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Săsăran MO, Mărginean CO, Koller AM. Impact of Helicobacter pylori Infection upon the Evolution and Outcome of Pediatric Immune Thrombocytopenic Purpura: A Comprehensive Review. Diagnostics (Basel) 2023; 13:3205. [PMID: 37892026 PMCID: PMC10606204 DOI: 10.3390/diagnostics13203205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/08/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
In adults with immune thrombocytopenic purpura (ITP), the identification of H. pylori infection and its subsequent eradication proved to aid platelet recovery. Similar findings, at a smaller scale, were allegedly reported by some pediatric studies. This review's objective was to establish the influence of H. pylori infection and its eradication upon platelet count and recovery in pediatric ITP. Three databases, namely Pubmed, Scopus and Web of Science, were searched for pediatric studies which investigated a link between H. pylori infection and thrombocytopenia. The search results retrieved a number of 21 articles which complied to the inclusion and exclusion criteria. Some studies report lower platelet values among children with ITP and documented H. pylori infection, as well as an improve in platelet numbers after H. pylori treatment. However, results are controversial, as multiple authors failed to identify a higher prevalence of H. pylori among children with ITP or a lack of significant change in therapeutic outcome with the addition of an eradication regimen to standard treatment. The main limitations of current pediatric studies remain the small study samples and the short follow-up periods of the included subjects. Hence, the long-term impact of H. pylori in children with ITP is still uncertain.
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Affiliation(s)
- Maria Oana Săsăran
- Department of Pediatrics 3, University of Medicine, Pharmacy, Sciences and Technology George Emil Palade from Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania;
| | - Cristina Oana Mărginean
- Department of Pediatrics 1, University of Medicine, Pharmacy, Sciences and Technology George Emil Palade from Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania
| | - Ana Maria Koller
- Clinics of Pediatrics, Emergency County Clinical Hospital, Gheorghe Marinescu Street No. 50, 540136 Târgu Mureș, Romania;
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2
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Yang L, Xiao D, Li X, Lai C, Chen Y, Pan L. Case report: A case of immune thrombocytopenia combined with Hashimoto's thyroiditis and Helicobacter pylori infection in a child. Front Pediatr 2023; 11:1169064. [PMID: 37360361 PMCID: PMC10288111 DOI: 10.3389/fped.2023.1169064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 05/25/2023] [Indexed: 06/28/2023] Open
Abstract
Immune thrombocytopenia (ITP) is one of the most prevalent acquired bleeding disorders in children, which is primarily characterized by a decrease in platelet count. It can be classified into two subtypes: primary ITP and secondary ITP. The underlying mechanisms causing ITP are complex and not fully comprehended. Helicobacter pylori (H. pylori) infections can lead to ITP and potentially trigger various autoimmune diseases. Furthermore, there is evidence of a correlation between thyroid disease and ITP. In this case report, we describe the case of an 11-year-old patient who presented with ITP, Hashimoto's thyroiditis (HT), and H. pylori infection. Following anti-H. pylori treatment and thyroxine supplementation, the child's platelet count increased compared to the previous count. The limitation of this report is that the platelet count of this child returned to normal after anti-H. pylori and thyroxine supplementation, so we cannot distinguish the effect of anti-H. pylori and thyroxine supplementation on the platelet count in this child. Despite this limitation, we still believe that early screening for thyroid function and H. pylori, as well as prompt eradication of H. pylori, along with thyroxine supplementation, may be beneficial in treating and improving the prognosis of children diagnosed with ITP.
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Affiliation(s)
- Lihong Yang
- Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Sichuan University, Chengdu, China
| | - Dongqiong Xiao
- Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Sichuan University, Chengdu, China
| | - Xihong Li
- Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Sichuan University, Chengdu, China
| | - Chunqi Lai
- Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Sichuan University, Chengdu, China
| | - Yuhao Chen
- Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Sichuan University, Chengdu, China
| | - Lingli Pan
- Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Sichuan University, Chengdu, China
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3
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Castagnini LA, Gilger MA. Helicobacter pylori. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2023:954-959.e5. [DOI: 10.1016/b978-0-323-75608-2.00174-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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4
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Ihtesham A, Maqbool S, Nadeem M, Bilawal Abbas Janjua M, Sundus O, Bakht Naqqash A, Inayat Mohamed W, Turab Haider S, Ahmad M, Ahmad Talha Mustafa M, Osama Mehboob H. Helicobacter pylori induced Immune Thrombocytopenic Purpura and perspective role of Helicobacter pylori eradication therapy for treating Immune Thrombocytopenic Purpura. AIMS Microbiol 2021; 7:284-303. [PMID: 34708173 PMCID: PMC8500795 DOI: 10.3934/microbiol.2021018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 08/30/2021] [Indexed: 12/12/2022] Open
Abstract
Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterised by production of autoantibodies against platelet surface antigens. Recent studies have demonstrated a paramount association of ITP and Helicobacter pylori (H-pylori) infection with significant rise in platelet count following H-pylori eradication therapy. The H-pylori infection induced ITP is validated by many proposed mechanisms such as molecular mimicry due to production of autoantibodies against H-pylori surface virulent factors (CagA) and cross reactivity of these antibodies with platelet surface antigens (GP IIb/IIIa, GP Ib/IX, and GP Ia/IIa), phagocytic perturbation due to enhanced phagocytic activity of monocytes, enhanced dendritic cell numbers and response, platelets aggregation due to presence of anti- H-pylori IgG and von Willebrand factor (vWf) and finally host immune response against H-pylori virulent factors CagA and VacA leading to ITP. The effectiveness of H-pylori eradication therapy has also been demonstrated with platelet count being used as a predictive factor for assessment of treatment efficacy. Out of 201 patients 118 were responding to the triple therapy and remaining 83 patients were non-responders, showing the response rate of 58.7%. Out of 118 responders 69 patients were showing complete response (CR) and 49 were showing partial response (PR) to the H-pylori eradication therapy. However, more studies are required to elucidate this association and treatment efficacy.
