Achalasia

Definition

1. Impaired LES relaxation with swallowing
2. Aperistalsis (absent peristalsis) in the smooth-muscle esophagus

Pathophysiology

• Inhibitory neurons (releasing NO and VIP) are lost first - they normally mediate LES relaxation and propagated peristalsis. Their destruction explains both key defects.
• Excitatory cholinergic neurons may also be impaired (partial preservation explains why botulinum toxin can help).
• Ganglion cell loss is progressive. The proposed disease sequence: EGJ outflow obstruction → Type II achalasia → Type I achalasia → end-stage (massive dilation).
• Type III appears distinct, with myenteric plexus inflammation and altered function rather than frank cell destruction.
• The ultimate cause is thought to be an autoimmune process in genetically susceptible individuals, likely triggered by latent HSV-1 infection. Cytotoxic T cells dominate the myenteric infiltrate, and anti-neuronal antibodies are found in patient sera, especially with specific HLA alleles.

Chicago Classification (HRM Subtypes)

Clinical Features

• Dysphagia: Universal. Both solids AND liquids. Onset is insidious (often present for years before diagnosis). Fluctuates, then plateaus.
• Regurgitation: Nonbilious, nonacid, mixed with copious saliva; food from hours or days earlier.
• Chest pain: In ~2/3 of patients early in disease; may spontaneously improve over time. Less responsive to treatment than dysphagia.
• Weight loss: Present in advanced disease.
• Heartburn: Paradoxically common complaint - but 24-hour pH studies show esophageal acidification from bacterial fermentation of retained food, NOT true GERD.
• Bronchopulmonary complications (recurrent aspiration, pneumonia): Up to 10% of advanced cases.
• Airway compromise/stridor: Rare; from dilated esophagus compressing the membranous trachea.
• Halitosis, hiccups: Also reported.

Diagnosis

Barium Swallow

• Classic "bird-beak" or "rat-tail" tapering at the GEJ with a dilated proximal esophagus.
• In end-stage: sigmoid deformity of the esophagus.

Esophageal Manometry (Gold Standard)

• Absent peristalsis in the smooth-muscle esophagus.
• Incomplete LES relaxation (elevated integrated relaxation pressure on HRM).
• HRM allows subtyping (Types I-III above).

Upper Endoscopy

• Essential to exclude pseudoachalasia (malignancy at the GEJ mimicking achalasia).
• Findings: dilated esophagus, residual food/fluid, tight LES that may "pop" open to endoscope.

Differential Diagnosis

• Pseudoachalasia: Malignancy (especially adenocarcinoma at GEJ), infiltrative disease - must be excluded, especially if age >60 or rapid weight loss.
• Chagas disease (Trypanosoma cruzi): Clinically and manometrically indistinguishable from idiopathic achalasia; distinguished by serology/PCR and multi-organ involvement (megacolon, cardiomyopathy). Endemic in South America.
• Distal esophageal spasm, EGJOO, scleroderma.

Treatment

1. Pharmacologic (Temporizing only)

• Calcium channel blockers (sublingual nifedipine 30-40 mg/day before meals) or nitrates (isosorbide dinitrate): reduce LES pressure. Limited efficacy, frequent side effects (headache, flushing, hypotension). Suitable only as short-term bridge therapy.
• Sildenafil (50 mg): blocks PDE-5, raises cGMP/NO, reduces LES pressure. Peaks at 15-20 min; effect lasts <1 hour. Limited by cost and side effects.

2. Botulinum Toxin Injection

• Intrasphincteric injection of 80-100 units into 4 quadrants of the LES via endoscope.
• Irreversibly blocks ACh release from presynaptic terminals.
• ~66% improve initially; minimal efficacy at 1 year. Repeat injection causes fibrosis.
• Best reserved for elderly or medically frail patients who are poor candidates for dilation or surgery.

3. Pneumatic Dilation

• Distends the LES to ≥3 cm using non-compliant Rigiflex balloons (3.0, 3.5, 4.0 cm) under fluoroscopic guidance, disrupting the circular muscle.
• Done outpatient under conscious sedation.
• Efficacy ~90% overall. Particularly effective for Type II (100% response in European RCT vs. 93% for Heller myotomy).
• Main risk: esophageal perforation (~1%).
• Often done in a graded fashion (start with 3.0 cm, escalate if needed).

4. Laparoscopic Heller Myotomy (LHM)

• Surgical division of the LES circular muscle fibers, typically extended 6 cm onto the esophagus and 2-3 cm onto the stomach.
• Almost always combined with an antireflux procedure (partial fundoplication - Dor or Toupet) to prevent post-operative GERD.
• Efficacy ~90%. Best for Type III achalasia (86% vs. 40% for pneumatic dilation).
• Risk of perforation ~1%, comparable to dilation.

5. Per-Oral Endoscopic Myotomy (POEM)

• Endoscopic technique: submucosal tunnel created from mid-esophagus to stomach; circular muscle fibers divided from inside.
• Particularly well-suited for Type III achalasia (allows longer myotomy extending onto the esophageal body).
• Efficacy comparable or superior to LHM. Higher post-operative GERD rate (lacks fundoplication).

Summary of treatment by subtype:

Complications of Untreated Achalasia

• Esophageal dilatation and sigmoid deformity
• Recurrent aspiration pneumonia
• Esophageal squamous cell carcinoma (long-term risk, ~3-fold increase, from chronic mucosal irritation by retained food)
• Malnutrition

Achalasia vs. Chagas Disease (Quick Comparison)