Transcript Systemic Lupus Erythematosus (SLE) in Pregnancy

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:
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’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
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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
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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
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Organs involved
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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
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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
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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
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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
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Drugs to avoid (immunosuppressant therapy)
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Mycophenolate mofetil
Cyclophosphamide
Methotrexate
Biologic medications
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Drugs with small risk of harm
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Etanerecpt, infliximab, anakinra
Until more data is available, these meds should be avoided
Aspirin
Prednisone/Glucocorticoids
Azathioprine
NSAIDs
Drugs that are probably safe
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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:
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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
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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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