Acute gastric mucosal lesions caused by acute infection of non-Helicobacter pylori Helicobacter: a case report

1 INTRODUCTION

Acute gastric mucosal lesions (AGML) is a typical clinical entity in acute gastritis, and is characterized by severe erosion, hemorrhage, ulceration, or a combination of these.

Except in only a few reports, non-Helicobacter pylori Helicobacter (NHPH) infection has not been reported as a cause of AGML. So, at present, NHPH is not widely recognized as a cause of AGML. We report here an extremely rare case of AGML caused by an acute infection of NHPH and discuss when to start eradication therapy.

2 CASE REPORT

A 52-year-old woman was admitted to our hospital with a two-day history of severe epigastric pain, nausea, and vomiting. Her family history was unremarkable. She had previously been well. No history of smoking or alcohol use was reported. Neither was nonsteroidal anti-inflammatory drugs (NSAIDs) use. She kept an indoor dog.

Informed consent was obtained from the patient for this case report.

On examination, the patient's blood pressure was 118/72 mm Hg, pulse rate was 68/min and her body temperature was 36.8℃.

Auscultation of the heart and lungs was normal. Abdominal palpation revealed severe epigastric tenderness without muscular defense. The remainder of the physical examination was normal.

Laboratory data on admission showed no abnormal findings, excluding a slightly elevated C-reactive protein of 0.35 mg/dl. Both serum anti-H. pylori antibody and H. pylori stool antigen tests were negative.

An abdominal computed tomography (CT) scan revealed a severe thickening of the antral and pyloric gastric walls (Figure 1). An esophagogastroduodenoscopy (EGD) was performed on the second hospital day, which revealed mucosal edema, multiple erosions, and ulcerations with slight hematin in the gastric antrum (Figure 2A).

Biopsy specimens were obtained from the largest antral ulcer for histological assessment with hematoxylin/eosin and Giemsa staining. Histopathological examination revealed moderate neutrophilic infiltration in the lamina propria and necrotic sludge (Figure 3A). Relatively long and tightly coiled organisms with a morphology distinct from H. pylori were observed in gastric pits; on the other hands, H. pylori were not seen (Figure 3B). The observed organisms were stained with anti-H. pylori staining (Figure 3C).

In order to search the existence of NHPH, a polymerase chain reaction (PCR) analysis using a formalin-fixed paraffin-embedded tissue sample was also performed. However, neither urease gene ¹ nor cholesterol-α-glucosyltransferase (αCgT) gene ² were successfully detected.

Both serum anti-H. pylori antibody and H. pylori stool antigen tests were negative.

Based on these results, this case was diagnosed as AGML caused by NHPH.

After administration of esomeprazole 20 mg for 14 days and an interval of the following 12 days, that is after 26 days in total, another EGD showed AGML had been cured endoscopically (Figure 2B). Microscopic examination of biopsy specimens and PCR analysis of urease gene and αCgT gene were performed again. Since both of these were negative for NHPH, we deemed the patient's AGML as cured and NHPH as eradicated. In addition, performing again the same set of examinations 10 months after the onset of this episode, we confirmed the cure and the success of eradication.

3 DISCUSSION

This case presented acute and severe epigastric pain as symptom and was diagnosed as AGML based on abdominal CT scan images, endoscopic findings, and histopathological findings.

There are a variety of causes for AGML: acute infection of H. pylori, psychological and physical stress, drugs (such as NSAIDs, antibiotics, adrenal corticosteroids, and antineoplastics), alcohol, chemicals, ischemia, and many others.^{3, 4}

In the present case, there was neither history of ingestion of drugs or poisons nor psychological or physical stress. Microscopic examination, serum anti-H. pylori antibody, and H. pylori stool antigen were all negative for H. pylori infection. On the other hand, microscopic examination revealed relatively long and tightly coiled organisms like NHPH, and anti-H. pylori immunostaining was positive. Immunostaining for H. pylori using anti-H. pylori antibody (Dako-Agilent technologies, Carpinteria, CA, USA) was performed. This antibody is generated using the whole H. pylori bacterial extract as the antigen, and it exhibits cross-reactivity with NHPH including H. suis.^{5, 6} Therefore, the results suggest that AGML, in this case, would have been caused by an acute infection of NHPH.

