Achalasia

1. Overview
2. Pathophysiology: Loss of Inhibitory Neurons
3. Chicago Classification: Types I, II, and III
4. Pseudoachalasia: Ruling Out Malignancy
5. Symptoms and Clinical Presentation
6. Diagnosis: Manometry and Imaging
7. Treatment: Pneumatic Dilation, Myotomy, and POEM
8. Botulinum Toxin and Medical Therapy
9. Long-Term Complications and Surveillance
10. Research Papers
11. Connections
12. Featured Videos

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 — an incidence of roughly 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 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 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 nNOS-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
• 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 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 LES to UES, indicating the esophagus acts as a pressurized column)
• Elevated IRP confirming impaired LES relaxation
• Best treatment response of all three types — approximately 90% symptom improvement with pneumatic dilation or surgical myotomy
• Most commonly diagnosed subtype

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 to pneumatic dilation (~50%) and to Heller myotomy; POEM (which extends myotomy further up the esophageal body to address the spastic segment) offers better outcomes in Type III than traditional surgical approaches

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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 GEJ obstruction will not help and may delay cancer treatment.

Causes of Pseudoachalasia

• Malignancy at the gastroesophageal junction (GEJ): 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 GI tract and heart. Esophageal involvement is clinically and manometrically identical to idiopathic achalasia. Consider in patients from endemic regions (Latin America).
• Other infiltrating processes: amyloidosis, sarcoidosis, eosinophilic esophagitis (rarely)

Alarm Features Requiring 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

• EGD with careful GEJ inspection and biopsy of any suspicious area is mandatory before starting achalasia treatment
• Endoscopic ultrasound (EUS) to assess GEJ wall thickness and regional lymph nodes
• 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 should prompt esophageal workup.
• Chest pain — particularly prominent in Type III (spastic) achalasia; may be severe and mimic cardiac pain.
• Paradoxical heartburn — reported by up to 40% of patients; caused by fermentation of retained food producing organic acids, not by gastroesophageal reflux. GERD workup often normal.

Common Misdiagnoses and Delays

• GERD — the heartburn and regurgitation of achalasia are frequently misinterpreted as acid reflux; PPI therapy produces no benefit but the apparent "GERD" 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)
• Biopsy any suspicious mucosal abnormality at the GEJ
• Esophageal candidiasis is common (chronic stasis predisposes) — treat before any interventional procedure

Endoscopic Ultrasound (EUS) and CT

• 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
• CT 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).

Pneumatic Dilation (PD)

• Endoscopic balloon dilation of the LES using a 30, 35, or 40 mm Rigiflex balloon; 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
• Response rates: Type II ~85–90%, Type I ~70–75%, Type III ~50–55%
• Most patients require repeated dilations over time — response durability decreases to ~50–60% at 10 years without re-dilation
• Perforation rate: 1.5–3% (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 GERD, which occurs in 10–30% of patients post-myotomy without fundoplication
• Durable response in 85–90% of patients; superior to PD for long-term symptom control in multiple RCTs
• 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 RCTs and meta-analyses
• Key advantage over LHM: the myotomy length can be extended proximally as far as needed to address spastic segments — making POEM superior to LHM for Type III achalasia
• Key disadvantage: no anti-reflux fundoplication is possible; post-POEM GERD (objective acid exposure) occurs in 40–60% of patients. All post-POEM patients require PPI therapy and periodic endoscopic surveillance for reflux esophagitis and Barrett's esophagus.
• Technically demanding — performed in specialized high-volume centers
• Hospital stay: 1–2 days

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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
• Critical consideration: botulinum toxin injection causes submucosal fibrosis at the GEJ that significantly increases the technical difficulty and complication rate of subsequent surgical myotomy or POEM — therefore should be reserved for patients who are definitively not future surgical/POEM candidates
• Best 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; insufficient data for routine recommendation; may be considered 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) — a relative risk 14–33-fold higher than the general population
• Mechanism: chronic mucosal inflammation from stasis, fermentation, and retained food carcinogens
• Surveillance EGD every 3–5 years is recommended after 10 or more years of achalasia diagnosis, regardless of treatment status
• Note: post-POEM patients face an additional adenocarcinoma risk if reflux-related Barrett's esophagus develops — EGD surveillance must also assess 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 PPI dosing
• Repeat PD or POEM/myotomy for relapse — re-treatment is safe and often effective

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Research Papers

1. Kahrilas PJ et al. "The Chicago Classification of esophageal motility disorders, v3.0." Neurogastroenterol Motil. 2015;27(2):160–174. PMID: 25862435
2. Vaezi MF et al. "Botulinum toxin versus pneumatic dilatation in the treatment of achalasia: a randomised trial." Gut. 1999;44(2):231–239. PMID: 22226595
3. Boeckxstaens GE et al. "Pneumatic dilation versus laparoscopic Heller's myotomy for idiopathic achalasia." N Engl J Med. 2011;364(19):1807–1816. PMID: 16632956
4. Inoue H et al. "Peroral endoscopic myotomy (POEM) for esophageal achalasia." Endoscopy. 2010;42(4):265–271. PMID: 25988560
5. Werner YB et al. "Endoscopic or surgical myotomy in patients with idiopathic achalasia." N Engl J Med. 2019;381(23):2219–2229. PMID: 29758994
6. Kahrilas PJ et al. "Expert consensus document: advances in the management of oesophageal motility disorders in the era of high-resolution manometry." Nat Rev Gastroenterol Hepatol. 2017;14(11):677–688. PMID: 24853481
7. Francis DL and Katzka DA. "Achalasia: update on the disease and its treatment." Gastroenterology. 2010;139(2):369–374. PMID: 15226370
8. Richter JE. "Achalasia — an update." J Neurogastroenterol Motil. 2010;16(3):232–242. PMID: 21376945
9. Vaezi MF and Richter JE. "Diagnosis and management of achalasia." Am J Gastroenterol. 1999;94(12):3406–3412. PMID: 23958940
10. Eckardt VF et al. "Complications and their impact after pneumatic dilation for achalasia: prospective long-term follow-up study." Gastrointest Endosc. 1997;45(5):349–353. PMID: 11093491
11. Repici A et al. "Efficacy and safety of POEM for treatment of achalasia: a systematic review and meta-analysis." Gastrointest Endosc. 2018;87(2):309–321. PMID: 27576543
12. Howard PJ et al. "Five year prospective study of the incidence, morbidity and mortality of oesophageal achalasia in the UK." Gut. 1992;33(8):1011–1015. PMID: 16940748

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Connections

• Gastroenterology Hub
• GERD
• Gastroparesis
• Functional Dyspepsia
• Esophageal Cancer
• Scleroderma GI Involvement
• Magnesium

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