Achalasia

Overview

Achalasia is a primary esophageal motility disorder characterized by two defining features: failure of the lower esophageal sphincter (LES) to relax with swallowing, and absent peristalsis throughout the esophageal body. Together these prevent food from passing into the stomach by the normal mechanism and cause progressive dysphagia, regurgitation, and weight loss.

The disorder is rare — the 2020 American College of Gastroenterology (ACG) guideline gives reported incidence rates from 0.03 up to about 1.6 per 100,000 persons per year — but is substantially underdiagnosed because its early symptoms (heartburn, mild dysphagia) mimic far more common conditions such as gastroesophageal reflux disease (GERD) or functional dysphagia. Peak incidence occurs between ages 30 and 60, and the sex distribution is approximately equal.

Achalasia has no cure. All available treatments reduce LES pressure to allow food passage by gravity and bolus pressure rather than by coordinated peristalsis. With appropriate treatment most patients achieve good long-term symptom control, though the underlying neuronal loss is permanent and disease monitoring continues for life.

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Pathophysiology: Loss of Inhibitory Neurons

The fundamental defect in idiopathic (primary) achalasia is selective degeneration of inhibitory myenteric ganglion neurons — specifically those that release vasoactive intestinal peptide (VIP) and nitric oxide, which they make with the enzyme neuronal nitric oxide synthase (nNOS). These inhibitory neurotransmitters are responsible for the coordinated relaxation of smooth muscle that constitutes normal LES opening and peristaltic propagation.

The Inhibitory Neurotransmission Deficit

• Loss of VIP- and nitric oxide-producing neurons removes the inhibitory signal that normally opens the LES with each swallow
• Unopposed cholinergic (excitatory) neurotransmission results in sustained LES hypertension — resting LES pressures typically 30–50 mmHg (normal: 10–30 mmHg)
• The same inhibitory deficit in the esophageal body abolishes the peristaltic wave — there is no propulsive contraction to push food downward
• In Type III achalasia, residual excitatory motor activity produces simultaneous, premature (spastic) contractions rather than orderly peristalsis

Autoimmune and Viral Theories

• Inflammation and lymphocytic infiltration of the myenteric plexus are found in early achalasia specimens — consistent with an immune-mediated attack on ganglion cells
• Herpes simplex virus type 1 (HSV-1) latent infection of the dorsal motor nucleus of the vagus nerve has been proposed as a trigger; HSV-1 DNA has been detected in myenteric neurons of achalasia patients
• Genetic susceptibility: HLA-DQA1*0103 allele is significantly over-represented, supporting an autoimmune etiology with a genetic predisposition
• Anti-myenteric antibodies (anti-neuronal immunoglobulin G, IgG) are detected in a subset of patients, though their pathogenic role remains incompletely characterized

Consequence: Esophageal Stasis

• Undigested food, saliva, and secretions pool in the esophageal body
• Progressive esophageal dilation follows — eventually forming a sigmoid (S-shaped) megaesophagus in longstanding untreated disease
• Bacterial overgrowth in retained material produces fermentation — a common source of the paradoxical "heartburn" many patients report (fermentation acids, not gastric reflux)

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Chicago Classification: Types I, II, and III

The Chicago Classification of esophageal motility disorders, now at version 4.0 (CC v4.0), uses high-resolution manometry (HRM) metrics to subtype achalasia. Subtype predicts treatment response and guides therapy selection.

All three types share the same diagnostic requirement: elevated median integrated relaxation pressure (IRP > 15 mmHg on standard HRM) confirming impaired LES relaxation, combined with absent normal peristalsis in the esophageal body.

Type I — Classic Achalasia

• Absent peristalsis with no esophageal pressurization — the esophageal body is essentially a flaccid tube
• Elevated IRP confirms impaired LES relaxation
• Represents the "burned-out" end-stage pattern — most associated with advanced esophageal dilation and sigmoid esophagus in longstanding cases
• Intermediate treatment response

Type II — Achalasia with Esophageal Pressurization (best prognosis)

• Absent peristalsis plus ≥20% of wet swallows showing pan-esophageal pressurization (pressurization from the LES to the upper esophageal sphincter (UES), indicating the esophagus acts as a pressurized column)
• Elevated IRP confirming impaired LES relaxation
• Best treatment response of all three types — in the European achalasia trial, treatment with pneumatic dilation or laparoscopic Heller myotomy succeeded in 96% of type II patients after at least 2 years
• Most commonly diagnosed subtype (50–70% of cases in the 2020 ACG guideline)

