Achalasia unveiled: a narrative review from pathophysiological mechanisms to modern diagnostic approaches

Background and Objective: Achalasia is a rare primary oesophageal motility disorder characterised by impaired relaxation of the lower oesophageal sphincter (LOS, also termed LES) and absent peristalsis, resulting in oesophageal outflow obstruction and significant impairment of quality of life. Despite advances in understanding its pathophysiology and diagnostic modalities, significant knowledge gaps persist. This narrative review aims to provide an overview of current understanding of pathophysiological mechanisms and modern diagnostic approaches for achalasia, integrating recent evidence from the Chicago Classification (CC) version 4.0 and emerging diagnostic technologies.Methods: We performed a literature search using PubMed, Scopus, Web of Science databases, Cochrane Library and manual reference searching from January 2015 to November 2025. Search terms included MeSH terms (“Oesophageal Achalasia”, “Oesophageal Motility Disorders”, “Manometry”) and free-text terms (achalasia, high-resolution manometry, Chicago Classification, pathophysiology, diagnosis). We included original articles, systematic reviews, meta-analyses, and clinical guidelines published in English.Key Content and Findings: The pathophysiology of achalasia involves selective loss of inhibitory neurons in the myenteric plexus, driven by predominantly cell-mediated immune mechanisms, with possible antibody-mediated contributions. Genetic predisposition, particularly HLA-DQβ1 associations, and viral triggers contribute to disease development. In the diagnostic process, it is important to rule out pseudo achalasia, a condition in which mechanical obstruction, frequently caused by infiltrating cancer, imitates primary achalasia. High-resolution manometry (HRM) remains the gold standard for diagnosis, with the CCv4.0 providing refined criteria for three distinct achalasia subtypes based on integrated relaxation pressure (IRP) and oesophageal body pressurisation patterns. Functional lumen imaging probe (FLIP) and timed barium oesophagram (TBE) are complementary tools that improve diagnostic accuracy, especially in cases where the results are unclear.Conclusions: Accurate diagnosis of achalasia requires integration of clinical presentation, endoscopic evaluation, HRM, and supportive testing. Understanding the pathophysiological basis and proper subtype classification is essential for optimising therapeutic outcomes. Future research should focus on identifying biomarkers for early diagnosis, elucidating the triggers of autoimmune neuronal destruction, and developing personalised treatment approaches based on disease phenotype.