REFERENCES symptoms of GERD during the day, too.downloads.hindawi.com/journals/cjgh/2011/621721.pdf · ALTANA Pharma, a Nycomed Company *TECTA® Product Monograph based on pantoprazole

Can J Gastroenterol Vol 25 No 6 June 2011298

Correspondence: Dr Greg A Rosenfeld, Department of Medicine, Division of Gastroenterology, University of British Columbia, 770-1190 Hornby Street, Vancouver, British Columbia V6Z 2K5. Telephone 604-688-6332, e-mail [email protected]

Re: Kuenstner JT. Mycobacterium avium paratuberculosis and the etiology of Crohn’s disease: Controversy requires the patient perspec-tive, not the clinician perspective. Can J Gastroenterol 2011;25:300.

To the Editor,

We thank Dr Kuenstner for his interest in our recent article on Mycobacterium avium paratuberculosis (MAP) and the etiology

of Crohn’s disease (CD). The intent of our article was to put forth an objective review of the currently available literature commonly cited to make arguments both for and against the role of MAP in the etiol-ogy of CD. The review was intended to give clinicians a perspective on the controversy, and review any possible diagnostic and thera-peutic options for treating MAP in CD.

Dr Kuenster cites a report by Zhang et al (1), which was not pub-lished at the time our manuscript was submitted for publication and, therefore, was not available for inclusion in our article. This new study is indeed relevant to this discussion given that it identified several gene mutations that may be involved in rendering patients susceptible to leprosy. The article and the accompanying editorial (2) propose that the genetic mutations in the NOD2/CARD15 regions, which are found in a high proportion of leprosy patients, are also found in CD patients, lending support to the notion that CD may be caused by a mycobacterial infection. We agree with the auth-ors of this paper that, although the results are hypothesis generating, they require further validation and that the genetic susceptibility supports the proposal that a proportion of CD patients may have this susceptibility. We need to determine whether a certain phenotype identifies this group of CD patients. Zhang et al do not suggest that this genetic susceptibility implies that a mycobacterium is the cause of CD in the majority of patients.

Others have previously reported finding a link between NOD2/CARD15 mutations and a susceptibility to the development of clin-ical CD (3,4). Patients with this mutation were found to have a defective innate response to bacterial infection, and this may be the link between the increased susceptibility to leprosy and an increased frequency of CD. However, this genetic susceptibility is neither necessary nor sufficient for the development of CD because not all patients with CD have this mutation, and not all patients with CD have evidence of MAP infection.

Dr Kuenstner’s letter also cites the veterinary literature for evi-dence of animals with asymptomatic shedding of MAP as an explan-ation for the patients with positive MAP serology who do not experience clinical symptoms of CD. Unfortunately, this does not

explain why most studies have found that the majority of patients with CD have no evidence of MAP infection. Once again, this may be explained by inadequacies in current detection methods; however, from a clinical perspective, there is still no viable test to determine in which patients with CD MAP may play a pathogenic role. The lack of a consistent serological test to confirm the presence of MAP infec-tion is a major source of difficulty in performing these trials (5). Improved testing would not only clarify the pathogenic role of MAP, but would also shed light on the effect of eradicating it.

Dr Kuenstner notes that the antibiotic trials aimed at eradicat-ing MAP have failed to show benefit in curing CD, nor have they confirmed that the MAP was eradicated using the antibiotics studied (6). We agree, but believe that there is insufficient evidence to sup-port a role for treating CD with antibiotics targeting MAP because this intervention has its own risks. If new therapeutic options for CD that target MAP prove to be more efficacious than currently avail-able therapies, gastroenterologists will undoubtedly embrace them.

The overall theme of Dr Kuenstner’s desire to advocate for more funding into this area of research is appreciated. Thoughtful evalua-tion of the state of the literature is critical to highlight the priorities the academic community must take to further the understanding of the role of MAP in the pathogenesis of CD.

Greg A Rosenfeld MD,Brian Bressler MD FRCP,

Department of Medicine, Division of Gastroenterology,University of British Columbia,

Vancouver, British Columbia

Continued from page 297Patients with CD understand that MAP association implies pos-

sible causation and, therefore, that their disease is potentially cur-able. Most CD patients do not want the chronic suppressive drug regimens sold by the pharmaceutical companies, which are rewarded with lifelong revenue streams from the current drugs. When thera-peutic drugs that more effectively eradicate this disease are found, patients will not favourably view gastroenterologists who dismiss MAP as merely ‘of academic interest’. When this controversy is finally resolved, CD will be understood as a syndrome with several causes – the most common being MAP, which causes infection in the genetically susceptible host.

J Todd Kuenstner MD,Department of Pathology,

Charleston Area Medical Center,Charleston, West Virginia, USA

REFERENCES1. Zhang F, Huang W, Chen S, et al. Genomewide association study

of leprosy. N Engl J Med 2009;361:2609-18.2. Schurr E, Gros PA. Common genetic fingerprint in leprosy and

Crohn’s disease? N Engl J Med 2009;361:2666-8.3. Harris NB, Barletta RG. Mycobacterium avium subsp. Paratuberculosis

in veterinary medicine. Clin Micro Rev 2001;489-512.4. Selby W, Pavli P, Crotty B, et al. Two year combination antibiotic

therapy with clarithromycin, rifabutin, and clofazimine for Crohn’s disease. Gastroenterology 2007;132:2313-9.

5. Chamberlin W, Naser SA. Blood cultures of 19 Crohn’s disease patients. Am J Gastroenterol 2008;103:802-4. (Lett)

6. Chamberlin W, Ghobrial G, Chehtane M, Naser SA. Successful treatment of a Crohn’s disease patient infected with bacteremic Mycobacterium paratuberculosis. Am J Gastroenterol 2007;102:689-91. (Lett)

7. Grant IR. Zoonotic potential of Mycobacterium avium ssp. Paratuberculosis: The current position. J App Micro 2005;98:1282-93.

LETTERS TO THE EDITOR

©2011 Pulsus Group Inc. All rights reserved

REFERENCES1. Zhang FR, Huang W, Chen SM, et al. Genomewide association study

of leprosy. N Engl J Med 2009;361:2609-18.2. Schurr E, Gros P. A common genetic fingerprint in leprosy and

Crohn’s disease? N Engl J Med 2009;361:2666-8.3. Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2

associated with susceptibility to Crohn’s disease. Nature 2001;411:603-6.4. Goyette P, Labbe C, Trinh TT, Xavier RJ, Rioux JD. Molecular

pathogenesis of inflammatory bowel disease: Genotypes, phenotypes and personalized medicine. Ann Med 2007;39:177-99.

5. Bernstein CN, Blanchard JF, Rawsthorne P, Collins MT. Population-based case control study of seroprevalence of Mycobacterium paratuberculosis in patients with Crohn’s disease and ulcerative colitis. J Clin Microbiol 2004;42:1129-35.

6. Selby W, Pavli P, Crotty B, et al. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn’s disease. Gastroenterology 2007;132:2313-9.

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REFERENCES symptoms of GERD during the day, too.downloads.hindawi.com/journals/cjgh/2011/621721.pdf · ALTANA Pharma, a Nycomed Company *TECTA® Product Monograph based on pantoprazole