lupus nephritis </li></ul>
  • 8. Lupus Nephritis (pathophsiology) <ul><li>Immune complexes </li></ul><ul><li>Glomerular Thrombosis (associated with antiphospholipid syndrome) </li></ul>
  • 9. Modified Classification of LN (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) <ul><li>Indicators of activity </li></ul><ul><li>Clinically relevant lupus nephritis </li></ul><ul><li>Anti C1q </li></ul><ul><li>Biopsy </li></ul><ul><li>Heavy proteinuria and edema are common with diffuse proliferative and membranous </li></ul><ul><li>HTN with diffuse proliferative </li></ul><ul><li>Systemic manifestations, CNS, serositis are associated with focal and diffuse proliferative </li></ul><ul><li>Asymptomatic may or insidious finding with mesangial and membranous </li></ul>
  • 11. Renal biopsy <ul><li>Should be considered especially in the first attack of nephritis </li></ul><ul><li>May be useful in recurrent nephritis </li></ul><ul><li>Biopsy gives idea about prognosis and outcome of nephritis and can alter management </li></ul><ul><li>Clinical situation can predict biopsy findings in 75% of cases , </li></ul><ul><li>Always perform biopsy if its findings will alter the ttt </li></ul><ul><li>Interpret biopsy with the clinical </li></ul><ul><li>Biopsy may depend on the pathologist </li></ul>(E- Medicine, Rheumatology, Nephritis, Lupus,2009)
  • 12. Biopsy spicimens
  • 13. Biopsy specimens
  • 14. Activity and Chronicity in Renal biopsy <ul><li>Glomerular sclerosis, segmental or global </li></ul><ul><li>Fibrous adhesion </li></ul><ul><li>Fibrous crescents </li></ul><ul><li>Endocapillary hypercellularity with or without leucocyte infiltration ; luminal reduction </li></ul><ul><li>Karyorrhexis </li></ul><ul><li>Fibrinoid necrosis </li></ul><ul><li>Rupture of GBM </li></ul><ul><li>Cellular or Fibrocellular Crescents </li></ul><ul><li>Subendothelial deposits on LM </li></ul><ul><li>Intraluminal Immune aggregates </li></ul>Chronicity Index Activity index
  • 15. Treatment of Lupus nephritis <ul><li>When to give steroids? </li></ul><ul><li>When to add cyclophosphamide? Aggressive disease, inadequate response, sensitivity to steroids </li></ul><ul><li>How to treat HTN and proteinuria? </li></ul><ul><li>Nutrition ( fat and protein) </li></ul><ul><li>Statins? </li></ul><ul><li>Active lupus nephritis should avoid pregnancy? How? </li></ul>
  • 16. Treatment of Lupus Nephritis 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 <ul><li>Goal of therapy? </li></ul><ul><li>Biopsy </li></ul><ul><li>Extra-renal lupus AND OTHER GENERAL MEASURES </li></ul>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 Lupus glomerulonephritis <ul><li>Treatment leading to normalization of proteinuria, HTN and renal dysfunction indicate a good prognosis. </li></ul><ul><li>Glomerulosclerosis usually predicts ESRD </li></ul>(Kumar and Clarks’s , Clinical Medicine 2009)
  • 19. Lupus cerebritis <ul><li>Is it lupus, the responsible? </li></ul><ul><li>Stroke? Is it a flare or athersclerosis or antiphospholipid </li></ul><ul><li>Siezures? Antiepiliptic </li></ul><ul><li>Headache </li></ul><ul><li>Cognitive dysfunction </li></ul><ul><li>Others </li></ul>
  • 20. Hematological abnormalities (cytopenias) <ul><li>Aetiology can be multifactorial </li></ul><ul><li>Are often mild. Treatment is not always necessary </li></ul><ul><li>Granulocyte colony stimulating factor? </li></ul><ul><li>Leucopenia </li></ul><ul><li>Thrombocytopenia (as ITP) </li></ul><ul><li>Anemia (hemolytic) </li></ul><ul><li>Ciclosporin may be considered in steroid resistant cases with caution of potential nephrotoxcicity </li></ul>Current , Rheumatology)
  • 21. Serositis <ul><li>NSAIDs </li></ul><ul><li>Moderate steroids </li></ul><ul><li>Hydroxychloroquine </li></ul><ul><li>Steroid sparing </li></ul>
  • 22. Cutaneous manifestations of Lupus
  • 23. Uncommom features <ul><li>Pnemonitis and diffuse alveolar hage </li></ul><ul><li>Mesentric vasculitis </li></ul>
  • 24. Pregnancy and Lupus <ul><li>Factors that influence pregnancy outcome in Women with lupus (activity, nephritis, antiphospholipid) </li></ul><ul><li>Lowest doses of cortisone for shortest periods to give responses </li></ul><ul><li>If antiphospholipid add heparin and aspirin </li></ul><ul><li>If anti Ro monitor fetus and deliver as soon as possible </li></ul>
  • 25. Lupus+ Antiphospholipid syndrome <ul><li>INR recommendations </li></ul>
  • 26. Prednisolone <ul><li>Long term use leads to osteoporsis, a vascular necrosis, HTN, diabetes,…etc </li></ul><ul><li>cataracts, glucoma, weight gain, myopathy and skin changes, mood changes…….. Growth retardation in children.. Adrenal insufficiency if stopped abruptly </li></ul><ul><li>Metabolism is increased by Liver enzyme inducers </li></ul><ul><li>B- fetal risk </li></ul><ul><li>Contraindications </li></ul><ul><li>No absolute , however severe bacterial, viral or fungal, active peptic ulcer , diabetes should be considered </li></ul>
  • 27. Methylprednisolone <ul><li>Less mineralocorticoid effect and should be considered in patients with edema </li></ul><ul><li>Oral and IV </li></ul><ul><li>Doses 10-40 mg/kg </li></ul>
  • 28. Cyclophosphamide <ul><li>500-1000 mg /month IV for 6 months </li></ul><ul><li>Then every 2-3 month </li></ul><ul><li>Adjust doses according to cbc, clinical response, toxcity, GFR </li></ul><ul><li>Phenobarb increases its toxcicity </li></ul><ul><li>Cyclophosphamime increases the effect of succynylcholine for up to 10 days with IV doses </li></ul><ul><li>Side effects: Nausea, vomiting hagic cystitis, alopecia, cytopenias, infection, infertility, teratogenicity, malignancies… </li></ul>
  • 29. MMF (Celcept) or Mycophenolic acid(Myfortic) <ul><li>Start with 500 bid then increase over 2 months to 1000 bid of MMF </li></ul><ul><li>Antacids reduce its absorption </li></ul><ul><li>Avoid live attenuated vaccines with its use </li></ul>
  • 30. Azathioprine <ul><li>2-3 mg/kg day single or divided doses </li></ul><ul><li>Start with 1 mg then increase </li></ul><ul><li>With allopurinol decrease the dose by 65-75% </li></ul><ul><li>May cause anemia nd leucopenia in combinartion with ACE </li></ul><ul><li>May decrease anti coagulant effect of warfarin </li></ul><ul><li>Contraindications; documented active infections, cytopenias, </li></ul><ul><li>Abnormal liver function test results may occur </li></ul>
  • 31. Ciclosporin
  • 32. Rutiximab
  • 33. Plasmaphresis <ul><li>If there is TTP or HUS </li></ul>
  • 34. Hydroxychloroquin
  • 35. References
  • 36. THANK YOU

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