Dysphagia is defined as difficulty swallowing foods at the oropharyngioesophageal level. This worrisome symptom requries evaluation.
The definition of sideropenic dysphagia is clinical and biologic: one symptom, upper esophageal dysphagia, and one main biologic manifestation, iron deficiency anemia. A group of less important features consists of changes in the skin and mucosa (1). In 1919, Paterson and Kelly (2,3) described the association of iron deficiency anemia, postcricoid dysphagia, and upper esophageal stenosis secondary to esophageal webs. Previously, Plummer (4) reported cases of esophageal spasm. In 1922, Vinson (5) reported cases with anemia and iron deficiency that he considered secondary to dysphagia. The esophageal webs are thin and transverse, protruding toward the lumen of the esophagus. They are found in the anterior wall at the level of the cricopharyngeus muscle and spread laterally; sometimes they are circumferential, manifesting normal mucosa or subepithelial inflammatory reaction or epithelial atrophy with hyperkeratosis and intense mitotic activity. They may be single or multiple (6). The etiopathogenesis of the syndrome and, more specifically, of the esophageal webs is unclear. A number of factors, such as genetic, environmental, nutritional, immunologic, and infectious, acting in concert with the iron deficiency may all play a role in the development of the syndrome (7).
The diagnosis is clinical with progressive and long-standing dysphagia associated with iron deficiency anemia. Only 10% of patients with these symptoms develop upper esophageal webs (8), radiologic and endoscopic findings. The cineesophagogram is the most effective and useful method for detecting the webs. We can observe them as a fine indentation on the barium column that comes from the anterior wall of the proximal esophagus and that on occasion may be circumferential. Sometimes the webs are undetectable in a first study. Esophagoscopy shows the esophageal web as a thin diaphragm with pale, fragile, or normal appearing mucosa that partially obstructs the lumen of the esophagus. Esophagoscopy is difficult to carry out in extreme stenosis. In the majority of cases, oral iron treatment quickly improves the dysphagia, even before the anemia is corrected, but there are very symptomatic cases with persistent dysphagia in which endoscopic dilation or rupture of the web is necessary (1). The prognosis is good, despite the fact that the syndrome is associated with increased risk for pharyngeal and esophageal cancers (9).
To our knowledge, only eight cases of Plummer-Vinson syndrome in children and adolescents have been reported. We report a new case of this syndrome occurring in a 13-year-old boy. The nature of the condition and its relationship with iron deficiency are discussed.
A 13-year-old boy came to our hospital with a 7-month history of episodes of choking and progressive dysphagia with solids; in the last 2 months, he also had choking and dysphagia with liquids and had sialorrhea. The boy described feeling that food was sticking in his throat. Sometimes, spasmolytics had been administered because deglutition of food was impossible. At birth, he was diagnosed with a complete cleft palate that was surgically repaired at 2 years of age. He had secondary velopharyngeal insufficiency. At 12 years of age, during preoperative laboratory testing for phimosis, iron deficiency anemia was noted but not treated. The patient reported a longtime history of anorexia, which had worsened, after the onset of dysphagia. He also had slow growth. Results of physical examination were normal except for weight and length at the third percentile and a nasal voice.
Complementary tests included hemoglobin, 8 g/dL (normal range, 12.5–14 g/dL); hematocrit concentration, 26% (normal range, 37–43%); mean corpuscular volume, 54 fentoliters (fL) (normal range, 82–93 fL); transferrin, 375 mg/dL (normal range, 204–360 mg/dL); leucocyte count within normal range; platelets 528 × 10 9 /L (normal range, 150–450 × 10 9 /L); serum iron <8 μg/dL (normal range, 60–175 μg/dL ); ferritin 2 ng/dL (normal range, 10–300 ng/dL); and coagulation tests were normal. The serum glucose, urea, creatinine, triglycerides, cholesterol, uric acid, aminotransferases, calcium, phosphorus, alkaline phosphatase, creatine phosphokinase, and immunoglobulins were all within normal ranges. Stool test for occult blood was negative. Antinuclear antibodies, anti–smooth muscle, IgA-antigliadin, and IgA-antiendomysial tests were negative. The first barium esophagram study was normal. During esophagoscopy (under anesthesia), it was impossible to pass the endoscope at the pharyngeal level; it was also impossible to pass a nasogastric tube. The barium esophagram was repeated, and at the pharyngoesophageal level, we observed an indentation on the anterior wall that extended laterally toward both sides (Fig. 1) and a stenotic area that was 7 cm long. The rest of the esophagus was normal. With the suspicion of Plummer-Vinson syndrome, treatment with oral iron was started, causing rapid disappearance of episodes of dysphagia. Anorexia also disappeared, and the patient began to gain weight. Hematocrit, hemoglobin, serum iron, ferritin, and mean corpuscular volume progressively normalized.
