Cytomegalovirus and ulcerative colitis: Place of antiviral therapy

Abstract

The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis (UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools (numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flare-ups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease.

Keywords: Flare-up; Ganciclovir; Human cytomegalovirus; Inflammation; Inflammatory bowel disease; Intestinal mucosa; Quantitative polymerase chain reaction; Ulcerative colitis; Viral load.

Figure 1

Techniques currently used for the detection of markers of cytomegalovirus infection. Analyses highlighted in orange are very useful, those highlighted in yellow of little use, and those without color of no use, for the diagnosis of CMV reactivation in inflammatory bowel diseases. ELISA: Enzyme-linked immunosorbent assay; IHC: Immunohistochemistry; CMV: Cytomegalovirus; HE staining: Hematoxylin and eosin staining; NAAT: Nucleic acid amplification test.

Figure 2

Therapeutic algorithm for the intake of flare-ups of refractory ulcerative colitis in patients aged > 30 years according to the quantification of cytomegalovirus density in colonic tissue. ¹Defined by steroid resistance or immunosuppressive treatment or anti-TNF drugs; ²Defined by quantification of CMV DNA in intestinal tissue of 10-250 copies/mg of inflamed tissue or low-grade CMV density by IHC in biopsy specimens (4 inclusions or less); ³Defined by quantification of CMV DNA in intestinal tissue of > 250 copies/mg of inflamed tissue or high-grade CMV density by IHC in biopsy specimens (more than 4 inclusions); ⁴Defined by a need for hospitalization and a Lichtiger score > 10. CMV: Cytomegalovirus; IHC: immunohistochemistry; TNF: Tumor necrosis factor.