| disease | Achalasia |
| alias | Esophageal Achalasia |
Esophageal achalasia, also known as cardiospasm or megaesophagus, is a disease caused by neuromuscular dysfunction of the esophagus. Its main features include the absence of esophageal peristalsis, high pressure in the lower esophageal sphincter (LES), and a weakened relaxation response to swallowing. Clinical manifestations include dysphagia, food regurgitation, and discomfort or pain in the lower retrosternal region. This is a rare condition (estimated to affect about 1 in 100,000 people) and can occur at any age, but is most commonly seen in the 20–39 age group. It rarely occurs in children, with roughly equal incidence between males and females, and is more prevalent in Europe and North America.
bubble_chart Pathogenesis
The disease cause of this condition remains unclear to date. It is generally believed that this disease is a neurogenic disorder. Pathological findings may reveal a reduction or even complete absence of vagus nerve fibers in the esophageal wall, as well as a decrease in ganglion cells in the myenteric plexus of the esophageal wall, though the reduction in the LES is less severe than in the esophageal body. Animal experiments have shown that freezing stimulation or bilateral transection of the vagus nerves above the thoracic level can lead to a lack of peristalsis in the lower esophagus and poor relaxation of the LES. However, unilateral transection or transection of the vagus nerves below the lower thoracic level does not affect LES function. This suggests that vagal innervation is limited to the upper esophagus, while the function of the lower esophagus is governed by the myenteric plexus of the esophageal wall, with neurotransmitters such as purine nucleotides and vasoactive intestinal peptide (VIP). Some studies have measured VIP levels in the LES of patients with this condition at 8.5±3.6 mol/g, significantly lower than in healthy individuals (95.6±28.6 mol/g). VIP inhibits LES tension at rest. The marked reduction of VIP in the LES leads to increased tension due to the loss of inhibitory effects, resulting in achalasia.
Some chronic animal models of esophageal achalasia are created through bilateral cervical vagotomy or by using toxins to destroy the dorsal vagal nucleus or ganglion cells in the myenteric plexus of the esophageal wall. Additionally, South American trypanosomes invading the esophageal muscle layer release exotoxins that damage the plexus, leading to LES tension and esophageal dilation (Chagas disease). Stomach cancer invading the myenteric plexus of the LES can also cause symptoms similar to this condition. Some patients with esophageal achalasia experience sudden onset of dysphagia, accompanied by degenerative changes in the vagus nerve and the myenteric plexus of the esophageal wall. Thus, it has been suggested that this disease may be caused by neurotoxic sexually transmitted disease toxins, though this has not been confirmed to date. Although there have been reports of multiple family members or even twins developing the condition, whether there is a genetic predisposition remains uncertain.
Normally, the LES reflexively relaxes at the onset of swallowing, with a drop in pressure to allow food to enter the stomach. When vagal function is impaired or the myenteric plexus of the esophageal wall is damaged, LES pressure can rise to around 6.67 kPa (50 mmHg). After swallowing, the pressure does not drop, and the LES fails to relax, preventing food from entering the stomach smoothly. Coupled with the absence of propulsive peristalsis in the esophagus, food cannot be pushed forward. As a result, large amounts of food and fluids accumulate in the esophagus until their weight exceeds LES pressure, allowing entry into the stomach. Due to food retention, the initial stage [first stage] of the esophagus exhibits fusiform dilation, which gradually elongates and curves over time. The degree of esophageal dilation is far more pronounced than that caused by esophagus cancer or other esophageal diseases, with a maximum capacity exceeding 1 liter. Additionally, the esophageal wall may develop secondary hypertrophy, inflammation, diverticula, ulcer, or cancerous changes, leading to corresponding clinical symptoms.bubble_chart Clinical Manifestations
(1) Dysphagia Painless dysphagia is the most common and earliest symptom of this disease, occurring in over 80–95% of cases. The onset is usually gradual but can also be acute. Initially, it may be mild, manifesting only as a feeling of fullness after meals. Dysphagia often occurs intermittently and can be triggered by emotional fluctuations, anger, anxiety, fright, or the consumption of overly cold or spicy foods. In the early stages, dysphagia may come and go, varying in severity, but in the late stage [third stage], it becomes persistent. A few patients find swallowing liquids more difficult than solid foods, a feature that can help differentiate this condition from other organic esophageal strictures. However, most patients experience greater difficulty swallowing solids than liquids, or find both equally challenging.
