Diffuse esophageal spasm

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Madhu Sigdel M.B.B.S.[2]

Diffuse or Distal esophageal spasm (DES) is an uncommon esophageal motility disorder causing chest pain and/or dysphagia. DES was first described by Osgood, in 1889 in 6 patients presenting with chest pain and dysphagia. Creamer et al. (1958) made the first manometric descriptions of DES. Development of high resolution esophageal manometry in 2000 has led to classification of esophageal motility disorders. Diffuse esophageal spasm can be classified as primary or secondary based on presence or absence of other disease associated with it. The exact pathogenesis of DES is not fully understood. Current high-resolution manometric studies suggests impairment of inhibitory neurons. These inhibitory neurons use nitric oxide (NO) as neurotransmitter. Exact cause of diffuse esophageal spasm is unknown. However, may be caused by consequence of various diseases and secondary to conditions like compression of nerves within esophageal wall, inflammation of the esophagus, stricture, GERD, psychological conditions like anxiety or depression. Diffuse esophageal spasm must be differentiated from other diseases that cause dysphagia, chest pain and weight loss such as angina, reflux esophagitis, esophageal carcinoma, systemic sclerosis, nutcracker esophagus, hypertensive LES, esophageal web/stricture, pseudoachalasia, stroke, esophageal candidiasis, Chagas disease etc. Common risk factors in the development of Diffuse Esophageal Spasm include: Age (60-80 years), obesity, mitral valve prolapse, presence of GERD, Hypertension, anxiety or depression, and drinks (eg. red wine, very hot or cold liquid or fluid). If left untreated, most patients are symptom free over the course of time. Very few cases report of progression to achalasia and nut cracker esophagus. The diagnostic study of choice for DES is manometry. An x-ray of esophagus after barium swallow (esophagogram) is the next best test to support manometric diagnosis. The mainstay of treatment for DES is medical therapy with calcium channel blockers, and/or tricyclic antidepressants.

Esophagus was described by Vasalius in 1543. Diffuse esophageal spasm was first described by Osgood in 1889 in 6 patients presenting with chest pain and dysphagia. Development of high resolution esophageal manometry in 2000 has led to classification of esophageal motility disorders.

Diffuse esophageal spasm can be classified as primary or secondary based on its association with other diseases.

The exact pathogenesis of DES is not fully understood. Current high-resolution manometric studies suggests impairment of inhibitory neurons. These inhibitory neurons use nitric oxide (NO) as neurotransmitter.

Exact cause of diffuse esophageal spasm is unknown. However, may be caused by consequence of various diseases and secondary to conditions like compression of nerves within esophageal wall, inflammation of the esophagus, strictures, GERD, and psychological conditions like anxiety or depression.

Diffuse esophageal spasm must be differentiated from other diseases that cause dysphagia, chest pain and weight loss such as angina, reflux esophagitis, esophageal carcinoma, systemic sclerosis, nutcracker esophagus, hypertensive LES, esophageal web/stricture, pseudoachalasia, stroke, esophageal candidiasis and Chagas disease etc.

Diffuse esophageal spasm is relatively uncommon disease with incidence of 1 per 100,000 in the USA. DES affects all age groups. There is no racial predilection to DES.

Common risk factors in the development of diffuse esophageal spasm include age (60-80 years), obesity, mitral valve prolapse, presence of GERD, hypertension, anxiety or depression, and drinks (eg. red wine, very hot or cold liquid or fluid).

There is insufficient evidence to recommend routine screening for DES.

If left untreated, most patients remain asymptomatic over the course of time. Very few cases report progression to Achalasia and nut cracker esophagus.

The diagnostic study of choice for DES is manometry.

The hallmark of DES is esophageal dysphagia for both solids and liquids and chest pain. Symptom onset is sudden, intermittent and non-progressive in nature. Chest pain usually retrosternal in location, which is intense and squeezing in nature and may be mistaken for Angina. Difficulty swallowing, is sometimes related to specific substances like red wine, very cold or hot liquid.

Patients with primary diffuse esophageal spasm usually appear normal. Physical examination of patients with DES is usually remarkable for findings related to secondary diseases.

There are no diagnostic laboratory findings associated with DES.

There are no ECG findings associated with DES.

An x-ray of esophagus after barium swallow (esophagogram) is the next best test to support manometric diagnosis.

There are no echocardiography/ultrasound findings associated with DES.

Chest CT scan may be helpful in the diagnosis of DES. Findings on CT scan suggestive of DES include esophageal wall thickening.

There are no MRI findings associated with diffuse esophageal spasm.

