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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; RPR1:1; 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 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 (5070) – 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/ antiRo/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 • • • Drugs with small risk of harm – – – – • Etanerecpt, infliximab, anakinra Until more data is available, these meds should be avoided 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!!