Download Sytemic Lupus Erythematosus(SLE) and Pregnancy

To discuss how pregnancy affects SLE in
increasing lupus flare rates
 To discuss the effects of SLE on maternal
and fetal outcome in pregnancy
 To discuss management of Lupus flare in
pregnancy
 To discuss ethical issues on the case

K. G.
 18/F
 Makati City
 CC: bipedal edema
 DOA: 3/18/08

Diagnosed case of Systemic Lupus Erythematosus since
Aug. 2007
1997 Revised Classification Criteria for Systemic Lupus Erythematosus [1]
Target Organ
Target Organ
Malar rash
Neurologic
disorder
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Renal disorder
1
Hematologic
disorder
Immunologic
disorder
Antinuclear
antibody
Kliegman, Robert, M.D., et al. Nelson’s Textbook of Pediatrics. 18th ed. USA: Sanders, 2007, pp. 1015-191
1 yr PTA
(+) alopecia, (+) malar rash
9 mo PTA
(+) fever, (+) discoid rash, (+) oral ulcers
(+) R eyelid swelling
(+) joint pain and swelling of hands
RHEUMA CLINIC A> SLE
Labs: ANA (+4) homogenous 1:80
leukopenia (3,800), anemia (10),
lymphopenia (ALC 0.934)
BUN 2.3 mol/L (N), Crea (N),
Proteinuria(++), RBC 0-1
2 mo PTA
1 wk PTA
4 d PTA
Pregnant
discontinued Prednisone
No consult done
(+) persistence of cough
(+) bipedal and periorbital
edema
(+) persistence of edema
(+) 2 pillow orthopnea
(-) PND, palpitations, chest
pain
2 d PTA
(+) easy fatigability
(+) difficulty of breathing
(+) vomiting
(+) epigastric pain
(+) diarrhea
(+) tea-colored urine
(+) oliguria
Rheuma clinic consult
PAY





General: (-) generalized weakness, (-)
weight loss, (-) anorexia
Neurologic: (-) seizure, (-) headache, (-)
change in sensorium, (-) change in
behavior
HEENT: (-) eye pain, blurring of vision, (-) sore
throat
Hematologic: (-) epistaxis, (-) hematemesis,
(-) hematochezia, (-) hemoptysis, (-) easy
bruisability, (-) increased bleeding,
Dermatologic: (-) active skin lesions

No intake of other Meds except Prednisone

(+) similar illness – grandmother, paternal
side
Family History
Birth/Maternal History

noncontributory
Immunization History

Completed at Local health center

Unremarkable
Nutritional History
Developmental History

At par with age
Obstetrics/Menstrual History
G1P0, (+) pregnancy test in February,
(+) spotting in February, (-) vaginal
discharge
 LMP: Dec 3, 2007, 30 days interval, 4
days duration, 3 pads/day, (+)
dysmenorrhea


Personal/Social History



2nd child from a brood of 9
Mother is a 39 y/o,housewife.
Father is 45 y/o, nurse at PGH PICU.

Home
› living with parents and siblings
› good relationship with them (closest to her
older sister)

Education
› incoming 1st year college student, taking up
BS Psychology
› She didn’t finished first year due to her illness
› plans to finish her study and work to help her
parents

Activity
› hangs out with friends in the mall or in their
house, go out preferably at night
› love to talk about gossips

Drugs
› Denies illicit drug use
› occasional beverage drinker
› doesn’t smoke

Sex
› one relationship and sexually active, with a 15
y/o guy, who is also the father of her present
pregnancy
› Her boyfriend impregnated another woman
prior to her
› no plans of getting married now

Suicidal ideations
› when scolded by parents
› felt very sad when she was diagnosed with SLE
General exam: conscious, coherent, not
in cardiorespiratory distress
 Vital signs: BP 140/80, PR 110, RR 24, T 38C,
wt 47 kg, ht 151 cm
 HEENT: slightly pale conjunctivae,
anicteric sclera, (+) periorbital edema,
bilateral
 (-) cervical lymphadenopathy, (-) anterior
neck mass, (-)neck vein engorgement, (-)
tonsillopharyngeal congestion

