Endoscopic predictors of iron deficiency in Helicobacter pylori gastritis: a Kyoto classification-based study

In general, when iron-deficiency anemia is diagnosed, upper gastrointestinal endoscopy should be performed to determine the underlying cause, as it is a secondary phenomenon due to chronic gastrointestinal bleeding. It can detect various diseases that can cause anemia, such as peptic ulcers, gastritis, and cancer, so that the exact cause can be identified, and appropriate treatment can be initiated. This study was conducted to characterize upper gastrointestinal endoscopy findings according to the Kyoto classification when primary iron deficiency occurs in conjunction with Helicobacter pylori infection. However, the study design did not completely exclude extra-gastric factors that could cause secondary iron deficiency, which may have limited the interpretation of the results.

Endoscopic findings such as atrophy, intestinal metaplasia, diffuse redness, petechial redness, mucosal edema, enlarged folds, sticky mucus, nodular and hyperplastic polyps, xanthoma, and depressed erosions have been emphasized to differentiate H. pylori infection.1,2 These findings are directly correlated with H. pylori infection. In contrast, regular arrangement of collecting venules, fundic gland polyps, linear red streaks, raised erosion, hematin, spotty redness, and geographic redness are negatively correlated with H. pylori infection.2,3 These findings are inconsistent and exhibit inter- and intra-observer variability. Furthermore, endoscopists’ response rates to endoscopic observation and technique for various findings were reported to be low or variable.4-6 In 2015, a global consensus meeting was held in Kyoto to develop a consensus on the classification of chronic gastritis, the appropriate diagnostic assessment of gastritis, and recommended treatment for H. pylori gastritis.7 Previously, the Endoscopic Kyoto Scoring System was reported to be a good predictor of H. pylori infection, with a high area under the curve and high accuracy.8,9 Specifically, the presence of atrophy, intestinal metaplasia, rugal thickening, nodularity, and diffuse erythema was incorporated into this system.

A previous literature review suggests that endoscopic findings of primary iron deficiency associated with H. pylori infection include atrophic gastritis, intestinal metaplasia, hypertrophic folds, and nodular gastritis.10,11 In particular, decreased gastric acid secretion can inhibit iron absorption and lead to anemia.12,13 Endoscopic findings include atrophic gastritis, in which the gastric mucosa becomes thin, erythema disappears, and blood vessels become visible. Next, intestinal metaplasia, in which gastric mucosal cells transform into duodenal or small intestinal cells, was observed. Another finding was hypertrophic folds, in which the folds of the gastric mucosa were thickened and swollen. Occasionally, nodular gastritis was observed, in which the lymphoid follicles in the gastric mucosa increased in size and appeared as small nodules (Fig. 1). The results of this study showed that iron deficiency was associated with female sex and nodular gastritis in patients with H. pylori gastritis, a finding similar to previous studies.10,11 However, this association was not significant in the multivariate analysis. Therefore, the application of the endoscopic Kyoto Scoring System for iron-deficiency anemia may have limitations. Notably, the results of this study14 show a correlation between gastric hyperplastic polyps and H. pylori infection, which causes iron deficiency. The most commonly accepted mechanism is iron loss due to chronic bleeding from the lesions. This finding is secondary and unlikely to be attributed to H. pylori infection, necessitating further large-scale clinical studies. Furthermore, the presence of gastric hyperplastic polyps was not a diagnostic criterion for endoscopic findings related to the Endoscopic Kyoto Scoring System, suggesting that the results contradict the objectives of the study.

Fig. 1.

Endoscopic findings of nodularity. (A) Endoscopically, nodular gastritis presents with a “goose-flesh” or “chicken skin” appearance to the gastric mucosa. (B) These nodular lesions are closely related to lympho-follicular gastritis and are often associated with Helicobacter pylori infection.

In patients with iron-deficiency anemia of unknown etiology, H. pylori infection may be the cause, and eradication therapy may help improve symptoms; however, this study did not prove this. Although the mechanism of H. pylori-associated iron deficiency has not yet been clearly established, H. pylori infection can cause iron deficiency anemia by inducing an inflammatory response that interferes with iron absorption.15,16 Therefore, iron deficiency anemia can be improved by eradicating bacteria through eradication therapy. The anticipated mechanism for the improvement in iron deficiency after H. pylori eradication is a reduction in inflammation and improved iron absorption. H. pylori causes inflammation in the gastric mucosa, increasing hepcidin production, a substance that interferes with iron absorption. Therefore, the eradication of H. pylori is expected to reduce inflammation, normalize hepcidin secretion, and improve iron absorption. Furthermore, normalizing gastric acid secretion after H. pylori eradication may increase the absorption of oral iron supplements and potentially enhance treatment efficacy. However, most of the existing studies are observational and have focused on children and adolescents. The quality of the literature was low, resulting in a “very low” level of evidence. Further large-scale prospective clinical trials are required to confirm these findings.