Achalasia

Incidence and Demographics:

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• Annual incidence: Approximately 1.6 cases per 100,000
• Affects both men and women equally
• Onset before adolescence is unusual
• Typically diagnosed in patients between the ages of 25 and 60 years

1. Autoimmune Hypothesis: Research suggests an autoimmune component in achalasia. Studies have found associations with specific HLA types, particularly HLA-DQw1. The presence of circulating antibodies against enteric neurons in some patients further supports this hypothesis.
2. Viral Infections: Research indicates a potential link between viral infections and achalasia. Studies have found T-cell reactivity to herpes simplex virus type 1 (HSV-1) in achalasia patients, suggesting its possible role in disease development. Other viruses, such as herpes zoster and measles, have also been identified as potential triggers.
3. Secondary or Pseudoachalasia: This condition mimics primary idiopathic achalasia but stems from different underlying causes, including malignancies and various diseases:
   • Chagas Disease: In Central and South America, this parasitic infection caused by Trypanosoma cruzi damages the esophagus and destroys intramural ganglion cells, leading to aperistalsis and incomplete LES relaxation.
   • Malignancy: Gastric carcinoma commonly causes pseudoachalasia by affecting esophageal neural plexuses either directly or through paraneoplastic syndrome. Other associated cancers include esophageal cancer, lung carcinoma, lymphoma, and pancreatic carcinoma.
   • Other Conditions: Several diseases can mimic achalasia, including amyloidosis, sarcoidosis, neurofibromatosis, eosinophilic gastroenteritis, multiple endocrine neoplasia type 2B, juvenile Sjögren’s syndrome, chronic idiopathic intestinal pseudo-obstruction, and Fabry disease.

Pathogenesis of Achalasia

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The precise cause of achalasia is not entirely elucidated, but it is associated with the progressive degeneration of ganglion cells in the myenteric plexus within the esophageal wall.

Theories on the Origin of Achalasia

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Several theories have been proposed to shed light on this degenerative process:

1. Autoimmune Hypothesis:
   • One theory posits that achalasia may be an autoimmune disorder where the body’s immune system targets its own nerve cells. This autoimmune response could potentially be triggered by a viral infection.
2. Viral Infection Connection:
   • Evidence of previous infections, including the presence of antibodies to various viruses, has been detected in individuals with achalasia.
3. Genetic Influence:
   • Another hypothesis suggests that genetic factors might contribute to achalasia. Genetic association studies have identified specific variations associated with an increased risk of the disease, although such cases are relatively rare.
4. Environmental Factors:
   • Some studies propose that environmental factors may intersect with genetic predisposition to increase susceptibility to achalasia. These environmental factors could potentially trigger the development of the condition in individuals with a genetic inclination.

Pathophysiology

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1. Neuronal Degeneration: Achalasia is marked by a decrease in ganglion cells within the myenteric plexuses of the esophageal wall. These remaining ganglion cells are surrounded by lymphocytes and eosinophils. The degeneration primarily affects nitric oxide-producing inhibitory neurons that relax esophageal smooth muscle. Meanwhile, cholinergic neurons, which maintain lower esophageal sphincter (LES) tone through muscle contraction, typically remain intact.
2. Brainstem and Vagal Involvement: In some patients, degenerative changes are found in the ganglion cells of the dorsal motor nucleus of the vagus in the brainstem. Additionally, Wallerian degeneration is observed in the vagal fibers supplying the esophagus. However, the primary cause of achalasia seems to be the loss of inhibitory neurons within the esophageal wall itself.
3. LES Dysfunction: The loss of inhibitory innervation in the LES leads to an increase in basal sphincter pressure and impairs its normal relaxation. This elevated LES pressure is a hallmark of achalasia and prevents the smooth passage of food and liquids from the esophagus into the stomach.
4. Esophageal Body Dysfunction: Within the smooth muscle portion of the esophageal body, the loss of inhibitory neurons results in aperistalsis, disrupting the coordinated contractions required for food propulsion.
5. Cholecystokinin (CCK) Test: The primary pathophysiological defect in achalasia, involving the loss of inhibitory innervation, is evident when conducting the CCK test. In normal individuals, CCK administration induces both LES smooth muscle contraction and the release of inhibitory neurotransmitters from esophageal wall ganglion cells. These inhibitory effects typically outweigh the direct stimulatory effect of CCK on the sphincter muscle, leading to a decrease in LES pressure. However, in patients with achalasia, the direct stimulatory effect of CCK on smooth muscle prevails, resulting in elevated LES pressure.
6. UES Dysfunction: Some individuals with achalasia may exhibit a subtle defect in reflex relaxation of the upper esophageal sphincter (UES). Normally, the UES relaxes in response to abrupt esophageal distention, allowing gas to escape through a belch. In achalasia, this reflex may be impaired, causing increased UES pressure without a belch. This abnormal reflex may contribute to esophageal distention and chest pain.
7. Gastric Relaxation: Impaired gastric relaxation has been observed in patients with achalasia, particularly under conditions of cold stress. This reduced gastric relaxation can lead to symptoms such as fullness and discomfort.

