Botulinum toxin for the treatment of achalasia in pregnancy

Introduction

Achalasia is a motor disorder of the smooth muscle of the esophagus in which the lower esophageal sphincter does not relax normally with swallowing, and the esophageal body undergoes non-peristaltic contractions [1]. Because of its rarity in pregnancy, there is a paucity of data on the perinatal management of this disease. Studies of treatment of women with achalasia are limited to case reports. Botulinum toxin is a well-described treatment for achalasia in non-pregnant women. Its effects on pregnancy and the fetus are not well-described. We present a patient with achalasia diagnosed and treated with botulinum toxin injection in the first trimester of pregnancy.

Case presentation

A 28-year-old gravida 2 para 1 initially presented to our institution with an intrauterine pregnancy at 11 weeks and 3 days, with dysphagia for both solids and liquids, abdominal pain, weight loss, and vomiting. The patient reported that her symptoms began approximately 2 years prior, but had markedly worsened with the onset of pregnancy. She noted that a “swallowing test” performed a year earlier demonstrated an esophageal stricture; however, she did not have the financial means for adequate follow-up and treatment at that time.

On presentation, she was afebrile and her initial vital signs were within normal limits. Physical exam revealed normal dentition, dry mucous membranes, normal heart sounds, a non-tender abdomen, and a non-tender uterus that was appropriately sized for gestational age. All bloodwork, including complete metabolic panel, complete blood count, liver function tests, thyroid function tests, and stool antigen testing for Helicobacter pylori were within normal limits. Urinalysis was notable for ketones. She was admitted to the antepartum service, where intravenous fluid hydration, thiamine and electrolyte repletion, and antiemetic therapy were initiated. A pelvic ultrasound demonstrated a viable singleton pregnancy, with a crown rump length that was consistent with her stated gestational age. An abdominal ultrasound revealed no abnormalities. A gastroenterology consultation was obtained, and an esophagogastroduodenoscopy and an esophageal manometry were performed. Esophageal manometry was notable for an elevated lower esophageal sphincter pressure of 42.7 mm Hg with incomplete relaxation and low amplitude non-peristaltic esophageal contractins, findings consistent with the diagnosis of achalasia. After discussion of possible treatment options, including expectant management, surgical myotomy, β-blocker therapy, or botulinum toxin injection, the patient opted to proceed with botulinum toxin injection. At 12 weeks’ gestation, she underwent an uncomplicated transesophageal injection of botulinum toxin A (btxA; 25 units per quadrant in 20 ml saline). Follow-up manometry performed immediately after the injection demonstrated a successful response with normalization of the lower esophageal sphincter pressure. The patient’s swallowing function improved over the subsequent month, and she gained weight. The patient progressed through the remainder of her pregnancy without further complications. A level II ultrasound performed at 32 + 1 weeks noted no fetal anomalies, and fetal growth was appropriate. At 39 + 1 weeks’ gestation, she presented in active labor and underwent an uncomplicated spontaneous vaginal delivery. The infant weighed 3955 g and had active respiration and normal muscle tone. The infant did not require admission to the neonatal intensive care unit. The patient was evaluated 4 weeks postpartum and was doing well and tolerating a regular diet. Surgical esophageal myotomy is planned for the near future.

Discussion

Information on the safety of botulinum toxin use in pregnancy is limited. There have been few case reports of botulinum toxin injection during pregnancy to treat esophageal dysmotility or other neurologic conditions. A case report from Thailand describes administering botulinum toxin to a pregnant woman in her third trimester with severe achalasia, with improvement of swallowing function soon after treatment. No deleterious effect was found in the neonate after delivery [5]. Newman et al. [3] reported four full-term uncomplicated pregnancies in a patient who received btxA during pregnancy for treatment of severe cervical dystonia without any effect on the pregnancy outcomes.

Although the effects of botulinum toxin are well documented, little is known about the effects of the toxin on the developing fetus. Passive diffusion of botulinum toxin across the placental membrane is unlikely because of the toxin’s molecular weight of approximately 150,000 kDa. It is not known, however, if an active transport mechanism exists. In a case report of foodborne botulinum toxin exposure during the second trimester of pregnancy, there was no evidence of the transport of toxin across the placental barrier [4]. In a study surveying physicians treating women with btxA for cosmetic purposes, headaches, dystonia, spasticity, pain, and other off-label uses, it was found that out of 900 physicians surveyed, 12 physicians reported injecting pregnant women with btxA. A total of 16 pregnant women were injected, mostly in the first trimester, with one patient undergoing a spontaneous abortion. Another woman underwent a therapeutic abortion. All other pregnancies delivered at term. No fetal anomalies were reported [2].

In our patient, botulinum toxin was used in the first trimester after an interdisciplinary team of maternal fetal medicine and gastroenterology specialists discussed the benefits and risks of the treatment with the patient. All diagnostic and treatment options were reviewed, including nitrates, calcium channel antagonists, temporizing pneumatic dilation vs. botulinum toxin injection, and surgical intervention. The decision was made for proceeding with a temporizing treatment with botulinum toxin followed by postpartum surgical intervention, should symptoms persist. Owing to the physiologic changes of pregnancy, including changes in lower esophageal sphincter function, there was concern that the patient’s current symptoms may not reflect her non-pregnant baseline. An invasive and irreversible surgical procedure was thought to be safer when performed postpartum, after resolution of pregnancy-related changes, when a true baseline clinical status could be ascertained. Furthermore, because of the potential maternal and fetal risks associated with surgery in pregnancy, medical management was deemed an appropriate initial intervention.

This report provides additional information on the outcomes of botulinum toxin use for medical indications in pregnant women.