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\begin{document}

\title{Management of labor and delivery by spinal and epidural analgesia in a
woman with systemic mastocytosis: a case report}



\author[1]{Chiharu   Kawagoe}%
\author[1]{Chiyo Ootaki}%
\author[1]{Yuki Kinishi}%
\author[1]{Chie  Matsuda}%
\author[2]{ Reiko  Uokawa.}%
\affil[1]{Osaka University School of Medicine Graduate School of Medicine}%
\affil[2]{Osaka University Faculty of Medicine Graduate School of Medicine}%


\vspace{-1em}



  
  \date{June 02, 2024}


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\selectlanguage{english}
\begin{abstract}
Systemic mastocytosis is a life-threatening disease in which mast cell
mediator release can lead to general symptoms. The most common triggers
are stress and pain during labor and delivery. We report the management
of labor and delivery in a case with severe systemic mastocytosis by
epidural analgesia.%
\end{abstract}%



\sloppy


\textbf{1. INTRODUCTION}

Mastocytosis is a rare disease caused by the abnormal proliferation of
mast cells. The prevalence of mastocytosis is estimated to be 13 per
100000 in all age categories {[}1,2{]}. Systemic mastocytosis is a
genetic disorder and is most commonly caused by a point mutation in the
gene for tyrosine kinase receptor Kit D816 V. The symptoms of
mastocytosis are quite diverse as mast cells accumulate in various
organs, especially the bone marrow, skin, liver, spleen, and lymph
nodes. Histamine, heparin, and tryptase are the most recognized
preformed mediators that are released from mast cells. Newly formed
mediators at the time of the reaction include prostaglandins,
leukotrienes, chemokines and cytokines {[}3{]}. Mast cell mediator
release can lead to general symptoms such as abdominal pain, urticaria,
pruritus, syncope, and vascular collapse, including death in severe
cases. Common triggers are insect stings and drugs, including
nonsteroidal anti-inflammatory drugs (NSAIDs), anesthetics, antibiotics,
food, and mechanical stimulation {[}2{]}. Stress and pain during labor
and delivery can activate the disease {[}3, 4{]}. Here, we report the
case of a pregnant woman with systemic mastocytosis who received
epidural analgesia to avoid labor pain.

\textbf{2. CASE PRESENTATION}

A 38-year-old woman at 39 weeks 6 days gestation (G1P0, height 159 cm,
weight 66 kg, 52 kg prepregnancy) presented to our hospital with labor
pains. She had a long history of mastocytosis, with the development of
pale brown chromatosis and hives from the back to the buttocks starting
at 26 years old. Her symptoms worsened at 29 years old, and a wheal
appeared while she was wearing and removing clothes. At the age of 32,
the skin eruption worsened, and she was diagnosed with urticaria
pigmentosa by a skin biopsy. She developed anaphylaxis twice with
generalized skin rash and dyspnea in response to ibuprofen and
diclofenac, and she was transferred to the emergency department and
treated with intravenous betamethasone both times. Six months later, a
skin biopsy and bone marrow biopsy performed at another hospital
revealed systemic mastocytosis. She experienced convulsions after the
use of an over-the-counter cold remedy and developed systemic erythema
and dyspnea after the use of loxoprofen. Before fertility treatment, an
allergy test was performed to identify the drugs that could be used
during delivery, but no tests were performed for the drugs that can be
used for labor analgesia. She became pregnant by in vitro fertilization,
and her pregnancy progressed smoothly. She was on famotidine and
ebastine for systemic mastocytosis before pregnancy and took additional
fexofenadine hydrochloride when her condition worsened. She regularly
took antihistamines and fewer oral steroids after the pregnancy.

During her pregnancy, the obstetricians, dermatologists, immunologists,
hematologists, and anesthesiologists discussed various delivery plans
and opted for epidural analgesia to avoid mast cell degranulation and
anaphylaxis. The obstetrician planned a vaginal delivery without
induction, based on evidence; systemic mastocytosis itself is not an
indication for cesarean section. The patient received a prenatal
anesthetic evaluation and was given an explanation of the anesthesia
plan: epidural analgesia would be placed to avoid stress, which could
trigger mast cell degranulation.

At 39 weeks 6 days of gestation, she complained of strong pain at the
time she was admitted to the hospital. At admission, a rash and general
cold sweat were found on her anterior chest wall and back. We suspected
labor pain and psychological stress as the triggers for those symptoms
and administered antihistamines and performed a combined spinal-epidural
analgesia (CSEA). Before anesthesia, there were no abnormal laboratory
data. The CSEA was placed at the L3-L4 level, and 1.5 mg 0.5\% isobaric
bupivacaine with fentanyl 15 \selectlanguage{greek}µ\selectlanguage{english}g was injected into the subarachnoid
space, then a catheter was introduced into the epidural space at a
cervical dilation of 4 cm and a pain NRS (Numerical Rating Scale) of 10.
After placing the CSEA, her NRS became 0, and her sensory analgesia
level was confirmed on both sides from Th5 to S5. Two hours after
placing the CSE, her labor analgesia was switched to a programmed
intermittent epidural bolus (PIEB) with 0.1\% ropivacaine, and fentanyl
2 \selectlanguage{greek}µ\selectlanguage{english}g/mL was set at 8 mL with a 60-minute interval. Her analgesia level
was kept at NRS 3--4, and her anesthesia level was kept at Th 8.9--S3
area until delivery. When the cervix was fully dilated, a rash and
pruritus were noted on her abdomen, but sufficient pain relief was
obtained with an NSR score of 3. H1 and H2 antihistamines were
administered, the pruritus was suppressed, and vaginal delivery was
performed as scheduled. The female infant weighed 3246 g and had Apgar
scores of 7 and 9 at 1 and 5 minutes, respectively. The patient and the
infant had an uncomplicated postpartum course and were discharged on
postpartum day 5.