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Affiliation(s)
| | | | | | | | - Omaima Sundus
- House officers Rawalpindi Medical University, Pakistan
| | | | | | | | - Muhmmad Ahmad
- House officers Services Institute of Medical Sciences, Pakistan
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Ikuse T, Toda M, Kashiwagi K, Maruyama K, Nagata M, Tokushima K, Ito N, Tokita K, Kyodo R, Hosoi K, Jimbo K, Kudo T, Shimizu T. Efficacy of Helicobacter pylori Eradication Therapy on Platelet Recovery in Pediatric Immune Thrombocytopenic Purpura-Case Series and a Systematic Review. Microorganisms 2020; 8:microorganisms8101457. [PMID: 32977477 PMCID: PMC7598273 DOI: 10.3390/microorganisms8101457] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/19/2020] [Accepted: 09/21/2020] [Indexed: 12/21/2022] Open
Abstract
Evidence relating to the efficacy of Helicobacter pylori eradication therapy for chronic immune thrombocytopenic purpura (cITP) in childhood is inadequate. The aim of this retrospective study was to determine the efficacy of H. pylori eradication therapy for platelet response in pediatric patients with cITP in our hospital, and to perform a systematic review of previous reports about pediatric patients with cITP who were positive for H. pylori infection and were treated with H. pylori eradication therapy. Analysis of the data of pediatric patients with cITP in our hospital and a systematic review of digital literature databases of studies in pediatric patients with cITP were performed. Data of 33 pediatric patients with cITP from our hospital records showed that the prevalence of H. pylori infection and the rate of response to platelet therapy were 15% and 33.3%, respectively. Data of 706 pediatric patients from 18 previous reports showed that the prevalence of H. pylori infection and rate of platelet response were 23% and 43.8%, respectively. Eradication therapy for H. pylori infection in pediatric cITP patients can be expected to result in a response equivalent to that in the adult population, with fewer adverse effects than other treatments for cITP.
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6
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Zendehdel A, Roham M. Biological evidence of the relationship between
Helicobacter pylori
and associated extragastric diseases. J Cell Biochem 2019; 120:12128-12140. [PMID: 30977160 DOI: 10.1002/jcb.28681] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 02/07/2019] [Accepted: 02/14/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Abolfazl Zendehdel
- Department of Geriatric Medicine, Ziaeian Hospital Tehran University of Medical Sciences Tehran Iran
| | - Maryam Roham
- Antimicrobial‐Resistant Research Center Iran University of Medical Sciences Tehran Iran
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COELHO LGV, MARINHO JR, GENTA R, RIBEIRO LT, PASSOS MDCF, ZATERKA S, ASSUMPÇÃO PP, BARBOSA AJA, BARBUTI R, BRAGA LL, BREYER H, CARVALHAES A, CHINZON D, CURY M, DOMINGUES G, JORGE JL, MAGUILNIK I, MARINHO FP, MORAES-FILHO JPD, PARENTE JML, PAULA-E-SILVA CMD, PEDRAZZOLI-JÚNIOR J, RAMOS AFP, SEIDLER H, SPINELLI JN, ZIR JV. IVTH BRAZILIAN CONSENSUS CONFERENCE ON HELICOBACTER PYLORI INFECTION. ARQUIVOS DE GASTROENTEROLOGIA 2018; 55:97-121. [PMID: 30043876 DOI: 10.1590/s0004-2803.201800000-20] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 02/22/2018] [Indexed: 02/06/2023]
Abstract
ABSTRACT Significant progress has been obtained since the III Brazilian Consensus Conference on H. pylori infection held in 2012, in Bento Gonçalves, Brazil, and justify a fourth meeting to establish updated guidelines on the current management of H. pylori infection. Therefore, the Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM), association linked to Brazilian Federation of Gastroenterology (FBG) held its fourth meeting again in Bento Gonçalves, RS, Brazil, on August 25-27, 2017. Twenty-six delegates, including gastroenterologists, endoscopists, and pathologists from the five regions of Brazil as well as one international guest from the United States, participated in the meeting. The participants were invited based on their knowledge and contribution to the study of H. pylori infection. The meeting sought to review different aspects of treatment for infection; establish a correlation between infection, dyspepsia, intestinal microbiota changes, and other disorders with a special emphasis on gastric cancer; and reassess the epidemiological and diagnostic aspects of H. pylori infection. Participants were allocated into four groups as follows: 1) Epidemiology and Diagnosis, 2) Dyspepsia, intestinal microbiota and other afections, 3) Gastric Cancer, and, 4) Treatment. Before the consensus meeting, participants received a topic to be discussed and prepared a document containing a recent literature review and statements that should be discussed and eventually modified during the face-to-face meeting. All statements were evaluated in two rounds of voting. Initially, each participant discussed the document and statements with his group for possible modifications and voting. Subsequently, during a second voting in a plenary session in the presence of all participants, the statements were voted upon and eventually modified. The participants could vote using five alternatives: 1) strongly agree; 2) partially agree; 3) undecided; 4) disagree; and 5) strongly disagree. The adopted consensus index was that 80% of the participants responded that they strongly or partially agreed with each statement. The recommendations reported are intended to provide the most current and relevant evidences to management of H. pylori infection in adult population in Brazil.
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8
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Wu SR, Kuo HC, Huang WC, Huang YF, Chiou YH, Chang YH, Nong BR. Incidence, clinical characteristics, and associated diseases in patients with immune thrombocytopenia: A nationwide population-based study in Taiwan. Thromb Res 2018. [PMID: 29522912 DOI: 10.1016/j.thromres.2018.02.146] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Immune thrombocytopenia (ITP) is an immune-mediated disease; it has been reported to be associated with several diseases. The data on ITP in patients with hepatitis B, tuberculosis, or thyroid diseases are relatively scarce. In addition, these diseases are not rare in Taiwan, together with hepatitis C and Helicobacter pylori which are also related to ITP. METHODS AND MATERIALS We identified 1223 ITP patients and characterized these patients between 2000 and 2013 from the National Health Insurance Research Database. The adult ITP patients were matched with non-ITP patients. RESULTS The overall incidence of ITP was 2.59/100,000 person-years. The frequencies of hepatitis B and C in adult ITP patients were much higher than those indicated in previous studies. The frequencies of non-traumatic intracerebral hemorrhage and gastrointestinal bleeding during hospitalization among ITP patients were low. The diseases associated with increased risks of ITP included hepatitis B (OR = 18.70, 95% CI = 9.71-36.03), hepatitis C (OR = 54.43, 95% CI = 15.94-185.88), hepatitis B and hepatitis C (OR = 7.02, 95% CI = 1.47-33.56), tuberculosis (OR = 5.37, 95% CI = 2.72-10.61), Helicobacter pylori infection (OR = 5.93, 95% CI = 3.16-11.10), hyperthyroidism (OR = 3.43, 95% CI = 2.09-5.64), hypothyroidism (OR = 6.70, 95% CI = 2.35-19.13), and simple and unspecified goiter (OR = 2.68, 95% CI = 1.43-5.03). CONCLUSIONS Surveying for the diseases which are frequent and related to increased risks of ITP among patients with newly diagnosed ITP should be considered.