Chest and Lungs: Equal chest expansion,
no retractions, (+) clear breath sounds, (-)
crackles/wheeze
 Cardiovascular: adynamic precordium,
distinct HS, tachycardic, normal regular
rhythm, AB at 5th LICS MCL, (-) murmur
 Abdomen: globular abdomen, (+) NABS,
soft, (+) epigastric tenderness, (-)
organomegaly, abdominal girth = 76 cm,
fundic height = 20 cm, fetal heart tone not
appreciated by stethoscope

Internal examination: (+) vulvar edema,
nulliparous vagina, corpus enlarged to
AOG, cervix soft closed, (-) abnormal
discharge or masses
 Extremities: Pink nailbeds, FEP, (-)
cyanosis, (+) bipedal edema, pitting,
grade 1
 External genitalia: grossly female, SMR 4
 Skin: (-) active dermatoses
 Neurologic exam: essentially normal

SLE in activity
Pregnancy Uterine 17 2/7 weeks by early
UTZ, NIL
UTI
Pregnancy
2. SLE
• Nephritis, Hypertension
• Pericarditis
• Anemia
3. Pulmonary edema, noncardiogenic
Pleural Effusion, B
4. Infection
1.
S
O
Amenorrhea
LMP: Dec 3, 2007
Sexual
intercourse
•Pregnancy Test
(+)
•UTZ: Pregnancy
Uterine 17 2/7
weeks, good
cardiiac and
somatic
acrtivities
A
Pregnancy
Uterine 17 2/7
weeks by early
UTZ, NIL
t/c APAS
P
•For APAS
•Serial Fetal
biometry
•Aspirin
•FeSO4, CaCO3,
MgSO4, Folic
acid, MV
S
•Edema
•Hematuia
O
•BP 140/80 on
admission, BP
spikes of
160/100)
•Proteinuria on
urinalysis and 24
hr urine
collection
•(+) fine, coarse,
waxy casts
•Raised
creatinine
A
Lupus Nephritis
Hypertension
P
•For Biopsy
•Albumin
transfusion
•Prednisone and
Azathioprine
•MPPT
•Multidrug antiHPN
S
•Easy fatigability
•Difficulty of
breathing
O
A
•(-) signs of
Lupus
cardiac
Pericarditis
tamponade
•CXR:
cardiomegaly
•2D echo : mod
pericardial
effusion, RA and
RV wall collapse,
fair LV systolic
function
P
•Serial 2D Echo
•MPPT
S
Slightly pale
conjunctivae
O
•On admission,
Hgb = 82 mg/dl
•At PICU, Hgb =
54 mg/dl
•Retic index 0.05
•Direct and
Indirect
Coomb’s (-)
A
Anemia of
chronic disease
P
BT of PRBC
S
•Dyspneic
•Sitting position
•Blood-tinged
sputum
O
•Moderate
cardiorespiratory
distress
•ABG metabolic
acidosis
•CXR: Bilateral
pleural effusion
Inhomogenous
opacities BLF
Pulmonary
infiltrates
•hypoalbumine
mia
A
Pulmonary
edema
Pleural Effusion,
Bilateral
P
•Transferred to
PICU
•O2 support
•Furosemide
S
O
A
P
1. On admission U/A: pyuria
UTI
Cefuroxime
2. At PICU
Nosocomial
sepsis
Ceftazidime
Blood CS: NG5d
Urine CS:
Micrococcus
luteus
U/A: pyuria
Ward stay – 17 days
 PICU stay – 10 days
 Discharged – on April 15, 2008

› Home Meds
 Prednisone
 Aspirin
 Azathioprine
 Nifedipine
 Methyldopa
 Hydralazine
 Multivitamins
 Folic acid
 MgSO4
 Fe

