Achalasia: physiology and etiopathogenesis

Abstract

Achalasia is a disorder of esophageal motility that has been well documented for over 300 years. Despite this, the initiating factor or factors and the underlying mechanisms leading to the characteristic features of achalasia, the absence of distal esophageal peristalsis and abnormal lower esophageal sphincter relaxation, are still not well understood. Recent work has shed light on changes in neurotransmission and cell signaling in the lower esophagus and lower esophageal sphincter that lead to achalasia. A number of recent reviews have thoroughly discussed diagnostic and therapeutic modalities and the reader is referred to these for in-depth review of these topics. The focus of this review will be on our current understanding of the physiology of esophageal peristalsis and lower esophageal sphincter function as it relates to achalasia and on available evidence for etiology and proposed pathophysiologic mechanisms.

Achalasia and thyroid disease: possible autoimmune connection?

“…In young patients, it is worth having Allgrove or Triple A syndrome (primary adrenal insufficiency, achalasia, and alagrimia) as a differential diagnosis (10). Despite the age, primary adrenal insufficiency was investigated in our patient and ruled out.…”

“…Probably, an unknown environmental insult may determine inflammation of the plexus in a genetically susceptive person, with progressive association with thyroid gland involvement. Therefore, autoimmunity may either be a co-factor or aid the pathogenesis of signs and symptoms (10). However, controversies continue to exist: whether we are dealing with a true cause-effect situation or a simple epiphenomenon.…”

“…in the serum of a subgroup of patients with achalasia (8)(9)(10)13). A cluster consisting of varied autoimmune diseases has been linked to achalasia: myasthenia gravis, polymyositis, autoimmune thyroid disease, among others, contributing to the argument that autoimmunity may be a cause for some idiopathic achalasia (17)(18)(19).…”

“…However, some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. Specifically, higher genotypic frequency of the human leukocyte antigen (HLA)-DQw1, DQA1*0101, DQA1*103, DQB1*0602, and DQB1*0603 alleles were observed in achalasia patients compared with controls (7,8,(10)(11)(12)(13). Descriptions of inflammatory infiltration in the affected regions of the esophagus in achalasia led to speculation of an autoimmune pathogenesis.…”

“…It is well known that the resting tonus of the LES is regulated by excitatory (acetylcholine, Substance P, among others), as well as inhibitory neurotransmitters (nitric oxide). Therefore, patients with achalasia have a significant imbalance between the excitatory and inhibitory pathways, resulting in hypertensive LES (10). Currently, the real physiopathogenesis of achalasia continues to be unknown.…”