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Affiliation(s)
- Shu-Ruei Wu
- Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Hsiao-Ching Kuo
- Research Center of Medical Informatics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Wei-Chun Huang
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yung-Feng Huang
- Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; Department of Pediatrics, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Yee-Hsuan Chiou
- Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Yu-Hsiang Chang
- Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Bao-Ren Nong
- Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; Department of Pediatrics, National Defense Medical Center, Taipei, Taiwan, ROC.
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9
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Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2017; 112:212-239. [PMID: 28071659 DOI: 10.1038/ajg.2016.563] [Citation(s) in RCA: 1008] [Impact Index Per Article: 126.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 10/07/2016] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process. For first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Details regarding the drugs, doses and durations of the recommended and suggested first-line and salvage regimens can be found in the guideline.
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Affiliation(s)
- William D Chey
- Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, USA
| | | | - Colin W Howden
- Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Steven F Moss
- Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
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Xiong LJ, Mao M. Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children. World J Clin Pediatr 2016; 5:82-88. [PMID: 26862506 PMCID: PMC4737697 DOI: 10.5409/wjcp.v5.i1.82] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 11/09/2015] [Accepted: 11/17/2015] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extra-intestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch-Schonlein purpura (HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum IgA, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP.
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11
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Rinaldi M, Perricone C, Ortega-Hernandez OD, Perricone R, Shoenfeld Y. Immune thrombocytopaenic purpura: an autoimmune cross-link between infections and vaccines. Lupus 2014; 23:554-67. [PMID: 24763539 DOI: 10.1177/0961203313499959] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Immune thrombocytopaenic purpura (ITP) is an autoimmune systemic disease detectable by the presence of low blood platelets count (<10(5)/µl) and the production of autoantibodies against glycoproteins expressed on the platelet surface. The clinical course is often acute, and life-threatening events may occur especially in children, with 52% of paediatric patients recovering either spontaneously or after treatment. A chronic ITP evolution is observed in 64% of adults, of whom 12% will develop an overlapping autoimmune disease. Several microbial agents such as CagA-positive Helicobacter pylori or Candida albicans and a number of viruses including CMV, EBV or HIV can potentially trigger ITP through molecular mimicry. Moreover, ITP improves after treatment of the underlying infection. Similarly, vaccines such as MMR may prompt ITP (IRR 5.48, 1.61-18.64, p < 0.006). Early recognition of the underlying microbial trigger and the removal of modifiable aetiopathogenetic factors should be integrated as a complementary treatment strategy in all patients who do not readily improve with standard ITP care.
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Affiliation(s)
- M Rinaldi
- 1Rheumatology, Allergology and Clinical Immunology, Department of Internal Medicine, University of Rome Tor Vergata, Italy
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12
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Campuzano-Maya G. Hematologic manifestations of Helicobacter pylori infection. World J Gastroenterol 2014; 20:12818-12838. [PMID: 25278680 PMCID: PMC4177465 DOI: 10.3748/wjg.v20.i36.12818] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2014] [Revised: 06/10/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases.
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13
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Brito HSH, Braga JAP, Loggetto SR, Machado RS, Granato CFH, Kawakami E. Helicobacter pylori infection & immune thrombocytopenic purpura in children and adolescents: A randomized controlled trial. Platelets 2014; 26:336-41. [PMID: 24832381 DOI: 10.3109/09537104.2014.911836] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Helicobacter pylori and immune thrombocytopenic purpura (ITP) association is not well established in chronic ITP (cITP) in children, although the cure of thrombocytopenia in approximately half of H. pylori eradicated adult patients has been described. The aim of this study was to investigate the effect of H. pylori eradication on platelet (PLT) recovery in cITP children and adolescents through a randomized, controlled trial. A total of 85 children (mean age 11.4 years) with cITP were prospectively enrolled. Diagnosis of H. pylori was established by two locally validated tests, (13)C-urea breath test and monoclonal stool antigen test. Twenty-two infected patients were identified, and randomly allocated into two groups: H. pylori treatment group (n = 11) and the non-intervention control group (n = 11). The control group was offered treatment if the thrombocytopenia persisted after the follow-up. At baseline, there were no differences regarding age, sex, duration of disease, and PLT count between groups. Sixty three of 85 patients were uninfected. PLT response was classified as complete response: PLT > 150 × 10(9 )l(-1); partial response: PLT 50-150 × 10(9 )l(-1), or an increase of 20-30 × 10(9 )l(-1); no response: PLT < 50 × 10(9 )l(-1) or an increase of <20 × 10(9 )l(-1) after at least 6 months of follow-up. Complete response was observed in 60.0% (6/10, one excluded) H. pylori eradicated patients vs. 18.2% (2/11) in non-eradicated patients (p = 0.08; OR = 6.75) after 6-9 months of follow-up. Among uninfected patients, only 13.8% (8/58) presented complete response. Two non-treated controls were treated after 6-12 months of follow-up, and PLT response was observed in 61.5% (8/13) of H. pylori eradicated patients, and in 19.0% (11/58) of uninfected patients (p = 0.004). Cytotoxin associated gene A and vacuolating cytotoxin gene A IgG antibodies were present in almost all infected patients. Therefore, the study suggests that H. pylori eradication plays a role in the management of H. pylori infected cITP children and adolescents.
