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Journal of Pediatric Gastroenterology & Nutrition:
Case Report

Helicobacter heilmannii Related Gastric Ulcer in Childhood

Sykora, Josef*; Hejda, Vaclav†; Varvarovská, Jana*; Stozicky, Frantisek*; Gottrand, Frederic‡; Siala, Konrad*

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*Department of Paediatrics, Faculty Hospital, Charles University, Plzen Czech Republic; †Department of Pathology, Faculty Hospital, Charles University, Plzen Czech Republic; ‡Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Lille University Hospital, Lille, France

Address correspondence and reprint requests to Sykora Josef, M.D., Department of Paediatrics, Charles University, Faculty Hospital, Plzen, Alej Svobody 80, 304 60 Plzen, Czech Republic (e-mail: sykorajo@fnplzen.Cz).

Helicobacter pylori (H. pylori) occurs worldwide. H. pylori infection is associated with chronic gastritis and peptic ulcer disease both in adults and children (1,2). Non-steroidal anti-inflammatory drugs (NSAIDs) have also been recognized as an important cause of peptic ulcer disease.

Some authors have reported an increased rate of non-H. pylori, non-NSAID duodenal and gastric ulcer disease in adults (3,4). Similar to the adult population, data regarding duodenal or gastric ulcers in children unrelated to H. pylori or other risk factors such as Crohn disease or drugs, are also available (5,6,7). However, the prevalence of non-H. pylori, non-NSAID peptic ulcer disease in children is unknown.

On the basis of published trials, it appears plausible that other unknown factors must be taken into account. However, H. pylori is not the only bacterial pathogen that colonizes the gastric mucosa. Helicobacter heilmannii (H. heilmannii), formerly Gastrospirillum hominis, similar to H. pylori, has been described in gastric biopsies in humans and has been strongly associated with gastritis both in children and adults (8,9,10).

To the best of our knowledge, there are no published studies regarding the association of gastric ulcer disease and H. heilmannii infection in children.

We describe here a 14-year-old girl with gastric ulcer disease in association with H. heilmannii infection. The purpose of this study is to alert the clinician to the possible etiologic role of H. heilmannii in gastric ulcer disease in children.

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CASE REPORT

A 14-year-old girl was referred for upper gastrointestinal endoscopy because of the sudden onset of epigastric abdominal pain, nausea, and hematemesis. Her history was significant in that she had never before complained of having dyspeptic symptoms nor was she given any NSAIDs. Her family had no pets.

The endoscoic appearance of the esophagus, the corpus mucosa, and the duodenum was normal. However, a deep gastric antral ulcer was found in the antrum. Biopsy specimens were fixed in 10% formalin, embedded in paraffin, and cut in 5-μm thick sections that were stained for light microscopy with hematoxylin-eosin and Whartin-Starry silver stain. Antral bioptic histopathologic examination revealed a normal morphology. Fundic biopsy samples showed a mild chronic gastritis Figure 1. Staining revealed the presence of long, spiral-shaped organims with characteristic morphologic appearance strongly suggestive of H. heilmannii in both antral and fundic biopsy specimens (8–10) Figure 2. Direct histologic examination and urease test of both antral and fundic biopsy specimens were negative for H. pylori. H. pylori serology (IgG), a 13 C urea breath test, and H. pylori stool antigen test (ELISA) were also negative. At that point, results were found to be consistent with the diagnosis of H. heilmannii infection.

Fig. 1
Fig. 1
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Fig. 2
Fig. 2
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The patient was successfully treated with a proton pump inhibitor (omeprazole), sucralfate, and antibiotics (amoxycillin, metronidazole) for 4 weeks with complete resolution of symptoms. Endoscopic reevaluation 3 weeks after the completion of treatment revealed the absence of both the ulcer and spiral shaped bacterial colonies in biopsy samples.

The patient remained well during a one-year follow-up with no ulcer recurrence.

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DISCUSSION

Gastric and duodenal ulcer disease occurs far less frequently in children than in adults. H. pylori infection has been established as a major etiologic factor in the development of peptic ulcer disease in adults (11) and children (2,12). H. pylori infection was found in 90% of children with duodenal ulcers and in 25% of children with gastric ulcers (13). In spite of a high prevalence of H. pylori infection worldwide, the incidence of duodenal ulcer disease in children is low (5). Primary gastric ulcers in childhood are very rare in comparison with the incidence of secondary ulcers (critically ill children, NSAID). Their etiology remains unclear and a hereditary predisposition has not been established.

