Achalasia

Harlan G. Rich, M.D.

Basic Information

Definition

Achalasia is a motility disorder of the esophagus classically characterized by incomplete relaxation of the lower esophageal sphincter (LES) and aperistalsis of the esophageal smooth muscle. The result is functional obstruction of the esophagus.

Synonyms

Achalasia and cardiospasm
Achalasia (of cardia)
Aperistalsis of esophagus
Megaesophagus
Esophageal achalasia
Esophageal cardiospasm

ICD-10CM CODES
K22.0	Achalasia of cardia

Epidemiology & Demographics

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Annual incidence is approximately 0.5-1.0 in 100,000 persons.
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Prevalence is <10 per 100,000 persons.
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Although the onset of symptoms may occur at any age, incidence is typically bimodal, 20 to 40 yr, then after 60 yr, with greater incidence in the older group.
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Men and women are affected equally.

Physical Findings & Clinical Presentation

Symptoms:

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Dysphagia (most commonly with both solids and liquids)
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Difficulty belching
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Regurgitation
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Chest pain and/or heartburn
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Globus
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Frequent hiccups
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Vomiting of undigested food
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Symptoms of aspiration such as nocturnal cough; possible dyspnea and pneumonia
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Weight loss

Physical findings:

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Focal lung examination abnormalities and wheezing also possible

Etiology

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Etiology is poorly understood.
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Loss of intrinsic inhibitory neurons in the myenteric plexus in the LES and smooth muscle portion of the esophagus as well as depletion of networks of interstitial cells of Cajal of the LES result in the loss of inhibitory neurotransmitters nitric oxide and vasoactive intestinal polypeptide and unopposed excitatory activity, leading to incomplete relaxation of the LES and loss of esophageal peristalsis.
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Loss of myenteric nerve fibers is associated with lymphocytic and eosinophilic infiltrates, capillaritis, plexitis, venulitis, nerve hypertrophy, and fibrosis.
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This disorder may be caused by autoimmune degeneration of the esophageal myenteric plexus in association with several HLA class II DQ antigens. Antimyenteric plexus and other antineural autoantibodies have also been described. Patients with achalasia are more likely to have other autoimmune diseases.
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Abnormal immune reactions to neurotropic viruses, such as varicella zoster, measles, and particularly herpes simplex type 1, have been implicated. A host T cell–mediated response may lead to neuronal injury; this has been suggested as the cause of types I and II achalasia (see Imaging Studies section).
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Achalasia is also seen in the rare autosomal recessive disorder Allgrove syndrome (achalasia, alacrima, autonomic disturbance, and acetylcholine insensitivity), which has been linked to a gene mutation on chromosome 12q13. Neurons in this syndrome may be susceptible to oxidative injury.
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Recent studies suggest that type III achalasia (see Imaging Studies section) is associated with myenteric inflammation but not neuronal loss and that downregulation of nitric oxide synthase expression and increased cholinergic sensitivity are cytokine mediated.

Diagnosis

Differential Diagnosis

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Primary achalasia:
1. 1.
  
  Idiopathic
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Secondary achalasia:
1. 1.
  
  Chagas disease
2. 2.
  
  Vagal injury or surgery, including fundoplication
3. 3.
  
  Achalasia-like esophageal dilation has been described after laparoscopic gastric banding
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Pseudoachalasia:
1. 1.
  
  Esophageal cancer
2. 2.
  
  Infiltrating gastric cancer
3. 3.
  
  Oat cell and bronchogenic lung cancer
4. 4.
  
  Lymphoma
5. 5.
  
  Amyloidosis
6. 6.
  
  Paraneoplastic syndrome
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Angina
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Bulimia
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Anorexia nervosa
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Gastric bezoar
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Gastritis
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Peptic ulcer disease
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Postvagotomy dysmotility

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Esophageal disease (Table 1):

1.

Gastroesophageal reflux disease
2.

Sarcoidosis
3.

Amyloidosis
4.

Esophageal stricture
5.

Esophageal webs and rings
6.

Scleroderma
7.

Barrett’s esophagus
8.

Esophagitis
9.

Diffuse esophageal spasm

TABLE1 Esophageal Motor DisordersFrom Andreoli TE et al: Andreoli and Carpenter’s Cecil essentials of medicine, ed 8, Philadelphia, 2010, Saunders.

