Plummer-Vinson syndrome pathophysiology: Difference between revisions

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{{Plummer-Vinson syndrome}}
{{Plummer-Vinson syndrome}}
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==Overview==
==Overview==
The exact pathogenesis of [disease name] is not fully understood.
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 [[Myasthenia|myasthenic]] changes in [[muscles]]. These [[Myasthenia|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]] ([[Esophageal web|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, [[Iron deficiency|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).
 
OR
 
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
 
OR
 
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
 
OR
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Pathophysiology==
==Pathophysiology==


===Pathogenesis===
===Pathogenesis===
*Plummer-Vinson syndrome is a rare condition characterized by iron-deficiency anemia, glossitis and dysphagia.  
*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.<ref name="pmid4449772">{{cite journal |vauthors=Chisholm M |title=The association between webs, iron and post-cricoid carcinoma |journal=Postgrad Med J |volume=50 |issue=582 |pages=215–9 |year=1974 |pmid=4449772 |pmc=2495558 |doi= |url=}}</ref><ref name="pmid8482199">{{cite journal |vauthors=Dantas RO, Villanova MG |title=Esophageal motility impairment in Plummer-Vinson syndrome. Correction by iron treatment |journal=Dig. Dis. Sci. |volume=38 |issue=5 |pages=968–71 |year=1993 |pmid=8482199 |doi= |url=}}</ref><ref name="pmid16978405">{{cite journal |vauthors=Novacek G |title=Plummer-Vinson syndrome |journal=Orphanet J Rare Dis |volume=1 |issue= |pages=36 |year=2006 |pmid=16978405 |pmc=1586011 |doi=10.1186/1750-1172-1-36 |url=}}</ref><ref name="pmid3016824">{{cite journal |vauthors=Ekberg O, Malmquist J, Lindgren S |title=Pharyngo-oesophageal webs in dysphageal patients. A radiologic and clinical investigation in 1134 patients |journal=Rofo |volume=145 |issue=1 |pages=75–80 |year=1986 |pmid=3016824 |doi=10.1055/s-2008-1048889 |url=}}</ref>
*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]].<ref name="pmid4449772">{{cite journal |vauthors=Chisholm M |title=The association between webs, iron and post-cricoid carcinoma |journal=Postgrad Med J |volume=50 |issue=582 |pages=215–9 |year=1974 |pmid=4449772 |pmc=2495558 |doi= |url=}}</ref><ref name="pmid8482199">{{cite journal |vauthors=Dantas RO, Villanova MG |title=Esophageal motility impairment in Plummer-Vinson syndrome. Correction by iron treatment |journal=Dig. Dis. Sci. |volume=38 |issue=5 |pages=968–71 |year=1993 |pmid=8482199 |doi= |url=}}</ref><ref name="pmid16978405">{{cite journal |vauthors=Novacek G |title=Plummer-Vinson syndrome |journal=Orphanet J Rare Dis |volume=1 |issue= |pages=36 |year=2006 |pmid=16978405 |pmc=1586011 |doi=10.1186/1750-1172-1-36 |url=}}</ref><ref name="pmid3016824">{{cite journal |vauthors=Ekberg O, Malmquist J, Lindgren S |title=Pharyngo-oesophageal webs in dysphageal patients. A radiologic and clinical investigation in 1134 patients |journal=Rofo |volume=145 |issue=1 |pages=75–80 |year=1986 |pmid=3016824 |doi=10.1055/s-2008-1048889 |url=}}</ref>
**Iron plays a major role in the expression of citric acid cycle enzymes such as citrate synthase, isocitric dehydrogenase, and succinate dehydrogenase.  
**[[Iron]] plays a major role in the expression of [[Citric acid cycle|citric acid (TCA) cycle]] enzymes such as [[citrate synthase]], [[isocitrate dehydrogenase]], and [[succinate dehydrogenase]].  
**Iron replete cells with normal citric acid cycle have an increased formation of reducing equivalents (NADH) thus leading to increased ATP formation via oxidative phosphorylation.
**[[Iron]] replete cells with a normal functioning [[Citric acid cycle|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, all these metabolic pathways (oxidative phosphorylation) are reduced. This promotes anaerobic metabolism with increased consumption of glucose and increased production of lactic acid.
***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.  
** In patients with iron deficiency, the iron-dependent oxidative enzymes are unable to function at optimum level and may lead to myasthenic changes in muscles.  
***This promotes [[anaerobic metabolism]] with increased consumption of [[glucose]] and increased production of [[lactic acid]] which can lead to [[Myasthenia|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.
***[[Myasthenia|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 obstructive lesions may have dysphagia resulting from muscular in-coordination.
***The [[dysphagia]] in Plummer-Vinson syndrome results from [[esophageal]] (postcricoid) [[Esophageal web|web]] or [[Esophageal stricture|stricture]].  
** 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.  
***However, patients who do not exhibit [[esophageal]] (postcricoid) [[Esophageal web|web]] or [[Esophageal stricture|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, [[Iron deficiency|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.