Among retrospective and prospective
studies [2]
› Lupus flare rates ranges from approximately
20% – 60%

Lupus that is active at the onset of
pregnancy is activated further during
pregnancy
2 Singh, Ajay K. Lupus nephritis and anti-phospholipid activity syndrome in pregnancy. Kidney
International. Vol 58. (2000), pp 2240-2254.
Manifestations
No. of Flares
(% Total)
1st
Trimester
2nd
3rd
Postpartum
Trimester Trimester
Arthritis
27 (69%)
3
8
3
13
Skin lesions
13 (33%)
3
2
2
6
Hemolytic anemia
4 (10%)
0
0
0
4
LN
4 (10%)
0
1
0
3
Thrombocytopenia
1 (3%)
0
1
0
0
Fever
Hepatitis
Serositis
3 (8%)
1 (3%)
1 (3%)
0
0
0
0
0
0
1
0
0
2
1
1
a Some patients experienced
multiple organ involvement during the same flare.
3 Cortez-Hernandez, J., et al. Clinical Predictors of Fetal and Maternal Outcome in Systemic Lupus Erythematosus, a
Prospective Study. Rheumatology. 2002; 41: 643-50.
Prednisone (1-2 mg/kg/day) – drug of
choice for most SLE manifestation
 Methylprednisone pulse 1g/day
fowllowed by oral Prednisone at 0.5-1.0
mg/kg/day – severe systemic disease
 Azathioprine (2 mg/kg/day) – for initial
mild flare
 Stress doses of Hydrocortisone – for
emergency surgery, cesarean section,
prolonged labor and delivery

5 Obstetric Emergencies: Management of Lupus Flare. www.obgmanagement.com. May 2006.
Table 2. Evidence for adverse effects of immunosuppressant used in pregnancy and breastfeeding[6]
Whether drug can be used
Drug
Hydroxychloroquine/
Chloroquine
Prednisone/
Methylprednisone
Azathioprine
Ciclosporin
Tacrolimus
IVIG
Mycophenolate mofetil
Cyclophosphamide
Methotrexate
Leflunomide
Biologic agents
Etanercept, Infliximab,
Adaluminab, Rituximab
Evidence
In pregnancy
In breastfeeding
No increased risk of miscarriage, congenital malformation, stillbirth at
doses 200-400 mg/day
Cessation increase risk of flare
Long half life means stopping does not prevent fetal exposure
Metabolized by placenta
In high doses have caused cleft palate in experimental animal models and
low birth weight in humans
Fetus lacks enzyme to convert to active form
Fetal and neonatal immunosuppression minimal if dose is <2 mg/kg and
maternal white cell count is normal
No increase in congenital malformation
Prematurity and IUGR trends not significant
Small amounts in breastmilk but no adverse effects noted
No increase in congenital malformation
Increased rates of prematurity related to maternal disease
In one case report, a baby received 0.02% of maternal dose via breastmilk
Cross the placenta after 32 weeks but with no adverse effects to fetus
Y
Y
Y
Y
Y
Y
Y
If benefits
outweigh potential
risks
Y
with caution
Increased risk of congenital abnormalities
Enterohepatic recirculation
Long half life
Alkylating agent
Teratogenic, fetotoxic
Risk of suppression of neonatal hematopoiesis
Folate antagonist
Teratogenic and Fetotoxic
Congenital abnormality in animal studies
Human studies limited
Long half life of active metabolites
Limited experience in human pregnancies but no adverse fetal or
neonatal outcomes to date
Y
Y
Y
N
(stop 6 weeks before
conception)
N
(stop 3 months before
conception)
N (stop 3 months before
conception and give Folic
acid 5 mg daily)
N (use cholestyramine to
increase clearance
preconception)
Limit to severe disease
N
6 Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus. BMJ.2007; 335: 93336.
N
N
N
Probably avoid
Whether drug can be used
Drug
Prednisone/
Methylprednisone
Azathioprine
Evidence
Metabolized by placenta
In high doses have caused cleft
palate in experimental animal
models and low birth weight in
humans
Fetus lacks enzyme to convert to
active form
Fetal and neonatal
immunosuppression minimal if
dose is <2 mg/kg and maternal
white cell count is normal
In
pregnancy
Y
In
breastfeeding
Y
Y
Y
6 Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus. BMJ.2007; 335: 93336.
Rule: To treat the lupus flare before
irreparable maternal harm occurs
 Use of other new line immunosuppressive
drugs

