Introduction
Background
The association of postcricoid dysphagia, upper esophageal webs, and iron deficiency anemia is known as Plummer-Vinson syndrome (PVS) in the United States and Paterson-Brown Kelly syndrome in the United Kingdom. The term sideropenic dysphagia has also been used, since the syndrome can occur with iron deficiency (sideropenia), but it is not associated with anemia.
Pathophysiology
The pathogenesis of PVS remains speculative. Recently, even the existence of the syndrome has been challenged. Postulated etiopathogenic mechanisms include iron and nutritional deficiencies, genetic predisposition, and autoimmune factors, amongst others.
The prevalent iron deficiency theory remains controversial. Older reports have implicated iron deficiency in the pathogenesis of esophageal webs and dysphagia in predisposed individuals. The depletion of iron-dependent oxidative enzymes may produce myasthenic changes in muscles involved in the swallowing mechanism, atrophy of the esophageal mucosa, and formation of webs as epithelial complications.
The improvement in dysphagia after iron therapy provides evidence for an association between iron deficiency and postcricoid dysphagia. Anecdotal reports have also been made of patients with PVS exhibiting impaired esophageal motility (with dysphagia) that recovers following iron therapy. Moreover, the decline in PVS seems to parallel an improvement in nutritional status, including iron supplementation.
However, population-based studies have shown no relationship between postcricoid dysphagia and anemia or sideropenia. Other studies have demonstrated that patients with webs are as likely to be iron deficient as controls, and webs are often found in patients without iron deficiency or dysphagia. Lastly, the iron deficiency theory does not explain the predilection of webs for the upper esophagus and the rarity of the syndrome in populations in which chronic iron deficiency is endemic (eg, eastern and central Africa).
PVS has also been viewed as an autoimmune phenomenon. The syndrome has been associated with autoimmune conditions, such as rheumatoid arthritis, pernicious anemia, celiac disease, and thyroiditis. In one study, a significantly higher proportion of patients with PVS had thyroid cytoplasmic autoimmune antibodies compared to controls with iron deficiency. The autoimmune theory, however, has gained little acceptance to date.
A complicated inlet patch (heterotopic gastric mucosa) has also been implicated in the pathogenesis of PVS. An ulcerated inlet patch in the upper esophagus can cause stricturing (weblike formation) and bleeding (with subsequent iron deficiency). However, most studies with biopsy or autopsy specimens have not demonstrated the presence of gastric metaplasia in the samples.
Frequency
United States
Reliable prevalence data on PVS are lacking. The syndrome is now a rarity, and its decline has been attributed to better nutrition and health care. Webs may be found in 5-15% of selected patients presenting with dysphagia, but most of these patients do not have PVS.
International
In the first half of the 20th century, PVS was a relatively common finding, particularly among middle-aged Scandinavian women. The rapid fall in prevalence of the syndrome in the latter part of the 20th century has paralleled an improvement in nutritional status, including widespread addition of iron to flour.
Mortality/Morbidity
Morbidity issues primarily relate to diet modification and repeat esophageal dilations (with a small risk of perforation) in patients with PVS who have recurrent dysphagia. Updated mortality data are unavailable for this rare syndrome, but, presumably, mortality is low.
Race
PVS has mainly been described in whites.
Sex
PVS is more frequently observed in women. In earlier studies from Scandinavia, up to 90% of patients were women.
Age
The typical age range at diagnosis is 40-70 years. A handful of cases have been reported in children.
Clinical
History
* Dysphagia, if present, is typically intermittent and limited to solids. It is usually felt in the throat.
* Choking spells and aspiration may occur because of the proximal location of the web.
* Weakness, fatigue, and dyspnea are secondary to iron deficiency anemia.
* Weight loss is uncommon.
Physical
* Manifestations of iron deficiency (with or without anemia) may be evident, including the following:
o Angular cheilitis
o Glossitis
o Koilonychia (spoon nails)
o Pallor
* Splenomegaly, edentia, and enlarged nodular thyroid glands are also described in a few patients with PVS.
Causes
* The cause of PVS is unclear. Proposed etiopathogenic mechanisms include iron and nutritional deficiencies, genetic predisposition, and autoimmunity.
* Seek the underlying cause of iron deficiency anemia (eg, gastrointestinal blood loss, celiac sprue).Differential Diagnoses
Esophageal Cancer
Esophageal Webs and Rings
Hypopharyngeal Cancer
Iron Deficiency Anemia
Other Problems to Be Considered
* Heterotopic gastric mucosa (inlet patch) with stricture
* Pill-induced stricture
* Hypopharyngeal bar (to differentiate from a web)
* Inflammatory conditions associated with web formation (eg, blistering skin diseases, chronic graft versus host disease)
Workup
Laboratory Studies
* Perform CBCs, peripheral blood smears, and iron studies (eg, serum iron, total iron-binding capacity [TIBC], ferritin, saturation percentage) to confirm iron deficiency, with or without hypochromic microcytic anemia.
Imaging Studies
* Barium esophagram and videofluoroscopy
o They are the most sensitive methods and diagnostic tests of choice to detect esophageal webs.
o Conventional barium swallow may detect the web, which characteristically appears as a thin projection off the postcricoid, anterior esophageal wall. The web is best visualized on lateral view (see following image). On occasion, multiple webs can be observed.
o
Postcricoid web. Courtesy of Alan Cameron, MD.
Postcricoid web. Courtesy of Alan Cameron, MD.
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Postcricoid web. Courtesy of Alan Cameron, MD.
Postcricoid web. Courtesy of Alan Cameron, MD.
o If conventional barium swallow findings are negative or equivocal and a high index of suspicion remains, a video swallow study can be performed. The latter can distinguish subtle true webs from weblike formations (false webs) due to insignificant mucosal foldings and submucosal phenomena.
