sle&pregnancy prs2

SLE and Pregnancy

Syed Atiqul HaqProfessor of Medicine-RheumatologyBSM Medical University, Dhaka, &

APLAR-COPCORD Coordinator

Basic Layout

Background

Management

Background

Effects on fertility

Effects of SLE on pregnancy

Effects of pregnancy on SLE

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

On Fetal Outcome

On Maternal Outcome

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

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

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

Management

Family planning & contraception

Patient in remission

Active disease & flares

Delivery

Puerperium and Lactation

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

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

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

Evaluation

Treatment

Follow-up Schedule

• Monthly up to 28 weeks

• Fortnightly 28 to 32 weeks

• Weekly afterwards

• More often in patients with active disease

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

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

Additional Tests at End of Each Trimester

Urine culture

Urine protein:creatinine ratio

Serum creatinine

Anti-ds-DNA

aCL

Anti-Ro/La Positive Mother

• FHR at each visit from 20 weeks

• Fetal echocardiography:

– Weekly 16 – 24 weeks

– Fortnightly 24 – 32 weeks

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.)

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

Classification of Flares

Mild

Moderate

Severe

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)

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

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

Steroid Maintenance Till Term

• Patients requiring maintenance

steroid before conception

• Recurrent mild flares

• Moderate to severe flares

Cyclophosphamide

• Indications:

– Acute anuric renal failure

– Alveolar heamorrage

– Refractory class IV nephritis

• Amniocentesis and karyotyping

• High risk of spontaneous abortion

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

Steroid Stress Coverage: Indication

• Treatment with systemic steroid within 2

years of the anticipated delivery

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

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

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

Conclusion

Safe motherhood possible with

• Increased awareness of the potential problems for mother and fetus

• Meticulous multidisciplinary follow up

• Effective disease control

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

Causes of Maternal Death

Pulmonary hypertension

Pulmonary embolus

HELLP syndrome

Cardiomyopathy

Severe renal flare

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%

Counselling

• Target: patient and family• Issues

• Chances of flare• Fetal loss• Prematurity• IUGR• Hypertension• Preeclampsia• Need for rigorous follow-up

Indications for Elective Abortion

Severe compromise of function of

• Kidneys

• Myocardium

• Lungs

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

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.)

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.)

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.)

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 ↓ =

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