Systemic Lupus Systemic Lupus Erythematosus (SLE) in Erythematosus (SLE) in

PregnancyPregnancy

Systemic Lupus Systemic Lupus Erythematosus (SLE) in Erythematosus (SLE) in

PregnancyPregnancyRachelle Darout, MDRachelle Darout, MD

PGY-1PGY-1Albert Einstein Family and Social MedicineAlbert Einstein Family and Social Medicine

Jack D. Weiler Hospital/Montefiore Medical CenterJack D. Weiler Hospital/Montefiore Medical CenterMarch 9, 2010March 9, 2010

SLE Case• HPI: 28 y.o F G5P1122 @ 375/7 weeks dated by

LMP 5/15/09 c/w 10 weeks sono; EDD 3/5/10 presents for IOL 2/2 to h/o SLE and Gestational Hypertension (GHTN); denies LOF, VB, CTX, +FM; denies HA, blurry vision, RUQ tenderness

• PNC: Dr. G since 12 weeks; Initial BP: 110/70 Range (100-150/60-100); Wt: 258-292 Δ 34 lbs

SLE Case• PNI:

– SLE: dx’d in ’01 w/ joint sx only; on prednisone and plaquenil; complete APLS w/u done @ 10 weeks; (AP-neg, Anti-Ro-Neg, Anti-dsDNA-pos); stable on meds

– Incompetent cervix: had prophylactic cerclage placement x 2; removed at 36 weeks for this pregnancy

– GHTN: BPs mildly elevated; no sx of Preclampsia (PEC)– h/o PEC-required Magnesium; delivery @ 36 weeks– Iron Deficiency Anemia w/ mild B12 deficiency: on Fe/Colace;

recommend B12– Pregravid Obesity: Initial BMI ~ 38– Multiparous: desires BTL

SLE Case• Labs: O+/Ab-; GCT-@105;HbsAg-Neg; RPR-

1:1; HgAA; Rub-I; GC/CT-Neg; PAP -• Sonos:

– Dating @ 10 weeks; EDC 3/5/10

– Anatomy @ 19 weeks; no anomalies

– Cerclage ~1.3 cm on 10/19/09; posterior placenta; AFI 21.5

SLE Case• PObhx:

– ’00 FT SVD M 6’7lbs– ’02 TOP x 1– ’05 20 weeks SAB tripletsdx’d w/ incompetent cervix– ’06 PT (36 weeks) SVD F 6’0 lbs c/b PEC

• PGynhx: 12/28/3-4 days; no h/o STDs, fibroids or abnormal PAPs

• PMH: SLE, -Asthma• PSH: cerclage x 1; D&C x 2

SLE Case• SH: none• All: NKDA• Meds: PNV, prednisone, plaquenil (antimalarial), ferrous

sulfate, colace• PE:143/73, 102; NAD; RRR; CTA b/l; Abd-obese, soft,

NT; no CVA tenderness– FHT: 140, mod variability, +accel, -decel– Toco: none– SVE: 3/50/-3, soft, mid; intact membrane; gynecoid pelvis– Sono: Vtx; EFW~ 3300g

SLE Case• A/P: 28 y.o F G5P1122 @ 375/7 weeks with SLE and GHTN for IOL

2/2 to medical problems– 1. Admit to L&D, NPO except ice chips; IVF-D5LR @ 125 cc/hr; check

CBC, RPR, T&S– 2. Labor: Latent phase; cervix favorable; Bishop score of 6; will start

pitocin for induction; pelvis adequate; SVD expected– 3. Fetus: Category 1 Tracing-Reassuring; EFW~3300g– 4. GBS: unknown: tx per risk factor– 5. Analgesia: desires epidural when needed– 6. SLE: no current flares; will need stress dose steroids during active

labor to help body respond normally to the physical stresses of childbirth– 7. GHTN: BPs in mild range; no sx of PEC; will f/u w/ PEC Labs– 8. DVT ppx: SCDs/TEDs; no need for anticoagulation for AP-Neg

Bishop Score

SLE Overview• Chronic inflammatory disease that can effect

various organs of the body• Characterized by production of antibodies to

components of cell nucleus • Who’s affected:

– Young women, peak incidence age 15-40 years with female: male ratio 5:1

– African Americans have higher lupus mortality risk compared to Hispanics and Caucasians

SLE Overview• Causes

– Unknown – Genetic factors– Environmental factors, which may include:

• Sunlight (UV rays)• Stress

– Viral or other type of infection– Drugs

• There are 38 known medications to cause Drug Induced Lupus• 3 that report the highest number of cases: hydralazine, procainamide, and isoniazid

• Pathogenesis– central immunologic disturbance is autoantibody production – commonly antinuclear antibodies (ANA) directed against components of cell nucleus (found in