Endoscopy may be helpful in the diagnosis of DES to exclude other esophageal lesion causing chest pain.

24-hour esophageal pH monitoring may be helpful in the diagnosis of secondary DES.

The mainstay of treatment for DES is medical therapy with calcium channel blockers, and/or tricyclic antidepressants.

The mainstay of treatment for DES is medical therapy. Surgery is usually reserved for patients with manometrically proven, symptomatic and those cases refractory to medical therapy.

There are no established measures for the primary prevention of diffuse esophageal spasm.

There are no secondary preventive measures available for insulinoma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Madhu Sigdel M.B.B.S.[2]

DES was first described by Osgood, in 1889 in 6 patients presenting with chest pain and dysphagia. Development of high resolution esophageal manometry in 2000 has led to classification of esophageal motility disorders.

• In 1543: Vesalius, a Belgian anatomist was the first to describe the anatomy of the esophagus.

• In 1674: T. Willis, an English physician used whale bone to dilate the esophagus.
• In 1806: Philipp Bozzini, a German physician develops an early endoscope using a mirror and reflected light from a candle in an attempt to see the upper esophagus.
• In 1843: Switzer, a Denmark physician invented esophageal dilators.
• In 1844: John Watson, an American surgeon first performed esophagotomy for the relief of esophageal stricture.
• In 1872: Christian Albert Theodor Billroth, an Austrian surgeon performed the first excision of the esophagus.
• In 1883: H. Kronecker and S. Meltzer first used inserted balloons to describe esophageal motility and pressure measurements.
• In 1954: L.R. Celestin first developed an esophageal tube for the treatment of malignant dysphagia.
• DES was first described by Osgood, in 1889 in 6 patients presenting with chest pain and dysphagia.

• In 2000, development of high resolution esophageal manometry has led to classification of esophageal motility disorders.
  

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Madhu Sigdel M.B.B.S.[2]

Diffuse esophageal spasm can be classified as primary or secondary based on association with other diseases.

• Diffuse esophageal spasm may be classified according to presence or absence of other diseases into 2 subtypes/groups:^[1]
  • Primary
  • Secondary
    • Chagas disease
    • Systemic sclerosis
    • Diabetes
    • Chronic idiopathic intestinal pseudo-obstruction
    • Chronic gastroesophageal reflux disease

• It is also categorized as one of the major disorders of peristalsis according to The Chicago Classification v.3.0.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Madhu Sigdel M.B.B.S.[2]

The exact pathogenesis of DES is not fully understood. Current high-resolution manometric studies suggests impairment of inhibitory neurons. These inhibitory neurons use nitric oxide (NO) as neurotransmitter.

The exact pathogenesis of DES is not fully understood. However, current high-resolution manometric studies suggest impairment of inhibitory myenteric plexus neurons in DES.^[1] These neurons use nitric oxide (NO) as neurotransmitter.^[2] Hence, these patients may also have dysregulation of endogenous NO synthesis or/and degradation. Inhibitory neurotransmitters are nitric oxide (NO), vaso-active intestinal peptide (VIP) and ATP whereas excitatory neurotransmitter are acetyl choline (ACh), glutamate and substance P.^[3] Anti-ganglionic acetylcholine receptor antibodies (anti-gAChR-Abs) are reported in some cases.^[4] The final result is premature and rapidly propagated or simultaneous contraction of smooth muscles of distal esophagus.

There are reports of families with Achalasia and esophageal spasm which supports the hypothesis that genetic traits may play role in pathogenesis of DES as well as association between the two disorders.^[5] However, genetic inheritance is not fully established.

DES occurs in association with other motility disorders of esophagus like achalasia. Esophageal epiphrenic diverticulum is also commonly associated with DES.^[6]

On gross pathology, gross thickening of muscularis propria layer and LES than normal subjects are characteristic findings of DES.^[7] This gross thickening is due to hyperplasia (not hypertrophy).

On microscopic histopathological analysis, degeneration of vagal fibres, inflammatory infiltration of myenteric plexus, and hyperplasia of smooth muscles are characteristic findings of DES. Data on microscopic pathology of DES are limited due to rarity of disease and even less common need of surgery as a treatment.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Madhu Sigdel M.B.B.S.[2]

Exact cause of diffuse esophageal spasm is unknown. However, may be caused by consequence of various diseases and secondary to conditions like compression of nerves within esophageal wall, inflammation of the esophagus, strictures, GERD, and psychological conditions like anxiety or depression.