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Affiliation(s)
- Helena Shino Hanai Brito
- Division of Pediatric Gastroenterology, Department of Pediatrics, Escola Paulista de Medicina/Universidade Federal de São Paulo , São Paulo, SP , Brazil
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14
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Pacifico L, Osborn JF, Tromba V, Romaggioli S, Bascetta S, Chiesa C. Helicobacter pylori infection and extragastric disorders in children: a critical update. World J Gastroenterol 2014; 20:1379-401. [PMID: 24587617 PMCID: PMC3925850 DOI: 10.3748/wjg.v20.i6.1379] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Revised: 11/10/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse relation of H. pylori prevalence and the increase in allergies, as reported from epidemiological studies, has stimulated research for elucidating potential underlying pathophysiological mechanisms. Although H. pylori is most frequently acquired during childhood in both developed and developing countries, clinicians are less familiar with the pediatric literature in the field. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. A further clinical challenge is whether the progressive decrease of H. pylori in the last decades, abetted by modern clinical practices, may have other health consequences.
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15
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Papagiannakis P, Michalopoulos C, Papalexi F, Dalampoura D, Diamantidis MD. The role of Helicobacter pylori infection in hematological disorders. Eur J Intern Med 2013; 24:685-690. [PMID: 23523153 DOI: 10.1016/j.ejim.2013.02.011] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2012] [Revised: 02/13/2013] [Accepted: 02/21/2013] [Indexed: 12/14/2022]
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium, classified as a carcinogen of class I, according to the World Health Organization (WHO). The infection is a major cause of gastritis, gastric and duodenal ulcer disease and increases the risk of gastric cancer. It has been implicated in the pathogenesis of several gastrointestinal, systemic or hematological diseases. The present review aims in deciphering the role of the bacterium in hematological disorders, increasing the awareness of gastroenterologists, hematologists and internal medicine practitioners, regarding the bacterium-associated hematological diseases. The efficacy of H. pylori eradication in increasing the platelet count in adult patients with primary immune thrombocytopenia (ITP) has been confirmed, linking the infection with the disease. Moreover, as the bacterium causes iron deficiency anemia (IDA) by several mechanisms, recent guidelines indicate H. pylori infection (Hp-I) to be sought in IDA patients if histology is negative and to be eradicated if present. Furthermore, it has been widely recognized that anti-H. pylori treatment causes regression of the low-grade B-cell gastric MALT lymphomas. Despite the well established associations of Hp-I with the aforementioned hematological disorders, we highlight the possible role of the infection to other hematological diseases or conditions such as non-Hodgkin lymphomas of the stomach, monoclonal gammopathy of undetermined significance, megaloblastic anemia and myelodysplastic syndromes. We finally underline the elevated risk of childhood leukemia and of hemorrhage in patients with coagulation disorders, due to the infection.
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MESH Headings
- Anemia, Iron-Deficiency/complications
- Anemia, Iron-Deficiency/microbiology
- Anemia, Megaloblastic/complications
- Anemia, Megaloblastic/microbiology
- Helicobacter Infections/complications
- Helicobacter Infections/drug therapy
- Helicobacter pylori
- Hematologic Diseases/complications
- Hematologic Diseases/microbiology
- Humans
- Lymphoma, B-Cell, Marginal Zone/complications
- Lymphoma, B-Cell, Marginal Zone/microbiology
- Lymphoma, Non-Hodgkin/complications
- Lymphoma, Non-Hodgkin/microbiology
- Monoclonal Gammopathy of Undetermined Significance/complications
- Monoclonal Gammopathy of Undetermined Significance/microbiology
- Myelodysplastic Syndromes/complications
- Myelodysplastic Syndromes/microbiology
- Purpura, Thrombocytopenic, Idiopathic/complications
- Purpura, Thrombocytopenic, Idiopathic/microbiology
- Stomach Neoplasms/complications
- Stomach Neoplasms/microbiology
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Affiliation(s)
- Panagiotis Papagiannakis
- Department of Haematology, Second Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki (AUTH), Faculty of Medicine, Thessaloniki, Greece
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Sierra MS, Hastings EV, Goodman KJ. What do we know about benefits of H. pylori treatment in childhood? Gut Microbes 2013; 4:549-67. [PMID: 24280768 PMCID: PMC3928165 DOI: 10.4161/gmic.27000] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Policy analysis shows that H. pylori test and treat strategies targeting adults at moderate to high risk of H. pylori-induced disease is likely to be cost-effective for preventing digestive diseases responsible for a large global disease burden. Little is known, however, about health benefits to children from eliminating this infection. We conducted a systematic review of the evidence regarding health benefits to children from treatment to eliminate H. pylori infection. We systematically searched Ovid MEDLINE for pertinent review articles published through 2012. We excluded reviews focused on treatment efficacy and scrutinized reference lists of selected reviews to identify additional eligible reviews. Fifteen reviews met specified inclusion criteria. Overall, they show that few reported studies investigating pediatric health effects of treatment for H. pylori infection were well designed with adequate statistical power. Thus, there is insufficient evidence for drawing conclusions about health benefits to children from treatment to eliminate H. pylori infection.
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Orrskog S, Medin E, Tsolova S, Semenza JC. Causal inference regarding infectious aetiology of chronic conditions: a systematic review. PLoS One 2013; 8:e68861. [PMID: 23935899 PMCID: PMC3723854 DOI: 10.1371/journal.pone.0068861] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Accepted: 05/31/2013] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The global burden of disease has shifted from communicable diseases in children to chronic diseases in adults. This epidemiologic shift varies greatly by region, but in Europe, chronic conditions account for 86% of all deaths, 77% of the disease burden, and up to 80% of health care expenditures. A number of risk factors have been implicated in chronic diseases, such as exposure to infectious agents. A number of associations have been well established while others remain uncertain. METHODS AND FINDINGS We assessed the body of evidence regarding the infectious aetiology of chronic diseases in the peer-reviewed literature over the last decade. Causality was assessed with three different criteria: First, the total number of associations documented in the literature between each infectious agent and chronic condition; second, the epidemiologic study design (quality of the study); third, evidence for the number of Hill's criteria and Koch's postulates that linked the pathogen with the chronic condition. We identified 3136 publications, of which 148 were included in the analysis. There were a total of 75 different infectious agents and 122 chronic conditions. The evidence was strong for five pathogens, based on study type, strength and number of associations; they accounted for 60% of the associations documented in the literature. They were human immunodeficiency virus, hepatitis C virus, Helicobacter pylori, hepatitis B virus, and Chlamydia pneumoniae and were collectively implicated in the aetiology of 37 different chronic conditions. Other pathogens examined were only associated with very few chronic conditions (≤ 3) and when applying the three different criteria of evidence the strength of the causality was weak. CONCLUSIONS Prevention and treatment of these five pathogens lend themselves as effective public health intervention entry points. By concentrating research efforts on these promising areas, the human, economic, and societal burden arising from chronic conditions can be reduced.
