Primary achalasia is the most common subtype and is associated with loss of ganglion cells in the esophageal myenteric plexus. These important inhibitory neurons induce LES relaxation and coordinate proximal-to-distal peristaltic contraction of the esophagus.
Secondary achalasia is relatively uncommon. This condition exists when a process other than intrinsic disease of the esophageal myenteric plexus is the etiology. Examples of maladies causing secondary achalasia include certain malignancies, diabetes mellitus, and Chagas disease.
Sir Thomas Willis first described achalasia in 1674. Willis successfully treated a patient by dilating the LES with a cork-tipped whalebone. Not until 1929 did Hurt and Rake first realize that the primary pathophysiology resulting in achalasia was a failure in LES relaxation.
Pathophysiology: The exact etiology of achalasia is not known. The most widely accepted current theories implicate autoimmune disorders, infectious diseases, or both. The last decade has witnessed much progress in the understanding of the cellular and molecular derangements in achalasia.
Degeneration of the esophageal myenteric plexus of Auerbach is the primary histologic finding. However, with early achalasia, a mixed inflammatory infiltrate of T cells, mast cells, and eosinophils is found in association with myenteric neural fibrosis and with a selective loss of inhibitory postganglionic neurons from the Auerbach plexus. In these patients with early achalasia, neurons of the myenteric plexus are relatively well preserved.
The inhibitory neurons produce nitric oxide (NO) and vasoactive intestinal peptide (VIP). NO and VIP are inhibitory neurotransmitters responsible for relaxation of the LES and for coordinated esophageal peristalsis. The loss of inhibitory neurons allows unopposed excitatory stimulation by postganglionic cholinergic neurons of the Auerbach plexus, which leads to a failure in LES relaxation and, eventually, to aperistalsis of the distal esophagus due to loss of the esophageal body latency gradient. Essentially, this means that this portion of the esophagus is unable to relax and subsequently generate a proper, sequential peristaltic wave.
Clinically important features defined by this pathophysiology include the following:
Frequency:
Mortality/Morbidity:
Race: No racial predilection has been described for achalasia.
Sex: Achalasia has no sex predilection.
Age: The incidence of achalasia peaks in those aged 20-40 years. The disease has been diagnosed in infants and in patients well into their 80s (Nihoul-Fekete, 1991).
Anatomy: The average length of the esophagus is 25 cm. As illustrated by Clemente, the esophagus begins just distal to that portion of the inferior pharyngeal constrictor muscle that originates on the cricoid cartilage (Clemente, 1981). The esophagus terminates at the gastroesophageal junction. By convention, the esophagus is typically divided into 3 segments: (1) the cervical esophagus, (2) the thoracic esophagus, and (3) the abdominal esophagus.
The esophageal musculature is composed of an outer longitudinal layer and an inner circular layer. According to Meyer and colleagues, the esophageal musculature is striated in the proximal 5% of the organ (Meyer, 1986). The following 30-40% contains both striated and smooth muscle. The distal 50-60% is composed solely of smooth muscle, which is relevant because the denervation that is the hallmark of achalasia affects the smooth-muscle segment of the esophagus.
Esophageal contraction and peristalsis are mediated by parasympathetic fibers traveling in the vagus nerves. The dorsal motor nucleus of the vagus nerve is responsible for controlling the smooth muscle. In contrast, the nucleus ambiguus controls skeletal muscle.
The esophagus contains 2 major nerve plexuses: the Auerbach plexus and the Meissner plexus. The Auerbach, or myenteric, plexus is embedded between the longitudinal and circular layers of esophageal muscle. Neurons of the Auerbach plexus receive input from vagal preganglionic efferent fibers responsible for smooth muscle control. The Meissner plexus can be found in the submucosa of the esophagus. This plexus of nerves carries afferent information from the esophagus to the vagal parasympathetic and thoracic sympathetic nerves, then onward to the central nervous system.
Clinical Details: Dysphagia is the most common presenting symptom in patients with achalasia. The ingestion of either solids or liquids can result in dysphagia, though dysphagia for solids is more common. Emotional stress and the ingestion of cold liquids are well-known exacerbating or precipitating factors. The natural history varies. Some patients notice that the dysphagia reaches a certain point of severity and then stops progressing. In others, the dysphagia continues to worsen, resulting in decreased oral intake, malnutrition, and inanition. Therefore, weight loss is included in the complex of signs and symptoms associated with achalasia, and it is usually a sign of advanced esophageal disease.
Approximately 25-50% of patients with dysphagia report episodes of chest pain, which are frequently induced by eating. Typically, chest pain is described as being retrosternal; this is a more common feature in patients with early or so-called vigorous achalasia. As the disease progresses and as the esophageal musculature fails, chest pain tends to abate or disappear.
As many as 80-90% of patients with achalasia experience spontaneous regurgitation of undigested food from the esophagus during the course of the disease. Some learn to induce regurgitation to relieve the retrosternal discomfort related to the distended esophagus.