Indeed, according to a review of recent publications in adults in developed countries involving peptic ulceration, up to 40% of the duodenal ulceration, and up to 50% of gastric ulceration, may be unrelated to H. pylori infection or other identifiable etiology such as NSAID intake, steroids use, or Crohn disease (3,4,14). Very little is known about the prevalence of non-H. pylori, non-NSAID peptic ulceration in the pediatric population. Hassal et al. described four children with duodenal ulceration with neither H. pylori infection nor NSAID intake (6). Others have documented 10 children with duodenal ulceration where H. pylori was detected in only 3 of them, and among 3 children with gastric ulceration, none had H. pylori infection (5). Oderda et al. identified 5 H. pylori negative children with duodenal ulceration (7). It is becoming increasingly clear that there might be yet unknown risk factors, other than H. pylori or drugs, in a significant proportion of gastric and duodenal ulcers in childhood.

However, H. pylori is not the only bacterial pathogen causing a chronic active gastritis. Since its discovery, at least 7 newer gastric helicobacters, specifically adapted to the gastric mucosa have been isolated (Table 1) (15). H. heilmannii is a less known and distinct gastric pathogen that nevertheless shares some properties with H. pylori (8). This bacterial organism has been found in the stomach of both animals and humans (8,16,17), and animal to person seems to be the most likely route of transmission (9). Since H. heilmannii is an uncultivatable, 7- to 10–μm long and 1 μm wide, spiral-shaped bacterium with four to six coils per cell and up to 12 sheeted flagella at each pole, currently, the confirmation of this infection is based on careful histologic examination of the gastric biopsy specimens and characteristic morphologic appearance (8–10,15,18). The organisms are weakly stained by hematoxylin eosin and display their structural characteristics well in the Giemsa, Steiner, and Warthin–Starry silver stains (8,9,15). H.heilmannii is mostly recognized focally and in small groups in the foveola, primarily in the antrum of the stomach (15). A specific feature is that H. heilmannii maintains a greater distance to the surface epithelium (19).

Table 1
Table 1
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Data on clinical symptoms specifically related to H. heilmannii infection among pediatric patients are scant (9,10). Compared to H. pylori, H. heilmannii associated gastritis in adults is milder with a less agressive inflammatory infiltrate both in the antrum and the corpus or even absent histologically (15,20,21). It may also be the reason for the rarity of concurrent erosions and ulcers in adults (20–22). Despite scant data on H. heilmannii infection in children, it appears that it is associated with a mild chronic gastritis of the antrum, associated with an interstitial infiltrate, that is indistinguishable to H. pylori gastritis (9). Nodular antral gastritis in H. heilmannii-infected children similar to that usually associated to chronic gastritis related to H. pylori has also been described (9).

To the best of our knowledge, no primary gastric ulcer associated with H. heilmannii infection in children has yet been reported and published. Our report is the first to describe H. heilmannii-positive ulceration presenting with acute epigastric pain and hematemesis in a child. These organisms were distributed in the antral and fundal mucosa. Histologically the affected gastric mucosa presented a mild chronic inflammation without activity. Concurrent H. heilmannii and H. pylori infection have also been reported (23), but this could be ruled out in our case.

Our case report allows us to identify a new agent that can play a role in the development of gastric ulceration in children.

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REFERENCES

1. Rowland H, Lamber J, Gormally S, et al. Carbon 13-labeled urea breath test for the diagnosis of H. pylori infection in children. J Pediatr 1997; 131:815–20.

2. Mac Arthur C, Saunders N, Feldman W. Helicobacter pylori, gastroduodenal disease, and recurrent abdominal pain in children. JAMA 1995; 273:729–34.

3. Anand BS, Graham DY. Ulcer and gastritis. Endoscopy 1999; 31:215–25.

4. Ciociola AA, Mc Sorley DJ, Turner K, et al. Helicobacter pylori infection rates in duodenal ulcer patients in the United States may be lower than previously estimated. Am J Gastroenterol 1999; 94:1834–40.