Common Symptoms of Achalasia

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The most prevalent symptoms associated with Achalasia encompass:

1. Dysphagia (Difficulty Swallowing):
   • The primary clinical feature of achalasia, affecting 91% for solids and 85% for liquids. Dysphagia for liquids strongly suggests achalasia.
2. Regurgitation of Food or Saliva:
   • This occurs when recently ingested food reverts up the esophagus after swallowing.
3. Heartburn:
   • Achalasia can lead to a persistent burning sensation in the chest, frequently confused with gastroesophageal reflux disease (GERD).
4. Belching:
   • Frequent burping or belching is another characteristic symptom of this condition.
5. Intermittent Chest Pain:
   • Chest discomfort that comes and goes, at times reaching severe levels, and potentially disrupting sleep.
6. Nocturnal Coughing:
   • Nighttime coughing can be triggered by the regurgitation of food or liquids into the throat.
7. Pneumonia:
   • Aspiration of food into the lungs can result in pneumonia, a concerning complication of Achalasia.
8. Weight Loss:
   • Difficulty in eating and swallowing often leads to unintended weight loss.
9. Vomiting:
   • Occasional vomiting may occur when the esophagus becomes excessively filled with ingested material.
10. Association with Triple A Syndrome: In children with achalasia, an association with adrenal glucocorticoid deficiency and alacrima (triple A syndrome) has been described. This association may also exist in adults, with some adult patients found to have deficient tear production.

Esophageal Cancer Risk:

• Patients with achalasia are at an increased risk of developing esophageal cancer, typically squamous cell type.
• The risk is highest in the first year after diagnosis due to tumor obstruction mimicking achalasia.
• Endoscopic surveillance for cancer is not universally recommended, but if considered, it may start 15 years after symptom onset.

Diagnosis of Achalasia

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To diagnose Achalasia, doctors use a combination of tests, including:

1. Esophageal Manometry:
   • Standard Manometry:
   • A manometric examination is suggested for confirmation in nearly all cases.
   • Three characteristic manometric features of achalasia:
     1. Elevated resting LES pressure.
     2. Incomplete LES relaxation after a swallow.
     3. Aperistalsis in the smooth muscle portion of the esophagus.
   • High-Resolution Manometry (HREPT):
   • This technique uses a larger number of sensors at closer intervals, providing enhanced detail.
   • It can subtype achalasia and predict response to therapy:
     • Type I (classic) achalasia: No significant change in esophageal pressurization upon swallowing.
     • Type II achalasia: Simultaneous pressurization spanning the entire length of the esophagus.
     • Type III (spastic) achalasia: Abnormal, lumen-obliterating contractions (spasms).
   • Response to treatment varies among subtypes.
2. X-rays of the Upper Digestive System (Esophagram):
   • Barium Swallow: This is the primary screening test when achalasia is suspected clinically. It has a diagnostic accuracy of approximately 95%. The barium swallow typically shows:
     • A dilated esophagus.
     • A beak-like narrowing at the lower esophageal sphincter (LES) due to persistent contraction.
     • Absence of normal gastric air bubble due to LES failure to relax.
     • Some cases may exhibit extreme esophageal dilation, assuming a sigmoid shape.
   • Fluoroscopy: Reveals the absence of peristalsis in the smooth muscle portion of the esophagus. Spastic contractions may be observed in some cases, known as “vigorous” achalasia.
3. Upper Endoscopy:
   • A thin, flexible tube equipped with a light and camera (endoscope) is inserted down the patient’s throat.
   • This procedure is performed to examine the inside of the esophagus and stomach.

