ORIGINAL ARTICLE
Year : 2017 | Volume
: 10 | Issue : 3 | Page : 257--262
Clinicohistopathological correlation and Helicobacter pylori status in patients with functional dyspepsia
Anita Basavaraj1, Rahul S Kulkarni1, Dilip B Kadam1, Vinay Thorat2,
1 Department of Medicine, B. J. Government Medical College, Pune, Maharashtra, India
2 Department of Medicine, Honorary Gastroenterologist, B. J. Government Medical College, Pune, Maharashtra, India
Correspondence Address:
Rahul S Kulkarni
Flat No F-1, Building No 35, Priyadarshini Apartment, Ambai Tank, Rankala Park, Kolhapur - 416 010, Maharashtra
India
Abstract
Background: Functional dyspepsia (FD) is a condition of immense clinical significance. Helicobacter pylori may be responsible for FD in a subset of patients. Materials and Methods: Upper gastrointestinal endoscopy was done in sixty patients of FD fulfilling ROME III criteria, and gastric and duodenal biopsies were taken. Duodenal histopathological findings and H. pylori status were correlated with the symptomatology. Standard treatment was given according to the H. pylori status, and the response was analyzed using 6-point Likert scale. Results: Sixty percent of cases were infected with H. pylori. 72.5% of cases with predominant epigastric pain were H. pylori-positive. 96.5% patients with early satiety had duodenal eosinophilia and duodenitis. Epigastric pain was significantly associated with H. pylori, and early satiety was associated with duodenal eosinophilia and duodenitis. Sixty-five percent of cases had increased duodenal intraepithelial lymphocyte count. 88.8% cases showing no response to treatment had duodenal eosinophilia. Conclusion: H. pylori infection constitutes an important subset of FD patients. H. pylori infection, duodenitis, and duodenal eosinophilia contribute to symptom generation. H. pylori eradication can provide symptomatic relief. A duodenal biopsy can identify an important subset of patients with duodenal eosinophilia and duodenitis which can be a contributor for poor treatment response and can be clinically amenable to new treatment avenues.
How to cite this article:
Basavaraj A, Kulkarni RS, Kadam DB, Thorat V. Clinicohistopathological correlation and Helicobacter pylori status in patients with functional dyspepsia.Med J DY Patil Univ 2017;10:257-262
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How to cite this URL:
Basavaraj A, Kulkarni RS, Kadam DB, Thorat V. Clinicohistopathological correlation and Helicobacter pylori status in patients with functional dyspepsia. Med J DY Patil Univ [serial online] 2017 [cited 2023 May 31 ];10:257-262
Available from: https://journals.lww.com/mjdy/pages/default.aspx/text.asp?2017/10/3/257/206571 |
Full Text
Introduction
Functional dyspepsia (FD) is a condition of great clinical significance and its management is a major challenge in today's medical practice. It has been shown that gastric Helicobacter pylori infection is associated with dyspeptic symptoms.[1] The prevalence of this infection varies worldwide being as low as 10% in developed western nations to higher than 80% among the indigent populations of many developing countries like India.[2],[3] It has been proposed that H. pylori may cause inflammation and dysmotility, initiate visceral hypersensitivity, and alter acid secretion.[4] Large population studies have shown that H. pylori is more frequently detected in dyspeptic patients than in controls; however, other studies have failed to show such an association. Furthermore, the role of H. pylori eradication in the treatment of FD is still unclear. Recently, postinfectious FD has been described following gastrointestinal infection and is characterized by persistent mucosal inflammation in the duodenum, thus indicating duodenal immune activation in FD.[5] As there are limited studies regarding the prevalence of H. pylori infection and its role in the causation of symptoms and correlation of the histopathological findings with symptomatology of FD in the Indian population, this study was conducted.
Materials and Methods
This is a prospective observational study performed in the Department of Medicine, B. J. Medical College, Pune, from February 2011 to February 2013. Sixty consecutive patients of FD, attending the gastrointestinal specialty outpatient department and diagnosed on the basis of ROME III criteria, were included in the study. Patients of age more than 13 years, with no previous history of peptic ulcer, negative previous investigations for dyspepsia, no history of use of any acid suppressive medication during last 1 month, and those with symptoms suggestive of epigastric pain, epigastric burning, early satiety, and postprandial fullness were included in the study. Patients below 13 years of age, history of peptic ulcer disease, gastric malignancy, gastric surgery, use of drugs such as analgesics, potassium supplements, and those having cardiopulmonary disease were excluded. The study protocol was approved by the Institutional Ethics Committee and written informed consent was taken by all participants. Clinical profile and symptomatology of these patients were recorded on a detailed pro forma. Upper gastrointestinal endoscopy was done, and gastric and duodenal biopsies were taken for rapid urease testing and histopathological examination, respectively. Duodenal biopsies were studied with a special reference to changes in villous architecture, intraepithelial lymphocytes (IELs)/100 epithelial cells, infiltration of eosinophils, metaplasia, and grade of duodenal inflammation. Duodenal inflammation was graded as mild, moderate, and severe grade based on the degree of neutrophilic infiltration (mild duodenitis - small increase in the number of chronic inflammatory cells in the lamina propria, associated with slight widening and flattening of villi. Severe duodenitis - intense, mixed acute, and chronic inflammatory cell infiltrate of the lamina propria with infiltration of polymorphonuclear neutrophils into the surface epithelium with changes in the mucosal architecture. Moderate duodenitis - severity that is between mild and severe). In case of increased IEL count, immunohistochemical typing for CD4 and CD8 was done to determine the phenotype of lymphocytic infiltration. Duodenal histopathological findings and H. pylori status were correlated with the symptomatology recorded on the standard pro forma. Standard treatment was given according to the H. pylori status (H. pylori-positive patients received H. pylori eradication therapy with combination of amoxycillin 750 mg, tinidazole 500 mg, and omeprazole 40 mg, given twice a day for 14 days, H. pylori-negative patients received acid suppression with proton pump inhibitors), and response was analyzed using 6-point Likert scale after 4 weeks of the completion of anti-H. pylori treatment or acid suppression therapy.
At the end of the study, the data were entered in SPSS version 11.5 (Statistical Package for the Social Scientists) and results were analyzed using Chi-square test, Fisher exact test, and unpaired t-test.
Results
The mean age of study population was 38.25 years. There was a slight male preponderance with 32 males and 28 females (male: female ratio - 1.2:1); however, there was no statistically significant difference in sex distribution. Postprandial fullness was overall the most common symptom seen in 70% of cases, followed by epigastric pain in 66.7% cases [Figure 1]. Of the 60 cases, 36 cases (60%) tested positive for H. pylori by rapid urease test [Figure 2]. Sixty-two percent of males and 57% of females were positive for H. pylori infection by rapid urease test, and there was no association found between H. pylori infection and sex. Most of our patients were found to have duodenitis (47 out of 60, i.e., 78.4% cases) on histopathology [Figure 3]b. The severity of inflammation was variable with mild duodenitis being the most predominant (31/60 = 51.7% cases) [Table 1]. Furthermore, 39 out of 60 cases (65% of the study population) had increased duodenal eosinophil counts (>22/5 high-power fields) [Figure 4] and [Figure 3]a. Of these 39 patients with duodenal eosinophilia, 22 patients (56.4%) were positive for H. pylori. Similarly, 39 cases (65%) had increased duodenal IEL counts (>25/100 epithelial cells) [Figure 5]. Of these 39 cases, 38 cases had predominantly CD8 + lymphocytic infiltration with decreased CD4 + lymphocytes [Figure 3]c and [Figure 3]d. Furthermore, 24 patients out of these 39 cases (61.5%) with increased duodenal IELs tested positive for H. pylori. However, when compared with H. pylori-negative patients, neither duodenal eosinophilia (P = 0.619) nor raised duodenal IEL counts (P = 0.956) could reach statistical significance. When correlated with the symptomatology, it was found that in patients with FD, having predominant epigastric pain, H. pylori was positive in 72.5% of cases. Thus, H. pylori infection was significantly associated with epigastric pain (P = 0.012) [Table 2]. Furthermore, in patients having early satiety, 96.5% had duodenal eosinophilia and duodenitis. Thus, early satiety was significantly associated with both duodenal eosinophilia (P < 0.001) [Table 3] and duodenitis (P = 0.003).{Figure 1}{Figure 2}{Figure 3}{Table 1}{Figure 4}{Figure 5}{Table 2}{Table 3}
Fifty-one out of 60 cases (85%) showed an overall response to treatment. Of these, 31 out of 36 cases (86%) infected with H. pylori showed symptomatic response bases on 6-point Likert scale, while five cases (14%) showed no improvement in symptoms even after conventional H. pylori eradication treatment. However, of the 60 cases who received treatment, only 8 patients (13.3%) showed a complete symptom relief. When subclassified according to the type of treatment given, only five cases out of 36 (13.9%) who were treated with H. pylori eradication treatment showed complete relief, whereas only 3 (12.5%) out of 24 H. pylori-negative cases who received acid suppression therapy had a complete symptom relief. We found that 88.8% cases showing no response to treatment had duodenal eosinophilia (P = 0.211). Thus, there was a nonsignificant increasing trend between the presence of duodenal eosinophilia and no response to treatment.
Discussion
It has been shown that gastric H. pylori infection is associated with dyspeptic symptoms. In our study, 60% cases tested positive for H. pylori by rapid urease test, thus indicating that H. pylori infection constitutes an important subset of FD patients. Furthermore, the epigastric pain was significantly associated with H. pylori infection (P = 0.012), thus favoring its role in dyspepsia symptom generation. According to studies conducted by Mirbagheri et al.[1] and Shrivastava et al.,[3]H. pylori infection was found in 67.3% and 65% cases of FD which is similar to our study. Furthermore, our study is on similar lines with studies conducted by Bazzoli et al.[6] and Shimatani et al.,[7] who have shown an association between H. pylori infection and epigastric pain. Furthermore, a significant number of cases (86%) responded to H. pylori eradication treatment suggesting the role of H. pylori in FD. Thus, testing and treating H. pylori can be beneficial in cases of FD.
In the present study, most of our patients were found to have duodenitis (47 out of 60, i.e., 78.4% cases) on histopathology with a predominantly mild grade of inflammation. A similar finding was observed in studies conducted by Toukan et al.,[8] Mirbagheri et al.,[1] and Futagami et al.,[9] where histological duodenitis was a common finding in cases of FD, especially postinfectious FD, suggesting that at least some represent part of a spectrum of subclinical peptic disease or postinfectious FD.
Another important observation in the present study was the presence of increased duodenal IELs as seen in 65% of cases. Of these cases, 97.4% cases had increased CD8 + T-cell phenotype with decreased CD4+ T-cells. Gargala et al.[10] and Memeo et al.[11] have also shown that duodenal IELs are raised in cases of FD, particularly H. pylori-infected or in cases of postinfectious dyspepsia. Memeo et al.[11] and Kindt et al.[12] also found that duodenal IELs in presumed postinfectious FD consisted almost exclusively of CD8+ cells with a significant reduction in the number of CD4+ cells which is similar to our study. It has been postulated that as a result of a relative deficiency in suppressive CD4+ cells, a certain degree of inflammatory change persists.[10] This chronic duodenal low-grade inflammation is contributory to persistent dyspeptic symptoms in this subset of cases even after treatment. Several infections such as H. pylori infections, as well as other gut infections such as salmonella and shigella, have been associated with a subset of FD patients,[13] thus supporting the role of immune dysfunction in these cases.
Duodenal eosinophilia was found in 65% of cases of FD in our study. In patients having early satiety, 96.5% had duodenal eosinophilia and duodenitis. The most common dyspeptic symptom was early satiety in patients with duodenal eosinophilia and postprandial fullness in those with duodenitis. However, statistical analysis showed that only early satiety symptom was significantly associated with both duodenal eosinophilia and duodenitis. A similar association has been found by Walker et al.[14] and Talley et al.,[15] where duodenal eosinophilia was significantly associated with early satiety. The exact mechanism of duodenal eosinophilia and early satiety is not fully understood; however, several mechanisms such as eosinophil-mediated axonal necrosis [16] and eosinophil interference with muscarinic receptors, major basic protein-induced vagal M2 receptor dysfunction increasing smooth muscle reactivity [17] and, importantly, eosinophil-stimulated T-cell activation and mast cell degranulation causing release of lipid mediators, leukotrienes, which are a potent stimulator of smooth muscle contraction, have been proposed.[18] In our study, a negative association was observed between bloating and duodenal eosinophilia which was an unexpected finding and we were unable to find any reference for the same in literature.
Another fact which requires mention is that although 85% of cases who received standard treatment (H. pylori eradication for H. pylori-infected patients and acid suppression with proton pump inhibitors) showed a symptomatic response, only 13.3% could achieve a complete symptom relief. Rest 15% cases (9 out of 60) did not respond to treatment. This indicates a possibility of certain factors still unexplored hindering the attainment of complete symptomatic relief. We tried to find out whether there is an association between duodenal eosinophilia and nonresponse to treatment. We found that of the nine cases who did not respond to treatment, eight cases had duodenal eosinophilia (88.8%), whereas 31 out of 51 responders (60.7%) had duodenal eosinophilia. Thus, there was an increasing trend of duodenal eosinophilia in cases who did not respond to conventional treatment; however, we could not find a statistical significance.
Drawbacks
In our study, response evaluation was done at the end of 1 month after the completion of treatment using 6-point Likert scale. However, repeat upper gastrointestinal endoscopy was done, and repeat biopsy for confirmation of eradication of H. pylori was not done as it was not a part of the study. Furthermore, regular follow-up and evaluation of duration of treatment response were not done. Being a small study limited to sixty patients, larger prospective studies with long-term follow-up and histopathological documentation of eradication of H. pylori and assessment of duration of treatment response are required for confirmation of these findings.
Conclusion
H. pylori infection constitutes an important subset of FD patients. Raised IELs and eosinophils in duodenal biopsy indicate the possibility of immune activation in the pathophysiology of FD. H. pylori infection, duodenitis, and duodenal eosinophilia contribute to symptom generation. Duodenal biopsy in patients with FD can identify an important subset of patients with duodenal eosinophilia and duodenitis which can be a contributor for poor treatment response and can be clinically amenable to anti-eosinophilic treatment like montelukast and can be explored to develop new avenues of treatment in FD. Hence, even though upper gastrointestinal endoscopy is normal in FD, it may be worth going “beyond the scope” to take a duodenal biopsy which can unravel new “dysfunctions” and explore new arenas in the field of FD.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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