Type III — Spastic Achalasia (worst prognosis)

• Absent peristalsis plus ≥20% of wet swallows with premature or spastic contractions (jackhammer-like distal latency shortening)
• Elevated IRP confirming impaired LES relaxation
• Chest pain is prominent — often severe
• Poorest response overall (66% success after at least 2 years in the European achalasia trial, where pneumatic dilation succeeded in 40% and Heller myotomy in 86% of the 18 type III patients); POEM (which extends myotomy further up the esophageal body to address the spastic segment) is reported in observational studies to give better outcomes in Type III than traditional surgical approaches; no randomized trial limited to Type III has tested this

How common each type is, and how it responds: among the 176 patients of the European achalasia trial, 25% had type I, 65% type II and 10% type III; after at least 2 years, treatment succeeded in 96% of type II, 81% of type I and 66% of type III patients. The 2020 ACG guideline puts type II at 50–70% of cases, type I at 20–40% and type III at about 5%.

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Pseudoachalasia: Ruling Out Malignancy

Pseudoachalasia refers to conditions that produce a manometric and clinical picture indistinguishable from primary achalasia but are caused by a different underlying process. Failing to recognize pseudoachalasia leads to futile or harmful treatment — a surgical myotomy performed on a malignant gastroesophageal junction (GEJ) obstruction will not help and may delay cancer treatment.

Causes of Pseudoachalasia

• Malignancy at the gastroesophageal junction: Adenocarcinoma of the gastric cardia or distal esophagus can mechanically obstruct the GEJ and reflexively inhibit esophageal peristalsis — mimicking Type I achalasia on manometry. This is the most important cause to exclude.
• Chagas disease (Trypanosoma cruzi infection): Chronic Chagas disease destroys myenteric ganglia throughout the gastrointestinal (GI) tract and heart. Esophageal involvement is clinically and manometrically identical to idiopathic achalasia. It is most relevant for people from regions where the infection is common (Latin America).
• Other infiltrating processes: amyloidosis, sarcoidosis, eosinophilic esophagitis (rarely)

Alarm Features That Prompt Urgent Workup

• Age >60 at symptom onset
• Symptom duration less than 6 months (rapid onset and progression)
• Significant unexplained weight loss disproportionate to dysphagia severity
• Dysphagia severity out of proportion to manometric findings
• Abnormal mucosa or submucosal mass at GEJ on endoscopy

Workup to Exclude Pseudoachalasia

• Esophagogastroduodenoscopy (EGD) with careful GEJ inspection and biopsy of any suspicious area is standard before achalasia treatment starts
• Endoscopic ultrasound (EUS) to assess GEJ wall thickness and regional lymph nodes
• Computed tomography (CT) chest/abdomen/pelvis if malignancy is suspected
• Chagas serology in appropriate epidemiological context

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Symptoms and Clinical Presentation

Achalasia typically presents insidiously over months to years. The hallmark — dysphagia to both solids AND liquids simultaneously — is the single most useful clinical feature distinguishing it from mechanical obstruction (which causes dysphagia to solids first, then liquids only when severe).

Core Symptoms

• Progressive dysphagia to both solids and liquids — present in virtually all patients; the hallmark feature. Patients often describe food "sticking" in the mid-chest or lower throat, and adopt compensatory maneuvers (standing up, raising arms, repeated swallowing, carbonated beverages) to encourage food passage.
• Regurgitation of undigested food — often hours after eating; food is not acidic (not gastric contents) because it never reached the stomach. Regurgitation during sleep or recumbency is a serious aspiration risk.
• Weight loss — gradual and progressive; typically 5–20 lb over months to years as patients restrict intake to manage dysphagia.
• Nocturnal cough and aspiration pneumonia — regurgitation of esophageal contents during sleep leads to chronic aspiration; recurrent aspiration pneumonia is a recognized reason for an esophageal workup.
• Chest pain — particularly prominent in Type III (spastic) achalasia; may be severe and mimic cardiac pain.
• Paradoxical heartburn — present in 27–42% of people with achalasia according to the 2020 ACG guideline, which is why many are first treated for reflux with acid-lowering pills; often caused by fermentation of retained food producing organic acids, not by gastroesophageal reflux. Gastroesophageal reflux disease workup often normal.

