A. Etiology

1. This is a disease of abnormal esophageal motility
   1. Lower Esophageal Sphincter (LES) fails to relax during swallowing
   2. Elevated resting LES pressure (that is, contracted sphincter)
   3. Absense of normal peristalsis in distal 2/3 of esophageal body
2. Esophageal dilatation - due to lack of ganglionic plexus, obstruction
3. Abnormal Neural Inputs [3]
   1. Achalasia is due to loss of myoenteric neurons or to dysfunction of inhibitory neurons
   2. Inhibitory neurons contain vasoactive intestinal polypeptide and nitric oxide
   3. Congenital losses of nerve control are most common (compare Hirchsprung's Disease)
   4. Relative preservation of cholinergic innervation
4. Pathogenesis
   1. Approximately 65% of patients with achalasia have autoantibodies against DARPP-32
   2. DARPP-32 is a dopamine carrying protein on surface of myenteric plexus cells

B. Epidemiology

1. Incidence ~1/100,000 (approximately 2000 patients in USA)
2. Peak onset in 3rd and 4th decades
3. Can affect all ages
4. No gender/ethnic prediliction
5. Disease Associations
   1. Idiopathic / Congenital
   2. Paraneoplastic Syndromes
   3. Chagas' Disease
   4. Parkinson's Disease
   5. Various familial syndromes - Allgrove's, Hereditary Ataxia, Familial Achalasia

C. Symptoms

1. Dysphagia to BOTH solids and liquids
2. Retention and regurgitation of liquids and solids
3. Weight loss
4. Atypical chest pain

D. Diagnosis

1. Esophageal Manometry
2. Barium Swallow: "parrot beak deformity" with dilated esophagus
3. Chest Radiograph
   1. Widened mediastinum
   2. Posterior mediastinal air fluid level
4. Differential (motility disorders)
   1. Diffuse Esophageal Spasm - usually has pain, manometry different
   2. Scleroderma - usually has pain due to reflux, decreased or absent tone in LES
   3. Stricture - Schatzsky's Ring, Radiation Esophagitis, Reflux Disease, Maliganancy

E. Treatment [4,5,6]

1. Medications
   1. Not very effective
   2. Smooth muscle dilators: eg. nitroglycerin, calcium chanel blockers
2. Pneumatic Dilatation [4,7]
   1. 200 mm Hg balloon dilatation (3.0-3.5cm balloon)
   2. Try twice if doesn't work at first
   3. Remission rates over 12 months ~70%
   4. Common to repeat procedure (63% after 10 years)
3. Myotomy [4]
   1. 90% effective - "Heller" method
   2. Reflux esophagitis occurs
   3. Anti-reflux surgery = modified Heller method
   4. Less frequent repeat procedures (37% at 10 years) than pneumatic dilatation
4. Botulinum Toxin
   1. Intramuscular (LES) injection of butulinum toxin
   2. Effective in decreasing symptoms 1 week after injection; lasts >6 months [8]
   3. ~90% of patients will respond initially; 65% >3 months [8]
   4. Efficacy drops off after 12 months (~30% symptomatic remissions) [7]
   5. After 28 months, nearly all patients relapse; some respond to reinjection [8]
   6. Late failures are more common with botulinum toxin than with pneumatic dilatation [7]
   7. Appears to be safe, but long term side effects unknown [9]
5. Note that Cola beverages often helps loosen LES and may improve symptoms

References

1. Richter JE. 2001. Lancet. 358(9284):823
2. Mittal RK and Balaban DH. 1997. NEJM. 336(13):924
3. Goyal RK and Hirano I. 1996. NEJM. 334(17):1106
4. Lopushinsky SR and Urbach DR. 2006. JAMA. 296(18):2227
5. Pasricha PJ, Ravich WJ, Hendrix TR, et al. 1995. NEJM. 332(12):774
6. Sandler RS, Nyren O, Ekbom A, et al. 1995. JAMA. 274(17):1359
7. Vaezi MF, Richter JE, Wilcox CM, et al. 1999. Gut. 44:231
8. Pasricha PJ, Rai R, Ravich WJ, et al. 1996. Gastroenterol. 110:1410
9. Cosmetic Use of Botulinum Toxin. 1999. Med Let. 41(1057):63