Lack of Association Between Helicobacter pylori Infection and Immmunoproliferative Small Intestinal Disease
R. Malekzadeh MD,* M.J. Kaviani MD,** S.Z. Tabei MD,** B. Abdolhadi MD,**
M. Haghshenas MD,** F. Navab, MD***
*Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, **Departments of Medicine and Pathology, Shiraz University of Medical Sciences, Shiraz, Iran and ***Department of Gastroenterology of Baystate Medical Center Springfield MA, U.S.A.
Background-To determine if there is an association between immunoproliferative small intestinal disease and Helicobacter pylori infection.
Methods-This is a retrospective study of 66 cases of immunoproliferative small intestinal disease in whom 21 had endoscopic biopsies of the stomach, compared with 42 patients with non-ulcer dyspepsia. Biopsies from the antrum and fundus were assessed for presence of H. pylori by histology.
Results-Chronic active gastritis was found in 8 (38%) of patients with immunoproliferative small intestinal disease and 35 (83%) of patients with non-ulcer dyspepsia. H. pylori infection was found in 6 (29%) of patients with immunoproliferative small intestinal disease compared with 33 (79%) of patients with non-ulcer dyspepsia.
Conclusions-In this patient population we failed to find an association between H. pylori infection and immunoproliferative small intestinal disease.
Introduction
It is recognized that infectious etiologies may play an important role in certain lymphoid malignancies.1 Thus, bacterial causes have been incriminated in mucosa-associated lymphoid tissue (MALT) lymphoma and immunoproliferative small intestinal disease (IPSID), and treatment with oral antibiotics in their early stages has been shown to reverse the clinical and pathologic findings.2 Epidemiologic studies have linked infection with H. pylori and MALT lymphoma,3 and regression of low-grade MALT has been described following eradication of this organism.4 Regression has also been reported after antibiotic therapy in early stages of IPSID, and some authorities have suggested that IPSID is a variant of low-grade MALT.5,6 It was therefore of interest to determine if an association is present between IPSID and H. pylori infection in our population.
Methods
The medical records and pathologic material from patients admitted to the University Hospital in Shiraz for assessment and treatment of IPSID and primary small intestinal lymphoma, between 1971 and 1995 were reviewed retrospectively. In the total patient population of 116 patients with a discharge diagnosis of IPSID and primary small intestinal lymphoma, 94 cases had completed medical records for review. The pathologic slides of these cases were reassessed; 28 cases had poor histologic material for adequate interpretation and were excluded, leaving 66 cases of IPSID for review. Fifty-three patients (80%) had laparotomy for staging, and mesenteric lymph node involvement was present in 29 (55%). Staging was performed according to Galian, et al.,8 with stage A: lymphoplasmacytic infiltrate confined to the mucosa and mesenteric lymph nodes, stage B: nodular mucosal infiltrates extending below the muscularis mucosae, and stage C: high-grade lymphoma. Six patients (9.1%) had stage A disease, 36 (54.5%) had stage B, and 24 (36.4%) had stage C. Other sites involved with lymphoma included the colon in two (3%), the brain in two (3%), and the ovaries in one (1.5%) patient. In 66 patients, 21 had endoscopic gastric biopsies, with at least two biopsies, stained with hematoxylin and eosin, from the antrum, and two from the fundus.
In this group, 6 out of 21 (29%) were taking tetracycline or metronidazole for diarrhea. This material and endoscopic gastric biopsies available from 42 patients with non-ulcer dyspepsia (NUD) seen during the same interval, were reviewed blindly by two pathologists. Statistical analysis was performed by the student t and Chi square tests.
Results
Demographic characteristics and presenting manifestations of 21 patients with IPSID, who had gastric biopsies and 42 patients with non-ulcer dyspepsia are shown in Table 1. In these two groups, there were no differences in age, sex ratio, or ethnic origin. Significantly more patients in the IPSID group presented with diarrhea, mid-abdominal pain, and weight loss.
