From the Guidelines
Achalasia is primarily caused by damage to the nerves in the esophagus, which can result from various factors including autoimmune reactions, viral infections, genetic predisposition, and neurodegeneration, as supported by recent studies such as the one published in Clinical Gastroenterology and Hepatology in 2024 1. The exact mechanisms behind achalasia are complex and involve multiple pathways. Key factors contributing to the development of achalasia include:
- Autoimmune reactions, where the body's immune system mistakenly attacks and damages esophageal nerves, as seen in conditions like Sjogren’s syndrome, systemic lupus erythematosus (SLE), and myositis 1.
- Viral infections, such as COVID-19, which may trigger an autoimmune response or directly damage esophageal nerves, leading to conditions like post-COVID dysmotility or achalasia 1.
- Genetic predisposition, where individuals may have a susceptibility to developing achalasia, although it is not typically inherited in a straightforward manner.
- Neurodegeneration, involving the progressive loss of nerve function in the esophagus over time, which can be influenced by various factors including age and underlying health conditions. It's crucial to understand that achalasia is not usually inherited or contagious and can develop at any age, with the majority of cases diagnosed in middle-aged or older adults. Recent evidence also suggests an association between achalasia and other conditions such as eosinophilic esophagitis (EoE), with studies indicating a higher relative risk of EoE in patients with achalasia, particularly those under 40 years old 1. Furthermore, infectious etiologies like Chagas disease, caused by Trypanosoma cruzi, can lead to esophageal dysfunction through immune cross-reactivity, resulting in achalasia-like symptoms 1. In the context of real-life clinical practice, considering these various causes and associations is essential for guiding diagnostic approaches and treatment strategies, which aim to manage symptoms and improve esophageal function.
From the Research
Causes of Achalasia
The exact causes of achalasia are not well understood, but several studies have shed some light on the possible underlying mechanisms:
- The pathophysiologic mechanism involves the destruction of the myenteric plexi responsible for esophageal peristalsis 2
- Achalasia is characterized by alterations of the motility of the esophageal body in conjunction with altered lower esophageal sphincter (LES) relaxation 3
- The disorder is featured by the altered relaxation of the esophagogastric junction in the absence of effective peristaltic activity 4
- The etiology of achalasia remains unclear, but it is a primary esophageal motility disorder that affects equally both genders and all ages 2
Possible Factors Contributing to Achalasia
Some studies suggest that achalasia may be related to:
- Destruction of the myenteric plexi, which are responsible for esophageal peristalsis 2
- Alterations in the motility of the esophageal body and LES relaxation 3
- Esophageal outflow obstruction, which can lead to clinical symptoms such as dysphagia, chest pain, weight loss, and regurgitation of indigested food 4
Current Understanding
While the exact causes of achalasia are still not fully understood, research has made significant progress in understanding the disorder's pathophysiology and diagnosis. High-resolution manometry and other diagnostic tools have improved the diagnosis and management of achalasia, and new therapeutic approaches such as peroral endoscopic myotomy (POEM) have emerged as alternative treatment options 3, 4