(2) Pain Present in approximately 40–90% of cases, the pain varies in nature and may be described as stuffy pain, burning pain, stabbing pain, cutting pain, or boring pain. The pain is typically located behind the sternum or in the upper abdomen but can also occur in the chest and back, right side of the chest, right sternal border, or left hypochondrium. Sometimes, the pain resembles cardiac colicky pain and may even be relieved by sublingual nitroglycerin. The mechanism of pain may involve strong contractions of esophageal smooth muscle or stasis-induced esophagitis. As dysphagia worsens and the esophagus above the obstruction further dilates, the pain may gradually diminish.
(4) Weight Loss Weight loss is related to the impact of dysphagia on food intake. Although patients often adopt strategies such as selective eating, slow eating, drinking fluids during or after meals to wash food down, or straightening the back, taking deep breaths, or holding their breath after meals to aid swallowing and ensure nutritional intake, prolonged cases may still lead to weight loss, malnutrition, and vitamin deficiencies. However, cachexia is rare.
(5) Bleeding and Anemia Patients often exhibit anemia, and occasional bleeding may occur due to esophagitis.
(6) Other Symptoms Due to increased lower esophageal sphincter tone, patients rarely experience hiccups, which is an important characteristic of this disease. In late-stage [third-stage] cases, the severely dilated esophagus may compress thoracic organs, leading to symptoms such as dry cough, shortness of breath, cyanosis, and hoarseness.
bubble_chart Auxiliary Examination
(1) X-ray Examination Most important for the diagnosis and differential diagnosis of this condition.
1. Barium Meal Examination Barium often has difficulty passing through the cardia and accumulates in the lower esophagus, displaying a symmetrical, membranous, funnel-shaped stenosis 1-3 cm long. The upper segment of the esophagus shows varying degrees of dilation, elongation, and curvature, with no peristaltic waves. If hot drinks are given, sublingual nitroglycerin tablets are administered, or amyl nitrite is inhaled, relaxation of the esophageal cardia is often observed; if cold drinks are given, the cardia becomes even more difficult to relax. Retained food residues may appear as filling defects during barium contrast imaging, so esophageal drainage and lavage should be performed before the examination.
(2) Methacholine (Mecholyl) Test In normal individuals, subcutaneous injection of 5-10 mg of methacholine increases esophageal peristalsis without a significant rise in pressure. However, in patients with this condition, within 1-2 minutes after injection, strong esophageal contractions occur; the intraesophageal pressure rises sharply, leading to severe pain and vomiting, and X-ray findings become more pronounced (atropine should be prepared during this test for use in case of severe reactions). An extremely dilated esophagus may not respond to this drug, resulting in a negative test; gastric cancer involving the esophageal myenteric plexus and certain cases of diffuse esophageal spasm may also yield positive results. Thus, this test lacks specificity.
(3) Endoscopy and Cytology Examination These are of limited help in diagnosing this condition but can be used for differential diagnosis between this disease and esophageal cardia cancer, among others.
Dysphagia, food regurgitation, and retrosternal pain are the typical clinical manifestations of this disease. If a barium swallow X-ray examination reveals the characteristic signs of this condition, a diagnosis can be made.
