Systemic Lupus Erythematosus (SLE) in Pregnancy Rachelle Darout, MD PGY-1 Albert Einstein Family and Social Medicine Jack D. Weiler Hospital/Montefiore Medical Center March 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 tripletsdx’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 Risk factors 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 Overview Malar 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 THANK YOU!!