	Achalasia	Scleroderma	Diffuse Esophageal Spasm
Symptoms	Dysphagia Regurgitation of nonacidic material	Gastroesophageal reflux disease Dysphagia	Substernal chest pain (angina-like) Dysphagia with pain
Radiographic appearance	Dilated, fluid-filled esophagus Distal bird-beak stricture	Aperistaltic esophagus Free reflux Peptic stricture	Simultaneous noncoordinated contractions
Manometric findings
Lower esophageal sphincter	High resting pressure Incomplete or abnormal relaxation with swallow	Low resting pressure	Normal pressure
Body	Low-amplitude, simultaneous contractions after swallowing	Low-amplitude peristaltic contractions or no peristalsis	Some peristalsis Diffuse and simultaneous nonperistaltic contractions, occasionally high amplitude

Workup

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Physical examination and laboratory analyses to rule out other causes (Table 2) and assess complications

TABLE2 Chicago Classification of Esophageal Motility DisordersFrom Feldman M, Friedman LS, Brandt LJ: Sleisenger and Fortran’s gastrointestinal and liver disease, ed 10, Philadelphia, 2016, Saunders.

Diagnosis	Diagnostic Criteria
Achalasia
Type I	100% failed peristalsis, mean IRP >10 mm Hg
Type II	No esophageal contraction and panesophageal pressurization with ≥20% of swallows; mean IRP >10 mm Hg
Type III	Premature contractions with ≥20% of swallows, mean IRP ≥17 mm Hg
EGJ outflow obstruction	Mean IRP ≥15 mm Hg; mix of normal, weak, rapid, hypertensive, failed peristalsis or panesophageal pressurization
Motility Disorders	(Patterns not observed in normal individuals)
Distal esophageal spasm	Mean IRP <17 mm Hg, ≥20% premature contractions
Hypercontractile esophagus (jackhammer esophagus)	At least one swallow DCI >8000 mm Hg⋅s⋅cm
Absent peristalsis	Mean IRP ≤10 mm Hg, 100% failed peristalsis
Peristaltic Abnormality	(Defined by exceeding statistical limits of normal)
Weak peristalsis	Mean IRP <15 mm Hg and ≥20% swallows with large breaks (≥5 cm) or ≥30% with small breaks (2-5 cm) in the 20-mm Hg isobaric contour Or DCI of 150-450 mm Hg⋅s⋅cm in ≥30% test swallows
Frequent failed peristalsis	>30%, but <100% of swallows with failed peristalsis
Rapid peristalsis	Rapid contraction with ≥20% of swallows, DL >4.5 s
Hypertensive peristalsis (nutcracker esophagus)	Mean DCI >5000 mm Hg⋅s⋅cm, but not meeting criteria for hypercontractile esophagus
Normal	Not achieving any of the above diagnostic criteria
DCI, Distal contractile interval; DL, distal latency; EGJ, esophagogastric junction; IRP, integrated relaxation pressure.

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Imaging studies, manometry, and endoscopy (may be supportive or complementary)

Laboratory Tests

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Assessment of nutritional status
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Complete blood count, ECG, stress test if diagnosis is in doubt
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Serologic assays for Trypanosoma cruzi (Chagas disease) in appropriate individuals

Imaging Studies

Barium swallow with fluoroscopy may demonstrate:

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Uncoordinated or absent esophageal contractions (loss of peristalsis)
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An acutely tapered contrast column (“bird’s beak”; Fig. 1)

FIG.1

Classic appearance of achalasia of the esophagus.

The dilated esophagus ends in a narrow segment.

From Hoekelman R [ed]: Primary pediatric care, ed 3, St Louis, 1997, Mosby.
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Dilation of the distal esophagus (smooth muscle portion)
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Esophageal air-fluid level with evidence of poor esophageal emptying
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Late-stage changes include tortuosity, angulation, dilated megaesophagus, retained food, and secretions

Manometry is generally considered to be the “gold standard” test to confirm the diagnosis.

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In classic achalasia, conventional manometric abnormalities are as follows: low-amplitude disorganized contractions/aperistalsis, incomplete or absent LES relaxation (with residual pressure >10 mm Hg) after swallow, and high resting LES pressure.
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A subset of patients with “vigorous achalasia” may have high-amplitude, long-duration, simultaneous esophageal contractions. This term is now thought to be imprecise because of a newer classification of the disease.
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High-resolution manometry (HRM), or high-resolution esophageal pressure topography (HREPT), has defined subsets of patients with achalasia who may have different responses to medical or surgical therapies. Unlike classic achalasia (type I), type II achalasia shows panesophageal pressurization to greater than 30 mm Hg with ≥20% of test swallows, and type III achalasia shows spastic lumen-obliterating contractions of the distal esophagus with ≥20% of swallows. This technique uses the integrated relaxation pressure (IRP) >15 mm Hg to define better the failure of esophagogastric junction relaxation.
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HREPT has also defined an achalasia variant described as esophagogastric junction outflow obstruction.
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Direct visualization by endoscopy, including careful visualization of the esophagogastric junction and cardia, should be performed to exclude other causes of dysphagia, including “functional esophagogastric junction obstruction,” strictures, secondary causes of achalasia (including infiltrating cancers), and pseudoachalasia.