<ref name="pmid23372354">{{cite journal |vauthors=Chong VH |title=Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus |journal=World J. Gastroenterol. |volume=19 |issue=3 |pages=331–8 |year=2013 |pmid=23372354 |pmc=3554816 |doi=10.3748/wjg.v19.i3.331 |url=}}</ref><ref name="pmid8508079">{{cite journal |vauthors=Buse PE, Zuckerman GR, Balfe DM |title=Cervical esophageal web associated with a patch of heterotopic gastric mucosa |journal=Abdom Imaging |volume=18 |issue=3 |pages=227–8 |year=1993 |pmid=8508079 |doi= |url=}}</ref><ref name="pmid19473208">{{cite journal |vauthors=Basseri B, Conklin JL, Mertens RB, Lo SK, Bellack GS, Shaye OA |title=Heterotopic gastric mucosa (inlet patch) in a patient with laryngopharyngeal reflux (LPR) and laryngeal carcinoma: a case report and review of literature |journal=Dis. Esophagus |volume=22 |issue=4 |pages=E1–5 |year=2009 |pmid=19473208 |doi=10.1111/j.1442-2050.2008.00915.x |url=}}</ref><ref name="pmid8122657">{{cite journal |vauthors=Jerome-Zapadka KM, Clarke MR, Sekas G |title=Recurrent upper esophageal webs in association with heterotopic gastric mucosa: case report and literature review |journal=Am. J. Gastroenterol. |volume=89 |issue=3 |pages=421–4 |year=1994 |pmid=8122657 |doi= |url=}}</ref><ref name="pmid4007426">{{cite journal |vauthors=Jabbari M, Goresky CA, Lough J, Yaffe C, Daly D, Côté C |title=The inlet patch: heterotopic gastric mucosa in the upper esophagus |journal=Gastroenterology |volume=89 |issue=2 |pages=352–6 |year=1985 |pmid=4007426 |doi= |url=}}</ref><ref name="pmid15056100">{{cite journal |vauthors=von Rahden BH, Stein HJ, Becker K, Liebermann-Meffert D, Siewert JR |title=Heterotopic gastric mucosa of the esophagus: literature-review and proposal of a clinicopathologic classification |journal=Am. J. Gastroenterol. |volume=99 |issue=3 |pages=543–51 |year=2004 |pmid=15056100 |doi=10.1111/j.1572-0241.2004.04082.x |url=}}</ref>
*Other factors involved in the [[pathogenesis]] of Plummer-Vinson syndrome include [[malnutrition]], [[genetic predisposition]] and [[autoimmune disorders]].<ref name="pmid23372354">{{cite journal |vauthors=Chong VH |title=Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus |journal=World J. Gastroenterol. |volume=19 |issue=3 |pages=331–8 |year=2013 |pmid=23372354 |pmc=3554816 |doi=10.3748/wjg.v19.i3.331 |url=}}</ref><ref name="pmid8508079">{{cite journal |vauthors=Buse PE, Zuckerman GR, Balfe DM |title=Cervical esophageal web associated with a patch of heterotopic gastric mucosa |journal=Abdom Imaging |volume=18 |issue=3 |pages=227–8 |year=1993 |pmid=8508079 |doi= |url=}}</ref><ref name="pmid19473208">{{cite journal |vauthors=Basseri B, Conklin JL, Mertens RB, Lo SK, Bellack GS, Shaye OA |title=Heterotopic gastric mucosa (inlet patch) in a patient with laryngopharyngeal reflux (LPR) and laryngeal carcinoma: a case report and review of literature |journal=Dis. Esophagus |volume=22 |issue=4 |pages=E1–5 |year=2009 |pmid=19473208 |doi=10.1111/j.1442-2050.2008.00915.x |url=}}</ref><ref name="pmid8122657">{{cite journal |vauthors=Jerome-Zapadka KM, Clarke MR, Sekas G |title=Recurrent upper esophageal webs in association with heterotopic gastric mucosa: case report and literature review |journal=Am. J. Gastroenterol. |volume=89 |issue=3 |pages=421–4 |year=1994 |pmid=8122657 |doi= |url=}}</ref><ref name="pmid4007426">{{cite journal |vauthors=Jabbari M, Goresky CA, Lough J, Yaffe C, Daly D, Côté C |title=The inlet patch: heterotopic gastric mucosa in the upper esophagus |journal=Gastroenterology |volume=89 |issue=2 |pages=352–6 |year=1985 |pmid=4007426 |doi= |url=}}</ref><ref name="pmid15056100">{{cite journal |vauthors=von Rahden BH, Stein HJ, Becker K, Liebermann-Meffert D, Siewert JR |title=Heterotopic gastric mucosa of the esophagus: literature-review and proposal of a clinicopathologic classification |journal=Am. J. Gastroenterol. |volume=99 |issue=3 |pages=543–51 |year=2004 |pmid=15056100 |doi=10.1111/j.1572-0241.2004.04082.x |url=}}</ref>
** Plummer-Vinson syndrome is seen in certain genetically predisposed individuals (such as malformation of esophagus) and those with malnutrition.
** Plummer-Vinson syndrome is seen in certain [[genetically]] predisposed individuals (such as [[mutation]] in TMPRSS6 gene) and those with [[malnutrition]].
** These patients have been associated with the presence of heterotopic gastric mucosa of the proximal esophagus (HGMPE).
** 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 also known as inlet patch or cervical inlet patch. HGMPE is a salmon colored patch and is located just distal to the upper esophageal sphincter.
*** The HGMPE is a congenital condition and also known as cervical inlet patch or inlet patch.  
** The HGMPE has been associated with increased laryngopharyngeal acid reflux and neoplastic transformation.
*** HGMPE is a [[salmon]] colored heterotopic gastric mucosa patch that is located just [[distal]] to the [[upper esophageal sphincter]].
** Thus patients with HGMPE have been associated with an increased frequency of bleeding (iron deficiency anemia) and ulceration leading to formation of web like structures in the esophagus
*** The HGMPE is associated with an increased [[Laryngopharyngeal Reflux Disease|laryngopharyngeal acid reflux]] and [[neoplastic]] transformation.
*** [[Laryngopharyngeal Reflux Disease|Laryngopharyngeal acid reflux]] results in an increased frequency of [[bleeding]] ([[iron deficiency anemia]]) and [[ulceration]] leading to formation of [[Esophageal web|web]] like structures in the [[esophagus]].
** Some researchers postulate that Plummer-Vinson syndrome may be due to an [[Autoimmune disease|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 disorders|autoimmune conditions]] such as [[pernicious anemia]], [[rheumatoid arthritis]], [[autoimmune thyroiditis]] and [[celiac disease]].<ref name="pmid10022662">{{cite journal |vauthors=Dickey W, McConnell B |title=Celiac disease presenting as the Paterson-Brown Kelly (Plummer-Vinson) syndrome |journal=Am. J. Gastroenterol. |volume=94 |issue=2 |pages=527–9 |year=1999 |pmid=10022662 |doi=10.1111/j.1572-0241.1999.889_r.x |url=}}</ref><ref name="pmid11059192">{{cite journal |vauthors=Malhotra P, Kochhar R, Varma N, Kumari S, Jain S, Varma S |title=Paterson-Kelly syndrome and celiac disease--a rare combination |journal=Indian J Gastroenterol |volume=19 |issue=4 |pages=191–2 |year=2000 |pmid=11059192 |doi= |url=}}</ref><ref name="pmid14193944">{{cite journal |vauthors=ELWOOD PC, JACOBS A, PITMAN RG, ENTWISTLE CC |title=EPIDEMIOLOGY OF THE PATERSON-KELLY SYNDROME |journal=Lancet |volume=2 |issue=7362 |pages=716–20 |year=1964 |pmid=14193944 |doi= |url=}}</ref>


