ABSTRACT

BACKGROUND/AIMS:

Celiac disease (CD) has been reported to be associated with chronic gastritis and immunological disorders. The aim of the study was to determine the association between Helicobacter pylori (H. pylori) infection and CD in children.

MATERIALS AND METHODS:

Two hundred and two patients with CD aged from 6 months to 17 years (mean: 7.12±4.64), and 209 age- and sex-matched children without CD were screened for H. pylori infection.

RESULTS:

Endoscopic appearance revealed significant differences between those patients with CD and the controls both in the antrum and the corpus (p<0.001). Those patients with CD had more frequent superficial gastritis than the control group. Panmucosal gastritis was common in the H. pylori-positive patients with CD. Lymphoid aggregates were significantly higher in the H. pylori-positive and H. pylori-negative patients with CD (p<0.001).

CONCLUSIONS:

The prevalence of H. pylori infection was not different between those pediatric patients with CD or without CD.

Keywords:

Celiac disease, children, H. pylori, infection, endoscopy

INTRODUCTION

Celiac disease (CD) is an immune-mediated disease characterized by malabsorption due to villous atrophy of the proximal small intestine triggered by gluten. The prevalence of CD in Turkey has been reported to be 0.47%.¹

It has been reported that 70-80% of adults and 30%–56.6% of children in Turkey are infected with Helicobacter pylori (H. pylori).² As H. pylori is the leading cause of chronic gastritis (more than 90%),³ it is speculated that the prevalence of H. pylori in patients with CD might be high. The autoimmune response against H. pylori can be a factor in the development of CD in patients infected with this bacterium.⁴

There are studies reporting no significant change in the prevalence of H. pylori in patients with CD when compared with the normal population and also no relationship between H. pylori and the natural course of CD.^5-11 An increased prevalence of H. pylori in those patients with CD has been established in some studies,¹²and a decreased prevalence in others.^13-15 In this study, the prevalence of H. pylori infection in pediatric patients with CD was determined and compared with the prevalence in children without CD.

MATERIALS AND METHODS

A total of 202 children with diagnosed CD and followed up between 2000 and 2015 at a division of pediatric gastroenterology were evaluated prospectively and compared with 209 controls who were recruited from children who had diagnostic upper gastrointestinal endoscopy for complaints such as abdominal pain, weight loss, growth retardation after CD had been excluded. The control group consisted of patients who were thought to have organic abdominal pain due to the fact that they had morning hunger pains, especially those who woke up during the night, and who had undergone endoscopy.

The diagnosis of CD was based on the criteria declared by ESPGHAN.¹⁶ The diagnosis was made only histopathologically. The modified Marsh classification was used for grading the histopathological changes of the small intestinal biopsies.¹⁷

Endoscopic Evaluation

Endoscopy was performed with an Olympus Q260 or Olympus GIF P30 (Olympus, Tokyo, Japan). Intravenous (0.1 mg/kg) or rectal (0.5 mg/kg) midazolam was given 30 minutes before the endoscopy for sedation. The biopsy specimens were taken from four sites (the body, antrum, esophagus, and the duodenal bulb), and they were fixed in 10% formalin, paraffin-embedded sections stained with hematoxylin and eosin. Two blinded pathologists evaluated the biopsy specimens.

Visual analogue scales according to the updated Sydney scoring system on a four-point scale (0=normal/absent, 1=mild, 2=moderate and 3=marked)¹⁸ was used for the scoring of H. pylori density.

Written informed consent was obtained from the parents before the procedures. The study was approved by the Şişli Hamidiye Etfal Training and Research Hospital Ethics Committee (number: 1100, date: 10.23.2018).

Statistical Analysis

Statistical analyses were performed by the IBM SPSS Statistics 22 (IBM Corp, Armonk, NY). All results are expressed as the mean ± standard deviation. The analysis was conducted using Fisher’s exact test, the chi-square test and Continuity (Yates) correction. P-values of <0.05 were considered statistically significant.

RESULTS

The mean age of the patients with CD was 7.12±4.64 years (range: 6 months–17 years), and 44.5% of them were male. The mean age of the controls was 7.12±4.64 years and 50% of them were male. The characteristics of the study participants are shown in Table 1.

Table 1

Significant correlation was only observed between patients with diarrhea and short stature at admission and the presence of H. pylori (p=0.027, p=0.025, respectively).

Endoscopic appearance was significantly different between those patients with CD and the controls both in the antrum and the corpus (p<0.001). Superficial gastritis was more common in those patients with CD than in the control group in the antrum and the corpus. Nodularity was more frequent in the control group in the antrum and the corpus than in the patient group. Comparison of the endoscopic findings between patients regarding whether they had CD or not are shown in Table 2. When the endoscopic appearance of the antrum and the corpus were compared, no significant difference was obtained in those patients with CD according to the presence of H. pylori (p>0.05), whereas a significant difference was observed in the histopathological findings between these patients (p<0.001). The H. pylori-positive patients with CD and the controls had more panmucosal gastritis than the H. pylori-negative ones. The lymphoid aggregates differed significantly between those patients with CD and the controls (p<0.001). No significant difference was observed between the H. pylori-positive and H. pylori-negative patients with CD according to the Marsh classification (p=0.09) and gluten free diet (GFD) (p=0.42).

Table 2

There was significant difference seen in macroscopic appearance both in the antrum and the corpus, and the histopathology in the antrum between the H. pylori-positive patients with CD and the controls (p<0.001). Nodularity in the corpus and the antrum was low and superficial gastritis was high in the H. pylori-positive patients with CD. No significant difference was observed in the H. pylori-positive patients and the controls in terms of lymphoid aggregates in the antrum (p=0.22) (Table 3), but lymphoid aggregates were significantly higher in the corpus of patients with CD than in the controls (p=0.001).

