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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 28  |  Issue : 2  |  Page : 319-324

Study of the effect of treatment of Helicobacter pylori on rheumatoid arthritis activity


1 Department of Rheumatology, Physical Medicine and Rehabilitation, Faculty of Medicine, Zagazig University, Zagazig city, Egypt
2 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
3 Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt

Date of Submission29-Apr-2014
Date of Acceptance24-Aug-2015
Date of Web Publication31-Aug-2015

Correspondence Address:
Maha M Abd El-Raof Salman
Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia 32511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.163879

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  Abstract 

Objective
The aim of the study was to assess the effect of Helicobacter pylori treatment on disease activity in patients with rheumatoid arthritis.
Background
A triggering infectious agent has long been postulated in rheumatoid arthritis. Data on the possible role of H. pylori infection are lacking.
Patients and methods
Forty adult patients with established rheumatoid arthritis and dyspeptic symptoms were recruited. In all, 17 patients were H. pylori positive and 23 patients were H. pylori negative on the basis of H. pylori fecal antigen test. All infected patients were treated successfully. We evaluated the disease activity using clinical [duration of morning stiffness, tender and swollen joints counts, Disease Activity Score 28 (DAS28), visual analog scale (VAS), and Health Assessment Questionnaire (HAQ)] and laboratory parameters such as complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP), and rheumatoid factor titer at baseline and after 2 months and compared the variations in the two subgroups.
Results
At the initiation of the study, H. pylori-positive patients had significantly longer duration of morning stiffness, more tender and swollen joint counts, and higher value of CRP than the negative group. In addition, the DAS28 and pain scores such as VAS and HAQ were significantly higher in the positive group. After 2 months, H. pylori-eradicated rheumatoid arthritis patients differed significantly (P = 0.009-0.001) from patients without H. pylori infection in terms of improvement of tender and swollen joints count, DAS28, VAS, and HAQ. At the same time point, several laboratory indices (CRP and rheumatoid factor titer) showed significantly lower values (P = 0.003-0.001) in the H. pylori-eradicated subgroup compared with the H. pylori-negative subgroup.
Conclusion
Our data suggest that H. pylori infection is implicated in the pathogenesis of rheumatoid arthritis; its treatment may induce a significant improvement of disease activity over 2 months. H. pylori treatment seems to be advantageous in infected rheumatoid arthritis patients, but controlled studies are needed.

Keywords: disease activity, Helicobacter pylori, rheumatoid arthritis


How to cite this article:
El-Hewala ASI, Khamis SS, Soliman SG, Alsharaki DR, Abd El-Raof Salman MM. Study of the effect of treatment of Helicobacter pylori on rheumatoid arthritis activity. Menoufia Med J 2015;28:319-24

How to cite this URL:
El-Hewala ASI, Khamis SS, Soliman SG, Alsharaki DR, Abd El-Raof Salman MM. Study of the effect of treatment of Helicobacter pylori on rheumatoid arthritis activity. Menoufia Med J [serial online] 2015 [cited 2020 Feb 28];28:319-24. Available from: http://www.mmj.eg.net/text.asp?2015/28/2/319/163879


  Introduction Top


Rheumatoid arthritis (RA) is an autoimmune disease that causes irreversible joint deformities and functional impairment. It results from an autoimmune reaction to unknown stimuli or infection with as yet unidentified microorganisms; however, other factors may be contributing [1] .

Warren and Marshall were the first to describe the presence of Helicobacter pylori, a Gram-negative curved and motile bacteria, in biopsy specimens from patients with gastritis. H. pylori can be identified in 70-90% of all incidences of gastritis and gastroduodenal ulcers [2] .

The role of H. pylori infection is explored extensively in extragastric diseases including rheumatic disorders [3] .

Chronic infection with H. pylori serves as a source of persistent antigenic stimulation and underlies the pathogens' ability to induce a systemic inflammatory response [4] . Autoantibodies, such as IgM rheumatoid factor (RF), anti-single-stranded DNA antibody, and antiphosphatidyl choline antibodies, were demonstrated to be produced by B cells after their activation by H. pylori components, particularly urease [5] .

The association of H. pylori infection in the pathogenesis of RA is controversial. Although in-vitro studies suggest a role for the bacterium in the development of autoimmunity, the clinical correlation between H. pylori infection and RA has been less convincing [6] .


