Plummer-Vinson syndrome is a condition that affects mostly middle-aged caucasian women and is defined by the triad of iron deficiency anemia, upper esophageal webs and postcricoid dysphagia. Given that it can involve iron deficiency (sideropenia) without anemia, it has been also called sideropenic dysphagia.
Dysphagia is the most prominent symptom in patients with PVS and is usually painless, intermittent to progressive, limited to solid food and sometimes associated with weight loss [18]. The presence of esophageal webs can also manifest with severe choking spells or aspiration. Iron deficiency is exhibited with symptoms typical for anemia, such as weakness, fatigue, dyspnea and tachycardia. Other manifestations of iron deficiency anemia are angular cheilitis, glossitis, koilonychia (spooned nails) and pallor [3] [19]. Patients with PVS can also present very uncommonly with splenomegaly, loss of teeth and an enlarged, nodular thyroid [3].
Workup in patients suspected to have PVS starts with diagnostic tests to confirm iron-deficiency anemia. These include a complete blood count (CBC), a peripheral blood smear and iron studies, such as serum iron, ferritin levels, total iron binding capacity (TIBC) and saturation percentage. Other tests are added, if needed.
Esophageal webs are usually detected with esophagograms or videofluoroscopy [3] [20]. A regular barium swallow can detect esophageal webs and is usually best performed with a lateral view. It would show thin projections of the anterior esophageal wall and the postcricoid. Sometimes these webs can be multiple. In case the barium swallow is negative or equivocal and the physician still maintains a high index of suspicion for PVS, a video swallow study is usually the next adequate diagnostic test. The video swallow test has the ability to distinguish true webs from false webs, which are usually caused by mucosal foldings and submucosal phenomena. Esophagogastroduodenoscopy is another potential diagnostic modality. It needs to be done very carefully, so as not to rupture the web. Otherwise, esophageal webs would go undetected. The web usually consists of a smooth, thin, gray mucosal membrane covered by squamous epithelium. They are present on the anterior esophageal walls of the proximal esophagus and extend laterally, but not to the posterior wall and are mostly crescent-shaped, although some are concentric [20].
Diagnosis is established by the confirmation of iron deficiency anemia in addition to the presence of dysphagia and one or multiple esophageal webs.
Treatment of PVS mostly occurs in the outpatient department. Iron therapy is the cornerstone for the treatment of iron deficiency anemia and is necessary for the resolution of anemia symptoms that accompany the disorder. Continuous iron supplementation beyond what is needed for the treatment of anemia is usually not required and has not proven effective [21].
Dysphagia can sometimes resolve with iron supplementation alone if not particularly severe, but obstructive dysphagia resulting from more advanced webs is better managed with mechanical dilation [22]. The passing of an endoscope can sometimes be sufficient in disrupting the web structure. Mechanical dilation is performed with the passage of a bougie (for example a Savary dilator) with a diameter of up to 17 mm after the endoscopic placement of a guidewire [23]. It is generally more appropriate to insert a single large dilator than to repeat the process more than once. Endoscopy is rarely performed under fluoroscopic guidance, unless the mechanical obstruction is so severe that it prevents the passage of the endoscope. Balloon dilation is not adequate, given the proximal location of the web, although reports of its use have been described when performed under fluoroscopic guidance [24] [25] [26]. Laser therapy and needle-knife electroincision are other potential therapeutic modalities, but their use is rarely required [27] [28] [23]. Surgery is reserved only for recalcitrant webs or those associated with Zenker diverticulum.
A change in dietary habits is important in the treatment of the disease. Solid food, especially meat, should be cut in small pieces and patients need to be advised to chew thoroughly and eat slowly.
Finally, because of the significant association of PVS with upper gastrointestinal carcinomas, patients need to be followed closely. A yearly surveillance with upper gastrointestinal endoscopy is recommended, although the effectiveness of this measure has not been confirmed [22].
Prognosis of PVS is excellent when it is not complicated by hypopharyngeal or esophageal carcinoma [14] [15]. The disease responds very well to a combination of iron supplementation, dietary changes and esophageal dilation. Morbidity is mostly related to dietary changes and repeated esophageal dilation in patients with recurrent dysphagia, with an increased risk of esophageal perforation. Mortality figures are uncertain, given the rarity of the disease, although it is thought that PVS has very low mortality.
Around 3 to 15% of patients with PVS ultimately develop cancers of the upper gastrointestinal tract (pharynx and esophagus) [12] [16]. These relatively high rates necessitate frequent follow-up and supervision of patients with PVS. Recent data demonstrate a decrease in the rate of cancer of the hypopharynx among women, probably because of a decrease in the prevalence of PVS and better follow-up [17]. Prognosis for the disease worsens significantly when cancer is diagnosed.
The cause of Plummer-Vinson syndrome remains unknown, although several factors have been proposed, including iron and other nutritional deficiencies, a genetic predisposition and autoimmune mechanisms [7]. The most prominent theory attributes the syndrome to iron deficiency, given its involvement in the classic defining triad of the syndrome and the positive response of dysphagia and esophageal webs to iron supplementation.