>95%); anti-dsDNA and anti-Sm specific to SLE • anti-SSA (anti-Ro) • anti-ssDNA • Others: anti-histones (H1, H2A, H2B, H3),anti-U1RNP,anti-SS-B

SLE Overview• Organs involved

– 90% joints– 80% skin, serous membranes, lungs– 67% kidneys, heart– 25% CNS, small vessels

• Risk factors– Genetic predisposition (i.e. black race, 25-50% monozygotic twin concordance,

5% dizygotic twin concordance– Postmenopausal hormone replacement therapy associated with increased risk for

developing SLE • Reference- (Ann Intern Med 1995 Mar 15;122(6):430 in Mayo Clinic Proc 1995

Sep;70(9):868)– Smoking associated with increased risk for SLE and ex-smokers have an increased

risk for SLE • Reference- (J Rheumatology 2001 Nov;28(11):2449 in J Musculoskeletal Med 2002

Jun;19(6):256)

SLE Overview• Diagnosis

– Diagnosis is clinical and may be made with ≥ 4 classification criteria present

– Criteria is (96% specific, 96% sensitive) – any 4 or more of 11 criteria, serially or simultaneously, during any

interval of observation • 1. malar (butterfly) rash - fixed erythema, flat or raised, over malar

eminences, tending to spare nasolabial folds• 2. discoid lupus - erythematous raised patches with adherent keratotic scaling

and follicular plugging, atrophic scarring may occur• 3. photosensitivity - skin rash resulting from unusual reaction to sunlight• 4. oral or nasopharyngeal ulcers - usually painless, observed by physician• 5. non-erosive arthritis - involving 2 or more peripheral joints with

tenderness, swelling or effusion

SLE OverviewMalar Rash & Discoid Lupus

SLE Overview• 6. serositis - pleuritis (pleuritic pain, pleuritic rub or pleural

effusion) or pericarditis (on ECG, rub or pericardial effusion)• 7. renal involvement - persistent proteinuria (> 500 mg/day or

3+ on dipstick) or cellular casts (red cell, hemoglobin, granular, tubular or mixed)

• 8. seizures or psychosis without other organic cause• 9. hematologic disorder

– hemolytic anemia with reticulocytosis, OR– WBC < 4,000 at least 2 times, OR– absolute lymphocyte count < 1,500/mm3 at least 2 times, OR– platelet count < 100,000/mm3 without thrombocytopenic drugs

SLE Overview• 10. immunologic disorder

– anti-DNA, antibody to dsDNA [native DNA] in abnormal titer, OR – anti-Sm Ab (antibody to Sm nuclear antigen), OR – positive finding of antiphospholipid antibodies based on

» abnormal serum level of IgG or IgM anticardiolipin antibodies, OR

» positive test for lupus anticoagulant using standard method, OR » false positive serologic test for syphilis for at least 6 months and

confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test

• 11. positive ANA of abnormal titer in absence of drugs associated with "drug-induced lupus"

SLE Overview• Treatment

– prompt evaluation of unexplained fever– lifestyle measures – medications guided by specific symptoms

• nonsteroidal anti-inflammatory drugs (NSAIDs)– generally effective for constitutional symptoms, musculoskeletal complaints and mild serositis – caution regarding renal toxicity

• antimalarials – most useful for skin manifestations and for musculoskeletal complaints unresponsive to

NSAIDs – ophthalmologic monitoring recommended every 6-12 months

• corticosteroids – topical steroids useful for skin manifestations – systemic steroids may be needed for severe symptoms in any organ system – many complications with long-term use

• immunosuppressive agents – used alone or with steroids – particularly effective for renal and CNS symptoms – low-dose methotrexate effective for arthritis

EBM: Omega-3 and SLE• Omega-3 fatty acids may be effective for SLE (level 2

[mid-level] evidence)• based on small randomized trial• 60 patients (mean age 48 years) with SLE randomized to

omega-3 fatty acids vs. placebo and followed for 24 weeks

• omega-3 fatty acid group had significant reductions from baseline in disease activity measures

• no change from baseline in placebo group• Reference - Ann Rheum Dis 2008 Jun;67(6):841

SLE in Pregnancy• Women with SLE have no increase in

infertility• Outcome is best for mother and child when

SLE has been controlled for at least 6 months prior to pregnancy

• 7-33% of women with SLE have flares during pregnancy

Pregnancy Complications with SLE

• Preeclampsia

• Fetal Loss

• Preterm Delivery

• Low Birth Weight Infant

• Deep Vein Thrombosis/Pulmonary Embolism

Preeclampsia• High blood pressure in the mother after 20

weeks of pregnancy

• Occurs in ~13% of women w/ SLE

• Tx: DELIVERY

• Delivery may be delayed in some women who are less than 34 weeks to give steroids