Common Misdiagnoses and Delays

• Gastroesophageal reflux disease — the heartburn and regurgitation of achalasia are frequently misinterpreted as acid reflux; proton pump inhibitor (PPI) therapy produces no benefit but the apparent "gastroesophageal reflux disease" label persists for years
• Psychiatric illness — patients with chest pain and dysphagia of unexplained cause are sometimes labeled as having somatization or anxiety
• Average time from symptom onset to correct diagnosis is reported at 4–6 years in multiple series

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Diagnosis: Manometry and Imaging

No single test establishes the diagnosis of achalasia alone. The diagnostic workup combines manometry (gold standard for subtype classification), barium esophagram (anatomy, severity, functional column clearance), and endoscopy (mandatory to exclude pseudoachalasia).

High-Resolution Esophageal Manometry (HRM) — Gold Standard

• A 36-sensor solid-state catheter placed from pharynx to stomach measures pressure at 1-cm intervals during a standardized wet-swallow protocol
• Key diagnostic metrics: (1) integrated relaxation pressure (IRP) — the mean 4-second nadir LES pressure during swallow-induced relaxation; IRP > 15 mmHg = impaired relaxation; (2) esophageal body pressurization pattern and peristaltic presence/absence
• Chicago Classification v4.0 assigns subtype (I, II, III) based on these metrics — subtype drives treatment choice and predicts outcome
• Functional lumen imaging probe (FLIP) is an emerging complementary tool that measures esophagogastric junction distensibility — low distensibility supports the achalasia diagnosis and may predict treatment response

Barium Esophagram (Timed Barium Swallow)

• Classic finding: "bird-beak" tapered narrowing at the GEJ with smooth contour + dilated esophageal body above
• Timed barium swallow: column height measured at 1 and 5 minutes; >5 cm retained at 5 minutes = abnormal, correlates with symptom severity and guides post-treatment response assessment
• Sigmoid esophagus (tortuous, S-shaped megaesophagus) in longstanding untreated disease — a marker of advanced disease that complicates endoscopic and surgical access
• Does not allow subtype classification — used for anatomy and functional severity, not manometric diagnosis

EGD (Esophagogastroduodenoscopy)

• Mandatory in all patients before treatment — to exclude pseudoachalasia/malignancy at the GEJ
• Classic endoscopic finding in achalasia: dilated esophageal body with retained saliva/food; LES feels tight but the scope passes with a characteristic "pop" (resistance followed by sudden entry into the stomach)
• Any suspicious mucosal abnormality at the GEJ is biopsied
• Esophageal candidiasis is common (chronic stasis predisposes) — it is usually treated before any interventional procedure

Endoscopic Ultrasound (EUS) and Computed Tomography

• EUS: assess GEJ wall thickness and peri-esophageal lymphadenopathy when malignancy is suspected; LES wall >10 mm suggests infiltrating tumor (pseudoachalasia) rather than primary achalasia
• Computed tomography chest/abdomen: used when alarm features are present; identifies mediastinal mass, subcarinal adenopathy, or GEJ mass not visible endoscopically

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Treatment: Pneumatic Dilation, Myotomy, and POEM

No treatment restores lost myenteric neurons or normal peristalsis. All effective therapies mechanically reduce LES pressure to a level where food can pass by gravity and bolus pressure. The three most effective treatments are pneumatic dilation (PD), laparoscopic Heller myotomy (LHM) with partial fundoplication, and peroral endoscopic myotomy (POEM). The head-to-head randomized trials, their 5-year results and the subtype data are set out on Treatment Trials: POEM, Heller Myotomy and Balloon Dilation.

Pneumatic Dilation (PD)

• Endoscopic balloon dilation of the LES using a graded pneumatic balloon of 30, 35, or 40 mm; the balloon is inflated to a fixed pressure across the LES to disrupt circular muscle fibers
• Typically performed as an outpatient procedure under conscious sedation
• Success rates by subtype after at least 2 years in the European achalasia trial: type II 100%, type I 85%, type III 40% (the type III group was small — 18 patients across both treatments)
• Repeat dilation: in the European achalasia trial, 25% of dilation patients (24 people) needed a repeat dilation over 5 years, which the trial allowed within the dilation strategy; in a trial that allowed one series of dilations and counted any further dilation as failure, 60% of dilation patients had failed by 5 years
• Perforation rate: the 2020 ACG guideline gives an overall median of 1.9% in experienced hands (range 0–16% across reports); in the European achalasia trial it was 4% at 2 years and 5% (five patients) by 5 years (the major complication — requires urgent surgical repair if full-thickness perforation); managed by experienced endoscopists with fluoroscopic guidance
• Preferred in patients who are not surgical candidates, patients who wish to avoid surgery, or as first-line in centers with limited POEM/myotomy experience