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Affiliation(s)
| | - Emma Medin
- Heron Evidence Development AB, Stockholm, Sweden
- Karolinska Institutet, Stockholm, Sweden
| | - Svetla Tsolova
- European Centres for Disease Prevention and Control, Stockholm, Sweden
| | - Jan C. Semenza
- European Centres for Disease Prevention and Control, Stockholm, Sweden
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Russo G, Miraglia V, Branciforte F, Matarese SMR, Zecca M, Bisogno G, Parodi E, Amendola G, Giordano P, Jankovic M, Corti A, Nardi M, Farruggia P, Battisti L, Baronci C, Palazzi G, Tucci F, Ceppi S, Nobili B, Ramenghi U, De Mattia D, Notarangelo L. Effect of eradication of Helicobacter pylori in children with chronic immune thrombocytopenia: a prospective, controlled, multicenter study. Pediatr Blood Cancer 2011; 56:273-8. [PMID: 20830773 DOI: 10.1002/pbc.22770] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The eradication of Helicobacter pylori has been associated with remission of immune thrombocytopenia (ITP) in approximately half of eradicated patients. Data on children are limited to small case series. PROCEDURE Children from 16 centers in Italy, who were less than 18 years of age and diagnosed with chronic ITP (cITP), were screened for H. pylori infection. Positive patients underwent standard triple therapy with amoxicillin, clarithromycin, and omeprazole. The eradication response was defined as follows: complete response, platelet (PLT) count ≥ 150 × 10(9) /L; partial response, PLT count of at least 50 × 10(9) /L; no response, PLT count <50 × 10(9) /L. RESULTS Of 244 screened patients, 50 (20%) had H. pylori infection, 37 of which received eradication therapy and completed follow-up. Eradication was successful in 33/37 patients (89%). PLT recovery was demonstrated in 13/33 patients after eradication (39%), whereas spontaneous remission was observed in 17/166 (10%) H. pylori-negative patients (P < 0.005). Responders more often required second line eradication (9/13), whereas a second cycle was required in 3/20 non-responders (P < 0.005). CONCLUSIONS Among the large cohort of patients, those who underwent successful H. pylori eradication showed a significantly higher PLT response. Therefore, it may be appropriate to look for H. pylori and eventually eradicate it in children with cITP.
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Affiliation(s)
- Giovanna Russo
- Centro di Riferimento di Ematologia ed Oncologia Pediatrica, Università di Catania, Catania, Italy.
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Ferrara M, Capozzi L, Russo R. Effect of Helicobacter pylori eradication on platelet count in children with chronic idiopathic thrombocytopenic purpura. ACTA ACUST UNITED AC 2010; 14:282-5. [PMID: 19843384 DOI: 10.1179/102453309x12473408860181] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Recent reports have suggested, particularly in adults, an association between Helicobacter pylori infection (HPI) and chronic idiopatic thrombocytopenic purpura (cITP) with improvement of platelet count after eradication therapy. We investigated the association of HPI and cITP and the effect of HP eradication therapy on thrombocytopenia in a population of 24 children of both sexes mean age 8.0+/-0.28 years (range 5.4-10.7 years), affected by cITP (PLT <or=50 x 10(9)/l) lasting more than 6 months. HPI was investigated by Helicobacter pylori stool antigens (HpSA). In eight out 24 patients (33.3%) HP infection was identified positive and bacterial eradication was successful following 7 days of triple therapy (amoxicillin, clarithromicin and proton pump inibitors). A follow-up of platelet count was performed for 1 year after HpSA detection. Six out eight patients (75%) had total recovery of platelet count during the first year after bacterial eradication (PLT before therapy 32.5+/-3.5 x 10(9)/l; after 1 year 275+/-106.06 x 10(9)/l) (P<0.05), two patients (25%) had partial recovery (PLT before therapy 30 x 10(9)/l, after 1 year 103.5 x 10(9)/l) although not reaching statistical significance (P>0.05). Non-significant differences were found in platelet count between infected and uninfected patients before eradication treatment (PLT 33.0+/-2.8 x 10(9)/l versus 34.0+/-5.75 x 10(9)/l) (P>0.05), while significant differences were observed after eradication therapy (PLT 315.0+/-7.07 x 10(9)/l versus 43.5+/-2.12 x 10(9)/l) (P<0.05). HP assessment should be performed in all cITP patients and eradication therapy should be attempted in positive cases.
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Affiliation(s)
- Mara Ferrara
- Department of Pediatrics, The Second University of Naples, Naples, Italy.
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20
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Treepongkaruna S, Sirachainan N, Kanjanapongkul S, Winaichatsak A, Sirithorn S, Sumritsopak R, Chuansumrit A. Absence of platelet recovery following Helicobacter pylori eradication in childhood chronic idiopathic thrombocytopenic purpura: a multi-center randomized controlled trial. Pediatr Blood Cancer 2009; 53:72-7. [PMID: 19301380 DOI: 10.1002/pbc.21991] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To investigate the effect of Helicobacter pylori eradication on platelet recovery in childhood chronic idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS A multi-center randomized controlled trial was conducted. Patients aged 4-18 years, diagnosed with chronic ITP, defined by platelet count below 100 x 10(9)/L lasting more than 6 months without identified causes, were enrolled and underwent (13)C-urea breath test for diagnosis of H. pylori infection. Patients who received prednisolone more than 0.5 mg/kg per day or received other platelet-enhancing therapy were excluded. Patients with H. pylori infection were randomized into two groups: treatment and control groups. Treatment group received a standard protocol for H. pylori eradication and repeated (13)C-UBT at 4-6 weeks to confirm successful therapy while the control group received no specific treatment. Monthly platelet count was monitored for 6 months in both groups. Primary outcome was platelet recovery, defined by platelet count over 100 x 10(9)/L for at least 3 months. RESULTS Of the 55 ITP children, 16 (29.1%) had H. pylori infection. There were no differences in age, sex, duration of disease, platelet count, and the dose of prednisolone between the treatment group (n = 7) and control group (n = 9). One patient in control group was withdrawn due to massive gastrointestinal bleeding requiring a high dose prednisolone. At 6 months, platelet recovery was demonstrated in one patient in the treatment group as well as one in the control group. CONCLUSION No beneficial effect of H. pylori eradication on platelet recovery in childhood chronic ITP was identified.