*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 associated with other autoimmune conditions such as pernicious anemia, rheumatoid arthritis, autoimmune thyroiditis and celiac disease.<ref name="pmid10022662">{{cite journal |vauthors=Dickey W, McConnell B |title=Celiac disease presenting as the Paterson-Brown Kelly (Plummer-Vinson) syndrome |journal=Am. J. Gastroenterol. |volume=94 |issue=2 |pages=527–9 |year=1999 |pmid=10022662 |doi=10.1111/j.1572-0241.1999.889_r.x |url=}}</ref><ref name="pmid11059192">{{cite journal |vauthors=Malhotra P, Kochhar R, Varma N, Kumari S, Jain S, Varma S |title=Paterson-Kelly syndrome and celiac disease--a rare combination |journal=Indian J Gastroenterol |volume=19 |issue=4 |pages=191–2 |year=2000 |pmid=11059192 |doi= |url=}}</ref><ref name="pmid14193944">{{cite journal |vauthors=ELWOOD PC, JACOBS A, PITMAN RG, ENTWISTLE CC |title=EPIDEMIOLOGY OF THE PATERSON-KELLY SYNDROME |journal=Lancet |volume=2 |issue=7362 |pages=716–20 |year=1964 |pmid=14193944 |doi= |url=}}</ref>
==Associated Conditions==
 
