Plummer-Vinson syndrome, PVS

Paterson-Kelly syndrome

Paterson-Brown Kelly syndrome

Sideropenic dysphagia

Plummer-Vinson syndrome is defined by the classic triad of dysphagia, iron-deficiency anemia and esophageal webs. Even though the syndrome is very rare nowadays, its recognition is important because it identifies a group of patients at increased risk of squamous cell carcinoma of the pharynx and the esophagus.

The syndrome eponym has been frequently discussed 12. The most used name is Plummer-Vinson syndrome, named after Henry Stanley Plummer (1874–1936) and Porter Paisley Vinson (1890–1959) who were physicians on the staff of the Mayo Clinic. In 1912, Plummer reported a series of patients with long-standing iron deficiency anemia, dysphagia and spasm of the upper esophagus without anatomic stenosis, which was described as hysterical 3. In 1919 Vinson reported another case of 'angulation' of the esophagus and attributed the first description of this entity to the earlier report of Plummer 4. Some years later he published a series of patients with dysphagia who were successfully treated with the passage of bougies; most of the patients were women 5.

Another term is Paterson-Kelly syndrome, named after Donald Ross Paterson (1863–1939) and Adam Brown-Kelly (1865–1941), both British laryngologists, who published their findings independently in 1919 67. They were the first to describe the characteristic clinical features of the syndrome. Paterson gave the fullest description but without reference to anemia. He was also the first to draw attention to an association with post-cricoid carcinoma. Brown-Kelly not only described the signs and symptoms of the condition, but also considered anemia.

Exact data about incidence and prevalence of the syndrome are not available. In the first half of the 20th century Plummer-Vinson syndrome seemed to be common in Caucasians of Northern countries, particularly among middle-aged women 8. Nowadays, it is extremely rare. In a series of 1000 consecutive patients who underwent a cineradiographic examination of the hypopharynx and cervical esophagus, webs were found in 5.5% of the cases but only six patients had dysphagia attributable to the webs, and none of the patients fulfilled the criteria for Plummer-Vinson syndrome 9. Only case reports (rather than series of patients) have been published in the literature in recent years. The rapid fall in the prevalence of the syndrome correlates with the improvement of nutritional status and disappearance of the widespread iron deficiency in countries where the syndrome had been previously described 10. In Africa, where both iron deficiency and malnutrition are common, the syndrome is very rare.

The main clinical features of Plummer-Vinson syndrome are postcricoid dysphagia, upper esophageal webs and iron deficiency anemia. Most of the patients are white middle-aged women, in the fourth to seventh decade of life 811 but the syndrome has also been described in children and adolescents 121314. The dysphagia is usually painless and intermittent or progressive over years, limited to solids and sometimes associated with weight loss. Symptoms resulting from anemia such as weakness, pallor, fatigue and tachycardia may dominate the clinical picture. Furthermore, it is characterized by glossitis, angular cheilitis and koilonychia (spoon-shaped finger nails). Enlargement of the spleen and thyroid may also be observed 11.

Plummer-Vinson syndrome has been identified as a risk factor for developing squamous cell carcinoma of the upper gastrointestinal tract. Three to 15 per cent of the patients with Plummer-Vinson syndrome, mostly women between 15 and 50 years of age, have been reported to develop esophageal or pharyngeal cancer 1516. A decreasing trend in the overall incidence of hypopharyngeal cancer in women was demonstrated, probably due to diminished prevalence of Plummer-Vinson syndrome 17.

The diagnosis is based on the evidence of iron-deficiency anemia and one or more esophageal webs in a patient with postcricoid dysphagia. Esophageal webs can be detected by barium swallow X-ray but the best way for demonstration is the videofluoroscopy 1137. Webs are also detectable by upper gastrointestinal endoscopy. They appear smooth, thin, and gray with eccentric or central lumen. The webs typically occur in the proximal part of the esophagus and may be missed and accidentally ruptured unless the endoscope is introduced under direct visualization 11.

The esophageal webs, which can also occur in the absence of anemia and Plummer-Vinson syndrome, are characterized by one or more thin horizontal membranes consisting of squamous epithelium and submucosa. They usually protrude from the anterior wall, extending laterally but not to the posterior wall, which means that they rarely encircle the lumen.

Laboratory examinations typically reveal iron deficiency anemia with decreased values of hemoglobin, hematocrit, mean corpuscular volume, serum iron and ferritin, and increased total iron binding capacity. Further laboratory abnormalities are usually not described.

Since dysphagia is a main clinical feature of Plummer-Vinson syndrome, the differential diagnosis includes all other causes of dysphagia especially malignant tumors, benign strictures or esophageal rings. Other reasons for dysphagia are diverticula, motility disorders such as achalasia, spastic motility disorders, scleroderma, diabetes mellitus, gastroesophageal reflux disease, and neuromuscular and skeletal muscle disorders.

The pathogenesis of Plummer-Vinson syndrome is unknown. The most important possible etiological factor is iron deficiency. This theory is primarily based on the finding that iron deficiency is a part of the classic triad of Plummer-Vinson syndrome together with dysphagia and esophageal webs and that dysphagia can be improved by iron supplementation. Indeed, impaired esophageal motility has been described in Plummer-Vinson syndrome and it was corrected by iron treatment 3839. It has been shown that iron deficiency can precede dysphagia 39. On the other hand, the alimentary tract is susceptible to iron deficiency; it rapidly loses iron-dependent enzymes due to its high cell turnover, which is speculated to cause mucosa degeneration and web formation. However, large clinical series suggested that for many patients iron deficiency is neither a necessary nor a sufficient cause of web formation 915.

Other etiologic factors including malnutrition, genetic predisposition or even autoimmune processes have been proposed. The latter is based on the association between Plummer-Vinson syndrome and certain autoimmune disorders such as celiac disease (which was the most frequently mentioned associated disease in the case reports published in recent years), thyroid disease and rheumatoid arthritis 19202226272940.

The first step in the management of Plummer-Vinson syndrome is to clarify the cause of iron deficiency in order to exclude active hemorrhage, malignancy or celiac disease.

Plummer-Vinson syndrome can be treated easily and effectively with iron supplementation and mechanical dilation. Iron supplementation alone can resolve dysphagia in many patients 11. However, in case of significant obstruction of the esophageal lumen by esophageal web and persistent dysphagia despite iron supplementation, rupture and dilation of the web should be performed. After endoscopic placement of a guidewire, dilators with a diameter of up to 17 mm can be used 41. Usually only one dilation is enough to relieve dysphagia, but occasionally multiple sessions are required. Also successful balloon dilation has been described 33. Since the Plummer-Vinson syndrome is associated with an increased risk of squamous cell carcinoma of the pharynx and the esophagus, the patients should be followed closely. A surveillance upper gastrointestinal endoscopy is recommended every year, even though the effectiveness of this recommendation is not definitively confirmed 11.

Prognosis of the Plummer-Vinson syndrome is excellent. As described above, dysphagia and anemia can be treated effectively. In case of an associated squamous cell carcinoma of the hypopharynx or upper esophagus the prognosis worsens dramatically.