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Affiliation(s)
- Suporn Treepongkaruna
- Faculty of Medicine, Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
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21
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Veres G, Karóczkai I, Bodánszky H, Marosi A, Magyarossi E, Dezsofi A, Arató A. [The role of Helicobacter pylori infection in children with chronic immune thrombocytopenic purpura]. Orv Hetil 2009; 150:801-4. [PMID: 19362936 DOI: 10.1556/oh.2009.28581] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
UNLABELLED Helicobacter pylori infection has been associated with immune thrombocytopenic purpura in adults, however, the few studies concerning this issue showed conflicting results in the paediatric field. Therefore, authors prospectively investigated the incidence of Helicobacter pylori infection and the effect of Helicobacter pylori eradication on platelet count recovery in children with immune thrombocytopenic purpura. PATIENTS AND METHODS The study included 27 children with immune thrombocytopenic purpura (13 boys and 14 girls) with a median age of 8.2 years (range, 18 months-18 years). 38 healthy children (controls) were also enrolled (20 boys, 18 girls, median age, 9.6 years, range, 4-18 years). Helicobacter pylori infection was diagnosed using 13 C urea breath test. Eradication was assessed at 6 weeks following the end of the treatment by 13 C urea breath. RESULTS 2 children out of 27 patients with immune thrombocytopenic purpura proved to be positive for Helicobacter pylori infection (7.7%) and were treated with combination therapy. Controls showed similar rate of Helicobacter pylori infection (3/38, 7.9%) in comparison to those with immune thrombocytopenic purpura. In the follow-up period (mean, 10 months, range, 6-14 months) platelets did not show any improvement in infected children following the eradication treatment and were identical to those of the uninfected patients. Eradication was successful in the 2 Helicobacter pylori infected patients with immune thrombocytopenic purpura. CONCLUSION The results do not suggest a pathogenetic role of Helicobacter pylori infection in the etiology of immune thrombocytopenic purpura. Screening of Helicobacter pylori infection among paediatric patients with immune thrombocytopenic purpura is not recommended.
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Affiliation(s)
- Gábor Veres
- Semmelweis Egyetem, Altalános Orvostudományi Kar, I. Gyermekgyógyászati Klinika, Budapest.
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Stasi R. Therapeutic strategies for hepatitis- and other infection-related immune thrombocytopenias. Semin Hematol 2009; 46:S15-25. [PMID: 19245929 DOI: 10.1053/j.seminhematol.2008.12.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Secondary thrombocytopenia may result from autoimmune diseases, lymphoproliferative disorders, infections, myelodysplastic syndromes, common variable immunodeficiency, agammaglobulinemia, hypogammaglobulinemia, immunoglobulin A deficiency, and drugs. The presence of thrombocytopenia may result from chronic infections with hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Helicobacter pylori and should be considered in the differential diagnosis of immune thrombocytopenic purpura (ITP). Studies have shown that upon diagnosis of infections, treatment of the primary disease allows for stabilization of platelet counts. Antiviral therapy with highly active antiretroviral therapy (HAART) for HIV has aided in platelet recovery with a corresponding decrease in circulating viral load. In some cases, the use of a thrombopoietin (TPO) agonist, eltrombopag, normalizes platelet levels in patients with these infections. Thrombocytopenia in the absence of other disease symptoms requires screening for H pylori, especially in regions where there is a high prevalence of the disease, such as in Japan, and in cases where platelets have normalized following eradication therapy. In other regions where these infections are not prevalent, such testing is controversial.
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Affiliation(s)
- Roberto Stasi
- Department of Medical Sciences, Ospedale Regina Apostolorum, Albano Laziale, Italy.
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Maghbool M, Maghbool M, Shahriari M, Karimi M. Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura? Pediatr Rep 2009; 1:e2. [PMID: 21589818 PMCID: PMC3096032 DOI: 10.4081/pr.2009.e2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2009] [Revised: 07/12/2009] [Accepted: 07/15/2009] [Indexed: 01/11/2023] Open
Abstract
Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10-15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×10(9)/L) or partial (platelet count between 50 and 150×10(9)/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients.
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Affiliation(s)
- Maryam Maghbool
- Pathology Department, Shiraz University of Medical Science, Shiraz, Iran
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Abstract
PURPOSE OF REVIEW Refractory immune thrombocytopenic purpura is infrequent in children, but carries substantial morbidity and even mortality. Management of these children is controversial despite the availability of several treatment options as these strategies have not been directly compared and there are many definitions for refractory immune thrombocytopenic purpura. This review will provide an update on the pathogenesis, diagnosis and treatment options for children with severe, acute and chronic refractory immune thrombocytopenic purpura. RECENT FINDINGS Recent studies have demonstrated a number of immunologic alterations (dominant proinflammatory state, inadequate thrombopoiesis, and various B and T lymphocyte disturbances) in the pathogenesis of chronic immune thrombocytopenic purpura. New agents that target certain of these mechanisms (e.g. anti-CD20 monoclonal antibody, thrombopoietic agents) have shown promising results in recent clinical trials, primarily but not solely in adults. SUMMARY Management of refractory immune thrombocytopenic purpura often requires multiple agents that may provide only short-term benefit. Lack of clear views about the use of these medications, their unwanted side effects and an inability to specifically target a particular patient's disease all lead to frustration among patients, family and the physicians. Better understanding of pathogenesis with the availability of newer therapies with different mechanisms of effect should, however, allow improved management of these patients.
