A 21-year-old woman experienced anaphylaxis after receiving buccal misoprostol for labor induction at 41 weeks of gestation. She developed pruritus, flushing, urticaria, and laryngeal edema. Epinephrine and cesarean delivery were performed, allowing for safe delivery of the neonate with minimal maternal morbidity. This case report describes a rare occurrence of anaphylaxis induced by misoprostol during labor, highlighting the importance of prompt recognition and treatment of anaphylaxis when inducing labor to prevent maternal and neonatal complications.

1. risks before conception so they can seek treatment early
and advocate for evaluation if they experience worri-
some symptoms. Because 41% of patients with internal
hernias presented with abdominal pain, it is important
for patients to be encouraged to seek immediate
evaluation when they experience symptoms.8
A multi-
disciplinary approach using Maternal Fetal Medicine,
Bariatric Surgery, and Intensive Care teams should be
utilized for evaluation and treatment. Radiologic evalu-
ation with computed tomography scan should be
reviewed by bariatric surgeons or radiologists with spe-
cialized expertise in this area.8
The decision of whether
to evacuate the uterus and how to accomplish this
should be based on the clinical condition of the patient.
The benefits of uterine evacuation to facilitate autotrans-
fusion in cases of shock must be weighed against the
potential to prolong the pregnancy and the ability to
perform intrauterine resuscitation. In cases of hemody-
namic instability with an unripened cervix, the hysterot-
omy at the time of exploratory laparotomy allowed for
the most expeditious way to accomplish uterine evacu-
ation. Patients with this surgical history and presenting
for evaluation of abdominal pain should undergo
a multidisciplinary approach including bariatric surgical
consultation with appropriate imaging early in the eval-
uation process.
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Anaphylaxis to Buccal
Misoprostol for Labor Induction
Corina Schoen, MD,
Sara Campbell, MD,
Amber Maratas, MD,
and Cheung Kim, MD
BACKGROUND: Misoprostol is a commonly used agent
for induction of labor. Anaphylactic reactions are infre-
quent but possible complications of drugs administered
to the pregnant patient. Although antibiotics, latex, and
anesthetic agents are more common triggers for ana-
phylaxis, induction agents are also a rare cause.
CASE: A 21-year-old woman received buccal misopros-
tol as a ripening agent for postdate labor induction and
experienced anaphylaxis and tachysystole. Prompt
administration of epinephrine and emergent cesarean
delivery allowed for the safe delivery of the neonate
and minimal maternal morbidity.
CONCLUSION: When inducing labor, prompt identifi-
cation and treatment of anaphylaxis and hypersensitivity
reactions are necessary to prevent maternal and neonatal
morbidity and mortality. Health care providers must be
aware of uncommon reactions to medications used to
induce labor.
(Obstet Gynecol 2014;124:466–8)
DOI: 10.1097/AOG.0000000000000268
Anaphylactic reactions to medications are uncom-
mon in pregnancy. An epidemiologic study of
women giving birth in Texas found a rate of 2.7 ana-
phylactic reactions per 100,000 deliveries.1
Most cases
of anaphylactic reaction during pregnancy involve ex-
posures to antibiotics (particularly penicillins or ceph-
alosporins) and latex.2
Much less frequently, agents
From the Departments of Obstetrics and Gynecology and Family Medicine,
Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
Corresponding author: Corina Schoen, MD, Department of Obstetrics and
Gynecology, Thomas Jefferson University Hospital, 833 Chestnut Street,
1st floor, Philadelphia, PA 19107; e-mail: corina.schoen@gmail.com.
Financial Disclosure
The authors did not report any potential conflicts of interest.
© 2014 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/14
466 Schoen et al Anaphylaxis to Buccal Misoprostol OBSTETRICS & GYNECOLOGY