Regarding NHPH species, H. suis is reported to be most common in Japan.^{7, 8} It is well-known that pigs and non-human primates are the natural host of H. suis and that human strains of H. suis are very similar to porcine strains.⁹ In the present case, though the patient had had no history of keeping pigs as pet nor as livestock, she had been keeping an indoor dog and having a close contact with it such as kissing and feeding from mouth to mouth. The patient may have been infected with some other species of NHPH than H. suis.¹⁰

Thus far only 3 cases of AGML caused by NHPH have been reported,^11-13 and the present case is the fourth. Despite the extreme rareness of these cases, NHPH should be considered just a cause of AGML in cases that are not attributed to the other causes already recognized.

Of the four cases including our case, two cases were not tested with PCR analysis of urease genes,^{11, 12} and it is only in one case that NHPH species were identified by PCR as H. feris.¹³ Though we also tried PCR using a paraffin sample, the gene was not successfully detected. It is relatively difficult to detect genes by PCR analysis using paraffin specimen. When the causes of the cases of acute gastritis such as AGML are not identified, it is advisable to perform biopsy during the initial EGD to obtain specimens just for PCR analysis in consideration of NHPH infection.

At present, there is no clear consensus on the eradication of persistently infected NHPH that causes chronic gastritis. A combination therapy with a proton pump inhibitor (PPI), amoxicillin, and clarithromycin or metronidazole has been reported to be effective to eradicate NHPH.^{7, 14-16} We previously reported two cases of chronic NHPH infection in which the patients were cured with a combination therapy of PPI, amoxicillin, and clarithromycin for one week at our institution ⁸ In addition, we reported in the same report that, in 4 of 6 (66.7%) patients who had had persistent infection of NHPH, NHPH was successfully eradicated with long-term (6 months) administration of PPI alone.⁸

On the other hand, Iwamoto et al. reported that AGML caused by H. pylori was cured spontaneously without eradication therapy in 21 of 26 cases.¹⁷

The three case reports of AGML caused by acute NHPH infection, mentioned above, also report eradication therapies performed on each case. In Koyanagi et al., the patient was cured by taking famotidine 40 mg and sucralfate 2700 mg, that is, without antibiotics.¹¹ In Yoshimura et al., the patient was cured by administration of lansoprazole 30 mg, clarithromycin 400 mg, and metronidazole 750 mg for 14 days.¹² In Ghysen et al., the patient was cured by amoxicillin 2000 mg, clarithromycin 1000 mg, and pantoprazole 80 mg for 14 days.¹³

In our case, by an EGD performed after 14 days of PPI administration and the following 12 days of interval, after 26 days in sum, we endoscopically deemed the patient's AGML as fully cured. Microscopic examination and PCR analysis which were performed at the same time as this EGD and were both negative for NHPH confirmed full cure of the patient's AGML and the success of NHPH eradication.

The full cure of AGML caused by NHPH infection in the present case may have been contributed by the effect of taking a PPI for 14 days. This is inferred from the fact that NHPH was eradicated in 66.7% of the cases of its persistent infection by means of administration of a PPI for six months at our institution.⁸ On the other hand, as in the cases of acute H. pylori infection, there is some possibility of spontaneous eradication. At least, it seems appropriate to confirm the persistent infection of NHPH before starting eradication therapy.

4 CONCLUSIONS

We presented a case of AGML caused by NHPH. Despite the extreme rareness of the cases, NHPH should be considered one possible cause of AGML in cases that are not attributed to the other causes already recognized. Since there is some possibility of spontaneous eradication, it seems appropriate to confirm the chronicity of NHPH infection before starting the eradication therapy.

CONFLICT OF INTEREST

The authors declare that they do not have any financial support or relationship that may pose conflict of interest. Funding for this case report was not provided by any person or institution.