Plummer-Vinson syndrome

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

The Plummer-Vinson syndrome, also called Paterson-Brown-Kelly syndrome or sideropenic dysphagia is a disorder linked to severe, long-term iron deficiency anemia, which leads to dysphagia, glossitis and esophageal webs. The disease is named after two American physicians Henry Stanley Plummer, and Porter Paisley Vinson. It is also called “Kelly-Paterson syndrome”, named after two British otolaryngologists, Adam Brown-Kelly and Donald Ross Paterson. The exact pathogenesis of Plummer-Vinson syndrome is not fully understood. It is postulated that Plummer-Vinson syndrome results from iron deficiency. Other possible factors include malnutrition, genetic predisposition and autoimmune disorders. On gross pathology, esophageal web and esophageal strictures are characteristic findings of Plummer-Vinson syndrome. On microscopic histopathological analysis, Plummer-Vinson syndrome presents with epithelial atrophy, chronic submucosal inflammation and epithelial atypia or dysplasia (in advanced cases). There are no established risk factors for Plummer-Vinson syndrome. However, chronic irritation of the esophagus may predispose to an increased risk of developing esophageal webs or strictures. Plummer-Vinson syndrome is a rare disease and the data pertaining to its incidence and prevalence is not evidently available. Overall improvement in nutritional status with better medical care has markedly reduced the number of cases of Plummer-Vinson syndrome. Common complications of Plummer-Vinson syndrome include hypopharyngeal cancer, esophageal cancer and malignant lesions of oral mucosa. Plummer-Vinson syndrome must be differentiated from other diseases that cause dysphagia such as reflux esophagitis, esophageal carcinoma, systemic sclerosis, esophageal spasm, pseudoachalasia, stroke, esophageal candidiasis, Zenker’s diverticulum and Chagas disease. Physical examination of patients with Plummer-Vinson syndrome is usually remarkable for glossitis, esophageal webs or strictures, and dysphagia. Laboratory findings consistent with the diagnosis of Plummer-Vinson syndrome include presence of iron deficiency anemia. The diagnosis of Plummer-Vinson syndrome is made in the presence of iron-deficiency anemia with esophageal webs, dysphagia and glossitis. An x-ray (barium esophagogram) is the best initial imaging study in a patient suspected with Plummer-Vinson syndrome. Other imaging studies include a videofluoroscopy or an esophagogastroduodenoscopy to visualise the esophageal webs. The mainstay of treatment for Plummer-Vinson syndrome is aimed at correcting iron deficiency anemia. Effective measures for the prevention of Plummer-Vinson syndrome include good nutrition with adequate intake of iron rich foods and an upper gastrointestinal endoscopy every year to rule out malignant transformation.

Plummer-Vinson syndrome was first discovered by Henry Plummer an American internist, in a case series of patients with long-standing iron deficiency anemia, dysphagia and spasm of the upper esophagus without anatomic stenosis in his article “Diffuse dilatation of the esophagus without anatomic stenosis.” In the year 1919, Porter Paisley Vinson an American surgeon at the Mayo Clinic further described Plummer-Vinson syndrome in his article “A case of cardiospasm with dilatation and angulation of the esophagus.” He reported a case of angulation of esophagus and attributed his findings to be consistent as described by Henry Plummer. In the year 1919, Donald Ross Patterson and Adam Brown Kelly, both British otolaryngologists described the characteristic clinical features of Plummer-Vinson syndrome in their article “A clinical type of dysphagia” and “Spasm at the entrance of the esophagus” respectively.

There is no established system for the classification of Plummer-Vinson syndrome.

