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To the Editor:

We read with interest the clinical review article by Lawlor and Moss1 on the role of cytomegalovirus (CMV) in exacerbations of inflammatory bowel disease (IBD). They mentioned that colonic polymerase chain reaction (PCR) for CMV DNA appears to have a high “false-positive” rate, due to the detection of viral DNA in the absence of histological signs of disease. They also described that there are insufficient data to determine whether antiviral therapy actually impacts outcomes such as colectomy and remission rates, except in cases of severe systemic reactivation when CMV reactivation has been detected in refractory patients. We believe a simple endoscopic feature predicts latent CMV infection in ulcerative colitis (UC) patients with positive mucosal viral assay in whom antiviral therapy is not required.

Many techniques have been developed for detecting CMV infection, such as histopathology, serology, endoscopy, CMV antigenemia assay, and CMV DNA assay. CMV antigenemia assay has been widely used to diagnose and monitor CMV infection, but antigenemia levels in UC patients are lower than those observed in transplant recipients with CMV infection.2 Because of its high sensitivity,3 the CMV DNA assay with the use of colonic tissue is more reliable than blood tests for detection of CMV reactivation in UC patients at an early stage. However, it is still a serious problem that the detection of CMV DNA may not always indicate active CMV infection because it is also possible to detect a latent CMV infection that is not associated with the exacerbation of UC.

Although the role of CMV in the exacerbation of UC has been much debated, the clinical significance of CMV reactivation complicating UC patients remains unclear.4, 5 Whereas detection of CMV infection at an early stage and start of appropriate treatment are important for UC patients, CMV is frequently reactivated in active UC patients, but disappears with clinical improvement without antiviral therapy.2 Some investigators suggested that CMV behaves in the intestine as a nonpathogenic bystander and innocent observer, and others reported that CMV has a crucial role in triggering the onset of inflammation, resulting in its complication.4, 5 There is no valid method to distinguish CMV infection requiring therapy from that disappearing without therapy, even with the use of a combination of several modalities.6

Recently, we evaluated a simple endoscopic feature, no large ulcer, as a predictor of latent CMV infection in active UC patients with positive mucosal viral assay.6 Patients with well-demarcated large ulcer (ulcerated group) were treated with antiviral therapy and UC therapy. Patients without large ulcer (nonulcerated group) were treated only with UC therapy. In the ulcerated group (n = 10), three patients retained active disease at 2 months and underwent colectomy. Although the other seven patients became in remission at 2 months, two of the three patients with CMV DNA-positive and two of the four patients with CMV DNA-negative were flare-up. Although all patients in the nonulcerated group (n = 10) became in remission and maintained remission, two patients were positive for the assay. Although there is no consensus about how to manage active UC patients complicated by CMV reactivation, we believe that patients without large ulcer develop remission without antiviral therapy.

REFERENCES

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  • 1
    Lawlor G, Moss AC. Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis. 2010; 16: 16201627.
  • 2
    Matsuoka K, Iwao Y, Mori T, et al. Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol. 2007; 102: 331337.
  • 3
    Yoshino T, Nakase H, Ueno S, et al. Usefulness of quantitative real-time PCR assay for early detection of cytomegalovirus infection in patients with ulcerative colitis refractory to immunosuppressive therapies. Inflamm Bowel Dis. 2007; 13: 15161521.
  • 4
    Papadakis KA, Tung JK, Binder SW, et al. Outcome of cytomegalovirus infections in patients with inflammatory bowel disease. Am J Gastroenterol. 2001; 96: 21372142.
  • 5
    Nakase H, Matsumura K, Yoshino T, et al. Systematic review: cytomegalovirus infection in inflammatory bowel disease. J Gastroenterol. 2008; 43: 735740.
  • 6
    Omiya M, Matsushita M, Tanaka T, et al. The absence of large ulcer predicts latent cytomegalovirus infection in ulcerative colitis with positive mucosal viral assay. Internal Med. 2010; 49: 22772282.

Mitsunobu Matsushita MD*, Toshihiro Tanaka MD*, Norimasa Fukata MD*, Mika Omiya MD*, Kazuichi Okazaki MD*, * Third Department of Internal Medicine Kansai Medical University, Osaka, Japan.