sle&pregnancy prs2
DESCRIPTION
TRANSCRIPT
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SLE and Pregnancy
Syed Atiqul HaqProfessor of Medicine-RheumatologyBSM Medical University, Dhaka, &
APLAR-COPCORD Coordinator
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Basic Layout
Background
Management
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Background
Effects on fertility
Effects of SLE on pregnancy
Effects of pregnancy on SLE
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Effects On Fertility
• Fertility of SLE patients usually unaltered
• Factors lowering fertility– Renal failure– Cyclophosphamide– Very active disease– Anti-phospholipid antibodies (aPLs) in high titers
– High dose steroid
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On Fetal Outcome
On Maternal Outcome
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Fetal Outcome
Effects Risk Factors
Abortions (6%-35%)
Stillbirths (4%-22%)
•Active lupus nephritis•Previous history of fetal death•The presence of the aPLs
IUGR (9-35%) Hypertension, pre-eclampsia, steroid
Prematurity (40-50%) Hypertension, pre-eclamsia
PROM Steroid treatment
NLE syndrome (5%)
CHB (1.7%)
Anti-Ro, anti-La
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Maternal Outcome
Effects Risk Factors
Toxemias DiabetesLN (30%)HypertensionToxemia in previous pregnancyThrombocytopeniaaPLs
HypertensionDiabetesInfections, UTI
Steroid treatment
Maternal death (1%, in ’60s 20%)
LN
Pulmonary hypertension
Cardiomyopathy
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Effects of Pregnancy on SLE
• Flare of disease activity during
– Any trimester of pregnancy (≈ 60%)
– Postpartum
– Commonly mild
– Severe renal flare if LN active during conception
• Permanent loss of renal function in a small proportion
• No change in the long term course
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Management
Family planning & contraception
Patient in remission
Active disease & flares
Delivery
Puerperium and Lactation
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Family Planning
• The best time for conception: after a 6-
12 months of cytotoxic-free remission
• Incidence of a flare with conception
after remission is 10% or less
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Contraception
• Mechanical barrier methods are safe
and effective, albeit less so than OCPs
• Intrauterine devices controversial
– Infections: endometritis, PID
– Perforation
– Menorrhagia
• Low estrogen contraceptive pills
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Oral Contraceptives• Contraindications:
– aPL, other thromboembolic diseases
– Highly active disease
– Migraine
– Raynaud’s phenomenon
– FH of breast cancer
• Specific indication:
– Cyclophosphamide therapy
• Mitigates against gonadotoxicity
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Evaluation
Treatment
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Follow-up Schedule
• Monthly up to 28 weeks
• Fortnightly 28 to 32 weeks
• Weekly afterwards
• More often in patients with active disease
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Evaluation at First Visit
Initial visit: Thorough evaluation of disease activity-
• A full history and examination, BP
• Routine urinalysis
• CBC and platelet count
• Serum creatinine
• A 24 hour urinary total protein, CCr
• Anti-ds-DNA, anti-Ro and –La, aPLs
• Fasting blood glucose if at high risk
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Evaluation at Subsequent Visits
• History and examination: detect flares, BP
• Routine urinalyses
• Blood counts incl. platelet, Hb%, ESR
• From 28 weeks biophysical profile (BPP) scoring
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Additional Tests at End of Each Trimester
Urine culture
Urine protein:creatinine ratio
Serum creatinine
Anti-ds-DNA
aCL
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Anti-Ro/La Positive Mother
• FHR at each visit from 20 weeks
• Fetal echocardiography:
– Weekly 16 – 24 weeks
– Fortnightly 24 – 32 weeks
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Sheet Anchor• Patient and family education & counseling
• Drugs:– Folic acid 400 µg/d during first trimester
– HCQ: 4 to 6 mg/kg/d throughout pregnancy
– Aspirin: 75 mg/d up to 38 weeks
• History in a previous pregnancy of
– Fetal loss after the 1st trimester
– IUGR
– Early onset pre-eclampsia requiring delivery before 32 weeks
• Nephritis
• aPLs
• (Aspirin may be continued throughout pregnancy and delivery if there is
H/O MI/stroke.)