Plummer-Vinson syndrome is a rare condition characterized by iron-deficiency anemia, glossitis and dysphagia. The exact pathogenesis of Plummer-Vinson syndrome is not fully understood. It is postulated that Plummer-Vinson syndrome results from iron deficiency. Other possible factors include malnutrition, genetic predisposition and autoimmune disorders. In patients with iron deficiency, the iron-dependent oxidative enzymes are unable to function at optimum level and the dependent metabolic pathways (oxidative phosphorylation) are reduced. This promotes anaerobic metabolism with increased consumption of glucose and increased production of lactic acid and may lead to myasthenic changes in muscles. These myasthenic changes are often seen in muscles involved in swallowing and may lead to atrophy of the esophageal mucosa and formation of esophageal webs. Patients who do not exhibit obstructive lesions (web or stricture) may have dysphagia resulting from muscular in-coordination. Patients with iron deficiency have low levels of myoglobin which may affect the muscles of the tongue and lead to glossitis. In Plummer-Vinson syndrome, deficiency of iron can lead to epithelial atrophy and a decrease in the regenerative capacity of the mucosa. The decrease in rate of healing allows the chronic irritants to act progressively, predisposing the oral cavity and esophagus to malignant transformation (squamous cell carcinoma). Genes involved in the pathogenesis of iron deficiency anemia associated with Plummer-Vinson syndrome include mutation in TMPRSS6 gene. The TMPRSS6 gene encodes instructions for the protein hepcidin. Increased levels of hepcidin leads to decreased release of iron from ferritin and subsequently presents as iron deficiency anemia. On gross pathology, esophageal web and esophageal strictures are characteristic findings of Plummer-Vinson syndrome. On microscopic histopathological analysis, Plummer-Vinson syndrome presents with epithelial atrophy, chronic submucosal inflammation and epithelial atypia or dysplasia (in advanced cases).

The exact cause of Plummer-Vinson syndrome is unknown; however, iron deficiency anemia, genetic factors and nutritional deficiencies may play a role. Iron deficiency anemia is the most widely regarded cause of Plummer-Vinson syndrome and can be due to increased iron demand, decreased intake and malabsorption syndromes.

Plummer-Vinson syndrome must be differentiated from other diseases that cause dysphagia such as reflux esophagitis, esophageal carcinoma, systemic sclerosis, esophageal spasm, pseudoachalasia, stroke, esophageal candidiasis, Zenker’s diverticulum and Chagas disease.

Plummer-Vinson syndrome is a rare disease and the data pertaining to incidence and prevalence is not evidently available. Overall improvement in nutritional status with better medical care has markedly reduced the number of cases of Plummer-Vinson syndrome. However, individuals of any age groups may develop Plummer-Vinson syndrome and it is most commonly seen in the age group of 40-70 years. Plummer-Vinson syndrome usually affects individuals of the caucasian race. Females are commonly affected than males with female to male ratio of 4:1. The majority of Plummer-Vinson syndrome cases are reported in Scandinavian countries or north European countries.

There are no established risk factors for Plummer-Vinson syndrome. However, chronic irritation of the esophagus may predispose to an increased frequency of esophageal webs or strictures. Conditions which can irritate esophagus includes thermal injury, mechanical injury, achalasia, esophageal diverticulum, chronic lye stricture, radiation therapy, injection sclerotherapy, gastric resection, celiac disease, tylosis and scleroderma.

There is insufficient evidence to recommend routine screening for Plummer-Vinson syndrome.

If left untreated, patients of Plummer-Vinson syndrome may progress to develop fatigue, dyspnea on exertion, esophageal strictures, and malignant lesions of the mouth and oral cavity. Common complications of Plummer-Vinson syndrome include hypopharyngeal cancer, esophageal cancer and malignant lesions of oral mucosa. Depending on the extent of Plummer-Vinson syndrome at the time of diagnosis, the prognosis may vary. Prognosis is generally good for patients who receive treatment. Iron replacement therapy and dilatation of esophageal web leads to rapid reversal of symptoms.

The diagnosis of Plummer-Vinson syndrome is made in the presence of iron-deficiency anemia with esophageal webs, dysphagia and glossitis.