\textbf{3. DISCUSSION}

We present a case of pregnancy complicated by the need for the
management of systemic mastocytosis with several prior anaphylaxis
episodes. We applied epidural analgesia to prevent exacerbation of the
disease and anaphylaxis during labor and delivery. Multiple stimuli can
provoke mast cell degranulation. The triggers include physical, chemical
and biologic agents {[}3,5{]}. Stress is also a well-known trigger for
mediator release in systemic mastocytosis {[}3,4{]}. Pregnancy
complications can be associated with increased levels of maternal
stress, and labor is clearly a time of increased maternal pain and
stress {[}3{]}. Based on the hypothesis that good pain management may
contribute to reducing stress and reducing the risk of exacerbation of
systemic mastocytosis, there are several prior reports of epidural
anesthesia for pain relief during labor in pregnant patients with
systemic mastocytosis. {[}6,7{]}. We planned early epidural placement to
avoid stress and labor pain, which can trigger systemic mastocytosis.

However, anaphylactoid reactions may also be triggered by drugs
administered during delivery, especially anesthesia. Testing for drug
hypersensitivity is generally recommended only in patients with a
history of drug allergy {[}8{]}. This patient had a history of drug
allergy. However, in this case, labor analgesics and general anesthetics
were not tested during pregnancy while planning the labor analgesia
because the allergy/immunology physician did not recommend it as the
testing could trigger mast cell degranulation. Therefore, we avoided the
use of anesthetics such as morphine, NSADs, meperdine, and ester local
anesthetics, which could trigger mast cell degranulation during labor
analgesia {[}9{]}.

This patient had an NRS score of 10 at the time she was admitted to the
hospital and complained of very strong pain. Although it should have
been introduced by the straight epidural method assuming the possibility
of fetal distress and a possible emergency cesarean section, the CSE
method was selected by the anesthesiologist in charge because CSE was
the most commonly used method. As our facility uses PIEB as a standard,
the level of anesthesia and her vitality were checked every hour to
avoid unexpected hypotension or high epidural levels.

Mastocytosis is subdivided into two categories as proposed by the WHO:
cutaneous and systemic mastocytosis {[}10,11{]}. Cutaneous mastocytosis
is the most common form of mastocytosis, which usually occurs in
childhood and appears as hyperplasia of the mast cells of the skin
{[}12{]}. Systemic mastocytosis is a very rare disease in which
myeloproliferative tumors derived from mast cells form multifocal
lesions and often infiltrate the skin, lymph nodes, digestive organs,
liver, and spleen. The diagnosis of systemic mastocytosis is based on
the presence of one major criterion and one minor criterion or three
minor criteria (Table 1). Symptoms of systemic mastocytosis include
abdominal pain, diarrhea, nausea, vomiting, skin pruritus and flushing,
anaphylactoid reactions, anemia, and pathological fractures. Our patient
was first diagnosed with urticaria pigmentosa, but later, she was
diagnosed with systemic mastocytosis by observing the proliferation of
mast cells in skin and bone marrow biopsies.

Approximately 22\% to 33\% of pregnant women with systemic mastocytosis
experience worsening of systemic symptoms due to increased physical and
psychological stress during pregnancy {[}6,9,13{]}. Theoretically,
hormonal changes associated with pregnancy and puerperium may promote
anaphylactic reactions. There are reports of anaphylactic episodes
during pregnancy {[}14{]}. Exacerbations of systemic mastocytosis during
pregnancy can cause life-threatening maternal and fetal complications.
There have been several reports of preterm labor and deliveries
{[}7,9{]}. There is also a case report of a fetal death due to an acute
exacerbation of systemic mastocytosis {[}3{]}. This fetal demise that
occurred at 31 weeks of gestation was caused by an exacerbation of
systemic mastocytosis, which resulted in severe hypotension and a
critical decrease in uterine blood flow.

In our case, there were no significant changes during pregnancy. The
anesthesiologist should prepare a plan for analgesia and anesthesia for
delivery to minimize the risk. Good pain control helps reduce overall
anxiety and reduces the risk of exacerbated mastocytosis during labor.
Our patient presented with minor skin symptoms during labor pain, but it
improved with antihistamines and immediate pain relief from epidural
analgesia without any serious complications.

\textbf{4. CONCLUSION}

For the effective management of pregnant women with mastocytosis,
triggers of mast cell degranulation should be avoided. Early epidural
analgesia is effective for relieving stress and pain during labor, and
it is necessary to avoid drugs that induce histamine release and to use
drugs that suppress it. The team involved in the delivery, including
anesthesiologists, obstetricians, and midwives, should discuss this with
patients with systemic mastocytosis from pregnancy to after delivery to
prevent an acute exacerbation of their symptoms.

\textbf{CONFLICTS OF INTEREST}

The authors declare that they have no competing interests.

\textbf{AUTHOR CONTRIBUTIONS}

CK drafted the manuscript. CK, CM, YK and RU carried out the anesthesia
for the entire course. CO supervised the drafting. All authors read and
approved the final version of the manuscript.

\textbf{CONSENT TO PARTICIPATE}

Informed consent for scientific publication was obtained from the
patient.

\textbf{ACKNOWLEDGMENTS}

The authors would like to extend their gratitude to the patient, her
family members and Osaka University obstetricians, dermatologists,
immunologists, and hematologists.

\textbf{REFERENCES}

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3. Kendra D. Watson, Katherine W. Arendt, MD, et al. Volcheck, MD.
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