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Anti-phospholipid Ab Syndrome
• Low dose aspirin
• LMWH or UFH– Women with prior pregnancy complications but no
thrombosis
• LMWH (0.5mg/kg twice daily) or UFH (10,000 IU twice daily)
– Women with previous history of thrombosis
• LMWH (1mg/kg twice daily) or UFH (Adjusted dose to prolong
the APTT to twice control)
• Calcium supplement (1.5 gm daily)
• Axial exercise
• Prednisolone has no added benefit
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Classification of Flares
Mild
Moderate
Severe
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Mild Flares
• Maximizing dose of HCQ to 6 to 6.5 mg/kg
• Prednisone/prednisolone: 0.1 – 0.3 mg/kg/day
– Tapered off if full remission achieved quickly
– Avoided or used in low dose in 1st trimester
• Mildest flares: may be treated initially with
– Sunscreen
– topical steroid
– paracetamol
– NSAIDs (late first and second trimesters)
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Moderate Flare
• Maximizing dose of HCQ
• Prednisone/Prednisolone: 0.3 – 0.5 mg/kg
– Attempt at gradual taper after full remission
• AZT or Cys A
– Flare recurrence with prednisone <7.5 mg/d
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Severe Flare
• Prednisone/Prednisolone: 1 mg/kg/day
– May be preceded by pulse MP
• Azathioprine: 1.5 to 2 mg/kg/day or
cyclosporin A 3 -- 4 mg/kg/day
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Steroid Maintenance Till Term
• Patients requiring maintenance
steroid before conception
• Recurrent mild flares
• Moderate to severe flares
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Cyclophosphamide
• Indications:
– Acute anuric renal failure
– Alveolar heamorrage
– Refractory class IV nephritis
• Amniocentesis and karyotyping
• High risk of spontaneous abortion
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Delivery Setting
• In a hospital with neonatal ICU
• Vaginal route preferred
• Routine caesarian delivery not recommended
• Indications for caesarian section
– As for women without lupus
– High incidence of non-reassuring BPP score leading to
caesarian delivery
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Steroid Stress Coverage: Indication
• Treatment with systemic steroid within 2
years of the anticipated delivery
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Steroid Stress Coverage: Protocol
• Day of delivery: Hydrocortisone 100 mg I/V just prior to onset of delivery and 8 hourly
• 2nd day: 50 mg 8 hourly
• Day 3 onwards:– No steroid if not on steroid before delivery
– Restart oral dose used before delivery
• If on more than 75 mg of prednisone daily– appropriate hydrocortisone equivalent for days 2 and 3
– then resume previous oral dose
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Post-partum Flare
• Risk groups:– Active disease at conception
– Significant end-organ damage
• Detection:– Focused history & examination
– Lab tests:• Urinalysis
• blood counts
• Serum creatinine
• Urine protein/creatinine ratio
• Anti-dsDNA
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Lactation• Safe drugs:
– short acting NSAIDs (not aspirin)
– prednisolone <15 mg/d
• Higher dose: after morning feed and next feed after 4 hrs
– HCQ
– Warfarin
– Heparin
• Drugs to be avoided
– AZT
– CysA
– MTX
– Cylophosphamide
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Conclusion
Safe motherhood possible with
• Increased awareness of the potential problems for mother and fetus
• Meticulous multidisciplinary follow up
• Effective disease control
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Neonatal Lupus Syndrome (NLE)
• Congenital heart block (CHB) – 1.7%
– CCHB carries 15 to 30% mortality
• Transient cutaneous lupus lesions
• Cytopenias
• Hepatic, and other systemic manifestations
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Causes of Maternal Death
Pulmonary hypertension
Pulmonary embolus
HELLP syndrome
Cardiomyopathy
Severe renal flare
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Flare During Pregnancy
• Usually mild with arthritis and rash
• Major organ flares may occur
– Kidneys 40%: in LN patients
• 50-60% if active during conception
• 7-10% if quiescent during conception
– Central nervous system 5%
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Counselling
• Target: patient and family• Issues
• Chances of flare• Fetal loss• Prematurity• IUGR• Hypertension• Preeclampsia• Need for rigorous follow-up
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Indications for Elective Abortion
Severe compromise of function of
• Kidneys
• Myocardium
• Lungs
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Mild Moderate
Muco-cutaneous Butterfly rash
Photosensitivity
Maculopapular
Mild oral ulcer
Mild DLE
Severe oral ulcer
Severe DLE
Diffuse SCLE
Lupus profundus
Skin vasculitis
Articular Arthralgia, mild polyartritis
Disabling polyarthritis
Therapeutic Classification
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Mild Moderate Severe
Renal Class I, IIa Class IIb, LN Class III, IV LN
Neuro-psychiatric
Lupus headache
ChoreaPeripheral neuropathy
Delirium
Encephalitis
Psychosis
Coma
Myelopathy
Therapeutic Classification (contd.)
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Mild Moderate Severe
Hematological Platelet30 to 100,000
Platelet
15 to 30,000 (preg: 30 to 100,000)
Hemolytic anemia
Lupus adenitis
Platelet <15,000
(preg: <30,000)
Cardiopulmonary Pleurisy Pleural effusion
Pneumonitis
Pericarditis
Mild myocarditis
Severe pneumonitis
Pulmonary hemorrhage
Cardiac tamponade
Severe myocarditis
Therapeutic Classification (contd.)
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Mild Moderate Severe
Gastro-intestinal
Mild hepatitis
Pancreatitis
Peritonitis
Severe hepatitis
Colitis
Protein-losing enteropathy
Mesenteric vasculitis
Miscellaneous Responsive fever
Fatigue
Myalgia
Refractory/high fever
Therapeutic Classification (contd.)
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Pre-eclampsia vs. Renal Flare
Feature Pre-eclampsia Lupus flare
Arthritis, rash -- +
Active sediment in urine
C3, C4 ↓ ↑
Anti-dsDNA = ↑
Uric acid, liver enzymes ↑ =
Urinary calcium ↓ =
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Treatment of Heart Block
• Dexamethasone 4 mg/day– Partial:
• If reverts or doesn’t progress: till delivery• If progresses to complete: taper
– Complete:• If reverts to partial: till delivery• If doesn’t revert after 6 weeks: taper