The exact cause of esophageal spasms remains unknown. However, it may be a consequence of various diseases and arise secondary to these conditions. Esophageal spasms may be more likely to occur with one or more of the following conditions:^[1]

• Compression of the nerves within the esophageal wall by solid masses or enlarged blood vessels.
• Esophagitis which is an inflammation of the esophagus. It is commonly caused by gastroesophageal reflux disease (GERD) and infections.
• Sandifer syndrome which is closely associated with GERD.
• Crohn’s disease of the esophagus marked by inflammation and ulceration of the esophageal wall.
• Dermatomyositis, multiple sclerosis and amyotrophic lateral sclerosis.
• Esophageal strictures or obstructions.
• Depression, anxiety and psychological stress.
• Eating disorders involving purging.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Madhu Sigdel M.B.B.S.[2]

Diffuse esophageal spasm must be differentiated from other diseases that cause dysphagia, chest pain and weight loss such as angina, reflux esophagitis, esophageal carcinoma, systemic sclerosis, nutcracker esophagus, hypertensive LES, esophageal web/stricture, pseudoachalasia, stroke, esophageal candidiasis and Chagas disease etc.

Diffuse esophageal spasm must be differentiated from other diseases that cause dysphagia, chest pain and weight loss such as angina, reflux esophagitis, esophageal carcinoma, systemic sclerosis, nutcracker esophagus, hypertensive LES, esophageal web/stricture, pseudoachalasia, stroke, esophageal candidiasis and Chagas disease etc.^{[1][2][3][4][5][6][7][8][9][10][11]}

Disease	Signs and Symptoms								Barium esophagogram	Endoscopy	Other imaging and laboratory findings	Gold Standard
	Onset	Dysphagia			Weight loss	Heartburn	Other findings	Mental status
		Solids	Liquids	Type
Plummer-Vinson syndrome	Gradual	+	–	Non progressive	+/-	–	Glossitis Koilonychia	Normal	Thin projections on the anterior esophageal wall Multiple upper esophageal constrictions	Direct visualization of esophageal webs Superior to esophagogram {{#ev:youtube|HFfsTgsB6Pg}}	Videofluoroscopy shows mucosal and submucosal foldings	Triad of Iron deficiency anemia Esophageal webs Glossitis
Esophageal stricture	Gradual Sudden onset	+	–	Progressive	+/-	+/-	Odynophagia Cough Chest pain	Normal	Sacculations Fixed transverse folds Esophageal intramural pseudodiverticula	Mucosal edema Circumferential thickening in GERD Pale mucosa with white exudate in lymphocytic esophagitis Swelling and hemorrhagic congestion in caustic ingestion {{#ev:youtube|vax5E-jMnQ}}	Manometry may show dysmotility CT scan for staging malignant strictures	Barium esophagogram
Diffuse esophageal spasm	Sudden	+	+	Non progressive	+	+	Chest pain	Normal	Nonperistaltic and nonpropulsive contractions Corkscrew or rosary bead esophagus	Inconclusive {{#ev:youtube|2ipA34iMA3c}}	Manometry shows high-amplitude esophageal contractions CT scan may show hypertrophy of esophageal muscles	Manometry
Achalasia	Gradual	+	+	Non progressive	+/-	–	Regurgitation of undigested food Chest pain	Normal	“Bird’s beak” or “rat tail” appearance Dilated esophageal body Air fluid level (absent peristalsis) Absence of an intragastric air bubble	Dilated esophagus Residual food fragments Normal mucosa {{#ev:youtube|ydLcskQzEjM}}	Residual pressure of LES > 10 mmHg Incomplete relaxation of the LES Increased resting tone of LES Aperistalsis	History of dysphagia with positive endoscopy and manometry
Systemic sclerosis	Gradual	+	+	Progressive	+/-	+	Muscle and joint pain Raynaud’s phenomenon Skin changes	Normal	Dysmotility Patulous esophagus	Mucosal damage Peptic stricture (advanced cases)	Positive serology for Antinuclear antibodies Rheumatoid factor Creatine kinase ESR	Skin biopsy
Zenker’s diverticulum	Gradual	+	–		+/-	–	Food regurgitation Halitosis Cough Hoarseness	Normal	Thin projections on esophageal wall over Killian’s triangle	Outpouching of posterior pharyngeal wall Exclude the presence of SCC {{#ev:youtube|FdEruFsNdVA}}	CT & MRI shows out-pouching over the posterior esophagus in the Killian’s triangle	Barium esophagography
Esophageal carcinoma	Gradual	+	+	Progressive	+	+/-	Lymphadenopathy Cachexia	Normal	Irregular stricture Pre-stricture dilatation	Esophageal obstruction Staging of disease {{#ev:youtube|5ucSlgqGAno}}	CT and PET scan is an optional test for staging of the disease	Biopsy
Stroke (Cerebral hemorrhage)	Sudden	+	+	Progressive	+	+/-	Dysarthria Limb weakness Fatigue	Impaired	Pooling of contrast in the pharynx Aspiration of barium contrast into the airway	Reduced opening of upper esophageal sphincter Reduced larynx elevation	CT without contrast shows acute hemorrhage as a hyperattenuating clot	CT without contrast
Motor disorders (Myasthenia gravis)	Gradual	+	+	Progressive	+/-		Ptosis Diplopia Fatigue	Normal	Stasis in pharynx and pooling in pharyngeal recesses	Velopharyngeal insufficiency Delayed swallowing function	CT may show anterior mediastinal mass (thymoma) Positive tensilon test	Anti–acetylcholine receptor antibody test
GERD	Gradual Sudden onset	+	–	Progressive	+/-	+	Cough Hoarseness	Normal	Free acid reflux Esophagitis with scarring Strictures Barrett’s oesophagus	Erythema, erosions and ulceration Barrett’s esophagus	Esophageal manometry may show decreased tone of LES	24 hour esophageal pH monitoring
Esophageal web	Gradual	+	+/-	Progressive	–	+/-	Findings of the underlying cause such as iron deficiency anemia or bullous pemphigoid	Normal	Symmetrical narrowing of the esophagus	Smooth membrane not encircling the whole lumen	Videofluoroscopy shows mucosal and submucosal foldings	Barium esophagogram