After 6 months, another esophagoscopy was performed. In the proximal esophagus, we observed circumferential lesions with friable erosions and ulcerations. Below this area, we found an extended purplish lesion followed by whitish mucosa with ulcerations (Fig. 2). The pathologic study showed a chronic inflammatory process. In the distal esophagus, we observed an elongated, friable, pinkish lesion surrounded by granular mucosa, histologically compatible with mild esophagitis. Twenty-four hours of continuously monitoring the distal esophageal pH demonstrated a mild-to-moderate gastroesophageal reflux. Treatment with H-2 blockers and prokinetics was added with clinical response. Esophageal manometry showed esophageal hypertonic sphincters, especially the inferior, but normal relaxation during peristaltic waves, which had normal symmetry and length. Further esophagoscopic tests were normal.
Plummer-Vinson syndrome in children is rare (10–15). Most patients described are over 13 years old. In our patient, iron deficiency was of nutritional origin, with poor chronic daily intake because of a prolonged anorexia accentuated since the onset of dysphagia. There was no occult blood in the stools. Oral iron treatment quickly improved the dysphagia.
The incidence/prevalence of the syndrome is difficult to estimate. Elwood et al. (16) reported a 10% prevalence. Most patients are middle-aged women and anemia is related to blood losses from pregnancies and menses. It has also been described in North Africa (1), in association with the iron deficiency anemia in celiac disease (17), and in Sjögren syndrome (18). Nowadays, it is less frequent because of improved nutrition and the recognition and treatment of ferropenic anemia (7).
The etiology and pathogenesis of Plummer-Vinson syndrome has been attributed to numerous factors (7) that include alterations in esophageal innervation (2). There is agreement that prolonged iron deficiency is necessary for the development of the syndrome; however, only a minority of patients with iron deficiency manifests the syndrome. Individual factors acting together may play an important role in the development of the syndrome. Other factors that have been studied are environmental; genetic, with no demonstrated association with HLA (19); and immunologic. Chisholm (9) investigated the relationship between autoimmunity and Plummer-Vinson syndrome to determine the incidence of autoantibodies in patients with iron deficiency, with or without webs, and compared them to a control group. A high incidence of antithyroid antibodies were found in both patient groups with iron deficiency compared with control subjects; however, no other autoimmune antibodies including antibodies specific to pharyngeal tissue were detected. No significant difference was found between patients with iron deficiency, with or without webs, confirming that autoimmune reactivity does not play a role in the pathogenesis of the syndrome.
With regard to the relationship between anemia and dysphagia, evidence in the literature suggests that the esophageal webs or stenosis are related to iron deficiency. Shamma'a et al. (20) showed a 66% association between iron deficiency and esophageal stenosis. Similar results were reported by a Swedish group (9). Cameron (21) showed that analytically demonstrated anemia preceded the onset of dysphagia in 20% of the cases, as in our patient.
The cause of dysphagia has been equally confusing because the webs often are undetected in the cases with anemia and dysphagia (22). Some authors attribute this to a mechanical obstruction (23), whereas others believe that it is caused by a spasm of the upper esophagus (3). Dysphagia in patients with a normal esophagus also has been reported, attributed to muscular impairment in food propulsion with an increase in intrabolus pressure. Iron treatment normalized these pressures, as shown by manometric studies. Moreover, the disappearance of dysphagia after iron treatment precedes the reduction of esophageal webs, as occurred in our patient. However, iron deficiency may produce myasthenic changes of the muscles related to deglutition. These changes are similar to those observed in progressive muscular dystrophy (24). Therefore, a lack of iron may clearly harm esophageal motility. This supports the etiologic role of iron deficiency in the syndrome's pathogenesis and can explain why some patients with normal esophagi shown in the endoscopy may note resolution of their symptoms with iron treatment alone.
The effect of iron deficiency on iron-dependent enzymes has not been taken into consideration, although clinical evidence suggested that changes in the hemoglobin content alone could not explain all the patients' abnormalities. Impairments of oxidative phosphorylation with a decrease in cytochrome c levels have been reported. This decrease parallels the reduction of muscular myoglobin. In organs with a high cell turnover, such as in the alimentary tract, the iron-dependent enzymes rapidly lose their activity with iron deficiency and are very sensitive to it (25). Therefore, histologic changes characteristic of this iron deficiency may contribute to web formation. Iron treatment is tissue specific (26), and this high cell turnover permits rapid recovery, explaining the rapid improvement of dysphagia after therapy with iron (27).
Plummer-Vinson syndrome is uncommon. This is the reason for the report of this new case. In all upper esophageal dysphagia, with or without stenosis, the origin may be iron deficiency. This case highlights that we must always think in this possibility when investigating its etiology. Thus, because Plummer-Vinson is considered a precancerous condition, we shall avoid recurrence and will begin a follow-up program.
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