Current Diagnostic and Therapeutic Approaches to Cytomegalovirus Infections in Ulcerative Colitis Patients Based on Clinical and Basic Research Data

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.

Keywords: HCMV colitis; human cytomegalovirus; inflammatory bowel disease; ulcerative colitis.

Figure 1

Latent infection and reactivation of human cytomegalovirus (HCMV). HCMV latently infects the CD33+/CD34+ cells in the bone marrow and the differentiated CD14+ monocytes in the peripheral blood. HCMV reactivation occurs when HCMV-infected cells enter the tissue and differentiate into macrophages or dendritic cells. Locally-reactivated HCMV infection is prevented from spreading to the whole body by anti -HCMV antibodies and CD8+ T cells. TNF-α: tumor necrosis factor-alpha, IFN-γ: interferon-gamma, GM-CSF: granulocyte-macrophage colony-stimulating factor.

Figure 2

Characteristic endoscopic findings of ulcerative colitis complicated by human cytomegalovirus infection. (a) Punched-out ulcers: the round shape of ulcerations with clear demarcation. (b) Longitudinal ulcers: ulcerations running along the lumen of the colon (arrows). (c) Diffuse mucosal defect: many mucosal defects with surrounding reddish and erythematous mucosa. (d) Geographic ulcers: shallow and widespread mucosal defects with unclear demarcation.

Figure 3

Proposed diagnostic and therapeutic strategy for the patients with ulcerative colitis and the patients with a suspected human cytomegalovirus colitis. UC: ulcerative colitis, HE: hematoxylin and eosin, IHC: immunohistochemistry, HCMV: human cytomegalovirus, PCR: polymerase chain reaction.