Читать книгу The Esophagus - Группа авторов - Страница 56

Primary achalasia is subdivided into three subtypes based on HRM findings with treatment implications depending on the specific subtype. While the manometric details of subclassifications are beyond the scope of this chapter, it is worth noting that achalasia Type II typically has the best response to therapy, whereas Type III usually has the worst response, in particular, for resolution of ECP [124].

The hallmark loss of ganglion cells in the myenteric plexus, albeit the underlying pathogenesis of primary achalasia, remains uncertain. Available data, however, strongly suggests an immune‐mediated response (both cell‐ and antibody‐mediated). This is supported by analysis of tissue samples taken after Heller myotomy for achalasia, which demonstrated an abundance of T‐lymphocytes, some eosinophils, plasma cells and B cells, along with occasional mast cells and macrophages surrounding ganglia and neurons in the myenteric plexus [125–127]. Notably, the T‐cells found in the myenteric infiltrate stained positive for TNF‐α, demonstrated IgM antibodies, and also evidence of complement activation, which taken together are thought to promote apoptosis of myenteric neurons [128, 129]. Additionally, impaired endogenous nitric oxide synthesis and degradation are thought to play a role in achalasia. The role of nitric oxide will be discussed later in detail in relation to distal esophageal spasm, which is also potentially considered a precursor to achalasia [124].

Antibodies specific to myenteric neurons have been seen in patients with primary achalasia, most notably in patients with HLA‐DQA1*0103 and HLADQB1*0603 alleles [130, 131]. These human leukocyte antigen (HLA) proteins play a pivotal role in antigen recognition, suggesting an anomalous immunity to a specific antigen. Several proposed theories have included herpes simplex (namely HSV‐1), human papillomavirus, and the measles virus, but available data to date has been inconclusive [132–136].

Pertinent to ECP, achalasia can have several symptoms, with dysphagia being the most common, followed by regurgitation, chest pain, and heartburn [137]. Typically, the symptoms experienced by patients depend on the degree and location of neural cell loss. In the distal esophagus, the inability for lower esophageal sphincter (LES) relaxation and impaired peristalsis results in dysphagia. As a consequence, the esophagus spasms and the esophageal lumen dilates. This produces sensations similar to heartburn, and thus patients are often misdiagnosed as having gastroesophageal reflux rather than underlying achalasia [138].

Achalasia is also thought to impact the upper esophageal sphincter (UES) [139]. Under normal circumstances, the UES relaxes with esophageal distention allowing for gas to escape through the mouth in the form of a belch. In patients with achalasia, air in the esophagus frequently causes a paradoxical increase in UES pressures without a belch. This further causes esophageal distention and resultant chest pain. It is estimated that up to 85% of patients have difficulty belching and that nearly 60% of patients complain of substernal CP [140]. In fact, the frequency of CP in patients with achalasia is so common that CP is one of the four components of the commonly used Eckardt score used to assess and monitor the severity of achalasia, with the other three being recent weight loss, dysphagia, and regurgitation [141].