Dear Editor,

Iron deficiency anemia (IDA) is one of the most common nutritional diseases worldwide. The basic treatment for IDA is oral iron medication; however, some patients with IDA are occasionally refractory to this type of therapy [1]. Recently, the role of Helicobacter pylori in the etiology of IDA has become a focus of considerable interest [2, 3]. Although the association of H. pylori with IDA has been examined extensively, most studies have focused on mild IDA in school-aged children and young people [4–6]. Here, we report two adult cases of severe IDA refractory to oral iron therapy in which the anemia was dramatically and promptly improved by H. pylori eradication (Fig. 1).

Fig. 1
figure 1

Clinical courses of cases 1 and 2. Refractory IDA was promptly improved by oral iron administration after H. pylori eradication and did not recur after withdrawal of iron therapy in both cases

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FormalPara Case 1

A 73-year-old male was referred to our hospital because of severe anemia. He had been receiving oral iron (100 mg/day) therapy for more than 6 months, but his anemia had not improved significantly. Laboratory examinations revealed severe IDA (red blood cell count 269 × 1010/l, hemoglobin 4.7 g/dl, hematocrit 17.5 %, mean corpuscular volume 65.1 fl, mean corpuscular hemoglobin concentration 17.5 pg, serum iron 8 μg/dl, serum ferritin 4.7 ng/ml, unsaturated iron binding capacity 487 μg/dl). Endoscopic examination of the upper and lower gastrointestinal (GI) tract revealed mild atrophic gastritis with H. pylori infection, but no bleeding was detected in any part of the GI tract. A stool occult blood test gave a negative result. CT examination also revealed no abnormalities. Because oral iron therapy had failed in this patient, iron was administered intravenously, and this resulted in a gradual increase in the hemoglobin level. H. pylori eradication was performed using a standard regimen of amoxicillin, clarithromycin, and lansoprazole. Eradication was successful, and iron was then administered orally (100 mg/day). In contrast to the lack of response to oral iron therapy before H. pylori eradication, the patient’s hemoglobin level promptly increased to normal. Since discontinuation of iron therapy, IDA has not recurred for more than 3 years.

FormalPara Case 2

A 36-year-old male was referred to our hospital because of severe IDA that was refractory to oral iron therapy. Laboratory examinations revealed the following values: red blood cell count 235 × 1010/l, hemoglobin 4.6 g/dl, hematocrit 17.0 %, mean corpuscular volume 72.3 fl, mean corpuscular hemoglobin concentration 19.6 pg, serum iron 10 μg/dl, serum ferritin 5.3 ng/ml, and unsaturated iron binding capacity 453 μg/dl. Endoscopic examination of the whole GI tract and CT scan revealed no abnormalities. Since H. pylori infection was detected, H. pylori eradication was performed. Similarly to the clinical course in case 1, IDA was promptly improved by oral iron administration. This patient also has shown no recurrence of IDA for more than 2 years after withdrawal of iron therapy.

Although an association between H. pylori infection and IDA has been established, it is still unknown how H. pylori mediates the pathogenesis of IDA. However, a number of possible mechanisms have been proposed, including impairment of gastric acidity by H. pylori infection [7]. Recently, it has been reported that H. pylori directly perturbs iron trafficking in epithelial cells [8, 9]. That is, CagA of H. pylori is able to alter the internalization, intracellular transport, and polarity of the transferrin/transferrin receptor iron uptake system [9]. The prompt improvement of iron adsorption observed after H. pylori eradication in the present two cases strongly suggests a direct interaction between H. pylori and iron transport. As it has also been reported that IDA accelerates H. pylori-induced carcinogenesis [10], H. pylori eradication is highly recommended in patients with IDA.