Table 3

There was no significant difference in antral appearance between the H. pylori-negative patients with CD and the H. pylori-negative controls (p>0.05), but a histopathological difference was observed between these groups (p<0.001) in both the antrum and the corpus. H. pylori-negative patients with CD had higher superficial gastritis in the antrum and the corpus than the H. pylori-negative controls. Lymphoid aggregates were significantly higher in the antrum of these patients than the controls (p=0.002) (Table 3).

Table 3

In addition to nonspecific findings in the duodenum of the control group, no histopathological findings were detected except lymphocytic, plasmacytic PNL and duodenitis.

Discussion

The exact mechanism of gastrointestinal diseases such as gastritis, peptic ulceration and atrophic gastritis in patients with CD is unknown.⁷ It has been proposed that H. pylori infection may affect the development of gluten-associated enteropathy by triggering and modulating the inflammation and immune responses in the small intestine,^7,13,14 and the pH and status of the gastric mucosa can play a key role in the digestion of gluten.¹⁵

Aydogdu et al.⁸ reported the possible association between CD and H. pylori gastritis, and stated that no effect was observed in the clinical presentation of the disease, except for abdominal distension. Luzza et al.⁵ observed that recurrent abdominal pain is the only distinctive symptom between H. pylori-positive and H. pylori-negative patients and a 3-month course of GFD improved all of the symptoms in these patients whether they had H. pylori or not. In our study, no relationship was determined between presence of H. pylori and gastrointestinal symptoms in those patients with CD. In contrast with the literature, we observed that prevalence of H. pylori was higher in those patients with growth retardation and lower in patients with diarrhea.

Borghini et al.⁹ excluded the correlation between CD and H. pylori infection by specific antibodies detected in gastric biopsy cultures. In the study conducted by Diamanti et al.⁷, no significant difference was observed in terms of histopathology and endoscopic findings between those patients with CD and those without, but there was a higher prevalence of H. pylori in patients with chronic gastritis in both groups. We observed a low prevalence of nodular appearance in both the antrum and the corpus in H. pylori-positive patients with CD. When compared with the controls, superficial gastritis was high and panmucosal gastritis was low in patients with CD independent of their H. pylori status. In contrast, Luzza et al.⁵ reported higher antral nodularity in both H. pylori-positive patients with CD and controls in comparison to H. pylori-negative ones, and they also stated that the prevalence of H. pylori did not increase in those patients with CD and that clinical and pathological signs could not be related with H. pylori. Similarly, Crabtree et al.⁶reported that gastritis in patients with CD is mostly related with H. pylori, but this was not significantly different from the normal population.

It has been stated that the prevalence of H. pylori was low among CD patients compared with controls, and it is estimated to be between 4% and 35%,^13-15 due to the effect of antigenicity of gliadin on the gastric acids. CD can develop at any age.^19,20 It is questionable if the presence of H. pylori is protective against the development of CD.^21,22 It has also been proposed that the presence of H. pylori can be associated with less severe villous atrophy.^21,23

The mechanism of protection of H. pylori against CD is unknown. The association between H. pylori and a decreased the risks of allergies, atopic diseases and other inflammatory disorders has been reported,^24-26 indicating the involvement of both local and systemic regulatory T-regulatory lymphocytes in the gastric mucosa in those patients with H. pylori.^27,28 Lebwohl et al.¹⁵ stated that those patients without H. pylori and gastric T-regulatory cells may not reduce immune responses to gluten and H. pylori may affect ingested gluten by modifying gastric pH or its proteases²⁹ and decrease its immunogenicity. Lucero et al.³⁰ mentioned that H. pylori infection rates were not different among participants whether they had CD or not, but patients with CD who had infection with cagA+ strains had milder histological damage, suggesting that cagA+ H. pylori may be protective against CD progression.

Luzza et al.⁵ reported that the rate of H. pylori positivity was similar among children whether they were given treatment or not, whereas Ciacci et al.¹³ observed that the H. pylori infection was significantly lower in untreated adult patients with CD than in the treated patients and the controls. Increased H. pylori prevalence in the treated patients can be explained by GFD-induced changes in the intestinal environment and/or the host immuno-response. In our study, no significant difference was observed in H. pylori prevalence between those patients who were compliant with GFDs and those who were not.

CONCLUSION

In conclusion, no significant correlation was established between CD and H. pylori infection in our study. We observed that H. pylori increases the rate of gastritis in pediatric patients with CD, but this difference was not significant when compared with those children without CD. As stated in the literature in recent years, we believe that it would be more enlightening to perform immunological studies of T-regulatory cells and their associated cytokines, both in the serum and in the tissue, in those patients with HP gastritis and CD, in order to explain the etiopathogenesis.

MAIN POINTS

● The association between H. pylori and the natural course of CD is controversial.

● H. pylori increases the rate of gastritis in pediatric patients with CD.

● No significant difference was observed in the prevalence of H. pylori infections between those pediatric patients with CD or without.

ETHICS

Ethics Committee Approval: The study was approved by the Şişli Hamidiye Etfal Training and Research Hospital Ethics Committee (number: 1100, date: 10.23.2018).

Informed Consent: Written informed consent was obtained from the parents before the procedures.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Concept: N.U., Design: N.U., Data Collection and/or Processing: Z.C., Analysis and/or Interpretation: B.Ö., Literature Search: Z.C., N.U., M.U., M.B.Ö., Writing: N.U., Critical Review: N.U., M.U.

DISCLOSURES

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The author declared that this study had received no financial support.

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