As the disease progresses, the likelihood that aspiration will occur increases. As a result, some patients may present with signs or symptoms of pneumonia or pneumonitis. Lung abscesses, bronchiectasis, and hemoptysis are some of the more severe pulmonary consequences of achalasia-associated aspiration.
Patients with achalasia are at increased risk for esophageal cancer. When esophageal cancer occurs, it is usually found in patients with a long history of achalasia.
Preferred Examination: The radiologic examination of choice in the diagnosis of achalasia is a barium swallow study performed under fluoroscopic guidance.
A diagnosis of achalasia supported by the results of radiologic studies must always be confirmed by performing upper gastrointestinal endoscopy and esophageal manometry. These tests allow the direct evaluation and inspection of the esophageal mucosa and an objective measurement of esophageal contractility.
Endoscopy, supplemented by biopsy when necessary, helps in excluding gastroesophageal malignancies, fungal or bacterial infections, and other disease processes that can mimic achalasia.
Manometry must be considered the criterion standard for diagnosis of the disease. Manometric findings consistent with achalasia include incomplete LES relaxation, which is present in more than 80% of patients; elevated LES pressure, which is present in some patients; and diminished-to-absent peristalsis in the distal esophagus.
If manometric findings are normal in a patient with clinical symptoms or radiographic evidence of achalasia, a condition termed pseudoachalasia may be present. Causes of pseudoachalasia include esophageal and gastric malignancies and other tumors involving distal esophagus or LES. In patients with these conditions, endoscopy with biopsy analysis and CT can be helpful.
Limitations of Techniques: A fluoroscopically guided barium swallow study that demonstrates 1 or more findings (see X-ray) is highly suggestive of achalasia. However, a definitive diagnosis can be made only by means of esophageal manometry, preferably with the addition of upper endoscopy.
Conversely, normal findings on barium swallow study do not completely exclude achalasia, especially in its early stages. This situation is when esophageal manometry is most valuable, because the physiologic derangements associated with achalasia precede the development of the anatomic findings discernible by using radiographic studies.
RADIOGRAPH
Findings: Plain chest radiographs occasionally offer clues in the diagnosis of achalasia. A double mediastinal stripe is occasionally depicted. An air-fluid level can be seen in the esophagus; this is frequently retrocardiac. Owing to the paucity of air progressing through the hypertensive LES, the gastric air bubble may be small or absent.
Features of achalasia depicted at barium study under fluoroscopic guidance include the following:
According to Schima and coworkers, approximately 90% of patients undergoing barium swallow examination for suspected achalasia have some esophageal dilation and a classic bird beak deformity (Schima, 1992).
A recent study from El-Takli and colleagues (2006) contradicts this claim. These investigators reviewed the barium-contrast radiographs of 51 patients with manometrically diagnosed achalasia. In only 58% of these studies was achalasia mentioned as a diagnostic possibility by the interpreting radiologist. The radiographs were then provided to an expert gastrointestinal radiologist, mixed in with normal control studies. This expert determined that typical radiological features of achalasia were absent in 50% of the studies performed on achalasia patients. The authors concluded that barium-contrast radiography is not sensitive for the diagnosis of achalasia, frequently due to the lack of characteristic and detectable radiologic features.
Kostic and coinvestigators (2005) published preliminary data on timed barium esophagograms in patients with achalasia and in normal controls. Subjects were fasted and then given 250 mL of low-density barium sulfate suspension orally. Radiographs were made 1, 2, and 5 minutes after the start of barium administration. The height and width of the barium column and the rate of change over time were recorded. The study was repeated in all subjects after an approximate 1-week interval. The controls uniformly achieved complete esophageal emptying within 2 minutes. The height and width of the barium column and the rate of esophageal emptying were all markedly abnormal in the achalasia patients. The static data were very reproducible between studies, but the functional (esophageal emptying) data were not, with a coefficient of correlation of only 0.50. The authors concluded that further studies were necessary before clinical usefulness of the timed barium esophagograms could be confirmed.
Degree of Confidence: Chest radiographic findings have low sensitivity and specificity for the diagnosis of achalasia. If suspected, achalasia should be confirmed with other radiologic examinations, such as barium swallow study under fluoroscopy, and with upper gastrointestinal endoscopy and manometry.
False Positives/Negatives: No normal variants exist; however, several disease processes can mimic achalasia on chest radiographs or barium swallow studies. These include colon adenocarcinoma, esophageal carcinoma, gastric carcinoma, non–small cell lung cancer, thoracic scleroderma, amyloidosis, Chagas disease, collagen-vascular disease, and lymphoma.
According to Gockel and colleagues (2005), pseudoachalasia, caused by carcinomas and other disease processes or iatrogenic conditions involving the cardia and gastroesophageal junction, may be difficult to differentiate from achalasia. Pseudoachalasia may be indistinguishable from achalasia when conventional endoscopic, manometric, and radiologic diagnostic means are used. In their report, they described that pseudoachalasia was caused by primary malignancies in 53.9%, secondary malignancies in 14.9%, and benign lesions in 12.6% of the 264 cases in the series. The remainder of the cases (11.9%) were due to sequelae of operations involving the distal esophagus or proximal stomach.