Review of the pathologic material in our patients with IPSID revealed that a diffuse lymphoplasmacytic infiltrate was present in the small intestinal lamina propria in all cases. In 10% of patients the infiltrate was limited to the mucosa; in 57% there was extension beyond the muscularis mucosa, and in 33% the features were characteristic of high-grade lymphoma.
Endoscopic biopsy material from the stomach was available in 21 of 66 (32%) of patients with IPSID (Table 2). Gastric histology was normal in 10 (48%), revealed a chronic inflammatory infiltrate in 8 (38%), lymphoplasmacytic infiltrate in 2 (9%), and high-grade lymphoma in one patient (5%).
With the diagnostic methods available, six of 21 (29%) patients with IPSID and 33 of 42 (79%) patients with non-ulcer dyspepsia were found to have evidence of H. pylori infection. In this population there were significantly fewer patients with IPSID infected with H. pylori compared with patients with non-ulcer dyspepsia.
Discussion
Most patients who are diagnosed with IPSID in the Middle East are young adults who come from low socioeconomic groups, and have grown up in conditions of poor hygiene.1,2,5 It has been suggested that in these childhood environmental conditions enteric organisms proliferate, and may be a risk factor stimulating a polyclonal and subsequent monoclonal plasmacytoid infiltrate in the small bowel.9 Moreover, it has been reported that antibiotic therapy can lead to complete regression of symptoms and resolution of the lymphoplasmacytic infiltration in early case.5 Childhood poverty and poor environmental hygiene have also been associated with H. pylori infection. Infection with this organism is now recognized to be an important etiologic factor in the MALT lymphoma, and there is evidence that in early cases, MALT may regress following eradication of H. pylori.4
In the present series, gastric biopsies were available in 21 of 66 (32%) of our patients with IPSID. H. pylori was detected in only 6 (29%) patients. Our results do not suggest that there is an association between IPSID and H. pylori infection in this patient population. However, certain caveats must be addressed before these findings can be accepted. First, only 9.1% of our patients had stage A disease, and it is not known if the association with H. pylori infection would have been higher with a larger proportion of early cases. Second, our diagnostic methods included only histologic assessment for H. pylori. However, previous observations indicate that the sensitivity and specificity of histology in diagnosis of H. pylori is between 85% and 100%.10 Third, 6 (29%) of patients with IPSID had been on tetracycline or metronidazole for diarrhea and this may have reduced the positive diagnosis of H. pylori on histology. Even if all the patients treated with antibiotics were infected with H. pylori the number of infected patients with IPSID would still be less than patients with NUD. The frequency of infection of 79% in our patients with NUD is in the range of previous information on the estimated prevalence of H. pylori infection in developing nations.11
There is evidence to suggest that in western countries gastric lymphoma accounts for approximately 60% of cases of primary gastrointestinal lymphomas,12 and the incidence of gastric lymphoma appears to be increasing.13 In the Middle East, approximately 50% of primary gastrointestinal lymphomas arise in the stomach.14 The apparent increase in incidence of gastric lymphoma has been associated with the recognition of MALT lymphoma and its close relationship to H. pylori.15 If the pathogenesis of MALT lymphoma and IPSID shared H. pylori as a common bacterial pathogen, eradication of the organism could be helpful in treatment of IPSID. One patient has been reported with MALT lymphoma of the duodenal bulb, with gastric metaplasia and H. pylori, associated with abdominal lymphoma and secretion of alpha heavy-chain protein. In this case lymphoma was refractory to chemotherapy and radiotherapy, but complete regression occurred after eradication of H. pylori.16
Although this patient came from Bangladesh, the case may not be truly representative of IPSID, as the location of involvement with lymphoma was the duodenal bulb, IPSID usually affects the small intestine from the second part and into the jejunum.17 The results of our study and the obvious clinical differences between these IPSID and MALT outlined in Table 3 suggest that the two conditions IPSID and MALT lymphoma do not share the same bacterial pathogenic etiologies.
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