1. 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

2. SLE Case
HPI: 28 y.o F 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 ( /60-100); Wt: Δ 34 lbs

3. SLE Case
PNI:
SLE: dx’d in ’01 w/ joint sx only; on prednisone and plaquenil; complete APLS w/u 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; 36 weeks
Iron Deficiency Anemia w/ mild B12 deficiency: on Fe/Colace; recommend B12
Pregravid Obesity: Initial BMI ~ 38
Multiparous: desires BTL

4. SLE Case
Labs: O+/Ab-; RPR-1:1; HgAA; Rub-I; GC/CT-Neg; PAP -
Sonos:
10 weeks; EDC 3/5/10
19 weeks; no anomalies
Cerclage ~1.3 cm on 10/19/09; posterior placenta; AFI 21.5

5. SLE Case
PObhx:
’00 FT SVD M 6’7lbs
’02 TOP x 1
’ 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

6. 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

7. SLE Case
A/P: 28 y.o F 375/7 weeks with SLE and GHTN for IOL 2/2 to medical problems
1. Admit to L&D, NPO except ice chips; 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

8. Bishop Score

9. 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 years with female: male ratio 5:1
African Americans have higher lupus mortality risk compared to Hispanics and Caucasians

10. 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

11. 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)

12. 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

13. SLE Overview Malar Rash & Discoid Lupus

14. 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

15. 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"

16. 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

17. 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

18. 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

19. Pregnancy Complications with SLE
Preeclampsia
Fetal Loss
Preterm Delivery
Low Birth Weight Infant
Deep Vein Thrombosis/Pulmonary Embolism

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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%

26. Neonatal Lupus

27. 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

28. 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

29. 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

30. 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

31. 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
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