Snapshot A 45-year-old man presents to his primary care physician complaining of difficulty swallowing solids and liquids for the past 5 months. He also reports unintentional weight loss of 20 lbs over the past 3 months. The patient denies any fever, diarrhea, or dyspnea but endorses chest pain that is worse following food ingestion. His past medical history is unremarkable except for an episode of dengue fever when he was traveling in South America 1 year ago. A barium study is subsequently ordered. Introduction Clinical definition motor disorder of the distal esophagus secondary to progressive degeneration of the Auerbach plexus (ganglion cells in the myenteric plexus) Epidemiology Incidence of 1.6 cases per 100,000 individuals Demographics occurs equally among men and women diagnosis occurs between the ages of 25 and 60 years Risk factors Chagas disease other diseases such as scleroderma (see etiology) Etiology The etiology of primary/idiopathic achalasia is unknown Secondary achalasia occurs due to diseases that cause esophageal motor abnormalities Chagas disease protozoan parasite Trypanosoma cruzi destroys intramural ganglion cells other diseases include amyloidosis, scleroderma, sarcoidosis, neurofibromatosis, Fabry disease, and eosinophilic esophagitis. Pathogenesis inflammation and degeneration of neurons of Auerbach plexus the cause of the degeneration is unknown but may be autoimmune as suggested by the association with variants in the HLA-DQ regions in affected patients and the presence of antibodies to enteric neurons primarily leads to loss of nitric oxide-producing, inhibitory neurons that affect the relaxation of esophageal smooth muscle results in loss of normal relaxation of the lower esophageal sphincter (LES) and rise in basal sphincter pressure results in aperistalsis Presentation Symptoms dysphagia for solids and liquids regurgitation difficulty belching vomiting heartburn/substernal chest pain weight loss imaging Chest radiography may demonstrate mediastinal widening Barium esophagram not a sensitive test for achalasia, as it may be interpreted as normal in up to 1/3 of patients positive findings include dilation of the proximal esophagus “bird-beak” appearance at the esophageal sphincter aperistalsis delayed emptying of barium Upper endoscopy esophageal mucosa usually appears normal often performed after esophageal manometry to rule out malignancy Esophageal manometry gold standard of diagnosing achalasia high-resolution manometry (vs. conventional manometry) allows for categorization of the achalasia subtype, which can guide management findings include increased LES pressure, inability of the LES to relax, decreased peristalsis, and diffuse esophageal spasm Studies Diagnostic testing diagnostic approach clinical suspicion is established if the patient has dysphagia to solids and liquids heartburn unresponsive to proton pump inhibitor trial retained food in the esophagus on upper endoscopy unusually increased resistance to the passage of an endoscope through the esophagogastric junction (EGJ) Differential Gastroesophageal reflux disease (GERD) distinguishing factor regurgitated food is typically sour tasting in GERD due to the presence of gastric acid will have nonspecific findings on manometry Pseudoachalasia due to malignancy distinguishing factor may have the same manometry findings but can be differentiated from achalasia via upper endoscopy DIAGNOSIS Diagnostic criteria aperistalsis in distal 2/3 of the esophagus incomplete lower esophageal sphincter relation on manometry Treatment First-line surgical management the preferred option for patients who have an average surgical risk, though the efficacy of treatments decreases over time 1/3-1/2 of patients will require repeat treatment within 10 years endoscopic balloon dilation of LES cure rate of 80% complication of perforation in < 3% of patients myotomy with fundoplication similar outcomes to that of dilation peroral endoscopic myotomy (POEM) endoscopic technique that allows for myotomy of more proximal esophageal muscle Second-line botulism toxin injections offered to patients who are at high risk for complications high initial success but have more frequent relapses and a shorter time to relapse compared to operative treatments Other treatments pharmacological treatments (e.g., nifedipine, nitrates, or calcium channel blockers) are often ineffective and are limited by side effects indicated in patients who fail treatment with botulism toxin Complications Increased risk of esophageal cancer Ulceration and bleeding