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Does Helicobater pylori initiate or perpetuate immune
Marc Michel, Nichola Cooper, Christelle Jean, Christine Frissora, and James B. Bussel
From the Department of Pediatrics, Division of Hematology/Oncology, and Department of Medicine, Division of Gastroenterology, Weill Medical College of Cornell University, New York–Presbyterian Hospital, New York, NY.
Seventy-four consecutive consenting patients, including 50 women (67.5%) and 24 men, with a mean age of 41 years (SD ± 18.3) fulfilling the inclusion criteria were enrolled and tested for the presence of H pylori. Sixty-three of the 74 patients (85%) were white, 7 (9.5%) were Hispanic, 3 (4%) were Asian, and 1 patient was African American.
Sixty-four (90%) of the enrolled patients had chronic ITP (ie, duration > 6 months) and 21 (28%) had previously undergone splenectomy.
Prevalence of H pylori infection
Sixteen of the 74 patients (21.6%) had a positive breath test. This rate of infection was lower than the prevalence of 32.5% assessed in 7465 healthy adults in the US population by means of serology14 (P = .04).
H pylori–positive patient characteristics
As expected, increased age was associated with a higher likelihood of H Pylori infection in both the healthy controls14 and the ITP patients (Figure 1). The mean age of the H pylori–positive patients (52.5 years, SD ± 15.9) was higher than the mean age of the H pylori–negative patients (38.5 years, SD ± 18.3; P = .0035). Although there was a trend for a longer duration of ITP in H pylori–positive patients (10.2 years versus 6.4 years in H pylori–negative patients; P = .07), only the mean age was significantly different when H pylori–positive and –negative patients were compared (Table 2).
Patients completed a questionnaire of GI symptoms to see if this would predict which patients were infected. There was a trend for patients with heartburn and gas or burping to be H pylori infected (Table 1).
Eradication of H pylori
The 16 H pylori–positive patients all had chronic ITP and 15 had been previously treated for their ITP by 1 to 6 therapies including splenectomy in 5 (Table 3). Since 1 patient had her platelet count return to normal prior to beginning treatment of H pylori, only 15 of the 16 H pylori–positive patients were treated. Fourteen patients received the Prevpac, one patient who was allergic to penicillin was first treated with clarithromycin and lansoprazole. Overall, H pylori was successfully eradicated in 14 of the 15 patients (93%). The H pylori was allowed to persist in a 74-year-old woman whose platelet count was stably greater than 50 x 109/L; she did not respond to the Prevpac and then developed diarrhea and vomiting during alternative treatment with metronidazole and doxycyclin.
Platelet outcome in H pylori–positive patients
The median follow-up of infected patients was 11.5 months (range, 3-18 months; Table 3). Three months after the treatment, the time point at which responses were seen in other studies, a significant increase of platelet count was observed in only one patient (patient no.12; Table 3). However, since the patient had a chronic relapsing ITP, the role of the Prevpac was difficult to ascertain. Moreover, after 7 months of follow-up, her platelet count was 53 x 109/L; a breath test was not performed at time of relapse. In another case (no. 13) in which no platelet change was seen at 3 months, mycophenolate mofetil and cyclosporin were begun and at 6 months the count was 100 000/µL. In total, 11 of the 15 patients (73%) required changes in their baseline treatment within 6 months after receiving the eradication regimen (Table 3).
Platelet outcome in H pylori–negative patients
After 3 months of follow-up, no significant increase in the platelet count was observed in any of the 9 consecutive H pylori–negative patients who were treated by the Prevpac or the one receiving an alternative regimen (Table 4). The increase in the platelet count observed in patient no. 5 was likely to be a consequence of the administration of mycophenolate mofetil that was started a month before for an underling systemic lupus erythematosus. After 6 months of follow-up, a CR or a PR was achieved in 4 patients (nos. 3, 4, 5, and 8) but in all cases after the initiation of new treatment (Table 4). Patient no. 10 was the only who did not require any change in her baseline ITP treatment after receiving the H pylori eradication regimen (Table 4).
Whether the investigation and eradication of H pylori infection should be pursued in patients with ITP is a matter of debate. Infectious agents such as HIV and hepatitis C virus (HCV) may trigger an immune-mediated thrombocytopenia and/or cause it to persist13 while other viruses resulting in chronic infections, such as human T-cell lymphoma/leukemia virus 1 (HTLV-1), do not seem to have this effect.16 Recent studies in primarily Italian and Japanese populations2-8 have suggested that H pylori could initiate and perpetuate ITP. Initiation would be suggested by an increased mutual coincidence of H pylori and ITP over that observed in the general population. Perpetuation would be suggested by amelioration of ITP as a result of H pylori eradication. In the studies cited above, although approximately half of the patients in whom H pylori was eradicated did not change their platelet counts (Table 5), perpetuation has been better demonstrated than initiation. If H pylori perpetuated ITP in as few as 10% to 20% of patients, then an appropriate strategy for management of ITP might involve testing for H pylori and eradicating it in those patients who were infected.
Since the relationship between H pylori and ITP remains controversial in adults11,12 and is far from being established in children,17 this study was performed to investigate the prevalence of H pylori infection in 74 North American patients with ITP aged 10 and older and to determine the effect of H pylori eradication. The determination of active H pylori infection was assessed by a breath test, a noninvasive, highly sensitive and specific method18 that has been used in almost all of the previous studies (Table 5 includes a literature review).