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Does Helicobater pylori initiate or perpetuate immune thrombocytopenic purpura?
Marc Michel, Nichola Cooper, Christelle Jean, Christine Frissora, and James B. Bussel
Division of Gastroenterology, Weill Medical College of Cornell University, New York–Presbyterian Hospital, New York, NY.
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To determine the prevalence of Helicobacter pylori (H pylori) infection in North American patients with immune thrombocytopenic purpura (ITP) and the effect of H pylori eradication on the platelet count, a prospective study was performed. Seventy-four patients aged 10 years and older (mean age of 41 years) with chronic ITP and a platelet count below 60 x 109/L were enrolled. H pylori infection was found in 22% of patients by means of a breath test and could not be predicted by gastrointestinal symptoms. H pylori–positive patients (52.5 years of age) were older than H pylori–negative patients (38.5 years of age; P = .0035). Fifteen of the 16 H pylori–positive patients were treated and the bacteria was eradicated in 14 (93%). After 3 months, a significant response (platelet count > 50 x 109/L and doubling the initial count) was observed in only one patient. After a median follow-up of 11.5 months, none of the 14 patients had responded. Ten H pylori–negative patients treated with the same regimen also did not increase their platelet counts. In conclusion, unlike several previous reports, this study does not implicate H pylori in the pathogenesis of ITP since the prevalence of H pylori infection was low and eradication of H pylori did not positively influence the course of the ITP
Helicobacter pylori (H pylori), a ubiquitous Gram-positive bacterium, was initially discovered in 1982 as an infectious cause of peptic ulcers. Following discovery of its causative role in gastritis and peptic ulcer disease, subsequent studies implicated H pylori in the pathogenesis of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. More recently, H pylori has been suspected to be involved in various autoimmune disorders including pernicious anemia and immune thrombocytopenic purpura (ITP).1-8
In 1998, Gasbarrini et al2 reported a substantial increase in the platelet count in all 8 H pylori–positive adults with immune thrombocytopenic purpura (ITP) in whom H pylori was eradicated. Subsequent uncontrolled studies from Italy3-5 and Japan6-8 all showed an apparently higher-than-expected prevalence of H pylori9,10 in patients with ITP. Furthermore, 38%7 to 73%4 of H pylori–positive patients with ITP achieved a partial or complete platelet recovery after H pylori eradication. On the other hand, additional studies have not supported a role for H pylori in ITP. The prevalence of H pylori infection was not increased in French patients with ITP when compared with age-matched controls,11 and while the prevalence of H pylori was high, no significant improvement of the platelet count was observed after H pylori eradication in a report from Spain.12
We therefore conducted a prospective study to assess the prevalence of H pylori infection in North American patients with ITP and the efficacy of H pylori eradication on the platelet count. If eradication of H pylori was not achieved with the initial regimen, treatment was pursued with alternative regimens. To determine if the H pylori eradication regimen could have nonspecific effects on the platelet count, 10 ITP patients whose H pylori test was negative were also treated with the same eradication regimen. In addition, a short questionnaire was completed by the patients at the time of testing to see if H pylori–infected patients with ITP could be identified by symptoms referable to their gastrointestinal (GI) tract.
All patients with ITP, defined according to the criteria set forth in the American Society of Hematology (ASH) Guidelines,13 who attended the Weill-Cornell center over the 12 month study period were eligible to enroll in this study if they fulfilled the following inclusion criteria: age of 10 years and older, a platelet count of less than 60 x 109/L within 2 weeks of H pylori testing, and no knowledge of a positive HIV test. Patients who were treated by immunosuppressive treatments or other drugs for their ITP at the time of inclusion were eligible if the doses of the ongoing medications were stable for at least 4 weeks before inclusion. After inclusion, both intravenous immunoglobulins (IVIg's) and intravenous anti-D (IV anti-D) were allowed as a rescue therapy if clinically required (ie, very low platelet count, grade III or IV bleeding symptoms, or scheduled invasive procedures). Patients were not eligible for the study if they had been treated for H pylori within 2 years or if they had been treated with either an antibiotic, lansoprazole (or another proton pump inhibitor), or bismuth within the past 4 weeks.
In order to see if the status of H pylori could be predicted by gastrointestinal symptoms or past medical history, all patients were asked to complete a short standardized questionnaire at the time of the breath test (Table 1).
Approval for this study was obtained from the Institutional Review Board of the New York Hospital–Cornell Medical Center and informed consent was provided by all subjects or their parents according to the Declaration of Helsinki. Patients 10 to 18 years of age provided their assent.
H pylori infection testing
All enrolled patients underwent at time of inclusion a BreathTek Urea breath test commercially available from Prometheus (San Diego, CA). In H pylori–positive patients, eradication was assessed by another urea breath test performed 1 to 2 months after completion of treatment. Patients not responding to eradication treatment had a third test performed after a subsequent treatment regimen was completed. The breath test initially required a 4-hour fast before it could be performed. This led several otherwise eligible patients to decline to participate.
H pylori eradication regimen
Patients infected with H pylori were treated according to a standard H pylori treatment protocol currently in use in the United States (referred to as the Prevpac, TAP Pharmaceutical Products, Lake Forest, IL). For patients older than 12 years of age, this consisted of lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1000 mg taken together twice a day for 2 weeks. Children 10 to 12 years of age received lansoprazole 30-mg capsules, clarithromycin tablets at a dose of 15 mg/kg/day to a maximum dose of 500 mg/day, and amoxicillin 500-mg tablets at a dose of 45 mg/kg/day to a maximum dose of 1000 mg/day. The penicillin-allergic patients were not given amoxicillin. If H pylori was not eradicated after initial treatment, the patient was referred to the study gastroenterologist (C.F.) to determine an alternative therapy.
To see if there was an effect on the platelet count after the Prevpac administration, all of the initial patients enrolled began treatment "blindly" at the time of the breath test screening before the results had returned. After 10 patients whose H pylori test was subsequently found to be negative had been treated (ITP treatment control group), only patients whose breath test was positive received the Prevpac. Nine of the 10 control patients received the Prevpac; 1 was penicillin allergic. In order to compare the prevalence of H pylori infection in our population of ITP patients to the prevalence in healthy individuals, recent epidemiologic data available in a North American population14,15 was used.
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