  Patients and methods Top


Patients

This study included 40 patients with RA who were randomly selected from the Physical Medicine and Rehabilitation Outpatient Clinic, Al-Menoufia University Hospitals, during the period between June 2012 and May 2013. Inclusion criteria were the presence of dyspeptic symptoms, and the patient's age was between 20 and 50 years. All patients approached agreed to participate in this study, and informed consent was obtained. Exclusion criteria were presence of other rheumatological disease, history of an active peptic ulcer or previous gastrointestinal surgery, and pregnancy. The patients were divided into two groups based on the presence or absence of H. pylori fecal antigen; H. pylori-positive and H. pylori-negative groups. The H. pylori-positive group received medical treatment for 14 days in the form of omeprazole (20 mg, twice a day), clarithromycin (500 mg, twice a day), and amoxicillin (1000 mg, twice a day) and were assessed for eradication of the bacterium. Clinical and laboratory parameters of disease activity were assessed at the initiation of the study and 2 months later. All patients gave their formal consent. The protocol was approved the Ethical committee of the faculty.

Methods

All patients were diagnosed as RA patients on the basis of the American College of Rheumatology 1988 revised criteria for the classification of RA[7] [Table 1] .
Table 7 Distribution of the studied positive fecal antigen titer group regarding their laboratory investigations at baseline and after 2 months of Helicobacter pylori treatment

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For classification purposes, a patient is considered to have RA if he or she has satisfied at least four of the seven criteria. Criteria 1 through 4 must be present for at least 6 weeks. Patients with two clinical diagnoses are not excluded. Designation as classic, definite, or probable RA is not to be made [7] .

The patients were questioned about current age and duration of RA. Inquiry was made about duration of morning stiffness, number of swollen and tender joints, and symptoms of dyspepsia.

Clinical examination was performed for all patients, including general and locomotor examination. Locomotor system assessment included assessment of the right and left shoulder, elbow, wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP), and knee joints. Joints were examined for both tenderness and swelling due to synovitis, then Disease Activity Score 28 (DAS28) was calculated for each patient. DAS28 includes the following parameters [8] :

  1. Tender joint count in 28 joints.
  2. Swollen joint count in 28 joints.
  3. Erythrocyte sedimentation rate (ESR).
  4. General health assessment on a visual analog scale (VAS) of 100 mm.
The modified DAS is calculated using the following formula:

DAS (four variables):

DAS28 =

0.56 × √(TJC28) + 0.28 × √(SJC28) + 0.70 × ln (ESR) + 0.014 × (generalhealth),

where ln(ESR) is the natural logarithm of the ESR (mm/1 h).

The level of disease activity can be interpreted as:

  1. Low (DAS28 ≤ 3.2).
  2. Moderate (3.2 < DAS28 ≤ 5.1).
  3. High (DAS28 > 5.1).
A DAS less than 2.6 corresponds to being in remission according to the American Rheumatism Association criteria.

The following laboratory investigations were performed: complete blood count, ESR (by Westergren method), RF titer (by Rose Waaler method), C-reactive protein (CRP), and H. pylori fecal antigen titer (FAT) (by ELISA).

Radiological assessment in the form of plain radiograph of the hands was performed. All radiographs were scored according to the method described by Larsen et al. [9] .

Pain severity evaluation was performed using the VAS. A line was taken to represent the persistence of pain, the ends defining the extremes of the experience - that is, 'no pain' and 'extreme pain'. Patients were asked to mark the line at a point corresponding to their estimate of pain and the distance from zero was taken to represent the severity of pain. The line has stops at either ends to limit the distribution of the results. The length of the line was 100 mm [10] .

Functional performance evaluation was performed regarding Stanford Health Assessment Questionnaire (HAQ) [Table 2] [11] .
Table 1 1988 Revised American rheumatism association criteria for classifi cation of rheumatoid arthritis

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Statistical analysis

Results were collected, tabulated, and statistically analyzed by IBM personal computer and statistical package for the social sciences (SPSS, version 14; SPSS Inc., Chicago, Illinois, USA). Two types of statistics were performed: descriptive statistics, which included percentage, range, mean (X), and SD, and analytical statistics, which included Student's t-test, Mann-Whitney test, Fisher's exact test, paired t-test, and Wilcoxon signed-rank test. P value had significant difference if P value was less than 0.05, nonsignificant difference if P value was greater than 0.05, and highly significant difference if P value was less than 0.001 [12] .


  Results Top


This study included 40 patients with RA and complaining of dyspeptic symptoms, four (10%) men and 36 (90%) women. Their ages ranged from 20 to 49 years (mean 30.1 ± 8.4 years).

At the initiation of study, there were 17 (42.5%) patients with positive H. pylori FAT and 23 (57.5%) patients with negative H. pylori FAT. After 2 months of treatment, there was no patient with positive titer (0%) and all patients had negative titer (100%). There was highly significant difference (P < 0.001) between FAT results at the initiation of study and after 2 months of treatment and follow-up [Table 3].
Table 2 Functional performance evaluation was performed regarding Stanford Health Assessment Questionnaire

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There was no statistically significant difference between FAT-positive and negative groups regarding age (P = 0.438), sex (P = 0.624), or RA disease duration (P = 0.434).

There was statistically significant difference between FAT-positive and negative groups regarding duration of morning stiffness (P = 0.033), tender joints count (P = 0.025), swollen joints count (P = 0.045), DAS (P = 0.044), pain score as the VAS (P = 0.010), and HAQ (P = 0.014) at the initiation of study [Table 4].
Table 3 Distribution of the studied patients regarding Helicobacter pylori fecal antigen titer at baseline and after 2 months

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There was no statistically significant difference between the two groups regarding hemoglobin level (P = 0.504), platelet count (P = 0.286), white blood cell count (P = 0.702), ESR (P = 0.753), and serum RF titer (P = 0.177), whereas there was highly significant difference regarding CRP (P = 0.001) between the two groups at baseline [Table 5].
Table 4 Distribution of the studied groups (fecal antigen titer positive and fecal antigen titer negative) regarding their clinical data and disease scores at baseline

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There was statistically highly significant difference (P < 0.001) regarding tender joints count and DAS and a significant difference regarding swollen joints count (P = 0.008), VAS (P = 0.001), and HAQ (P = 0.009) of H. pylori FAT-positive group at the initiation of study and after 2 months of H. pylori treatment [Table 6].
Table 5 Distribution of the studied groups (fecal antigen titer positive and fecal antigen titer negative) regarding their laboratory investigations at baseline

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There was statistically significant difference regarding CRP (P = 0.001) and serum RF titer (P = 0.003) of H. pylori FAT-positive group at the initiation of study and after 2 months of H. pylori treatment, whereas other parameters (hemoglobin level, platelet count, white blood cell count, ESR) showed no significant change between the two readings [Table 7].
Table 6 Distribution of the studied positive fecal antigen titer group regarding their clinical data and disease scores at baseline and after 2 months of Helicobacter pylori treatment

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  Discussion Top


The association of H. pylori infection in the pathogenesis of RA is controversial. As the incidence of upper gastrointestinal tract lesions is significantly higher in patients with RA and a microbiological etiology to RA is broadly considered, a relationship between H. pylori and RA should be a strong possibility [13] .

In this study, we found that 42.5% of RA patients had positive H. pylori FAT. Graff et al. [14] reported that the seroprevalences of H. pylori in RA patients was 32%. Zentilin et al. [15] reported that the seroprevalences of H. pylori in RA patients was 48%. Other studies found higher prevalence (80-88%) of H. pylori infection in RA patients than our results [16-18].

In this study, we found that there was no significant difference in age between both H. pylori FAT-positive and negative groups. This is in agreement with the studies by Graff et al. [14] , Raybαr et al. [19] , and Nakamura et al. [16] .

In our study regarding sex, positive titer was common in female patients than in male patients, which is in contrast to the studies by Graff et al. [14] and Nakamura et al. [16] who found that the sex of RA patients did not affect H. pylori status.

In our study, similar to the studies by Nakamura et al. [16] and Ishikawa et al. [20] , the positive group had longer RA disease duration than the negative group but the difference was not significant.

In agreement with the study by Graff et al. [14] and in contrast to the study by Zentilin et al. [15] , we found that the FAT-positive group had significant (P = 0.04) longer duration of morning stiffness than the negative group.

In our study, we found that the FAT-positive group had significantly more tender joints count and swollen joint count than the negative group, in contrast with the studies performed by Graff et al. [14] and Zentilin et al. [15] .

In our present study, we found no significant difference between H. pylori FAT-positive and negative patients regarding hemoglobin level at baseline. This result was similar to the results obtained by Zentilin et al. [15] and Ishikawa et al. [20] .

In addition, we found that there was no significant difference (P = 0.753) between H. pylori FAT-positive and negative groups regarding the ESR level at baseline. This is similar to the result of Ishikawa et al. [20] and in contrast with the result of Zentilin et al. [15] .

In this study, we found that the FAT-positive group had significantly higher level of CRP than the negative group at baseline. This is in agreement with the studies by Zentilin et al. [15] and Wen et al. [18] . In contrast, Ishikawa et al. [20] reported no significant difference between H. pylori-positive and negative patients regarding CRP level at baseline.

In this study, we found that the FAT-positive group had higher level of RF titer than the negative group; however, the difference was not significant (P = 0.177). In contrast, Nakamura et al. [16] found that the presence of a RF was inversely related to H. pylori infection, and the value of the RF was lower in patients with the infection.

In this study, we found that the FAT-positive group had significantly higher DAS such as DAS28 than the negative group. This is in agreement with the result of Wen et al. [18] and in contrast with the result of Zentilin et al. [15] .

In contrast with the result of Graff et al. [14] , we found that there was a significant difference between H. pylori FAT-positive and negative patients regarding pain scores by VAS and HAQ scores at baseline.

In this study, we found that, after treatment of H. pylori, the tender joints count was significantly decreased (P < 0.001). This is in agreement with the study by Zentilin et al. [15] and in contrast with the study by Graff et al. [14] .

In this study, in agreement with the studies by Seriolo and Bruno [21] and Zentilin et al. [15] , we found that after treatment of H. pylori the swollen joints count was significantly decreased. In contrast, Graff et al. [14] stated that there was no significant difference (P = 0.12) in the number of swollen joints in the H. pylori-positive group after H. pylori eradication.

In our present study, we found no significant difference (P = 0.323) between H. pylori FAT-positive group at baseline and after 2 months of H. pylori treatment regarding hemoglobin level. This is similar to the result of Zentilin et al. [15] .

In this study, we found no significant difference in ESR level (P = 0.146) between H. pylori FAT-positive group at baseline and after 2 months of H. pylori treatment. This was against the results of Graff et al. [14] , Zentilin et al. [15] , and Seriolo and Bruno [21] who reported a significant decrease in the ESR of the patients after H. pylori treatment. In contrast, Matsukawa et al. [22] reported that there was an exacerbation in the ESR level following H. pylori eradication.

In this study, we found that the value of CRP was significantly reduced after treatment of H. pylori. This result is in agreement with the result of Zentilin et al. [15] and in contrast with the result of Matsukawa et al. [22] . In contrast, Graff et al. [14] found no significant difference (P = 0.14) in the CRP level in the H. pylori-infected RA patients at baseline and after eradication.

In this study, against the results of Matsukawa et al. [22] , we found that after treatment of H. pylori the value of DAS28 was significantly reduced.

In addition, in our study, we found a highly significant difference in the pain scores by VAS in H. pylori FAT-positive patients at the initiation of the study and after 2 months of H. pylori eradication. This is in agreement with the result of Zentilin et al. [15] and against the results of Graff et al. [14] .

In our study, we found that there was a significant difference (P = 0.009) between HAQ score of H. pylori FAT-positive patients at the initiation of the study and after 2 months of H. pylori eradication. This is in agreement with the result of Zentilin et al. [15] and against the results of Graff et al. [14] .


  Conclusion Top


Our results showed that patients with RA are more susceptible to develop dyspeptic symptoms. H. pylori infection in a RA patient is associated with higher disease activity and high levels of CRP and serum RF titers. Treatment of H. pylori infection with triple therapy is associated with significant reduction in RA disease activity and CRP and RF titers.


  Acknowledgements Top


Conflicts of interest

None declared.

 
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    Figures

  [Table 1]
 
 
    Tables

  [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


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