Obtaining a history gives important information in making a diagnosis of Plummer-Vinson syndrome. Complete history should be obtained regarding onset, duration, and progression of symptoms such as dysphagia (solids or liquids), weakness, fatigue, dyspnea, and history of choking spells or aspiration. The common symptoms of Plummer-Vinson syndrome are difficulty in swallowing (more for solids), burning sensation in mouth, dry tongue and pale color of the skin. Less common symptoms include cold intolerance, reduced resistance to infection and craving for for unusual items (such as ice or cold vegetables).

Physical examination of patients with Plummer-Vinson syndrome is usually remarkable for glossitis, esophageal webs or strictures, and dysphagia. Other findings on physical examination include pallor, stomatitis, atrophy of lingual papillae, splenomegaly (33%), achlorhydria and koilonychia.

Laboratory findings consistent with the diagnosis of Plummer-Vinson syndrome include presence of iron deficiency anemia. Patients suspected of Plummer-Vinson syndrome should be tested with complete blood count (CBC), iron studies, peripheral smear, stool test for occult blood, blood lead levels and bone marrow biopsy for stainable iron.

Videofluoroscopy may be helpful in the diagnosis of Plummer-Vinson syndrome. Videofluoroscopy is done in patients with normal barium esophagogram who have a high probability of Plummer-Vinson syndrome. Videofluoroscopy is superior to barium esophagogram and has the ability to detect small esophageal webs resulting from insignificant mucosal and submucosal foldings which may otherwise go undiagnosed.

Esophagogastroduodenoscopy (EGD) may be helpful in the diagnosis of Plummer-Vinson syndrome. EGD can directly visualize the upper gastrointestinal tract and aid in diagnosing esophageal webs seen in Plummer-Vinson syndrome. Findings suggestive of esophageal webs include thin elevated mucosal membrane covered by normal squamous epithelium on the walls of esophagus.

The mainstay of treatment for Plummer-Vinson syndrome is aimed at correcting iron deficiency anemia. Patients with Plummer-Vinson syndrome should receive oral iron salts (ferrous sulphate) and iron supplementation in their diet. Parenteral iron is used in patients who are unable to tolerate oral iron or with malabsorption syndromes. Another important aspect in treating Plummer-Vinson syndrome is to identify the cause of iron deficiency in order to exclude active hemorrhage, malignancy or celiac disease.

Surgery is not the first-line treatment option for patients with Plummer-Vinson syndrome. However, procedure such as mechanical dilatation with the use of an endoscope may be used in patients who are unresponsive to medical therapy, have multiple obstructive esophageal webs and long-standing dysphagia.

Effective measures for the primary prevention of Plummer-Vinson syndrome include good nutrition with adequate intake of iron rich foods. Patients of Plummer-Vinson syndrome are at a risk (10-15%) of developing malignant lesions (squamous cell carcinoma) of the oral mucosa, hypopharynx and esophagus. Effective measures for the secondary prevention of Plummer-Vinson syndrome include an upper gastrointestinal endoscopy every year to rule out malignant transformation.

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

Plummer-Vinson syndrome was first discovered by Henry Plummer an American internist, in a case series of patients with long-standing iron deficiency anemia, dysphagia and spasm of the upper esophagus without anatomic stenosis in his article “Diffuse dilatation of the esophagus without anatomic stenosis.” In the year 1919, Porter Paisley Vinson an American surgeon at the Mayo Clinic further described Plummer-Vinson syndrome in his article “A case of cardio-spasm with dilatation and angulation of the esophagus.” He reported a case of angulation of esophagus and attributed his findings to be consistent as described by Henry Plummer. In the year 1919, Donald Ross Patterson and Adam Brown Kelly, both British otolaryngologist described the characteristic clinical features of Plummer-Vinson syndrome in their article “A clinical type of dysphagia” and “Spasm at the entrance of the esophagus” respectively.

