Objectives: Long-term follow-up studies with Helicobacter pylori eradication therapy in children with H. pylori -associated iron-deficiency anemia (IDA) are scarce. We investigated whether successful H. pylori eradication would result in maintaining resolution of recurrent and/or refractory IDA in a cohort of teenagers in Japan. Methods: In this case series, 7 H. pylori -infected patients with recurrent and/or refractory IDA (12–16 y old) received successful eradication therapy and were then followed for a median of 20 months (range, 9–76 mo) after oral iron supplementation therapy (1–4 mo) was discontinued. Five patients of our study cohort participated in rigorous sports activities. Results: No visual appearance of ulcerations or erosions was found by esophagogastroduodenoscopy. In all patients studied, the gastric biopsies showed histological evidence of chronic gastritis without significant atrophy and intestinal metaplasia. Compared with the baseline (median values: hemoglobin, 6.3 g/dL; serum iron, 9 μg/dL; serum ferritin, 1.5 ng/mL), values of hemoglobin ( P < 0.001), serum iron ( P < 0.005), and ferritin ( P < 0.001) significantly increased, on average, 2–3 months after eradication therapy and these iron indices were maintained at the same or higher levels at the endpoint of follow-up (median values: 14.2 g/dL, 102 μg/dL, and 29.3 ng/mL, respectively). No patient had recurrence of IDA at the time of final follow-up. Conclusions: H. pylori infection can be closely associated with recurrent or refractory IDA in teenage children. It is speculated that increased iron demands as a result of growth spurt in adolescents may play a synergistic role in combination with H. pylori in the pathogenesis of IDA.

Many epidemiological studies and meta-analyses show that persistent Helicobacter pylori infection in the gastric mucosa can lead to iron deficiency or iron deficiency anemia (IDA), particularly in certain populations of children and adolescents. Moreover, it has been demonstrated that H. pylori infection can lead to and be closely associated with recurrent and/or refractory iron deficiency and IDA. However, the pathogenesis and specific risk factors leading to this clinical outcome in H. pylori-infected children remain poorly understood. In general, most of pediatric patients with H. pylori-associated IDA do not show evidence of overt blood loss due to gastrointestinal hemorrhagic lesions. In adult populations, H. pylori atrophic gastritis is reported to cause impaired iron absorption due to impaired gastric acid secretion, which, subsequently, results in IDA. However, significant gastric atrophy, and the resultant substantial reduction in gastric acid secretion, has not been shown in H. pylori-infected children. Recently, it has been hypothesized that competition between H. pylori and humans for iron availability in the upper gastrointestinal tract could lead to IDA. Many genes, including those encoding major outer membrane proteins (OMPs), are known to be involved in iron-uptake mechanisms in H. pylori. Recent studies have been published that describe H. pylori virulence factors, including specific OMP genes that may be associated with the pathogenesis of IDA. Daily iron demand substantively increases in children as they begin pubertal development starting with the associated growth spurt, and this important physiological mechanism may play a synergistic role for the microorganisms as a host pathogenetic factor of IDA. Like in the most recent pediatric guidelines, a test-and-treat strategy in H. pylori infection should be considered, especially for children and adolescents in whom IDA is recurrent or refractory to iron supplementation and other definitive causes have not been identified. This review will focus on providing the evidence that supports a clear biological plausibility for H. pylori infection and iron deficiency, as well as IDA.