Other Tests
* Order specific tests, as necessary, for evaluation of the etiology of iron deficiency.
Procedures
* Esophagogastroduodenoscopy
o A thin web can be easily ruptured and can go unnoticed during passage of the endoscope into the upper esophagus. If webbing is suspected, the endoscope should be advanced carefully under direct vision through the upper esophageal sphincter. The web typically appears as a thin mucosal membrane covered by normal squamous epithelium. Most webs are located along the anterior esophageal wall in the shape of a crescent (see following images), but a few are concentric.
o
Upper esophageal web.
Upper esophageal web.
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Upper esophageal web.
Upper esophageal web.
o
Upper esophageal web.
Upper esophageal web.
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Upper esophageal web.
Upper esophageal web.
o Carefully examine the upper esophagus for presence of an inlet patch. The differential diagnosis at endoscopy should also include inflammatory or infectious stricture, postcricoid cancer, or extrinsic compression from a submucosal venous plexus.
o Potential causes of iron deficiency anemia may be found, including Cameron erosions within a large diaphragmatic hernia or angioectasias. It is also prudent to obtain small bowel biopsies at the time of endoscopy to exclude villous atrophy from celiac sprue as the cause of iron deficiency anemia.
Histologic Findings
The web is composed of a thin layer of normal squamous mucosa and submucosa. Sometimes, chronic inflammatory cells may be observed in the submucosa.Treatment
Medical Care
* Treat iron deficiency and its underlying cause.
o Iron replacement is necessary to correct the anemia, if present, and to resolve most of the physical signs of iron deficiency. The necessity for continued iron treatment is doubtful other than for anemia correction.
o Dysphagia may improve with iron replacement alone, particularly in patients whose webs are not substantially obstructive. Dysphagia caused by more advanced webs is unlikely to respond to iron replacement alone and, thus, is managed with mechanical dilation.
o Address the cause of the iron deficiency (eg, celiac sprue, bleeding angiectasias).
* Treat dysphagia and the web.
o Aside from iron replacement, diet modification may be sufficient in mildly symptomatic patients (see Diet). Those with significant and long-standing dysphagia usually require mechanical dilation. The web can often be disrupted during simple passage of the endoscope into the esophagus. Otherwise, passage of a bougie (eg, Savary dilator) is quite effective. In most cases, passage of a single large dilator is adequate and is thought to be more effective than serial progressive dilations.
o Fluoroscopic guidance is usually not required unless a tight web precludes further passage of the endoscope. The proximal location of the webs in PVS makes endoscopic balloon dilation difficult, but it has been performed successfully by radiology under fluoroscopic guidance.
o ND:YAG laser therapy has also been reported as a successful means of disrupting an esophageal web. This modality is rarely required.
Surgical Care
* Surgery is rarely needed and is reserved for patients whose webs are recalcitrant to dilation or associated with Zenker diverticulum.
Consultations
* Gastroenterologists - For management of dysphagia requiring dilation
Diet
* Advise patients to eat slowly and chew thoroughly. Solid foods should be prepared and cut in small pieces, especially meats.
Activity
Unrestricted
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Iron preparations
Iron replacement is an important component of the treatment of PVS.
Ferrous sulfate (Feosol)
A nutritionally essential inorganic substance used to treat iron deficiency anemia associated with PVS.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
325 mg PO qd or divided bid/tid
Pediatric
<15 kg: 5 mg/kg/d PO
15-30 kg: 1/2 adult dose PO
>30 kg: Administer as in adultsFollow-up
Further Inpatient Care
* PVS is usually managed on an outpatient basis.
Further Outpatient Care
* Perform follow-up CBCs and iron studies in 3 months, after initiation of iron replacement, to document resolution of sideropenia and anemia.
* Provide follow-up care for patients whose treatment has been initiated for the specific cause, if any, of the iron deficiency anemia.
* Repeat esophageal dilations may be required in patients with recurrent dysphagia.
Inpatient & Outpatient Medications
* Ferrous preparations are administered to correct the deficiency in iron (with or without anemia).
Complications
* Although reports are inconsistent, patients with PVS seem to be at an increased risk for hypopharyngeal and esophageal cancers.
o A high prevalence of hypopharyngeal cancers in Swedish women in the 1930s and 1940s was attributed to PVS.
o The reported frequency of postcricoid carcinoma associated with PVS varies (4-16% in older studies) and remains a matter of debate.
Prognosis
* Prognosis is generally good, unless PVS is complicated by hypopharyngeal or esophageal carcinoma. Patients with PVS usually respond well to iron therapy, diet modification, and, if necessary, esophageal dilation.
Patient Education
* Instruct patients with PVS on dietary modification and eating habits.
* Educate patients with PVS about the potential association of PVS and hypopharyngeal and esophageal cancers to ensure appropriate follow-up care.
* For excellent patient education resources, visit eMedicine's Arthritis Center; Blood and Lymphatic System Center; Esophagus, Stomach, and Intestine Center; and Endocrine System Center. Also, see eMedicine's patient education articles Rheumatoid Arthritis, Anemia, Celiac Sprue, and Thyroid Problems.
Miscellaneous
Medicolegal Pitfalls
* Consider endoscopy to exclude alternative and/or serious diagnoses, such as upper esophageal carcinoma.
* No guidelines are established for cancer surveillance in patients with PVS. Some authors endorse regular (annual or biennial) endoscopic surveillance to exclude malignancy in patients with bona fide PVS. This is a reasonable precaution.
Special Concerns
* The major concern in patients with PVS is the potential increased risk for upper gastrointestinal tract cancer, as described above.
