Importance of Early Detection of Cytomegalovirus Infection in Refractory Inflammatory Bowel Disease

To the Editor: Cases of inflammatory bowel disease (IBD) associated with cytomegalovirus (CMV) infection is a very important issue for gastroenterologist.1,2 In patients with IBD refractory to conventional therapy, we should always consider the possibility of CMV infection. We note with great interest the article by Dimitroulia et al.3 Data for patients with IBD who were investigated in that study demonstrated that the CMV genome in intestinal tissue was detected by polymerase chain reaction (PCR) in 32.9% of total IBD patients, while the CMV genome in the blood was detected in 27.1% of these patients. A positive ratio of CMV genome in intestinal tissue is higher in patients with ulcerative colitis (UC) than in those with Crohn's disease. Moreover, 5.9% of IBD patients had detectable CMV genome in their intestinal samples but not in their blood. On the other hand, in the control group who had no inflammatory disease, 11.9% of individuals had a detectable CMV genome in their blood, but 2.2% in their intestine. The authors suggested that a potential role of CMV in the mucosal immune disturbance of IBD might be suspected because CMV infection occurred in intestinal tissue more dominantly than in the blood. However, they described that a definitive causal role of CMV in exacerbating IBD is still unknown. The detection of the CMV genome in colonic tissue may not necessarily indicate active CMV infection because infection usually results from reactivation of latent virus. Recently, we clearly demonstrated that the detected copy number of CMV DNA by our PCR method is higher in the inflamed colonic tissue than that in noninflamed colonic tissue in patients with UC refractory to immunosuppressive therapy.4 Moreover, our data demonstrated that all three patients with UC were positive for the CMV genome in inflamed colonic tissue alone, although neither CMV antigenemia nor CMV inclusion bodies were detected. In addition, we investigated more patients with refractory UC. As a result, 18 (94.7%) of 19 patients with refractory UC who were positive for CMV DNA in inflamed colonic mucosa by our PCR method had neither CMV inclusion body nor CMV antigenemia. All patients were successfully treated with antiviral therapy (unpubl. data). These results strongly support that CMV infection was involved in the deterioration of patients with UC and the investigation of CMV DNA in inflamed colonic tissue by the PCR method is necessary for early detection of CMV infection. Thus, both Dimitroulia's and our data included important points in considering diagnosis and therapy for patients with moderate or severe IBD who might have concomitant CMV infection. In summary, we strongly believe that CMV infection is involved in exacerbation of patients with IBD. Therefore, early detection of CMV infection in intestinal tissue is absolutely necessary for developing a therapeutic strategy. Quantitative real-time PCR assay in gastrointestinal tissue is a promising modality for the diagnosis of CMV infection.