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25
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Stasi R, Provan D. Helicobacter pylori and Chronic ITP. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2008; 2008:206-211. [PMID: 19074084 DOI: 10.1182/asheducation-2008.1.206] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
Eradication of Helicobacter pylori infection has been variably associated with a platelet response in patients with immune thrombocytopenic purpura (ITP). Responses occur in approximately half of ITP patients infected with this bacterium, more frequently in Japan and Italy than in other countries. For those with severe ITP (platelet count<30x10(9)/L) and a long duration of disease, eradication therapy seems to be less effective. Despite extensive efforts, distinctive clinical features and factors predicting the response to eradication therapy have not been consistently identified. There is no established mechanism to explain how H pylori could be implicated in the pathogenesis of an immune-mediated platelet destruction. Several theories have been proposed to explain the platelet response to anti-H pylori therapy, including molecular mimicry, platelet aggregation, and the induction of a Th1 phenotype that favors the onset and/or persistence of ITP. The role of bacterium-related factors, such as the CagA (cytotoxin-associated gene A) protein, are still under investigation. Eradication therapy is simple and inexpensive, with limited toxicity and the advantage of avoiding long-term immunosuppressive treatment for those who respond. Although the evidence and follow-up are limited, it appears reasonable to routinely screen patients with ITP for H pylori, particularly in those populations with a high background prevalence of H pylori infection.
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MESH Headings
- Aging
- Anti-Bacterial Agents/therapeutic use
- Antigens, Bacterial/immunology
- Bacterial Proteins/immunology
- Cross Reactions
- Drug Therapy, Combination
- Gastric Mucosa/microbiology
- Helicobacter Infections/complications
- Helicobacter Infections/drug therapy
- Helicobacter Infections/epidemiology
- Helicobacter Infections/immunology
- Helicobacter pylori/isolation & purification
- Humans
- Italy/epidemiology
- Japan/epidemiology
- Platelet Count
- Platelet Transfusion
- Purpura, Thrombocytopenic, Idiopathic/epidemiology
- Purpura, Thrombocytopenic, Idiopathic/etiology
- Purpura, Thrombocytopenic, Idiopathic/immunology
- Purpura, Thrombocytopenic, Idiopathic/therapy
- Stomach/microbiology
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Affiliation(s)
- Roberto Stasi
- Department of Medical Sciences, Ospedale Regina Apostolorum, Albano Laziale, Italy.
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Helicobacter pylori in children with chronic idiopathic thrombocytopenic purpura: are the obstacles in the way typical in pediatric hematology? J Pediatr Hematol Oncol 2008; 30:2-3. [PMID: 18176171 DOI: 10.1097/mph.0b013e31815bcdcd] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Abstract
Recent reports have suggested that Helicobacter pylori infection may be a causative agent of adult chronic idiopathic thrombocytopenic purpura (cITP) and antimicrobial treatment may increase platelet counts. As there is limited experience in pediatric age, we investigated the prevalence of H. pylori infection and the effects of H. pylori eradication therapy in a series of children with cITP. Twenty-four children with cITP were investigated for H. pylori infection using the C-urea breath test or H. pylori fecal antigen. In cases of H. pylori infection, antimicrobial treatment was given with amoxicillin, clarithromycin, and proton pump inhibitors. Response was assessed at 6 months and defined as complete (platelet count >150x10/L) or partial (platelet count between 50 and 150x10/L). H. pylori infection was found in 8 patients (33%) and 3 of them showed a response after eradication therapy, but 2 of them relapsed later on. Two patients had a spontaneous increase in platelet count in the group of H. pylori-negative patients. Given that spontaneous improvements in platelet count can occur in children with cITP, we were unable to demonstrate that H. pylori plays a major role in cITP occurring in pediatric age.
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Loffredo G, Marzano MG, Migliorati R, Miele E, Menna F, Poggi V, Staiano A. The relationship between immune thrombocytopenic purpura and Helicobacter pylori infection in children: where is the truth? Eur J Pediatr 2007; 166:1067-8. [PMID: 17136353 DOI: 10.1007/s00431-006-0344-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2006] [Accepted: 10/11/2006] [Indexed: 12/13/2022]
Affiliation(s)
- Giuseppe Loffredo
- Department of Paediatric Oncology, Azienda Santobono-Pausilipon, Pausilipon Hospital, Naples, Italy
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Emilia G, Luppi M, Zucchini P, Morselli M, Potenza L, Forghieri F, Volzone F, Jovic G, Leonardi G, Donelli A, Torelli G. Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles. Blood 2007; 110:3833-41. [PMID: 17652264 DOI: 10.1182/blood-2006-12-063222] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Eradication of Helicobacter pylori may lead to improvement of chronic immune thrombocytopenic purpura (ITP), although its efficacy over time is uncertain. We report the results of H pylori screening and eradication in 75 consecutive adult patients with ITP. We also used molecular methods to investigate lymphocyte clonality and H pylori genotypes in the gastric biopsies from 10 H pylori-positive patients with ITP and 19 H pylori-positive patients without ITP with chronic gastritis. Active H pylori infection was documented in 38 (51%) patients and successfully eradicated in 34 (89%) patients. After a median follow-up of 60 months, a persistent platelet response in 23 (68%) of patients with eradicated infection was observed; 1 relapse occurred. No differences in mucosal B- or T-cell clonalities were observed between patients with ITP and control participants. Of note, the frequency of the H pylori cagA gene (P = .02) and the frequency of concomitant H pylori cagA, vacAs1, and iceA genes (triple-positive strains; P = .015) resulted statistically higher in patients with ITP than in control participants. All asymptomatic H pylori-positive patients with ITP were suffering from chronic gastritis. Our data suggest a sustained platelet recovery in a proportion of patients with ITP by H pylori eradication alone. Overrepresentation of specific H pylori genotypes in ITP suggests a possible role for bacterium-related factors in the disease pathogenesis.
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MESH Headings
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antigens, Bacterial/biosynthesis
- Antigens, Bacterial/genetics
- B-Lymphocytes/metabolism
- B-Lymphocytes/pathology
- Bacterial Outer Membrane Proteins/biosynthesis
- Bacterial Outer Membrane Proteins/genetics
- Bacterial Proteins/biosynthesis
- Bacterial Proteins/genetics
- Blood Platelets/metabolism
- Blood Platelets/pathology
- Chronic Disease
- Female
- Follow-Up Studies
- Gastritis/blood
- Gastritis/complications
- Gastritis/genetics
- Gastritis/microbiology
- Genotype
- Helicobacter Infections/blood
- Helicobacter Infections/complications
- Helicobacter Infections/genetics
- Helicobacter Infections/therapy
- Helicobacter pylori/genetics
- Helicobacter pylori/metabolism
- Helicobacter pylori/pathogenicity
- Humans
- Male
- Middle Aged
- Purpura, Thrombocytopenic, Idiopathic/blood
- Purpura, Thrombocytopenic, Idiopathic/complications
- Purpura, Thrombocytopenic, Idiopathic/genetics
- Purpura, Thrombocytopenic, Idiopathic/microbiology
- Purpura, Thrombocytopenic, Idiopathic/pathology
- Purpura, Thrombocytopenic, Idiopathic/therapy
- Recovery of Function
- T-Lymphocytes/metabolism
- T-Lymphocytes/pathology
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Affiliation(s)
- Giovanni Emilia
- Department of Oncology and Hematology, Section of Hematology, University of Modena and Reggio Emilia, Modena, Italy.