The historical perspective associated with Plummer-Vinson syndrome is as below:^{[1][2][3][4][5][6][7][8][9][10][11]}

• In 1543, Vesalius, a Belgian anatomist was the first to describe the anatomy of the esophagus.
• In 1592, Fabricius Aquapendente, an Italian surgeon used wax tampers to remove foreign bodies from the esophagus.
• In 1674, T. Willis, an English physician was the first to dilate the esophagus using whale bone.
• In 1764, Ludlow gave the first anatomic and pathophysiological description of pharyngoesophageal diverticulum.
• In 1806, Philipp Bozzini, a German physician developed 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 the year 1912, Henry Plummer an American internist, was the first to describe Plummer-Vinson syndrome in a case series of patients with long-standing iron deficiency anemia, dysphagia and spasm of the upper esophagus without anatomic stenosis in his article “Diffuse dilatation of the esophagus without anatomic stenosis.”
• In the year 1919, Porter Paisley Vinson an American surgeon at the Mayo Clinic further described Plummer-Vinson syndrome in his article “A case of cardiospasm with dilatation and angulation of the esophagus.” He reported a case of angulation of esophagus and attributed his findings to be consistent as described by Henry Plummer.
• In the year 1919, Donald Ross Paterson and Adam Brown Kelly, both British otolaryngologist described the characteristic clinical features of Plummer-Vinson syndrome in their article “A clinical type of dysphagia” and “Spasm at the entrance of the esophagus” respectively.
• In 1954, L.R. Celestin first developed an esophageal tube for the treatment of malignant dysphagia.
• In 1982, D. Fleischer was the first to use endoscopic laser as palliative therapy for esophageal carcinoma.

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

There is no established system for the classification of Plummer-Vinson syndrome.

There is no established system for the classification of Plummer-Vinson syndrome.

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

Plummer-Vinson syndrome is a rare condition characterized by iron-deficiency anemia, glossitis and dysphagia. The exact pathogenesis of Plummer-Vinson syndrome is not fully understood. It is postulated that Plummer-Vinson syndrome results from iron deficiency. Other possible factors include malnutrition, genetic predisposition and autoimmune disorders. In patients with iron deficiency, the iron-dependent oxidative enzymes are unable to function at optimum level and the dependent metabolic pathways (oxidative phosphorylation) are reduced. This promotes anaerobic metabolism with increased consumption of glucose and increased production of lactic acid and may lead to myasthenic changes in muscles. These myasthenic changes are often seen in muscles involved in swallowing and may lead to atrophy of the esophageal mucosa and formation of esophageal webs. Patients who do not exhibit obstructive lesions (web or stricture) may have dysphagia resulting from muscular in-coordination. Patients with iron deficiency have low levels of myoglobin which may affect the muscles of the tongue and lead to glossitis. In Plummer-Vinson syndrome, deficiency of iron can lead to epithelial atrophy and a decrease in the regenerative capacity of the mucosa. The decrease in rate of healing allows the chronic irritants to act progressively, predisposing the oral cavity and esophagus to malignant transformation (squamous cell carcinoma). Genes involved in the pathogenesis of iron deficiency anemia associated with Plummer-Vinson syndrome include mutation in TMPRSS6 gene. The TMPRSS6 gene encodes instructions for the protein hepcidin. Increased levels of hepcidin leads to decreased release of iron from ferritin and subsequently presents as iron deficiency anemia. On gross pathology, esophageal web and esophageal strictures are characteristic findings of Plummer-Vinson syndrome. On microscopic histopathological analysis, Plummer-Vinson syndrome presents with epithelial atrophy, chronic submucosal inflammation and epithelial atypia or dysplasia (in advanced cases).

