Bridging therapy for achalasia in a second trimester pregnant patient.

We present the case of a 28-year-old female who presented for primary care at 22-week gestation with type II achalasia and worsening solid/liquid dysphagia leading to pregnancy weight loss. Considering that durable therapies such as surgical myotomy and pneumatic dilatation have considerable risk, botulinum A toxin injection was selected as a temporizing bridging therapy. She had an uncomplicated post procedure course and had significant rapid improvement in dysphagia symptoms, which enabled her to progress to normal peripartum weight. This case highlights the need for early recognition of achalasia and an unique niche for use of botulinum toxin A as a temporizing therapy in this risk averse population.

Introduction

Esophageal achalasia is a rare idiopathic motility disorder characterized by an incomplete relaxation of the lower esophageal sphincter (LES).[1] Its prevalence is roughly 10 cases per 100,000, with an incidence of 0.5 cases per 100,000 population per year.[12] Achalasia has an insidious onset and diagnosis is usually delayed due to symptoms mimicking gastroesophageal reflux disease; a high degree of suspicion is needed for diagnosis. Patients may present to primary care with symptoms of long-standing dysphagia to both liquids/solids as well as pyrosis not responding to a trial of proton pump inhibitor. Long-term sequelae include weight loss, regurgitation of undigested food, and phagophobia. Exact pathophysiology of achalasia has not been fully discerned, although functional loss of myenteric plexus ganglion cells in the distal esophagus and LES is thought to play a role.[3] The Chicago Classification 3.0 is a well-known criteria which divides achalasia into three distinct subtypes based on high-resolution manometry. Type I (classic achalasia) has impaired relaxation without significant pressurization within the esophageal body. It is defined by 100% failed peristalsis and elevated median integrated relaxation pressure (IRP). Type II achalasia is characterized by lack of peristalsis and swallowing of liquids causing rapid pan-esophageal pressurization and an elevated IRP. Type III is associated with absent peristalsis in the context of preserved fragments of contraction or premature spastic contractions >20%. Treatment for Type I and Type II achalasia responds well to pneumatic dilation, Heller myotomy, or botulinum toxin A injections. Type III responds less to pneumatic dilation, with the treatment of choice being surgical myotomy.[1] Several treatment options exist, including diet modifications, pharmacotherapy (i.e., calcium channel blockers, nitrates, botulinum toxin A), surgical myotomy, and endoscopic pneumatic balloon dilation. Pneumatic dilation and myotomy have superior durability than botulinum toxin A injections in treating patients with achalasia, although are less appealing among pregnant patients due to increased complication risk. Botulinum toxin A is especially attractive for use in high-risk patient populations such as in pregnant or elderly patients, where surgical therapy is relatively contraindicated.

Case Presentation

We report a unique case of a 28-year-old female with Type II achalasia, G2P0 at 12-week gestational age who presented from her primary care center with pregnancy weight loss secondary to worsening solid and liquid dysphagia. She was diagnosed by high-resolution manometry 2 years ago with findings of elevated IRP, absent peristalsis, and pan-esophageal pressurization consistent with Type 2 achalasia [Figure 1]. Different treatment modalities were discussed with the patient including surgery, pneumatic balloon dilation, botulinum A toxin injections, and peroral endoscopic myotomy (POEM). Because she was in her second trimester of pregnancy, she was considered to be at high risk for esophageal perforations with pneumatic dilation, and hence, alternative treatment options were considered. Given the lower complication profile and relative ease of administering botulinum toxin A, it was felt to be the best option for bridging therapy during her pregnancy. Coordinating care via a multidisciplinary team including anesthesia and obstetrics, she was electively admitted to the hospital to undergo intravenous fluids, enteric nutritional supplementation, fetal monitoring, and endoscopic therapy with botulinum toxin A injections. Her endoscopy was notable for a puckered hypertonic gastroesophageal junction (GEJ) and dilated esophagus with retained saliva [Figure 2]. The patient was brought to the operating room with monitored anesthesia care with pre and post fetal heart monitoring. One hundred units of botulinum toxin A was mixed with 5 cc of normal saline into a syringe. A 5-mm injector needle was used to inject 4 aliquots of 1 cc (20 units) of botulinum A toxin circumferentially 1 cm proximal to the LES. The patient experienced no complications and fetal heart tones remained normal. She had immediate improvement in dysphagia symptoms over the next 3 days, and had recovery in dysphagia at 1 month follow up while delivering a healthy baby to term.

Figure 1

Characteristic findings in esophageal high-resolution manometry in Type II achalasia

Figure 2

Characteristic findings on upper endoscopy of achalasia

Discussion

Botulinum toxin A has had an increased role in the medical management of various diseases. Botulism toxin is a potent inhibitor of acetylcholine release from presynaptic terminals.[4] Blocking unopposed cholinergic stimulation caused by the loss of interneurons which release neurotransmitters relaxing the smooth muscle within the LES is the therapeutic objective.[4] First described in 1994 by Pasricha et al. for use in achalasia, it was noted that at 1 week 90% of botulism toxin groups showed significant symptom reduction and a significant decrease in mean LES pressure.[5]

Earlier recognition of dysphagia can prompt expedited referral to gastroenterology for diagnosis with endoscopy and esophageal high-resolution manometry. Treatment decisions must take into account patient's history and identify those deemed to be at higher risk for procedural complications including pregnant patients and those with multiple comorbidities such as the elderly. Botulinum toxin A injections have a relatively low complication rate, although lack longevity with a high remission rate in 65–90% of the patients after 6 months.[167] Most common side-effects include epigastric pain, chest pain, heartburn, vertigo, nausea, and vomiting.[17] Serious complications include mediastinitis, although reported at a low incidence of 0.04%.[17] Repeated botulinum toxin A injections can induce submucosal fibrosis of the GEJ and obscure surgical planes, making subsequent endoscopic myotomy or surgery more challenging.[789] This in turn leads to increased risk for esophageal perforation and treatment failure.[9]

Although no treatment modality is without complications, botulinum toxin A injections has proven to be a very safe, well-established treatment modality for high-risk achalasia patients. This case highlights the importance of early symptom recognition during primary care to expedite the definitive management of achalasia and reduce morbidity. Botulinum toxin injections are the mainstay bridging therapy for pregnant patients with clinically significant dysphagia caused by achalasia obviating the need for more invasive therapeutics. Ideally, a multidisciplinary approach with primary care, registered dietician, gastroenterology, and surgery is ideal for the long-term management of complicated achalasia to meet symptom and nutritional benchmarks.

Informed patient consent was obtained for publication.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.