			Manifestations		Diagnostic tools
	Achalasia		Dyspnea[12] Dysphagia for solids and liquids is the most common feature, being seen in 91 % and 85% of patients respectively[2] Regurgitation of undigested food occurs in 76-91% of patients[2] Cough mainly when lying down in 30%[2]		Esophagogastroduodenoscopy findings include a dilated esophagus with residual food fragments, normal mucosa and occasionally candidiasis (due to the prolonged stasis). Barium swallow shows the characteristic bird’s beak appearance.
	GERD		Retrosternal burning chest pain. Cough and hoarseness of voice. May present with complications such as strictures and dysphagia.[3]		Upper GI endoscopy shows the complications such as esophagitis and barret esophagus. Esophageal manometry may show decreased tone of the lower esophageal sphincter. 24-hour esophageal pH monitoring may be done to confirm the diagnosis.
	Esophageal carcinoma		Dysphagia Odynophagia– fluids and soft foods are usually tolerated, while hard or bulky substances (such as bread or meat) cause much more difficulty[4] Weight loss Pain, often of a burning nature, may be severe and worsened by swallowing, and can be spasmodic in character Nausea and vomiting[4]		Upper GI endoscopy and esophageal biopsy the gold standard for the diagnosis of esophageal
	Esophageal stricture		Patient may present with the symptoms of the underlying GERD. Dysphagia and odynophagia.[7]		Barium esophagography provides information about the site and the diameter of the stricture before the endoscopic intervention.[8]
	Plummer-Vinson syndrome		Common symptoms of Plummer-Vinson syndrome include:[9][10][11] Difficulty swallowing (more for solids) Weakness Pain Burning sensation in mouth Dry tongue Painful cracks in the angles of a dry mouth Pale color of the skin Less common symptoms Cold intolerance Reduced resistance to infection Altered behavior Craving for for unusual items (such as ice or cold vegetables)		Lab tests are consistent with the diagnosis of iron deficiency anemia. Findings on an x-ray (barium esophagogram) suggestive of esophageal web/strictures associated with Plummer-Vinson syndrome appear as either: Thin projections on the anterior esophageal wall. Multiple upper (cervical) esophageal constrictions consistent with esophageal webs.

