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Iron Deficiency Anemia and Plummer–Vinson Syndrome: Current Insights

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Iron Deficiency Anemia and Plummer–Vinson Syndrome: Current Insights Journal name: Journal of Blood Medicine Article Designation: REVIEW Year: 2017 Volume: 8 Journal of Blood Medicine Dovepress Running head verso: Goel et al Running head recto: Dysphagia and iron deficiency anemia open access to scientific and medical research DOI: http://dx.doi.org/10.2147/JBM.S127801 Open Access Full Text Article REVIEW Iron deficiency anemia and Plummer–Vinson syndrome: current insights Amit Goel1 Abstract: Plummer–Vinson syndrome (PVS), a rare clinical condition, is characterized by a Satvinder Singh Bakshi2 triad of dysphagia, iron deficiency anemia and esophageal web in the post-cricoid region. It Neetu Soni3 was first described over a century ago. However, literature on this condition remains scanty, and Nanda Chhavi4 its prevalence appears to be declining worldwide, possibly due to improvements in nutrition over time. The condition has been reported most commonly in thin-built, middle-aged, white 1Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute women. The esophageal webs in PVS are thin mucosal folds, which are best seen either in lat- of Medical Sciences, Lucknow, India; eral views at barium swallow or at esophagoscopy. These are usually semilunar or crescentic, 2 Department of Otorhinolaryngology being located most often along the anterior esophageal wall, but can be concentric. The exact and Head and Neck Surgery, Mahatma Gandhi Medical College cause and pathogenesis of PVS remain unclear, though iron and other nutritional deficiencies, and Research Institute, Puducherry, genetic predisposition and autoimmunity have all been implicated in formation of the webs. 3 India; Department of Radiodiagnosis, Treatment includes correction of iron deficiency and endoscopic dilation of the esophageal Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; webs to relieve dysphagia. PVS is associated with an increased risk of hypopharyngeal and 4Department of Pediatrics, Era’s esophageal malignancies. Correction of iron deficiency may arrest and reverse the mucosal Lucknow Medical College, Lucknow, changes and possibly reduces this risk. India Keywords: Plummer –Vinson syndrome, Paterson–Brown–Kelly syndrome, esophageal web, dysphagia, iron deficiency anemia Introduction Difficulty in swallowing or dysphagia is a common symptom. Esophageal webs are an infrequent cause of dysphagia. These have been found to occur in association with iron deficiency anemia (IDA) and dysphagia. This clinical triad – of IDA, esophageal web and dysphagia – has been named variously as “Plummer–Vinson syndrome” (PVS; primarily in the USA) and as “Paterson–Brown–Kelly syndrome” (used primarily in the UK).1 The former term was derived from the names of two physicians – Henry Stanley Plummer and Porter Paisley Vinson, at the Mayo Clinic – who separately described this condition and speculated that “cardiospasm”2 and “angulation”3 of the esophagus, respectively, were responsible for the dysphagia. Around the same time, two laryngologists from Britain, Donald Ross Paterson and Adam Brown-Kelly, pro- vided detailed clinical descriptions of this condition and also noticed its association with anemia and post-cricoid webs,4,5 helping establish this entity as an independent Correspondence: Amit Goel syndrome, a contribution recognized by the name “Paterson–Brown–Kelly syndrome”. Department of Gastroenterology, Sanjay This review uses the term PVS throughout because of its somewhat more frequent use Gandhi Postgraduate Institute of Medical Sciences (SGPGI), Rae Bareli Road, in the recent published literature. Lucknow 226014, India PVS is a rare condition that continues to be enigmatic, even though a century has Tel +91 522 249 5549 Email [email protected] passed since its first description.2 The literature available on its pathogenesis, treatment submit your manuscript | www.dovepress.com Journal of Blood Medicine 2017:8 175–184 175 Dovepress © 2017 Goel et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work http://dx.doi.org/10.2147/JBM.S127801 you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Goel et al Dovepress and natural history is limited to case reports, retrospective malnutrition, genetic predisposition, autoimmune processes short case series and a few large series.6,7 In this review, we and other dietary deficiencies (such as of pyridoxine or have attempted to collate the available information on PVS. riboflavin). Epidemiology Iron deficiency