Fetal Loss• Death of fetus @ 10 weeks or more of pregnancy• Occurs in 17% of women w/ SLE• Women with persistent high titers of

antiphospholipid antibodies (i.e. lupus anticoagulants and anticardiolipin antibodies) are at increased risk

• Women w/ lupus nephritis have increased risk of fetal loss by 75%; 2/2 worsening kidney function

Preterm Delivery• Delivery before 37 weeks

• Severe stress can lead to the release of hormones that cause uterine contractions

• Common in those who require high doses of glucocorticoids during pregnancy

Low Birth Weight Infant• Infant less than 2500g• Glucocorticoids causes growth restriction• Prenatal excess of glucocorticoids modifies the

development of several organs, including the lung, heart, gut, and kidney

Deep Vein Thrombosis (DVT)/Pulmonary Embolism

(PE)• Pregnancy and the puerperium are well-established risk

factors for DVT and PE, which are collectively referred to as venous thromboembolic disease (VTE)

• Risk of DVT and PE increases dramatically with SLE• Tx: Warfarin is teratogenic!!!!; low molecular weight

heparin is used during pregnancy; must monitor PTT (50-70)– Encourage pt to ambulate prior to pregnancy– Be sure to use SCD/TEDs

Neonatal Lupus• Occurs in about 2% of babies born to mothers w/ anti-

Ro/SSA and or anti-La/SSB antibodies• Caused by passage of the antibodies from the mother’s

bloodstream across the placenta to the developing baby after about 20 weeks

• Signs of neonatal lupus includes red, raised rash on the scalp and around the eyes that resolves by 6-8 months (because the antibodies clear the blood stream)

• SLE complications in babies: complete heart block and learning disabilities

• Risk of neonatal lupus in subsequent pregnancy is 17%

Neonatal Lupus

Preparing for Pregnancy with SLE

• Discuss desire to have child w/ rheumatologist, Obstetrical provider/Primary Care Doctor

• Follow-up with prenatal visits– After 28 weeks, visits will be weekly for fetal monitoring (i.e. BPP and

NST)• Women w/ lupus nephritis are encouraged to delay pregnancy until

their disease is inactive for at least 6 months• Discuss medication effects on women/men and baby• Women w/ SLE may need anticoagulation

– Used in women with antiphospholipid syndrome– Low dose < 160 mg/day is safe– Increased rates of stillbirth has been shown with aspirin doses greater

than 325 mg/day

Medications during Pregnancy

• Drugs to avoid (immunosuppressant therapy)– Mycophenolate mofetil– Cyclophosphamide– Methotrexate– Biologic medications

• Etanerecpt, infliximab, anakinra• Until more data is available, these meds should be avoided

• Drugs with small risk of harm– Aspirin– Prednisone/Glucocorticoids– Azathioprine– NSAIDs

• Drugs that are probably safe– Antimalarials (hydroxychloroquine)– No evidence that antimalarials increases risk of miscarriages or birth defects at normal doses

Recommendations

• Delivery: will need stress dose during active labor• Breastfeeding: recommended even for women with SLE• Birth control: IUD is effective; OCP can be used but

should be avoided in women with the following:– Migraine headaches– Raynaud Phenomenon– Past h/o DVT– Presence of antiphospholipid antibodies– Kidney disease and active SLE

Patient Course• NSVD of vigorous infant female; APGAR 9:9; placenta

delivered spontaneously; no lacerations to repair; Pitocin given; fundus was massaged until firm

• Pt kept in PACU for observation of BP; Magnesium was ultimately started for severe range BP and seizure ppx; PEC labs were collected and were within normal limits

• Pt had good urine output and no sx of magnesium toxicity while in PACU

• When BP returned to normal-mild range; magnesium and foley catheter were discontinued and pt was transferred to PP floor

References• Clark, CA, Spitzer, KA, Laskin, CA. Decrease in pregnancy loss rates in

patients with systemic lupus Erythematosus over a 40-year period. J Rheum 2005; 32:1709.

• Erkan, D, Sammaritano, L. New insights into pregnancy-related complications in systemic lupus erythematosus. Curr Rheum Rep 2003; 5:357.

• Guballa, N, Sammaritano, L, Schwartzman, S, et al. Ovulation induction and in vitro fertilization in systemic lupus erythematosus and antiphospholipid syndrome. Arthritis Rheum 2000; 43:550.

• Repke, JT. Hypertensive disorders of pregnancy. Differentiating preeclamsia from active systemic lupus erythematosus. J Reprod Med 1998; 43:350.

• Internet Sources– DynaMed– Uptodate

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