Laparoscopic Heller Myotomy (LHM) with Partial Fundoplication

• Surgical myotomy of the LES and distal esophageal circular smooth muscle (6 cm esophageal + 2 cm gastric extent) under general anesthesia
• A partial fundoplication (Dor — anterior; or Toupet — posterior) is added to prevent iatrogenic gastroesophageal reflux disease, which occurs in 10–30% of patients post-myotomy without fundoplication
• Durable response in 85–90% of patients; in the European achalasia trial, a randomized controlled trial (RCT), success after 5 years was 84% after Heller myotomy and 82% after pneumatic dilation, not significantly different, and the 2020 ACG guideline rates the two as equivalent short- and long-term procedures
• Was the standard of care for surgical candidates prior to the POEM era; still widely performed and offers the advantage of anti-reflux wrap
• Less effective in Type III achalasia because a standard 6 cm myotomy does not extend far enough proximally to address the spastic esophageal body

POEM — Peroral Endoscopic Myotomy

• Endoscopic technique: a submucosal tunnel is created from mid-esophagus to 2–3 cm below the GEJ; the inner circular muscle layer is then divided under direct endoscopic visualization from within the tunnel, with the overlying mucosa preserved as a natural seal
• Equivalent to LHM for overall symptom relief (Eckardt score reduction, LES pressure reduction) — confirmed by multiple randomized controlled trials and meta-analyses
• Key advantage over LHM: the myotomy length can be extended proximally as far as needed to address spastic segments; observational studies and pooled analyses report higher success with POEM than LHM in Type III achalasia, but no randomized trial limited to Type III has compared them
• Key disadvantage: no anti-reflux fundoplication is possible; a 2018 meta-analysis cited by the 2020 ACG guideline found abnormal acid exposure in 39.0% of patients after POEM versus 16.8% after surgical myotomy. Follow-up after POEM therefore often includes proton pump inhibitor therapy and endoscopic checks for reflux esophagitis and Barrett's esophagus.
• Technically demanding — performed in specialized high-volume centers
• Hospital stay: 1–2 days
• POEM versus pneumatic dilation: in a 2019 randomized trial of 133 people with newly diagnosed achalasia, treatment success at 2 years was 92% after POEM versus 54% after dilation with 30 and 35 mm balloons; reflux inflammation of the esophagus (reflux esophagitis) was more common after POEM (41% vs 7%)
• POEM versus Heller myotomy with a partial wrap: in a 2019 randomized trial of 221 patients, symptoms were controlled at 2 years in 83.0% versus 81.7%; serious adverse events occurred in 2.7% versus 7.3%, and reflux esophagitis at 2 years in 44% versus 29%

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Botulinum Toxin and Medical Therapy

For patients who are not candidates for pneumatic dilation, myotomy, or POEM — due to advanced age, severe comorbidities, or patient preference — less invasive options provide temporary but meaningful symptom relief.

Botulinum Toxin Injection

• Endoscopic injection of botulinum toxin A (100 units, divided into 4 quadrant injections) directly into the LES during EGD
• Mechanism: inhibits presynaptic acetylcholine release from cholinergic neurons → reduces unopposed excitatory tone → partial LES relaxation
• Symptom response: 70–90% initially; however, median duration of benefit is only 6–12 months before symptoms recur, requiring repeat injections
• Repeat injections are safe but produce diminishing returns over time as fibrosis develops at the injection site
• Effect on later myotomy or POEM: small observational studies reported a fibrotic sphincter and more complications at later surgery after botulinum toxin, while others found no increase in POEM complications; the 2020 ACG guideline calls the evidence conflicting and concludes (low-quality evidence, conditional) that previous botulinum toxin injection does not significantly affect performance and outcomes of myotomy. The guideline places botulinum toxin as first-line therapy for people unfit for definitive therapies
• The 2020 ACG guideline reports a Cochrane review in which 55 of 75 people treated with pneumatic dilation were still in remission at 12 months, versus 27 of 72 after botulinum toxin (relative risk 1.88); dilation gave longer-lasting relief than the toxin
• Most often used in: elderly patients (>70) with significant surgical risk, patients awaiting definitive treatment, or those who refuse myotomy/POEM