*[[Celiac disease]]
OR
*[[Hiatus hernia]]
*It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
*Chronic [[gastrointestinal bleeding]]
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
*[[Pharyngeal cancer (patient information)|Pharyngeal cancer]]
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
*[[Esophageal cancer]]
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
*[[Pernicious anemia]]
*The progression to [disease name] usually involves the [molecular pathway].
*[[Rheumatoid arthritis]]
*The pathophysiology of [disease/malignancy] depends on the histological subtype.
*[[Autoimmune thyroiditis]]


==Associated Conditions==
==Genes==
*Celiac disease
The [[gene]](s) involved in the [[pathogenesis]] of Plummer-Vinson syndrome include:<ref name="pmid28491880">{{cite journal |vauthors=Pinto J, Nobre de Jesus G, Palma Anselmo M, Gonçalves L, Brás D, Madeira Lopes J, Meneses J, Victorino R, Faustino P |title=Iron Refractory Iron Deficiency Anemia in Dizygotic Twins Due to a Novel TMPRSS6 Gene Mutation in Addition to Polymorphisms Associated With High Susceptibility to Develop Ferropenic Anemia |journal=J Investig Med High Impact Case Rep |volume=5 |issue=2 |pages=2324709617701776 |year=2017 |pmid=28491880 |pmc=5405884 |doi=10.1177/2324709617701776 |url=}}</ref><ref name="pmid28460265">{{cite journal |vauthors=Yaish HM, Farrell CP, Christensen RD, MacQueen BC, Jackson LK, Trochez-Enciso J, Kaplan J, Ward DM, Salah WK, Phillips JD |title=Two novel mutations in TMPRSS6 associated with iron-refractory iron deficiency anemia in a mother and child |journal=Blood Cells Mol. Dis. |volume=65 |issue= |pages=38–40 |year=2017 |pmid=28460265 |doi=10.1016/j.bcmd.2017.04.002 |url=}}</ref><ref name="pmid21789471">{{cite journal |vauthors=Camaschella C, Silvestri L |title=Molecular mechanisms regulating hepcidin revealed by hepcidin disorders |journal=ScientificWorldJournal |volume=11 |issue= |pages=1357–66 |year=2011 |pmid=21789471 |doi=10.1100/tsw.2011.130 |url=}}</ref><ref name="pmid20620132">{{cite journal |vauthors=Franchini M, Montagnana M, Lippi G |title=Hepcidin and iron metabolism: from laboratory to clinical implications |journal=Clin. Chim. Acta |volume=411 |issue=21-22 |pages=1565–9 |year=2010 |pmid=20620132 |doi=10.1016/j.cca.2010.07.003 |url=}}</ref><ref name="pmid21789471">{{cite journal |vauthors=Camaschella C, Silvestri L |title=Molecular mechanisms regulating hepcidin revealed by hepcidin disorders |journal=ScientificWorldJournal |volume=11 |issue= |pages=1357–66 |year=2011 |pmid=21789471 |doi=10.1100/tsw.2011.130 |url=}}</ref>
*Pernicious anemia
*[[Genes]] involved in the [[pathogenesis]] of [[iron deficiency anemia]] associated with Plummer-Vinson syndrome include [[mutation]] in TMPRSS6 [[gene]].
*Rheumatoid arthritis
*[[Mutation]] in TMPRSS6 [[gene]] results in iron-refractory [[iron deficiency anemia]] ([[Iron deficiency anemia|IRIDA]]).
*Autoimmune thyroiditis
*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|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]].