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Kuwana M, Ikeda Y. Helicobacter pylori and immune thrombocytopenic purpura: unsolved questions and controversies. Int J Hematol 2007; 84:309-15. [PMID: 17118756 DOI: 10.1532/ijh97.06188] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Immune thrombocytopenic purpura (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies. Recent accumulating evidence indicates that eradication of Helicobacter pylori (H pylori) is effective in increasing platelet count in nearly half of ITP patients infected with this bacterium. The H pylori eradication therapy for adult ITP is becoming very popular in Japan and is now chosen as an initial treatment in H pylori-infected patients. The lack of efficacy of the H pylori eradication regimen in H pylori-negative ITP patients clearly indicates that platelet recovery results from the disappearance of H pylori itself. Despite extensive efforts, clinical features characteristic to H pylori-related ITP and factors predicting the response after the H pylori eradication therapy have not been identified. Great variability in the efficacy of the H pylori eradication therapy in ITP patients exists among countries: a higher response rate has been found in Japan and Italy than in the United States and non-Italian European countries. Some children infected with H pylori show the platelet response after successful eradication of H pylori, but the H pylori eradication therapy is ineffective in patients with secondary ITP. The pathogenesis of ITP associated with H pylori remains obscure; the mechanisms are not simple and may involve multiple steps, including cross-reactivity between H pylori antigen and platelets, and suppression of the reticuloendothelial system. Further studies to evaluate the mechanisms responsible for the platelet response in ITP patients after successful eradication of H pylori may be useful in clarifying the pathogenesis of ITP and developing new therapeutic strategies for ITP.
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Affiliation(s)
- Masataka Kuwana
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
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Jaing TH, Tsay PK, Hung IJ, Chiu CH, Yang CP, Huang IA. The role of Helicobacter pylori infection in children with acute immune thrombocytopenic purpura. Pediatr Blood Cancer 2006; 47:215-7. [PMID: 16261593 DOI: 10.1002/pbc.20577] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The outcome of immune thrombocytopenic purpura (ITP) is classified as acute or chronic depending on whether platelet count returns to normal. The prevalence of Helicobacter pylori infection increases with age and is independent of gender. We investigated the prevalence of H. pylori infection in Chinese children from Northern Taiwan and analyzed the association between H. pylori infection and acute ITP. Our prospective cohort studies found no statistically significant relation between H. pylori infection and acute ITP. There is therefore no indication to screen children with presumed acute ITP for H. pylori infection.
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Affiliation(s)
- Tang-Her Jaing
- Division of Hematology/Oncology, Chang Gung Children's Hospital, Taoyuan, Taiwan.
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Abstract
Idiopatic thrombocytopenic purpura (ITP), a disorder characterized by autoantibody-mediated platelet destruction, may be primary or secondary to various illnesses including lymphoproliferative, autoimmune, or infectious diseases. There are increasing data on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura and the significant increase in platelet count after bacterial eradication. The aim of this review is to consider the studies so far published on Helicobacter pylori infection and idiopathic thrombocytopenic purpura in order to evaluate a possible pathogenic correlation between these two conditions. A review of the literature data show that Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura is effective in increasing platelet count in approximately half of the cases. However, since the studies so far published are few, sometimes controversial and involve small series of patients, further controlled studies on larger numbers of patients with longer follow-up are needed to confirm these preliminary findings.
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Affiliation(s)
- Massimo Franchini
- Servizio di Immunoematologia e Trasfusione, Azienda Ospedaliera di Verona, Verona, Italy.
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Jackson S, Beck PL, Pineo GF, Poon MC. Helicobacter pylori eradication: novel therapy for immune thrombocytopenic purpura? A review of the literature. Am J Hematol 2005; 78:142-50. [PMID: 15682423 DOI: 10.1002/ajh.20250] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Eradication of Helicobacter pylori (H. pylori ) from the gastric mucosa has been associated with improvement of several systemic diseases, including immune thrombocytopenic purpura (ITP). Over the last 5 years, several studies have reported improved platelet counts in H. pylori-positive ITP patients following standard triple H. pylori eradication therapy. Review of published studies in which eradication of H. pylori has been performed in the ITP population indicates an overall response rate of 52% in 193 subjects in whom H. pylori was eradicated. Cohorts from Japan and Italy report higher response rates. There is no established mechanism to explain how this organism, which does not invade the gastric mucosa, could be implicated in the pathogenesis of this immune-based platelet disorder. Several theories including molecular mimicry, platelet aggregation, and immunomodulatory effects of macrolides have been proposed to explain the platelet response to anti-H. pylori therapy. Large randomized-controlled studies enrolling patients from various ethnic backgrounds will be necessary to determine the response rate and mechanism of response and to gain a better understanding of the pathogenesis of ITP.
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Affiliation(s)
- Shannon Jackson
- Division of Hematology, Department of Medicine, University of Calgary, Alberta, Canada.
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Kurekci AE, Atay AA, Sarici SU, Ozcan O. Complete platelet recovery after treatment of Helicobacter pylori infection in a child with chronic immune thrombocytopenic purpura: a case report. Pediatr Hematol Oncol 2004; 21:593-6. [PMID: 15626015 DOI: 10.1080/08880010490500962] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Helicobacter pylori gastritis has been associated with autoimmune disease, including immune thrombocytopenic purpura (ITP). The most recent reports also have supported this association in adults. ITP in children differs from that in adults in terms of clinical picture and mechanisms of thrombocytopenia. The authors report a case of a 12-year-old boy with chronic ITP, in whom they detected H. pylori infection and observed a complete platelet recovery after the eradication of H. pylori.
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Affiliation(s)
- A Emin Kurekci
- Gülhane Military Medical Academy, Department of Pediatric Hematology, 06018 Etlik, Ankara, Turkey.
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