References

1. ↑ Ferri, Fred (2015). Ferri’s clinical advisor 2015 : 5 books in 1. Philadelphia, PA: Elsevier/Mosby. ISBN 978-0323083751.
2. ↑ ^{2.0 2.1 2.2 2.3} Boeckxstaens GE, Zaninotto G, Richter JE (2013). “Achalasia”. Lancet. doi:10.1016/S0140-6736(13)60651-0. PMID 23871090.CS1 maint: Multiple names: authors list (link)
3. ↑ ^{3.0 3.1} Badillo R, Francis D (2014). “Diagnosis and treatment of gastroesophageal reflux disease”. World J Gastrointest Pharmacol Ther. 5 (3): 105–12. doi:10.4292/wjgpt.v5.i3.105. PMC 4133436. PMID 25133039.
4. ↑ ^{4.0 4.1 4.2} Napier KJ, Scheerer M, Misra S (2014). “Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities”. World J Gastrointest Oncol. 6 (5): 112–20. doi:10.4251/wjgo.v6.i5.112. PMC 4021327. PMID 24834141.
5. ↑ Matsuura H (2017). “Diffuse Esophageal Spasm: Corkscrew Esophagus”. Am. J. Med. doi:10.1016/j.amjmed.2017.08.041. PMID 28943381.
6. ↑ Lassen JF, Jensen TM (1992). “[Corkscrew esophagus]”. Ugeskr. Laeg. (in Danish). 154 (5): 277–80. PMID 1736462.CS1 maint: Unrecognized language (link)
7. ↑ ^{7.0 7.1} Ruigómez A, García Rodríguez LA, Wallander MA, Johansson S, Eklund S (2006). “Esophageal stricture: incidence, treatment patterns, and recurrence rate”. Am. J. Gastroenterol. 101 (12): 2685–92. doi:10.1111/j.1572-0241.2006.00828.x. PMID 17227515.
8. ↑ ^{8.0 8.1} Shami VM (2014). “Endoscopic management of esophageal strictures”. Gastroenterol Hepatol (N Y). 10 (6): 389–91. PMC 4080876. PMID 25013392.
9. ↑ ^{9.0 9.1} López Rodríguez MJ, Robledo Andrés P, Amarilla Jiménez A, Roncero Maíllo M, López Lafuente A, Arroyo Carrera I (2002). “Sideropenic dysphagia in an adolescent”. J. Pediatr. Gastroenterol. Nutr. 34 (1): 87–90. PMID 11753173.
10. ↑ ^{10.0 10.1} Chisholm M (1974). “The association between webs, iron and post-cricoid carcinoma”. Postgrad Med J. 50 (582): 215–9. PMC 2495558. PMID 4449772.
11. ↑ ^{11.0 11.1} Larsson LG, Sandström A, Westling P (1975). “Relationship of Plummer-Vinson disease to cancer of the upper alimentary tract in Sweden”. Cancer Res. 35 (11 Pt. 2): 3308–16. PMID 1192404.
12. ↑ Ferri, Fred (2015). Ferri’s clinical advisor 2015 : 5 books in 1. Philadelphia, PA: Elsevier/Mosby. ISBN 978-0323083751.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Madhu Sigdel M.B.B.S.[2]

Diffuse esophageal spasm is relatively uncommon disease with incidence of 1 per 100,000 in the USA. DES affects all age groups. There is no racial predilection to DES.

• The incidence of DES is approximately 1 per 100,000 individuals in USA.^[1]

• The prevalence of DES is 400 per 100,000 patients referred for esophageal symptoms; 7 per 100 morbidly obese patients undergoing bariatric surgery, 2-7% among patients with known cardiac diseases.^[2][3]
• Large series of patients undergoing esophageal motility testing for related symptoms had prevalence of DES 400-1,000 per 100,000.^[4]

• There are no reported cases of mortality due to DES.

• Patients of all age groups may develop DES, but limited study results shows more common in age group 60-80 years and the prevalence of disease increases with age.

• There is no racial predilection to DES.

• Females are more commonly affected by DES than male.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Madhu Sigdel M.B.B.S.[2]

Common risk factors in the development of diffuse esophageal spasm include age (60-80 years), obesity, mitral valve prolapse, presence of GERD, hypertension, anxiety or depression, and drinks (eg. red wine, very hot or cold liquid or fluid).

Common risk factors in the development of diffuse esophageal spasm include:

• Age (60-80 years)

• Obesity

• Mitral valve prolapse

• Presence of GERD

• Hypertension

• Anxiety or depression

• Drinks (eg. red wine, very hot or cold liquid or fluid)^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Madhu Sigdel M.B.B.S.[2]

There is insufficient evidence to recommend routine screening for DES.

There is insufficient evidence to recommend routine screening for DES

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Madhu Sigdel M.B.B.S.[2]

If left untreated, most patients remain asymptomatic over the course of time. Very few cases report progression to Achalasia and nut cracker esophagus.

• DES is generally non-progressive, if left untreated there are very few case reports of progression to Achalasia and nut cracker esophagus.

• Common complications of DES include:
  • Achalasia
  • Nut cracker esophagus

• Prognosis is generally excellent and the disease has no mortality recorded.