› Benefits must be outweighed by potential
risks

No conclusive data suggest pregnancy
termination will ameliorate lupus flare.
5 Obstetric Emergencies: Management of Lupus Flare. www.obgmanagement.com. May 2006.

counseled on appropriate timing of planned
pregnancy
› remission of at least 6 months and preferably more
than 12 months and minimal or no need of
immunosuppressives


Risks to patient and fetus are discussed in detail
The following baseline investigations are
obtained at the start
›
›
›
›
CBC
Urea, creatinine, electrolytes
Liver function tests
ANA, anti dsDNA, aPL, anti-Ro/anti-La
Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus.
BMJ.2007; 335: 93336.
follow-up frequency is dependent on
disease activity
 hydroxychloroquine is given to prevent
flares
 Low dose aspirin is administered to
prevent preeclampsia
 If APLS positive or history of thrombosis or
fetal loss, treatment with heparin or
LMWH and low dose aspirin

Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus. BMJ.2007; 335: 93336.

fetus is regularly monitored by
obstetrician using Doppler UTZ
› 20 weeks, a detailed morphology scan is
done
› Regular growth scans at 28, 32 and 36 weeks
is done
› If with anti-Ro and anti-La, fetal heart pulsed
Doppler echocardiography at 18 weeks and
3rd trimester

Delivery method and timing depends on
obstetric indications
Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus. BMJ.2007; 335: 93336.

Nutrition management
› Megavitamin therapy
› adequate dietary intake
› Breastfeeding is contraindicated when
taking the following drugs: mycophenolate,
cyclophosphamide, methotrexate and
leflunomide
› Breastfeeding is appropriate if the maternal
dose of prednisone is <30 mg/d, to take her
medications just after breast-feeding
Ferris, Ann M., et al. Nutritional consequences of chronic maternal conditions during pregnancy and lactation: lupus and
diabetes. American Journal of Clinical Nutrition. 1994; 59 (suppl): 465S-73S.





Spontaneous
abortion
Preeclampsia
IUGR
Fetal death rate
Preterm delivery






Thromboembolism
Lupus nephritis
Renal failure
Antiphospholipid
syndrome
Active disease at
conception
First presentation of
SLE at pregnancy
7 Molad, Yair. Sytemic Lupus in Pregnancy. Current Opinion in Obstetrics and Gynecology.2006; 18: 613-617.
Mortality
Survival #%
Total
Full term
delivery
2 (5%)
16 (38%)
18 (43%)
Preterm
delivery
Abortion
12 (28%)
4 (10%)
16 (38%)
8 (19%)
0
8 (19%)
Total
22 (52%)
20 (48%)
8 Valdez, Corazon, et al. Systemic Lupus Erythematosus in Pregnancy: a 23-year review. Acta Medica Philippina
On regular follow up to Rheuma, Renal,
Perinatology
 Maintained on Prednisone, Azathioprine,
Aspirin, megavitamin
 Controlled hypertension
 Normal fetus on serial scans
 EDC: Aug. 26, 2008the
 Awaiting APAS
 Father is alienating the patient.

Whether pregnancy does exacerbate
SLE is a controversial issue.
 Women with SLE can have successful
pregnancies.
 In the care of lupus pregnant patient,
the most diffiucult dilemma is saving both
the mother and the unborn child.