• Plummer-Vinson syndrome is a rare condition characterized by iron-deficiency anemia, glossitis and dysphagia.
• The exact pathogenesis of Plummer-Vinson syndrome is not fully understood. It is postulated that Plummer-Vinson syndrome results from iron deficiency. Other possible factors include malnutrition, genetic predisposition and autoimmune disorders.^[1][2][3][4]
  • Iron plays a major role in the expression of citric acid (TCA) cycle enzymes such as citrate synthase, isocitrate dehydrogenase, and succinate dehydrogenase.
  • Iron replete cells with a normal functioning citric acid (TCA) cycle have increased formation of reducing equivalents (such as NADH) leading to increased ATP formation via oxidative phosphorylation.
    • In patients with iron deficiency, the iron-dependent oxidative enzymes are unable to function at optimum level and the dependent metabolic pathways (oxidative phosphorylation) are reduced.
    • This promotes anaerobic metabolism with increased consumption of glucose and increased production of lactic acid which can lead to myasthenic changes in muscles.
    • Myasthenic changes are often seen in muscles involved in swallowing which can lead to atrophy of the esophageal mucosa and formation of esophageal webs.
    • The dysphagia in Plummer-Vinson syndrome results from esophageal (postcricoid) web or stricture.
    • However, patients who do not exhibit esophageal (postcricoid) web or stricture (obstructive lesions) may have dysphagia resulting from muscular in-coordination.
  • Iron is also important in the synthesis of myoglobin which is responsible for meeting the energy demands of the muscle. Patients with iron deficiency have low levels of myoglobin which may affect the muscles of the tongue and lead to glossitis.
  • In Plummer-Vinson syndrome, deficiency of iron can lead to epithelial atrophy and a decrease in the regenerative capacity of the mucosa. The decrease in rate of healing allows the chronic irritants to act progressively, predisposing the oral cavity and esophagus to malignant transformation (squamous cell carcinoma).

• Other factors involved in the pathogenesis of Plummer-Vinson syndrome include malnutrition, genetic predisposition and autoimmune disorders.^{[5][6][7][8][9][10]}
  • Plummer-Vinson syndrome is seen in certain genetically predisposed individuals (such as mutation in TMPRSS6 gene) and those with malnutrition.
  • Recent research have shown that heterotopic gastric mucosa of the proximal esophagus (HGMPE) may predispose individuals to an increased risk of Plummer-Vinson syndrome.
    • The HGMPE is a congenital condition and also known as cervical inlet patch or inlet patch.
    • HGMPE is a salmon colored heterotopic gastric mucosa patch that is located just distal to the upper esophageal sphincter.
    • The HGMPE is associated with an increased laryngopharyngeal acid reflux and neoplastic transformation.
    • Laryngopharyngeal acid reflux results in an increased frequency of bleeding (iron deficiency anemia) and ulceration leading to formation of web like structures in the esophagus.
  • Some researchers postulate that Plummer-Vinson syndrome may be due to an autoimmune condition. This can be attributed to the fact that Plummer-Vinson syndrome has been observed to occur with an increased frequency in patients with other autoimmune conditions such as pernicious anemia, rheumatoid arthritis, autoimmune thyroiditis and celiac disease.^[11][12][13]

• Celiac disease
• Hiatus hernia
• Chronic gastrointestinal bleeding
• Pharyngeal cancer
• Esophageal cancer
• Pernicious anemia
• Rheumatoid arthritis
• Autoimmune thyroiditis

The gene(s) involved in the pathogenesis of Plummer-Vinson syndrome include:^{[14][15][16][17][16]}

• Genes involved in the pathogenesis of iron deficiency anemia associated with Plummer-Vinson syndrome include mutation in TMPRSS6 gene.
• Mutation in TMPRSS6 gene results in iron-refractory iron deficiency anemia (IRIDA).
• TMPRSS6 gene is located on long arm (q) of chromosome 21 at position 22q12.3.
• The TMPRSS6 gene encodes instructions for the protein hepcidin.
• At least 40 different types of mutations have been identified in the TMPRSS6 gene.
• Mutated TMPRSS6 gene leads to uninhibited production of hepcidin.
• Overproduction of hepcidin leads to internalization and degradation of ferroportin. Ferroportin is present in the basolateral membrane of duodenal cells and mediates the transfer of iron from duodenal cells to transferrin in blood.
• Increased levels of hepcidin leads to decreased release of iron from ferritin and subsequently presents as iron deficiency anemia.

• On gross pathology, esophageal web and esophageal strictures are characteristic findings of Plummer-Vinson syndrome.