The prevalence of PVS was considerably more elevated in the first half of the 20th century and then displayed a steep decline with the concomitant improvements in nutritional status, particularly with the addition of iron supplements to flour [8]. Nowadays, it is mostly found in northern European countries among middle-aged white women in the age range of 40 to 70 years, although cases involving children and adolescents have also been reported [9] [10]. It is worth noting that despite widespread malnutrition and iron deficiency in African populations, the disease remains very rare amongst this population[8].
The pathophysiology of PVS is unknown, although several theories have been proposed. They mostly involve iron deficiency, malnutrition, genetic predisposition and autoimmunity [7] [11].
The most prominent theory identifies iron deficiency as the causative mechanism and postulates that such a deficiency leads to a depletion of critical oxidative enzymes, ultimately resulting in atrophy of the esophageal mucosa, formation of webs and disturbances in muscle fiber involved in swallowing. The validity of this theory remains unaccepted and is based mostly on studies showing an improvement of dysphagia with iron supplementation, in addition to sparse and anecdotal reports of a positive response of impaired esophageal motility in patients with PVS to iron therapy [6] [12]. Nonetheless, other scientific work has cast doubt on this mechanism. Large population-based studies failed to find any association between dysphagia and anemia or sideropenia, while other work demonstrated that patients with esophageal webs are just as likely to be iron deficient as control subjects and that esophageal webs can be commonly found in patients without iron deficiency or dysphagia [6].
On the other hand, the association of PVS with several autoimmune conditions such as rheumatoid arthritis, pernicious anemia, celiac disease and thyroiditis has fueled speculation that PVS is an autoimmune disorder [7] [13]. One study reported that patients with PVS had significantly elevated levels of thyroid cytoplasmic autoimmune antibodies, when compared to control subjects with iron deficiency [7]. Overall, however, the autoimmune theory is not widely accepted.
Iron supplementation, either through dietary changes or the administration of ferrous preparations, can prevent the development of the disease in patients with or without iron deficiency anemia. It can also resolve the condition if malignancy has not yet developed.
Plummer-Vinson syndrome (PVS) is a rare disorder characterized by a triad of dysphagia, esophageal webs and iron deficiency anemia [1] [2] [3] [4] [5]. In the United States, it is also known as Paterson-Brown-Kelly syndrome. It is also associated with a significantly increased risk of squamous cell carcinoma of the pharynx and the esophagus. PVS is mostly prevalent among Caucasian middle-aged women with a history of chronic iron deficiency anemia [6]. The cause of PVS has not been established, but it is believed that a deficiency in iron leads to depletion of important oxidative enzymes and the development of myasthenic phenomena that are displayed by muscles that mediate swallowing, as well as mucosal and submucosal atrophic alterations. Patients with PVS usually present with dysphagia and symptoms of anemia, such as fatigue, weakness and dyspnea. Diagnosis is established by the presence of dysphagia and independent confirmation of iron deficiency anemia and esophageal webs. The latter is most commonly identified with barium swallow, X-Rays or videofluoroscopy. PVS usually responds to iron therapy although esophageal obstruction necessitates endoscopy and dilation. Close follow-up and periodic upper gastrointestinal endoscopy are recommended to monitor any development of cancer. PVS can be prevented in patients with chronic iron deficiency through iron supplementation and prognosis is excellent if the disease is not complicated by the development of esophageal or pharyngeal cancer.
Plummer-Vinson syndrome (PVS) is a rare disorder that manifests mostly among middle-aged white women suffering from chronic iron deficiency anemia. Patients with this condition typically develop webs of thin tissue that can block the upper third of the alimentary tract known as the esophagus, leading to problems in swallowing food.
The exact cause of this disorder is unknown but scientists suspect that a deficiency in iron (as well as other nutrients) and genetic causes play a major role. Iron is an important component of many biochemical reactions in our body and its deficiency is thought to impair the muscles involved in normal swallowing, as well as the tissue that lines the esophagus (esophageal mucosa).
Patients with PVS most commonly complain of a difficulty in swallowing (dysphagia), usually regarding solid food, that is not associated with pain, as well as symptoms of anemia such as fatigue, weakness, pallor and shortness of breath. In order to diagnose the disease, the doctor will perform a number of blood tests to confirm iron deficiency anemia. Esophageal webs are best identified with a barium swallow X-Ray or a video swallow test that enables the doctor to visualize any webs of tissue limiting the patency of the esophagus.
PVS is most commonly treated with iron supplementation, although severe obstruction of the esophagus requires mechanical intervention. This is done by mechanically rupturing the esophageal webs using a dilator or an endoscope. Patients with PVS usually respond very well to treatment. Nonetheless, the major risk of PVS is the development of cancer of the esophagus and throat, which illustrates the importance of regular follow up with a doctor if diagnosed. General recommendations suggest the performance of a yearly endoscopy of the upper gastrointestinal tract to detect the development of any possible cancer. The development of PVS in patients who are iron deficient can be prevented with iron supplementation.