anemia It is interesting to note that, after passage of a century since IDA is the most extensively studied and currently the most its first description, literature on PVS is still restricted to case widely accepted causative association of PVS. The assumed reports and small case series.8–10 PVS has been reported from role of IDA in the formation of esophageal webs is based all parts of the world. In the initial decades after its descrip- primarily on: 1) its common association with such webs in tion, several reports of PVS emerged from Europe11–14 and patients with PVS, 2) a high prevalence of IDA in patients North America,15–17 reflecting its increasing recognition in the with post-cricoid dysphagia, 3) reports of improvement areas from where it was first described. However, with eco- in dysphagia and disappearance of esophageal web25 and nomic growth and improvement in nutrition in these regions, associated esophageal motility disturbances following iron the condition appears to have disappeared there. Instead, in therapy,26,27 and 4) the presence of risk factors for IDA, such the last few decades, PVS has been increasingly recognized as post-gastrectomy status, atrophic gastritis, achlorhydria in developing countries of Asia, with most of the reports com- and female gender, in patients with esophageal webs.28 ing from this continent.8,18–21 The sharp decline in reports on However, the IDA hypothesis fails to explain several PVS from the developed world has temporally coincided with observations, namely, the occurrence of webs in some patients the disappearance of iron deficiency, because of combined in the absence of IDA,29 lack of concordance between the effects of improved nutritional status and hygiene, reduced geographic distribution of IDA and esophageal webs, rarity worm infestation, iron supplementation and fortification of of web formation despite a high prevalence of IDA in African dietary substances with iron.22 Interestingly, despite a high populations, poor association of severity of IDA with the prevalence of IDA in Africa, PVS has rarely been reported severity of dysphagia, the exclusive post-cricoid location there, though this may reflect the low contribution of this of esophagus webs in patients with IDA, and the failure to continent to the published medical literature.10,20,23 induce similar lesions in animal models with iron deficiency.30 PVS is a rare condition, and the data on its incidence or Thus, though the current knowledge suggests a central prevalence rate are limited to a single population-based study role for IDA in predisposing the post-cricoid mucosa to web conducted in South Wales in early 1960s.14 In this study, formation, it does not appear to be adequate by itself and 1994 men and 2346 women were screened for post-cricoid appears to require the presence of some additional factors. dysphagia using a questionnaire followed by a barium study Further information on the role of iron in the formation of in those reporting symptoms. The prevalence of post-cricoid post-cricoid webs is available in an excellent review on the webs was found to be 0.3%–1.1% and 8.4%–22.4% among subject, albeit published several years ago.30 women overall and in women with dysphagia, respectively. None of the men were found to have a post-cricoid web.14 Other nutritional deficiencies In a large radiologic study from New York, 1000 con- Deficiencies of some B vitamins, such as riboflavin, thiamine secutive cineradiographs of the hypopharynx and cervical and pyridoxine, have been proposed as a cause for PVS, esophagus were examined, and esophagus webs were found though the evidence for this is weak and inconclusive. Muco- in 5.5% of these. However, of the 55 patients with webs, only sal changes in the oropharynx, such as stomatitis, atrophy of 6 had dysphagia attributable to these webs, and none met the the lingual epithelium, loss of lingual papillae and angular criteria for PVS.24 cheilosis, have been described in persons with riboflavin and pyridoxine deficiencies, and can be induced experimentally in Etiology animal models. Frequent occurrence of dysphagia, hypopha- The exact cause for PVS and of web formation remains ryngeal and oral cancers has been described among women unknown. Several hypotheses have been proposed to explain from remote rural areas in northern Sweden, where vitamin their pathogenesis, each supported by relatively weak evi- deficiencies were common, because of long winter seasons dence, consisting primarily of the clinical associations of and consequent poor supply of fresh vegetables, meat and esophageal
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