==Gross Pathology==
==Gross Pathology==
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On [[gross pathology]], [[esophageal web]] and [[Esophageal stricture|esophageal strictures]] are characteristic findings of Plummer-Vinson syndrome.


==Microscopic Pathology==
==Microscopic Pathology==
On microscopic histopathological analysis, Plummer-Vinson syndrome presents with the following findings:
On [[microscopic]] [[histopathological]] analysis, Plummer-Vinson syndrome presents with the following findings:
*Epithelial atrophy
*Epithelial atrophy
*Chronic submucosal inflammation
*[[Chronic]] [[submucosal]] [[inflammation]]
*Epithelial atypia or dysplasia (in advanced cases)
*[[Epithelial]] [[atypia]] or [[dysplasia]]
(Images shown below are courtesy of Melih Aktan MD, Istanbul Medical Faculty - Turkey)
*[[Squamous cell carcinoma]] of [[esophagus]] (in advanced cases)


<div align="left">
[[File:Esophageal squamous cell carcinoma.jpg|thumb|center|Histology of esophageal squamous cell carcinoma ([By Nephron (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons])]]
<gallery heights="175" widths="175">
Image:Iron deficiency anemia 0001.jpg|Iron deficiency anemia
Image:Iron deficiency anemia 0002.jpg|Iron deficiency anemia
Image:Iron deficiency anemia 0003.jpg|Iron deficiency anemia
</gallery>


==References==
==References==
Line 91: Line 68:
[[Category:Gastroenterology]]
[[Category:Gastroenterology]]
[[Category:Hematology]]
[[Category:Hematology]]
<references />

Latest revision as of 19:18, 27 November 2017

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

Overview

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).

Pathophysiology

Pathogenesis

Associated Conditions

Genes

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

Gross Pathology

Microscopic Pathology

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

Histology of esophageal squamous cell carcinoma ([By Nephron (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons])

References

  1. ↑ Chisholm M (1974). "The association between webs, iron and post-cricoid carcinoma". Postgrad Med J. 50 (582): 215–9. PMC 2495558. PMID 4449772.
  2. ↑ Dantas RO, Villanova MG (1993). "Esophageal motility impairment in Plummer-Vinson syndrome. Correction by iron treatment". Dig. Dis. Sci. 38 (5): 968–71. PMID 8482199.
  3. ↑ Novacek G (2006). "Plummer-Vinson syndrome". Orphanet J Rare Dis. 1: 36. doi:10.1186/1750-1172-1-36. PMC 1586011. PMID 16978405.
  4. ↑ Ekberg O, Malmquist J, Lindgren S (1986). "Pharyngo-oesophageal webs in dysphageal patients. A radiologic and clinical investigation in 1134 patients". Rofo. 145 (1): 75–80. doi:10.1055/s-2008-1048889. PMID 3016824.
  5. ↑ Chong VH (2013). "Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus". World J. Gastroenterol. 19 (3): 331–8. doi:10.3748/wjg.v19.i3.331. PMC 3554816. PMID 23372354.
  6. ↑ Buse PE, Zuckerman GR, Balfe DM (1993). "Cervical esophageal web associated with a patch of heterotopic gastric mucosa". Abdom Imaging. 18 (3): 227–8. PMID 8508079.
  7. ↑ Basseri B, Conklin JL, Mertens RB, Lo SK, Bellack GS, Shaye OA (2009). "Heterotopic gastric mucosa (inlet patch) in a patient with laryngopharyngeal reflux (LPR) and laryngeal carcinoma: a case report and review of literature". Dis. Esophagus. 22 (4): E1–5. doi:10.1111/j.1442-2050.2008.00915.x. PMID 19473208.
  8. ↑ Jerome-Zapadka KM, Clarke MR, Sekas G (1994). "Recurrent upper esophageal webs in association with heterotopic gastric mucosa: case report and literature review". Am. J. Gastroenterol. 89 (3): 421–4. PMID 8122657.
  9. ↑ Jabbari M, Goresky CA, Lough J, Yaffe C, Daly D, Côté C (1985). "The inlet patch: heterotopic gastric mucosa in the upper esophagus". Gastroenterology. 89 (2): 352–6. PMID 4007426.
  10. ↑ von Rahden BH, Stein HJ, Becker K, Liebermann-Meffert D, Siewert JR (2004). "Heterotopic gastric mucosa of the esophagus: literature-review and proposal of a clinicopathologic classification". Am. J. Gastroenterol. 99 (3): 543–51. doi:10.1111/j.1572-0241.2004.04082.x. PMID 15056100.
  11. ↑ Dickey W, McConnell B (1999). "Celiac disease presenting as the Paterson-Brown Kelly (Plummer-Vinson) syndrome". Am. J. Gastroenterol. 94 (2): 527–9. doi:10.1111/j.1572-0241.1999.889_r.x. PMID 10022662.
  12. ↑ Malhotra P, Kochhar R, Varma N, Kumari S, Jain S, Varma S (2000). "Paterson-Kelly syndrome and celiac disease--a rare combination". Indian J Gastroenterol. 19 (4): 191–2. PMID 11059192.
  13. ↑ ELWOOD PC, JACOBS A, PITMAN RG, ENTWISTLE CC (1964). "EPIDEMIOLOGY OF THE PATERSON-KELLY SYNDROME". Lancet. 2 (7362): 716–20. PMID 14193944.
  14. ↑ Pinto J, Nobre de Jesus G, Palma Anselmo M, Gonçalves L, Brás D, Madeira Lopes J, Meneses J, Victorino R, Faustino P (2017). "Iron Refractory Iron Deficiency Anemia in Dizygotic Twins Due to a Novel TMPRSS6 Gene Mutation in Addition to Polymorphisms Associated With High Susceptibility to Develop Ferropenic Anemia". J Investig Med High Impact Case Rep. 5 (2): 2324709617701776. doi:10.1177/2324709617701776. PMC 5405884. PMID 28491880.
  15. ↑ Yaish HM, Farrell CP, Christensen RD, MacQueen BC, Jackson LK, Trochez-Enciso J, Kaplan J, Ward DM, Salah WK, Phillips JD (2017). "Two novel mutations in TMPRSS6 associated with iron-refractory iron deficiency anemia in a mother and child". Blood Cells Mol. Dis. 65: 38–40. doi:10.1016/j.bcmd.2017.04.002. PMID 28460265.
  16. ↑ 16.0 16.1 Camaschella C, Silvestri L (2011). "Molecular mechanisms regulating hepcidin revealed by hepcidin disorders". ScientificWorldJournal. 11: 1357–66. doi:10.1100/tsw.2011.130. PMID 21789471.
  17. ↑ Franchini M, Montagnana M, Lippi G (2010). "Hepcidin and iron metabolism: from laboratory to clinical implications". Clin. Chim. Acta. 411 (21–22): 1565–9. doi:10.1016/j.cca.2010.07.003. PMID 20620132.
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