Mycoplasma
ITP REVERSAL .
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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
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.
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The prevalence of 21.6% of H pylori infection found in the 74
patients with ITP was surprisingly low compared with the prevalence
of 32.5% assessed by presence of serum IgG antibodies in 7465
healthy adults in the United States.14 The difference in the method
of H pylori detection and the ethnic distribution of our patient
population are unlikely to explain this low rate of infection.
Indeed, in a previous study, the prevalence of H pylori infection
among 239 healthy white Americans was 34% using a urea breath
test.19 While 25% of children 6 to 19 years old are infected in the
United States,15 none of the 11 patients aged of 19 or younger
included in the series reported here had a positive breath test.
Even eliminating these adolescents, the prevalence of H pylori
infection only reached 25.3% in the adults (16/63). These data do
not support H pylori initiating ITP in our patient population.
Could H pylori infection be predicted? The questionnaire contained 2
variables that showed a trend toward identifying H pylori infection:
heartburn or gas burping. As with the healthy controls, increased
age was associated with a higher likelihood of H pylori infection.
Therefore, if one wished to test ITP patients, one approach would be
to test those older than 50 years of age and those younger than 50
years of age with heartburn or gas burping. In the series reported
here, this would have identified 15 of the 16 infected patients
while testing only 52 of the total of 74.
Can eradication of H pylori cure ITP? One limitation of previous
studies was that at most 25% of the H pylori--positive patients who
received the eradication regimen were those with chronic severe
thrombocytopenia (ie, platelet count < 30 x 109/L and/or previous
splenectomy4; Table 5). By comparison, among the 15 H
pylori--positive patients treated in this study, all had chronic ITP
with a platelet count less than 55 x 109/L (7 were < 30 x 109/L) and
all have been previously treated for their ITP by 2 to 6 different
treatments including splenectomy in 5 cases (33%). Therefore, these
patients had a very low likelihood of spontaneous improvement and
the effectiveness of H pylori eradication on ITP outcome was easier
to assess. The eradication rate was 93% since alternative treatment
was pursued when the initial regimen was ineffective. However,
despite this good rate of eradication and unlike previous
studies,2-8 only one of our H pylori--positive patients achieved a
significant response 3 months after eradication and this response
did not last.
In this study, 3 months was chosen as the time limit for seeing an
effect of H pylori eradication. If no response was seen at that
time, other therapies were initiated if necessary. Previous studies
that provided time frames all demonstrated platelet recovery within
60 days after H pylori eradication.2,6,8 In this study, extending
the time beyond 3 months following H pylori eradication did not seem
to affect the response since the only platelet changes observed were
in those patients who had initiated other therapies. To explain the
high rates of response reported by others (Table 5), a nonspecific
effect of the drugs used to eradicate the bacteria seems unlikely
since in this present study none of the 10 H pylori--negative
patients who received the Prevpac experienced a significant
improvement in their platelet count.
The striking discrepancies between this report and those from Italy
and Japan suggest several hypotheses. One hypothesis is that the
response to H pylori infection could be influenced by the host's
immunogenetic background.20,21 However, the contradictory findings
reported in patients of similar European origin (ie, Spain, France,
and Italy)2,3,4,11,12 (Table 5) do not support this hypothesis.
Another possibility is that different strains of H pylori, namely
those with different cag or vag (cytotoxicity/virulence-associated
genes) proteins,20 could exert different immunologic effects on the
host T and B cells and hence on ITP. A third hypothesis is that the
expression of various Lewis (Le) antigens by H pylori isolates22 and
the subsequent production of anti-Le antibodies could play a role in
ITP pathogenesis since platelets may adsorb Lewis antigens from the
serum.
The management of ITP in adults is complex and may require
immunosuppressive therapies and/or splenectomy. One of the
challenges for physicians caring for patients with ITP is to find
less toxic and more effective approaches. The expectation at the
beginning of this study was that a percentage of patients could be
"cured" by administration of the Prevpac for 2 weeks. Unexpectedly,
in this study there was not a greater prevalence of H pylori in ITP
patients. Furthermore, and unlike most of the previous studies, none
of the patients substantially improved their platelet count as a
result of H pylori eradication. Therefore, even if the success of
treatment of the H pylori--infected patients could be predicted by
age and questionnaire, it is not obvious from this study that one
would choose to test and eradicate infection in them. Future studies
performed in this setting should be randomized and controlled and
should include large numbers of patients requiring therapy. In
addition to tracking the platelet count, other parameters that might
be important determinants of response as suggested in the hypotheses
considered above should also be studied.
Footnotes
Does Helicobater pylori initiate or perpetuate immune
thrombocytopenic purpura?
Submitted March 25, 2003; accepted July 28, 2003.
Prepublished online as Blood First Edition Paper, August 14, 2003;
DOI 10.1182/blood-2003-03-0900.
The publication costs of this article were defrayed in part by page
charge payment. Therefore, and solely to indicate this fact, this
article is hereby marked "advertisement" in accordance with 18 U.S.C.
section 1734.
Reprints: Marc Michel, New York Presbyterian Hospital, Department of
Pediatrics, Division of Pediatric Hematology/Oncology, Weill Medical
College of Cornell University, 525 East 68th St, New York, NY 10021;
e-mail: drmarcmichel@hotmail.com.
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