Achalasia: Pathogenesis, clinical manifestations, and diagnosis
- Stuart J Spechler, MD
Stuart J Spechler, MD
- Berta M and Cecil O Patterson Professor of Medicine
- University of Texas Southwestern Medical Center at Dallas
Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter, accompanied by a loss of peristalsis in the distal esophagus. This topic will review the etiology, pathogenesis, clinical manifestations, and diagnosis of achalasia. The management of achalasia is discussed separately. (See "Overview of the treatment of achalasia" and "Pneumatic dilation and botulinum toxin injection for achalasia" and "Surgical myotomy for achalasia".)
Achalasia is an uncommon disorder with an annual incidence of approximately 1.6 cases per 100,000 individuals and prevalence of 10 cases per 100,000 individuals . Men and women are affected with equal frequency. The disease can occur at any age, but onset before adolescence is rare. Achalasia is usually diagnosed in patients between the ages of 25 and 60 years.
Achalasia may occur in association with adrenal insufficiency and alacrima in patients with triple A syndrome or Allgrove syndrome, a rare autosomal recessive genetic disorder [2,3]. (See "Unusual causes of adrenal insufficiency", section on 'Triple A (Allgrove syndrome)'.)
The etiology of primary or idiopathic achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor abnormalities similar or identical to those of primary achalasia (table 1). In Chagas disease, which occurs predominantly in Central and South America, esophageal infection with the protozoan parasite Trypanosoma cruzi can result in a loss of intramural ganglion cells, leading to aperistalsis and incomplete lower esophageal sphincter relaxation . Other diseases that have been associated with achalasia-like motor abnormalities include amyloidosis, sarcoidosis, neurofibromatosis, eosinophilic esophagitis, multiple endocrine neoplasia type 2B, juvenile Sjögren syndrome, chronic idiopathic intestinal pseudo-obstruction, and Fabry disease [5-11]. (See "Chagas disease: Pathology and pathogenesis".)
Achalasia results from inflammation and degeneration of neurons in the esophageal wall (figure 1) . The cause of the inflammatory degeneration of neurons in primary achalasia is not known. The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder [13-15]. Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive [16,17]. A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection . A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome. (See 'Epidemiology' above and "Unusual causes of adrenal insufficiency", section on 'Triple A (Allgrove syndrome)'.)
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- CLINICAL FEATURES
- Clinical manifestations
- Radiographic findings
- DIAGNOSTIC EVALUATION
- Diagnostic approach
- Esophageal manometry
- - Conventional manometry
- - High-resolution manometry
- Barium esophagram
- Upper endoscopy
- Endoscopic ultrasound
- DIFFERENTIAL DIAGNOSIS
- NATURAL HISTORY AND PROGNOSIS
- Disease course
- Cancer risk
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS