Helicobacter pylori infection in patients with autoimmune thrombocytopenic purpura

Abstract

AIM: To compare the prevalence of Helicobacter pylori (H pylori) infection in autoimmune thrombocytopenic purpura (AITP) patients with that of nonthrombocytopenic controls, and to evaluate the efficacy of the treatment in H pylori(+) and H pylori(-) AITP patients.

METHODS: The prevalence of gastric H pylori infection in 38 adult AITP patients (29 female and 9 male; median age 27 years; range 18-39 years) who consecutively admitted to our clinic was investagated.

RESULTS: H pylori infection was found in 26 of 38 AITP patients (68.5%). H pylori infection was found in 15 of 23 control subjects (65.2%). The difference in H pylori infection between the 2 groups was not significant. Thrombocyte count of H pylori-positive AITP patients was significantly lower than that of H pylori-negative AITP patients (P < 0.05). Thrombocyte recovery of H pylori-positive group was less than that of H pylori-negative group (P < 0.05).

CONCLUSION: H pylori infection should be considerecd in the treatment of AITP patients with H pylori infection.

Key Words: $[Keywords]

INTRODUCTION

Autoimmune thrombocytopenic purpura (AITP) is an acquired bleeding disorder in which autoantibodies bind to platelet surface, leading to platelet destruction[1,2]. The mechanism triggering the production of platelet autoantibodies are poorly understood[2].

Helicobacter pylori (H pylori) is a spiral shaped bacterium that resides in the stomach mucosa. H pylori has been considered for years as the etiologic agent of gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma[3-5]. More recently, H pylori has been found to be associated with a number of autoimmune disorders, such as rheumatoid arthritis[6], autoimmune thyroiditis[7], Sjogren’s syndrome[8], Schonlein-Henoch purpura[9], and AITP[10,11].

There are data consistent with an association between H pylori infection and AITP[12-14]. In addition a significant increase of platelet count following H pylori eradication has been reported in a proportion of AITP patients[12]. AITP in adults is most often chronic, and up to 25% of cases of chronic AITP are refractory to standard therapy[1]. However, although there is some evidence implicating H pylori in some autoimmune disorders, the association between AIPT and H pylori infection is speculative.

The aim of this study was to compare the prevalence o f H pylori infection in AITP patients with that of nonthrombocytopenic controls and to evaluate the efficacy of the treatment in H pylori(+) and H pylori(-) AITP patients.

MATERIALS AND METHODS

Between May 2001 and October 2003 we investigated the presence of gastric H pylori infection in 38 adult AITP patients (29 females, 9 males, median age: 27 years, range: 18-39 years) consecutively admitted to our clinic. AITP was diagnosed on the basis of the presence of isolated thrombocytopenia (< 100 × 10⁹/L) and megakaryocytic hyperplasia in bone marrow. Other causes of thrombocytopenia (drugs, pseudothrombocytopenia, hepatitis B and C virus infections, human immunodeficiency virus infection, malignancy) were excluded. Patients considered at bleeding risk who would require active treatment were also excluded. Age- and sex-matched 23 (18 females, 5 males, median age: 26 years, range: 18-35 years) nonthrombocytopenic patients without dyspeptic complaints were used as control group. None of the patients and controls had received antibiotics, proton pump inhibitors, and H₂-receptor blockers during 4 wk before the onset of AITP.

All patients underwent 1 mg/(kg.d) steroid therapy for 3 wk following diagnosis, and then the dose gradually tapered every week until withdrawal. Our second choice of therapy was intravenous immunoglobulin administration [400 mg/(kg.d) for 5 d], but we did not use it.

An agglutination method was used to detect anti-H pylori antibodies of IgG type in both patients and controls (Ridascreen^®, R-Biopharm, Darmstadt, Germany). Hemogram analysis was done by Coulter^® STKS (Coulter Corporation, Miami, Florida, USA).

Although demonstration of H pylori in gastric biopsies is the gold standard of H pylori detection, we prefered blood antibody detection due to following reasons. Endoscopy might cause unexpected bleeding in thrombocytopenic patients especially in those whose thrombocyte counts were less than 50 × 10⁹/L. Urea breath test could not allow the detection of H pylori infection retrospectively. Both sensitivity and specificity of such kits were demonstrated in previous studies (95% <)[15].

Statistical analysis

Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U tests. Mean values were calculated for every variable in each group and compared between different groups. P < 0.05 was considered as statistically significant.

RESULTS

There was no age or sex difference between controls and patients. H pylori infection was found in 26 of 38 patients with AITP (68.5%), and in 15 of 23 control subjects (65.2%). The difference between the 2 groups for H pylori infection was not significant (Table 1). Thrombocyte count of H pylori-positive AITP patients was lower than that of H pylori-negative AITP patients (P < 0.05). Thrombocyte recovery of H pylori-positive group was less than that of H pylori-negative group (Table 2) (P < 0.05).

Table 1 General characteristics of subjects in the study.

Subjects	n	%	Mean age (range)	Sex (F/M)
H pylori-negative controls	8	(34.8)	25 (18-32)	6/2
H pylori-positive controls	15	(65.2)	27 (25-35)	12/3
H pylori-negative patients	12	(31.5)	29 (24-34)	8/4
H pylori-positive patients	26	(68.5)	26 (22-37)	21/5

Table 2 Platelet counts (× 10⁹/L) of AITP patients before and after steroid therapy.

Parameters	H pylori-positive patients (n = 26)	H pylori-negative patients (n = 12)
Platelet counts (× 109/L) (mean, range)	15 (10-22)a	29 (21-42)
Response to steroid (number, %)	17 (65) a	10 (83)
Post-treatment platelet counts (× 109/L) (mean, range)	77 (61-112)	140 (124-180)

^aP < 0.05 vs H pylori negative patients.

DISCUSSION

AITP is an autoimmune disease caused by autoantibodies against platelets[16]. Several lines of direct and indirect evidences suggest that infectious agents may influence the occurence or the course of some autoimmune diseases[17]. The role of some bacterial or viral agents in the pathogenesis of AITP is well known. It has been demostrated that the mimicry of human antigens by infectious agents represents the mechanism underlying this phenomenon[18].

H pylori is a ubiquitous Gram-positive bacterium involved in the pathogenesis of gastric and duodenal ulcers. Recently, the involvement of H pylori has also been suggested in various autoimmune diseases[6-9]. H pylori has been shown to cause immunological responses to the production of large amounts of proinflammatory substances and mucosal damage through autoimmunity[19]. Previous in vitro studies suggested that H pylori has the potential to initiate autoreactivity through molecular mimicry. Recently, a role of H pylori in the pathogenesis of AITP has been suggested because significant increases in thrombocyte count were reported after eradication of H pylori[10,11]. Michel et al[2] and Jargue et al[14] found no evidence of an association between H pylori infection and AITP. But the role of H pylori in the pathogenesis of AITP is still controversial.

Regarding the association between H pylori and AITP, Gasbarrini et al[11] reported that 61% of 18 AITP cases were infected with H pylori. Emilia et al[10] then reported that 43% of 30 AITP patients were H pylori positive. Kohda et al[18] found that H pylori was positive in 62.5% of 40 AITP patients in Japan. The prevalence of H pylori in our series was 68.5%. The prevelance of H pylori infection in healthy population of Italy, where Gasbarrini’s and Emilia’s studies were held, was about 63%[20]. In Japan the prevelance of H pylori infection was about 25%-45%[21]. We found H pylori infection in 65.2% of healthy controls in Turkish population.

Steroid is considered as the most effective treatment for AITP in adults. But, most patients relapsed when steroids were withdrawn and only 10%-30% of them maintained a long lasting remission[22]. Kohda et al[18] and Michel et al[2] found that there was no significant difference regarding thrombocyte counts between H pylori-positive and H pylori-negative AITP patients. In our series the thrombocyte count of H pylori-positive group was higher than that of H pylori-negative group at the initial presentation, and the difference between two groups was significant (P < 0.05). Following treatment increase in the thrombocyte count of H pylori-positive patients was less than that of H pylori-negative patients. The difference was also significant (P < 0.05).

Although the pathogenetic mechanism underlying H pylori-induced thrombocytopenia remains obscure, H pylori has been presumed to induce the formation of autoantibodies by way of a chronic immunological stimulus or cross mimicry between itself and platelets[23]. It has been demonstrated that autoantibodies against H pylori can also react with some extragastric tissues, such as glomerular capillary membrane, ductal cells of salivary glands, and renal tubular cells[24]. Platelets may also be a target of such antibodies although there is no proof for this cross reactivity.

In conclusion, H pylori infection should be searched in all AITP patients, and we suggest that H pylori should eradicated in H pylori-positive AITP patients.