On microscopic histopathological analysis, Plummer-Vinson syndrome presents with the following findings:

• Epithelial atrophy
• Chronic submucosal inflammation
• Epithelial atypia or dysplasia
• Squamous cell carcinoma of esophagus (in advanced cases)

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

The cause of Plummer-Vinson syndrome is unknown; however, iron deficiency anemia, genetic factors and nutritional deficiencies may play a role. Iron deficiency anemia is the most widely regarded cause of Plummer-Vinson syndrome and can be due to increased iron demand, decreased intake and malabsorption syndromes.

The cause of Plummer-Vinson syndrome is unknown; however, iron deficiency anemia, genetic factors and nutritional deficiencies may play a role. Iron deficiency anemia is the most widely regarded cause of Plummer-Vinson syndrome and can be due to:

Common causes of iron deficiency anemia associated with Plummer-Vinson syndrome include conditions which lead to iron demand, decreased intake and malabsorption syndromes. These conditions are described below:^{[1][2][3][4][5]}

• Physiological conditions with increased iron requirements such as:
  • Growth
  • Pregnancy
  • Frequent blood donation

• Conditions promoting blood loss leads to an increased demand of iron by the body. These include:
  • Menstruation
  • Gastrointestinal tract disorders such as:

    • Peptic ulcers
    • Hemorrhoids
    • Esophageal varices
    • NSAIDs (aspirin,ibuprofen)
    • Cancer of esophagus, stomach, or colon
    • Hookworms

  • Genitourinary tract disorders such as:

    • Glomerulonephritis
    • Renal calculi
    • Renal or bladder carcinoma

  • Hemoptysis (alveolar hemorrhage)
  • Nosocomial blood loss; phlebotomy for diagnostic tests in hospitalized patients
  • Following gastric or small bowel surgery: due to loss of gastric acidity, increased transit time for food, and decreased absorption of iron
• Conditions leading to impaired iron absorption
  • Celiac disease
  • Tropical sprue
  • Gastric surgery
  • Hypochlorhydria
  • Taking too many antacids that contain calcium
  • Whipple disease
  • Kwashiorkor disease
  • Alcoholism

• Hereditary hemorrhagic telangiectasia (recurrent hemorrhage)
• Intravascular hemolysis (paroxysmal nocturnal hemoglobinuria)
• Iatrogenic causes such as frequent blood draws, particularly in hospitalized patients
• Inadequate diet in children (excessive consumption of whole cow’s milk)

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

Plummer-Vinson syndrome must be differentiated from other diseases that cause dysphagia such as reflux esophagitis, esophageal carcinoma, systemic sclerosis, esophageal spasm, pseudoachalasia, stroke, esophageal candidiasis and Chagas disease.

Plummer-Vinson syndrome must be differentiated from other diseases that cause dysphagia such as reflux esophagitis, esophageal carcinoma, systemic sclerosis, esophageal spasm, pseudoachalasia, stroke, esophageal candidiasis and Chagas disease.^{[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

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

Plummer-Vinson syndrome is a rare disease and the data pertaining to its incidence and prevalence is not evidently available. Overall improvement in nutritional status with better medical care has markedly reduced the number of cases of Plummer-Vinson syndrome. However, individuals of any age groups may develop Plummer-Vinson syndrome and it is most commonly seen in the age group of 40-70 years. Plummer-Vinson syndrome usually affects individuals of the caucasian race. Females are commonly affected than males with female to male ratio of 4:1. The majority of Plummer-Vinson syndrome cases are reported in Scandinavian countries or north European countries.

The epidemiology and demographics of Plummer-Vinson syndrome is as below:^{[1][2][3][4][5][6]}

• Plummer-Vinson syndrome is a rare disease and the data pertaining to its incidence is not evidently available. Overall improvement in nutritional status with better medical care has markedly reduced the number of cases of Plummer-Vinson syndrome.

• Plummer-Vinson syndrome is a rare disease and the data pertaining to its prevalence of the syndrome is not evidently available. Overall improvement in nutritional status with better medical care has markedly reduced the number of cases of Plummer-Vinson syndrome.

• Patients of all age groups may develop Plummer-Vinson syndrome.
• In adults, Plummer-Vinson syndrome commonly affects individuals in fourth to seventh decade of life.
• In children, Plummer-Vinson syndrome commonly affects females in the age group of 10-18 years.

• Plummer-Vinson syndrome usually affects individuals of the caucasian race.

• Women are more commonly affected by Plummer-Vinson syndrome than men.
• In Plummer-Vinson syndrome the female to male ratio is 4:1.
• Among women, Plummer-Vinson syndrome is seen commonly in premenopausal and married women (fourth and fifth decade of life).

• The majority of Plummer-Vinson syndrome cases were reported in Scandinavian countries or north European countries.

Template:WH Template:WS

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

There are no established risk factors for Plummer-Vinson syndrome. However, chronic irritation of the esophagus may predispose to an increased frequency of esophageal webs or strictures. Conditions which can irritate esophagus includes thermal injury, mechanical injury, achalasia, esophageal diverticulum, chronic lye stricture, radiation therapy, injection sclerotherapy, gastric resection, celiac disease, tylosis and scleroderma.

There are no established risk factors for Plummer-Vinson syndrome. However, chronic irritation of the esophagus may predispose to an increased frequency of esophageal webs or strictures. Conditions which can irritate esophagus includes:^[1][2]

• Thermal injury
• Mechanical injury
• Achalasia
• Esophageal diverticulum
• Chronic lye stricture
• Radiation therapy
• Injection sclerotherapy
• Gastric resection
• Celiac disease
• Tylosis
• Scleroderma

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

There is insufficient evidence to recommend routine screening for Plummer-Vinson syndrome.

There is insufficient evidence to recommend routine screening for Plummer-Vinson syndrome.

Template:WS Template:WH

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

If left untreated, patients of Plummer-Vinson syndrome may progress to develop fatigue, dyspnea on exertion, esophageal strictures, and malignant lesions of the mouth and oral cavity. Common complications of Plummer-Vinson syndrome include hypopharyngeal cancer, esophageal cancer and malignant lesions of oral mucosa. Depending on the extent of Plummer-Vinson syndrome at the time of diagnosis, the prognosis may vary. Prognosis is generally good for patients who receive treatment. Iron replacement therapy and dilatation of esophageal web leads to rapid reversal of symptoms.

• The symptoms of Plummer-Vinson syndrome usually develop in the fourth decade of life, and start with symptoms such as fatigue, swollen tongue and pain while swallowing.
• If left untreated, patients of Plummer-Vinson syndrome may progress to develop dysphagia, esophageal strictures, pharyngeal and esophageal cancer.
  • Initially patients of Plummer-Vinson syndrome presents with dysphagia for solid food.
  • As the disease progresses, esophageal webs and strictures become more apparent and progress to present with dysphagia for solid, choking spells and aspiration.
  • Untreated Plummer-Vinson syndrome has the potential to transform into hypopharyngeal and esophageal carcinoma (squamous cell carcinoma).

• Common complications of Plummer-Vinson syndrome include:^[1][2]
  • Hypopharyngeal cancer
  • Esophageal cancer
  • Malignant lesions of oral mucosa
  • High-output heart failure
  • Preterm delivery
  • Developmental delay

• Depending on the extent of Plummer-Vinson syndrome at the time of diagnosis, the prognosis may vary.^[3][4][5]
  • Prognosis is generally good for patients of Plummer-Vinson syndrome who receive treatment unless the disease has been complicated by pharyngeal or esophageal carcinoma.
  • Anemia and esophageal webs seen in Plummer-Vinson syndrome can be rapidly reversed with iron replacement therapy and esophageal dilatation respectively.
  • Studies have shown that patients of Plummer-Vinson syndrome are at a risk (10-15%) of developing malignant lesions of the oral mucosa, hypopharynx and esophagus. Therefore, patients require regular surveillance (upper gastrointestinal endoscopy is recommended every year) and close follow up.^[6]

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