Mediastinal tumors present no difficulty in differential diagnosis. Colicky pain is often induced by exertion, whereas this disease is triggered by swallowing and accompanied by dysphagia, which serves as a distinguishing feature. Esophageal Guanneng disorders (such as globus hystericus) mostly manifest as a sensation of obstruction from the pharynx to the esophagus, but there are no choking symptoms during eating. Benign esophageal strictures and reflex esophageal spasms caused by gastric or gallbladder pathologies result in only grade I dilation of the esophagus. The differential diagnosis between this disease and esophageal cancer or cardia cancer is most critical. The X-ray features of cancerous esophageal strictures include local mucosal destruction and disarray, with grade II dilation at the stricture site, whereas this disease often leads to extreme dilation.
bubble_chart Treatment Measures
(1) Medical Therapy It is advisable to eat smaller, more frequent meals, chew food thoroughly, and avoid excessively cold, hot, or irritating foods. For patients with psychological or neurological tension, psychotherapy and sedatives may be administered. Some patients employ the Valsalva maneuver to facilitate the passage of food from the esophagus into the stomach, relieving retrosternal discomfort. Sublingual nitroglycerin can alleviate esophageal spasmodic pain and accelerate esophageal emptying. Prostaglandin E can reduce the resting pressure of the lower esophageal sphincter (LES) in patients, offering some therapeutic benefit for this condition. In 1978, Weiser et al. first discovered that the calcium channel blocker nifedipine (10 mg, four times daily) could alleviate symptoms after several weeks. Esophageal motility studies also confirmed that this drug reduces the resting pressure of the LES, the amplitude of esophageal contractions, and the frequency of transient contractions, while also improving food emptying in the esophagus. Subsequently, other calcium channel blockers such as verapamil (isoptin) and diltiazem were found to have similar effects in reducing LES resting pressure, though the clinical efficacy of the latter is less pronounced. For patients with extreme esophageal dilation, esophageal drainage and lavage should be performed before bedtime, accompanied by fasting, fluid infusion, and prompt correction of typical edema, electrolyte imbalances, and acid-base metabolic disturbances.
(2) Esophageal Dilation Therapy Balloon or bougie dilation is used to relax the junction between the esophagus and stomach. Under fluoroscopic guidance, a bougie-guided balloon is inserted orally, with the bougie advancing into the stomach while the balloon is positioned at the esophagogastric junction. Air or liquid is then injected, and the injection is stopped when chest pain occurs. The balloon is left in place for 5–10 minutes before removal. A five-year follow-up after a single treatment showed an efficacy rate of 60–80%. The criterion for efficacy is the disappearance of dysphagia, allowing the resumption of a normal diet. However, the risk of esophageal rupture with this therapy ranges from 1–6%, so caution is required during the procedure.
(3) Surgical Therapy There are several surgical methods, with the Heller myotomy of the lower esophageal sphincter being the most commonly used. For patients with severe esophageal dilation, significant fibrosis at the diaphragmatic hiatus, or marked contraction of the lower esophagus, resection and reconstruction of the cardia and lower esophagus are recommended. The symptomatic improvement rate after surgical treatment is approximately 80–85%, but complications such as esophageal mucosal rupture, hiatal hernia, and gastroesophageal reflux may occur.
(1) Aspiration Respiratory Tract Infection When refluxed esophageal contents are inhaled into the airways, they can cause bronchial and pulmonary infections, particularly during sleep. Approximately one-third of patients may experience nocturnal paroxysmal coughing or recurrent respiratory infections.
(2) Complications of the Esophagus This condition can lead to secondary complications such as esophagitis, esophageal mucosal erosion, ulcers and bleeding, pulsion diverticula, esophageal-tracheal fistula, spontaneous esophageal rupture, and esophageal cancer. The incidence of esophageal cancer in this disease ranges from 0.3% to 20%. A review of 5,235 cases of achalasia reported in the literature between 1908 and 1975 identified 173 cases complicated by esophageal cancer, with an average incidence of 3.3%, significantly higher than that in the general population, warranting attention.