5. Elitsur Y, Lawrence Z. Non-Helicobacter pylori related duodenal ulcer disease in children. Helicobacter 2001; 6:239–43.

6. Hassall EG, Dimmick JE. Unique features of Helicobacter pylori disease in children. Dig Dis Sci 1991; 36:417–23.

7. Oderda G, Vaira D, Holten J, et al. Helicobacter pylori in children with peptic ulcer and their families. Dig Dis Sci 1991; 36:572–6.

8. Heilmann KL, Borchard F. Gastritis due to spiral shaped bacteria other than Helicobacter pylori: clinical, histologic, and ultrastructural findings. Gut 1991; 32:137–40.

9. Mention K, Michaud L, Guimber D, et al. Characteristics and prevalence of Helicobacter heilmannii infection in children undergoing upper gastrointestinal endoscopy. J Pediatr Gastroenterol Nutr 1999; 14:420–25.

10. Oliva MM, Lazemby AJ, Perman A. Gastritis associated with Gastrospirillum hominis in children. Comparison with Helicobacter pylori and review of the literature. Mod Pathol 1993; 6:513–15.

11. NIH. Helicobacter pylori in peptic ulcer disease. NIH Consensus Conference. JAMA 1994; 272:65–9.

12. Yeung CK, Fu KH, Yeunn KY, et al. Helicobacter pylori and associated duodenal ulcer. Arch Dis Child 1990; 65:1212–6.

13. Huang FC, Chang MH, Hsu HY, Lee PI, Shun CT. Long-term follow–up of duodenal ulcer in children before and after eradication of Helicobacter pylori. J Pediatr Gastroenterol Nutr 1999; 28:76–80.

14. Jyotheeswaran S, Shah AN, Jin HO, et al. Prevalence of Helicobacter pylori in peptic ulcer patients in greater Rochester, NY. Is empirical triple therapy justified? Am J Gastroenterol 1998; 93:574–8.

15. Malfertheiner P, Bohr URM, Gunter T. Infection with Helicobacter heilmanii (formerly Gastrospirillum hominis): characterization, epidemiology and therapy. In: Hunt RH, Tytgat GNJ, Eds. Helicobacter pylori, basic mechnisms to clinical cure 2000. Dordrecht Boston London: Kluwer Academic Publishers, 2000:73–83.

16. Hilzenrat A, Lamoureux E, Weintrub J, Alpert E, Lichter M, Alpert L. Helicobacter heilmannii-like spiral bacteria in gastric mucosal biopsies: Prevalence and clinical significance. Arch Pathol Lab Med 1995; 119:1149–53.

17. Geyer C, Colbatzky F, Lechner J, Hermanns W. Occurence of spiral-shaped bacteria in gastric biopsies of dogs and cats. Vet Record 1993; 133:18–19.

18. Solnick JV, O'Rourke J, Lee A, Paster BJ, Dewhirst FE, Tompkins LS. An uncultured gastric spiral organism is a newly identified helicobacter in humans. J Infect Dis 1993; 168:379–85.

19. Holck S, Ingeholm P, Blom J et al. The histopathology of human gastric mucosa inhabited by Helicobacter heilmannii-like (Gastrospirillum hominis) organisms, including the first culturable case. Apmis 1997; 105:746–56.

20. Stolte M, Kroher G, Meining A, Morgner A, Bayerdorffer E, Bethke B. A comparison of Helicobacter pylori and H. heilmannii gastritis. A matched control study involving 404 patients. Scand J Gastroenterol 1997; 32:28–33.

21. Dudorkinova D, Ivanco A. Chronic gastritis in Helicobacter heilmannii infection. Cas Lek Ces 1999; 138:316–17.

22. Cales V, Pariente A, Benazzouz P, Berthelemy P, Etcharry F. Helicobacter heilmannii ulceronecrotic acute gastritis: apropos of 5 cases. Ann Pathol 2000; 20:612–15.

23. Queiroz DMM, Cabral MDAC, Nogueira AMM, Barbosa AJA, Rocha GA, Menders EN. Mixed gastric infection by Gastrospirillum hominis and Helicobacter pylori. Lancet 1990; 336:507.

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© 2003 Lippincott Williams & Wilkins, Inc.

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