2. for inducing labor cause anaphylaxis.3
We report
a case of buccal misoprostol as a cause of anaphylaxis
during labor induction.
CASE
A 21-year-old primigravid woman was admitted for a post-
date induction of labor at 41 weeks of gestation. She
reported feeling painful contractions for “days” and re-
ported good fetal movement with no vaginal bleeding or
leakage of fluid. Her antenatal course was uncomplicated.
She had no previous obstetric, gynecologic, medical, or
surgical history. In addition, she was taking no medications
and denied any known drug or nondrug allergies. Her
social history was noncontributory. On admission, her
blood pressure was 103/56 mm Hg, pulse 80 beats
per minute, respirations 16 breaths per minute, and tem-
perature 98.1˚F. Fetal heart tracing was Category I with
a baseline heart rate of 130 beats per minute, moderate
variability, and accelerations. External tocometry indicated
she was contracting irregularly, every 2–6 minutes, and she
appeared comfortable.
Her cervix was 1 cm dilated, 50% effaced, and the fetal
vertex was at 23 station. Her Bishop score was 3. Induction
of labor was started with 25 micrograms buccal misoprostol
at 5:00 PM. At 5:22 PM, the patient reported pruritus and
flushing and was given 25 mg diphenhydramine by intra-
venous push. Uterine tachysystole was evident. As a result
of increasing urticaria, an additional 25 mg diphenhydra-
mine was given. Physical examination revealed facial flush-
ing and a normal lung examination without evidence of
oropharyngeal edema. She was mildly tachycardic at 110
beats per minute but normotensive. The urticaria rapidly
evolved. The fetal tracing remained Category I with a base-
line of 160 beats per minute. The patient then was given
0.3 mg 1:1,000 epinephrine intramuscularly for presumed
anaphylaxis. After administration of epinephrine, the
patient started to report lip tingling and became increas-
ingly tachycardic to 130 beats per minute but remained
normotensive. At 5:45 PM the fetal heart tracing began
showing variable decelerations and eventual deterioration
to fetal bradycardia of 70 beats per minute. There was con-
tinued tachysystole, but terbutaline was not given for fear of
worsening the maternal tachycardia. Magnesium sulfate
also was considered as treatment for the uterine tachysys-
tole, but fetal bradycardia and evolving maternal dyspnea
led to the decision for an emergent cesarean delivery,
which was performed under general endotracheal anesthe-
sia. Laryngeal edema was noted at laryngoscopy. Immedi-
ately before delivery, the fetal heart rate was 80 beats
per minute. Incision-to-delivery time was 8 minutes, and
the neonate had Apgar scores of 7 at 1 minute and 9 at
5 minutes and was taken to the term nursery. Arterial
cord blood gas showed a pH of 7.04 and base deficit of
7.7 mmol/L. The mother remained intubated overnight as
a result of her persistent laryngeal edema and was extu-
bated the next day. Serum tryptase level drawn 5 hours after
the event was 16 ng/mL (normal 2–10 ng/mL). The remain-
der of her postoperative course was uncomplicated and she
and the neonate were discharged home on postoperative
day 3.
COMMENT
The rates of allergic reactions and anaphylaxis to
misoprostol have not been quantified. We performed
an English language PubMed search using relevant key
words (“misoprostol,” “labor,” “allergy,” and “anaphy-
laxis”) from 1950 to 2013 and retrieved no results.
Using the additional search term “dermatoses,” we
Fig. 1. Algorithm to treat anaphylaxis in pregnancy. *These
medications may be used to treat mild to moderate allergic
reactions but should never replace epinephrine in the set-
ting of anaphylaxis.
Schoen. Anaphylaxis to Buccal Misoprostol. Obstet Gynecol 2014.
VOL. 124, NO. 2, PART 2, AUGUST 2014 Schoen et al Anaphylaxis to Buccal Misoprostol 467

3. found a case report that describes a lichenoid drug
eruption that occurred 2 months after 800 micrograms
misoprostol vaginally was used to induce a first-
trimester abortion.4
When we expanded our search
to include all languages, we found one case (in French)
of anaphylaxis and myocardial myocytic necrosis with
the concurrent use of diclofenac and misoprostol.5
To
our knowledge, even with the frequent use of miso-
prostol for second-trimester losses and third-trimester
induction of labor, there are no other reported cases
of acute anaphylaxis.
This case is consistent with a moderate-to-severe
(Class 3 on the Ring and Messmer Scale) IgE-
mediated hypersensitivity reaction characterized by
pruritus, flushing, urticaria, tachycardia, dyspnea, and
laryngeal edema.6
Tryptase is a protease found almost
exclusively in mast cells. An increase in serum levels
is highly sensitive for identifying mast cell activation.
Elevated tryptase levels can be used to confirm an
IgE-mediated allergic reaction compared with a non-
allergic anaphylactic event, which is not controlled by
immunologic mechanisms. The optimal time to draw
a serum tryptase level is 1–4 hours after the acute
event and compare it with a control specimen taken
at least 24 hours afterward. False-negative tryptase
levels have been reported, so skin testing should be
strongly encouraged if the clinical suspicion is high. In
this case, the increase in tryptase drawn 5 hours after
the event confirmed an IgE-mediated reaction. Usu-
ally tryptase levels will peak at 1 hour and decline
linearly with a half-life of 2 hours.6
The patient’s tryp-
tase level was just above the upper limit of normal;
however, the sample was drawn well after the ex-
pected peak. We can infer that at 1 hour, her tryptase
level would have been even higher, diagnosing this
reaction as a hypersensitivity reaction, although opti-
mally testing should have been initiated sooner.
Only three cases previously have reported ana-
phylaxis secondary to the use of a progesterone
induction agent during labor.3
These cases all were
associated with intracervical placement of dinopro-
stone gel and were followed by respiratory distress,
tetanic contractions, and fetal distress. Our literature
search recovered no reported cases of anaphylaxis
caused by misoprostol by any administration method
during labor induction. Oxytocin, another frequently
used induction agent, is rarely associated with allergic
reactions in women who have a latex allergy. This
may be secondary to the homology in the protein
sequence between oxytocin and the latex antigen, pa-
latin.7
Timely appropriate treatment of anaphylaxis is
critical to optimize maternal and perinatal outcomes
(Fig. 1). Hepner and colleagues2
reviewed a series of
anaphylaxis cases in pregnancy and found that neo-
natal deaths and neurologic morbidity (eg, seizure-like
activity, brain damage, hypoxic encephalopathy) may
be attributed to incorrect dosing or delayed adminis-
tration of epinephrine. Epinephrine is more effective
than other vasoconstrictors in increasing systemic vas-
cular resistance and improving cardiac output, utero-
placental perfusion, and ultimately fetal perfusion and
oxygenation.8
Treating physicians must also consider
immediate delivery (10–15 minutes) in these cases.
There were no cases in the series that had a poor neo-
natal outcome when cesarean delivery was performed
within this time frame. However, in 50% of the cases
with a poor neonatal outcome, the cesarean delivery
was delayed (time from anaphylactic event to delivery
30–120 minutes). Therefore, prompt correction of
maternal perfusion and immediate delivery remains
the most effective means of ensuring fetal perfusion
and a good pregnancy outcome.
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468 Schoen et al Anaphylaxis to Buccal Misoprostol OBSTETRICS & GYNECOLOGY