Differential Diagnosis of Achalasia:

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1. Gastroesophageal Reflux Disease (GERD)
   • GERD commonly causes dysphagia and regurgitation, along with heartburn and acid reflux. Unlike achalasia, GERD shows normal or low LES pressure and maintains normal peristalsis on manometry.
2. Esophageal Malignancy (Pseudoachalasia)
   • Tumors near the gastroesophageal junction can mimic achalasia by causing obstruction and disrupting normal movement. Key signs include rapid symptom onset, major weight loss, and older age at diagnosis. Endoscopy and imaging are crucial for ruling out cancer.
3. Esophageal Stricture
   • Both benign and malignant strictures cause progressive difficulty swallowing, starting with solids. Unlike achalasia’s “bird’s beak” appearance, imaging shows a distinct narrowing.
4. Diffuse Esophageal Spasm (DES)
   • Features periodic swallowing difficulty and chest pain. Manometry distinguishes it from achalasia by showing uncoordinated contractions with normal LES relaxation.
5. Scleroderma (Systemic Sclerosis)
   • Causes swallowing problems, heartburn, and regurgitation. Unlike achalasia, testing shows weak muscle movement and a loose, underperforming LES, often with severe reflux.
6. Chagas Disease
   • Causes achalasia-like symptoms when Trypanosoma cruzi infection damages nerve clusters. Diagnosis relies on travel history to Latin American regions and blood tests.
7. Other Esophageal Motility Disorders
   • Jackhammer esophagus: Shows unusually strong contractions with normal LES function
   • Ineffective esophageal motility: Features weak muscle movement, often linked to other conditions
   • Esophagogastric junction obstruction: Shows restricted LES opening without other achalasia signs
8. Zenker’s Diverticulum
   • Causes upper throat swallowing problems, food regurgitation, and bad breath. Imaging reveals a pouch above the upper esophageal sphincter.
9. Neurological and Myopathic Disorders
   • Conditions like myasthenia gravis and stroke can affect swallowing but show other nerve-related symptoms.
10. Esophageal Webs and Rings
    • Create occasional swallowing difficulties, mainly with solid foods. Tests show thin tissue bands in the esophagus.

Treatment Options for Achalasia

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Achalasia is a challenging esophageal disorder that can be managed through various therapeutic approaches. Below are the primary treatment options:

1. Medical Therapy:

• Nitrates and calcium channel blockers (e.g., nifedipine) are used for patients who cannot tolerate more invasive treatments.
• These medications relax the lower esophageal sphincter (LES) and are usually taken sublingually 10 to 30 minutes before meals.
• Efficacy varies, with success rates ranging from 50% to 90%, and side effects observed in up to 30% of patients.

2. Botulinum Toxin Injection:

• Botulinum toxin injected into the LES disrupts excitatory neurons, reducing LES pressure.
• Initial success rates are around 80%, but symptom relief decreases over time, often necessitating further treatment.

3. Dilation of the Lower Esophageal Sphincter:

• Two primary modalities are used for dilation: bougie esophageal dilation (bougienage) and pneumatic balloon dilation.
• Bougienage provides temporary and incomplete relief, suitable for patients with a lower risk of esophageal perforation.
• Pneumatic balloon dilation involves forceful stretching of the LES, achieving high initial success rates (85%), but with potential complications like esophageal perforation (1.6%) and heartburn (45%).
• Success rates decline with time, and additional dilations may become less effective.

4. Surgical Myotomy:

• Surgical myotomy weakens the LES by cutting its muscle fibers.
• Open surgical myotomy via abdominal or thoracic approaches results in initial symptom relief in 70% to 90% of patients.
• Laparoscopic or thoracoscopic techniques have become popular, offering shorter recovery times.
• Reflux esophagitis is a common complication (10-30%), depending on whether antireflux procedures are performed.

5. Peroral Endoscopic Myotomy (POEM):

• POEM is an endoscopic method for myotomy of the LES.
• Initial studies show symptom relief in 94% of patients, with a decrease in LES pressure.
• The long-term role of POEM in achalasia treatment is still being investigated.

The choice between these treatment options depends on patient preferences, the availability of experienced personnel, and the specific clinical characteristics of the case.