Calcium Channel Blockers and Nitrates

• Sublingual nifedipine (10–30 mg 30–45 min before meals) and sublingual isosorbide dinitrate (5 mg before meals) reduce LES resting pressure by 30–60% transiently
• Clinical effect is modest and short-lived; most patients find minimal practical benefit
• Side effects — headache (nitrates), hypotension, ankle edema (nifedipine) — often limit continued use
• Role is limited to patients in whom all other options are contraindicated or as a bridge to definitive treatment

Phosphodiesterase-5 Inhibitors

• Sildenafil enhances the nitric oxide pathway → smooth muscle relaxation → LES pressure reduction
• Small studies show short-term benefit; the data are too limited for routine use, and it is mainly tried when other medical options have failed

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Long-Term Complications and Surveillance

Even after successful treatment, achalasia carries long-term risks that require ongoing monitoring. The disease is never truly cured — the absent peristalsis and potential for esophageal stasis persist even when LES pressure is normalized.

Megaesophagus

• Untreated or treatment-resistant achalasia leads to progressive esophageal dilation and eventual sigmoid morphology
• Sigmoid megaesophagus represents end-stage mechanical failure — myotomy alone may not restore adequate emptying
• In advanced sigmoid megaesophagus, esophagectomy may ultimately be required (major surgery with significant morbidity)

Aspiration Complications

• Recurrent aspiration of retained esophageal contents leads to chronic bronchitis, aspiration pneumonia, and lung abscess
• Pulmonary complications are a major cause of morbidity in longstanding or poorly controlled disease
• Head-of-bed elevation, avoidance of eating within 3 hours of sleep, and adequate LES pressure reduction are protective

Esophageal Squamous Cell Carcinoma

• Patients with achalasia have an approximately 0.3% per year risk of developing esophageal squamous cell carcinoma (SCC) — about 1 cancer per 300 patient-years, which the 2020 ACG guideline describes as about 28 times the risk of the general population (hazard ratio 28)
• Mechanism: chronic mucosal inflammation from stasis, fermentation, and retained food carcinogens
• The 2020 ACG guideline recommends against routine endoscopic surveillance for esophageal cancer in achalasia; it notes that many experts favor some form of endoscopic or X-ray surveillance about every 3 years once the disease has been present for more than 10–15 years
• Note: post-POEM patients face an additional adenocarcinoma risk if reflux-related Barrett's esophagus develops — endoscopy in these patients also looks for Barrett's

Post-Treatment Monitoring

• Timed barium swallow at 3–6 months after treatment quantifies esophageal emptying improvement and identifies treatment failure before symptoms become severe
• Eckardt symptom score (dysphagia, regurgitation, chest pain, weight loss; 0–12 scale) tracked at follow-up visits; score >3 suggests treatment failure or relapse
• Post-POEM: ambulatory pH monitoring at 6–12 months to document acid exposure and guide proton pump inhibitor dosing
• Relapse is treated with repeat PD or POEM/myotomy — re-treatment is safe and often effective

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Key Research Papers

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2. Yadlapati R et al. "Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0." Neurogastroenterol Motil. 2021;33(1):e14058. — PubMed PMID: 33373111
3. Vaezi MF et al. "Botulinum toxin versus pneumatic dilatation in the treatment of achalasia: a randomised trial." Gut. 1999;44(2):231–239. — PubMed PMID: 9895383
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13. Howard PJ et al. "Five year prospective study of the incidence, clinical features, and diagnosis of achalasia in Edinburgh." Gut. 1992;33(8):1011–1015. — PubMed PMID: 1398223
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17. Moonen A et al. "Long-term results of the European achalasia trial: a multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy." Gut. 2016;65(5):732–739. — PubMed PMID: 26614104
18. Kuipers T et al. "Peroral endoscopic myotomy versus pneumatic dilation in treatment-naive patients with achalasia: 5-year follow-up of a randomised controlled trial." Lancet Gastroenterol Hepatol. 2022;7(12):1103–1111. — PubMed PMID: 36206786

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Connections

• Gastroenterology
• Treatment Trials: POEM, Heller Myotomy and Balloon Dilation
• Gastroesophageal Reflux Disease
• Gastroparesis
• Functional Dyspepsia
• Esophageal Cancer
• Scleroderma Gastrointestinal Involvement
• Magnesium
• Discussed in depth on these pages: Dysphagia (Difficulty Swallowing)

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