Treatment Decisions in SLEAhmed ElshebinyAhmed Elshebiny

University of MenoufyiaUniversity of Menoufyia

General Principles Treatment should 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

Treatment Plan

General measures

Assessment of disease activity Various global or individual organ scoring

systems( SLEDAI, SLAM, BILAG, ECLAM, LAI..)

SLICC /ACR damage indexPractice points : assess Disease activity Disease damage Co morbidities especially infection Drug side effects Quality of life

Causes of mortality Early 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%

Lupus Nephritis 1/3 of 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

Lupus Nephritis (pathophsiology) Immune complexes Glomerular Thrombosis (associated with

antiphospholipid syndrome)

Modified Classification of LNClass Histological Clinical

IMinimal mesangial LNA symptomatic

IIMesangial proliferative LNMild renal disease

IIIFocal LN10-20% of cases

Hematuria and proteinuria

IVDiffuse LNProgression to NS, HTN, and Renal imp.

Most common and most severe

VMembranous10-20% of cases

Good prognosis

VIAdvanced sclerosingProgressive renal failure

(Kumar and Clarks’s , Clinical Medicine 2009)

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

Renal biopsy Should be 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)

Biopsy spicimens

Biopsy specimens

Activity and Chronicity in Renal biopsy

Activity indexChronicity IndexEndocapillary hypercellularity with or without leucocyte infiltration ; luminal reductionKaryorrhexisFibrinoid necrosisRupture of GBMCellular or Fibrocellular CrescentsSubendothelial deposits on LMIntraluminal Immune aggregates

Glomerular sclerosis, segmental or globalFibrous adhesionFibrous crescents

Treatment of Lupus nephritis 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?

Treatment of Lupus Nephritis base on biopsy Class

ClasasTreatment

INon specific

II20-40 for 1 -3 months

IIIPrednisolone 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

IV

VPrednisone for 1-3 months followed by low dose for 1-2 years

Azathioprin , chlorambucil, cyclophosphamide or MMF may decrease proteinuria

VIPrepare for hemo which is better than peritoneal

Arrange for renal Tx, treat extra-renal lupus

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)

Prognosis of Lupus glomerulonephritis 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)

Lupus cerebritis Is it lupus, the responsible? Stroke? Is it a flare or athersclerosis or

antiphospholipid Siezures? Antiepiliptic Headache Cognitive dysfunction Others

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)

Serositis NSAIDs Moderate steroids Hydroxychloroquine Steroid sparing

Cutaneous manifestations of Lupus

Uncommom features Pnemonitis and diffuse alveolar hage Mesentric vasculitis

Pregnancy and Lupus Factors 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

Lupus+ Antiphospholipid syndrome INR recommendations

Prednisolone Long term use 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 riskContraindicationsNo absolute , however severe bacterial, viral or fungal,

active peptic ulcer , diabetes should be considered

Methylprednisolone Less mineralocorticoid effect and should be

considered in patients with edema Oral and IV Doses 10-40 mg/kg

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…

MMF (Celcept) or Mycophenolic 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

Azathioprine 2-3 mg/kg day 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

Ciclosporin

Rutiximab

Plasmaphresis If there is TTP or HUS

Hydroxychloroquin

References