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
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Renal disorder

Neurologic
disorder
Hematologic
disorder
Immunologic
disorder
Antinuclear
antibody

Kliegman, Robert, M.D., et al. Nelsons Textbook of Pediatrics. 18 th ed. USA: Sanders, 2007, pp.
1015-191
1

1 yr PTA
9 mo PTA

(+) alopecia, (+) malar rash

(+) 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
Family
History

Family History

(+) similar illness grandmother, paternal

side

Birth/Maternal History

noncontributory

Completed at Local health center

Unremarkable

Immunization History
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 didnt 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
doesnt 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

1.
2.

3.
4.

Pregnancy
SLE
Nephritis, Hypertension
Pericarditis
Anemia
Pulmonary edema, noncardiogenic
Pleural Effusion, B
Infection

S
Amenorrhea
LMP: Dec 3,
2007
Sexual
intercourse

O
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

Lupus Nephritis
Hypertension

For Biopsy
Albumin
transfusion
Prednisone and
Azathioprine
MPPT
Multidrug antiHPN

S
Easy
fatigability
Difficulty of
breathing

(-) 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

On admission,
Hgb = 82 mg/dl
At PICU, Hgb =
54 mg/dl
Retic index
0.05
Direct and
Indirect
Coombs (-)

Anemia of
chronic disease

P
BT of PRBC

Dyspneic
Sitting position
Blood-tinged
sputum

Moderate
cardiorespirator
y distress
ABG metabolic
acidosis
CXR: Bilateral
pleural effusion
Inhomogenous
opacities BLF
Pulmonary
infiltrates
hypoalbumine
mia

Pulmonary
edema
Pleural Effusion,
Bilateral

P
Transferred to
PICU
O2 support
Furosemide

S
1. On
admission
2. At PICU

U/A: pyuria

UTI

Cefuroxime

Blood CS: NG5d

Urine CS:
Micrococcus
luteus
U/A: pyuria

Nosocomial
sepsis

Ceftazidime

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.

Manifestation
s
Arthritis

No. of
Flares
(% Total)
27 (69%)

Skin lesions

13 (33%)

Hemolytic
anemia
LN

(10%)

(10%)

Thrombocytope
nia
Fever
Hepatitis
Serositis

(3%)

3
1
1

(8%)
(3%)
(3%)

0
0
0

0
0
0

1
0
0

2
1
1

1st
2nd
3rd
Postpart
Trimest Trimest Trimes
um
er
er
ter
3
8
3
13

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]
Drug
Hydroxychloroquine/
Chloroquine

Prednisone/
Methylprednisone
Azathioprine

Ciclosporin

Tacrolimus

IVIG
Mycophenolate mofetil

Cyclophosphamide

Methotrexate

Leflunomide

Biologic agents
6 Mackillop,
Lucy H., et

Evidence
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
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

Whether drug can be used

In pregnancy
In
breastfeeding
Y

If benefits
outweigh
potential risks
Y
with caution

N
N
(stop 6 weeks
before conception)
N
N
(stop 3 months
before conception)
N (stop 3 months
N
before conception
and give Folic acid 5
mg daily)
Congenital abnormality in animal studies
N (use
N
Human studies limited
cholestyramine to
Long half life of active metabolites
increase clearance
preconception)
experience
human pregnancies
but no adverse BMJ.2007;
Limit to severe
Probably avoid
al.Limited
Pregnancy
plus inSystemic
Lupus Erythematosus.
335: 93336.

Whether drug can

be used
Drug

Evidence

In
In
pregnanc breastfeedi
y
ng
Y
Y

Metabolized by placenta
In high doses have caused
cleft palate in experimental
animal models and low
birth weight in humans
Fetus lacks enzyme to
Azathioprine
Y
convert to active form
Fetal and neonatal
immunosuppression
minimal if dose is <2
6 Mackillop, Lucy H., et al. Pregnancy plus Systemic Lupus Erythematosus. BMJ.2007; 335: 93336.
mg/kg and maternal white

Prednisone/
Methylprednis
one

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

12 (28%)

4 (10%)

16 (38%)

Abortion

8 (19%)

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.