Treatment

Nonpharmacologic Therapy

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The goals of therapy are to decrease LES pressure to relieve the functional obstruction, relieve symptoms, and prevent progression to a dilated esophagus, sometimes referred to as a megaesophagus. Treatment does not improve esophageal peristalsis. Achalasia is treatable but incurable.
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Pneumatic dilation to disrupt the LES muscle fibers may benefit 65% to 90% of patients. Multiple sessions may be required, and most protocols use a graded dilation approach, starting with a 30-mm balloon, and repeating if required with a 35-mm or 40-mm balloon. Some studies suggest this may be more effective in females, older patients, or HRM type II patients. Esophageal rupture or perforation is a rare complication (2% to 4%) that may be managed conservatively in some stable patients with a small perforation.
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Surgical: laparoscopic, or now less commonly, open (Heller’s) esophagomyotomy is effective (90%). Approximately 35% of patients undergoing surgery will develop reflux disease. As a result, some surgeons will perform a “loose” or partial antireflux repair (fundoplication) as part of the surgical procedure. Some studies suggest this may be more effective in men and younger patients. An observational study has suggested that those who have had prior endoscopic treatment before myotomy may not do as well as those who have a primary myotomy.
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Studies suggest that type II patients respond better than type I patients, and type III patients have poorer treatment responses to these therapies.
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A large European study suggested that in experienced hands, patients may expect similar medium-term outcomes from myotomy and balloon dilation. A meta-analysis suggests better long-term durability of myotomy. Balloon dilation may be the more cost-effective treatment. A small percentage (20 to 30%) of patients undergoing either therapy may require re-treatment within 5 to 7 years.
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Assessment of esophagogastric junction distensibility by an endoscopic functional luminal imaging probe may help to better evaluate the efficacy of treatment.
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Endoscopic submucosal myotomy (per-oral endoscopic myotomy [POEM ]) has a high success rate comparable to laparoscopic Heller myotomy (even in HRM type III patients), few adverse events (which can include pneumomediastinum, pneumothorax, pneumoperitoneum, pleural effusion, and bleeding), and exceedingly rare mortality. Because no antireflux procedure is performed, there is a modest risk (up to 53%) of developing pathologic reflux. For now, it should only be performed at high-volume centers.
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Esophagectomy has been performed in patients with end-stage achalasia with a dilated, often sigmoid-shaped or megaesophagus, who have failed myotomy or pneumatic dilation.

General Rx

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Medications may be useful for short-term symptom relief and in patients with refractory chest pain. They should only be considered in patients unable to receive, or who are scheduled for, more definitive procedures. LES pressure may be lowered by up to 50% through sublingual use of long-acting nitrates (e.g., isosorbide dinitrate 5 to 20 mg) or calcium channel blockers (e.g., nifedipine 10 to 30 mg). Side effects are common and duration of relief tends to be short. Sildenafil was shown to be effective in a few small, short-term studies, but it is generally not recommended.
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Botulinum toxin injection will benefit up to 85% of patients by inhibiting acetylcholine release from cholinergic nerve endings, blocking the unopposed cholinergic stimulation of the LES, but having no impact on the myogenic tone; up to half of these patients will require repeat injections by 6 months. A few studies have suggested that repeated injections can lead to fibrosis, which may complicate subsequent attempts at surgical therapy.
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Many patients will require proton pump inhibitor therapy for gastroesophageal reflux after effective disruption of the LES.

Pearls & Considerations

Comments

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Medication has a limited role in treatment.
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Botulinum toxin is transiently effective in improving symptoms. Pneumatic dilation, surgical myotomy, and POEM provide more durable long-term responses and are the treatment of choice for most patients. Botulinum toxin should be considered primarily in patients too elderly or ill to be considered for these other therapies.
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Patients with achalasia may be at long-term risk of squamous cell carcinoma of the esophagus and non–reflux-associated esophagitis. Treated patients may be at long-term risk for reflux esophagitis, Barrett’s esophagus, and adenocarcinoma. Endoscopic surveillance is not routinely recommended in these patients.

Ferri – Achalasia