Intest Res.  2014 Jan;12(1):5-11. 10.5217/ir.2014.12.1.5.

Diagnosis and Treatment of Ulcerative Colitis with Cytomegalovirus Infection: Importance of Controlling Mucosal Inflammation to Prevent Cytomegalovirus Reactivation

• Nakase H
• Honzawa Y
• Toyonaga T
• Yamada S
• Minami N
• Yoshino T
• Matsuura M

• KMID: 2174332
• DOI: http://doi.org/10.5217/ir.2014.12.1.5

Abstract

Human cytomegalovirus (HCMV) is a member of the herpesvirus family. HCMV infection persists throughout the host lifespan in a latent state following primary infection. The ability of HCMV to escape control by the host immune system and its resulting reactivation suggests the importance of ongoing immune surveillance in the prevention of HCMV reactivation. HCMV is a common cause of opportunistic infection that causes severe and fatal disease in immune-compromised individuals. In inflammatory bowel disease patients, particularly those with ulcerative colitis (UC), HCMV is often reactivated because these patients are frequently treated with immunosuppressive agents. This reactivation exacerbates colitis. Additionally, HCMV infection can induce severe colitis, even in patients with UC who have never been treated with immunosuppressive agents. However, the role of HCMV in colonic inflammation in patients with UC remains unclear. Here, we present previous and current clinical data on the diagnosis and treatment of HCMV infection in UC. Additionally, our experimental data from a newly established mouse model mimicking UC with concomitant CMV infection clearly demonstrate that inflammation could result in the exacerbation of UC disease activity with induction of HCMV reactivation. In summary, optimal control of colonic inflammation should be achieved in UC patients who are refractory to conventional immunosuppressive therapies and are positive for HCMV.

Keyword

Cytomegalovirus; Ulcerative colitis; Tumor necrosis factor alpha

MeSH Terms

Animals
Colitis
Colitis, Ulcerative*
Colon
Cytomegalovirus Infections*
Cytomegalovirus*
Diagnosis*
Humans
Immune System
Immunosuppressive Agents
Inflammation*
Inflammatory Bowel Diseases
Mice
Opportunistic Infections
Tumor Necrosis Factor-alpha
Ulcer*
United Nations
Immunosuppressive Agents
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Effect of granulocyte and monocyte adsorptive apheresis (GMAA) on UC patient with concomitant human cytomegalovirus (HCMV) infection. Cases of steroid-resistant UC patients with concomitant HCMV infection who were successfully treated with GMAA. Forty-nine female patients with UC, who were refractory to 60 mg of prednisolone (PSL), were transferred to our hospital. HCMV antigenemia, immunohistochemistry (IHC), and HCMV-DNA in the colonic mucosa were observed. After starting gancyclovir (5 mg/kg), abdominal symptoms such as hematochezia and abdominal pain did not subside. We initiated intensive GMAA (twice/week). After 10 applications of GMAA, the abdominal symptoms disappeared and PSL could be completely tapered. Sigmoidoscopy 3 months after initiation of GMAA showed the disappearance of the ulcerative lesions and scar formation. 5-ASA, 5-aminosalicylic acid.

• 

  Fig. 2 Histologic findings in the proximal and distal colon in T cell receptor (TCR)-α knockout (KO) mice with and without mouse cytomegalovirus (MCMV) infection at 12 weeks. In comparison with uninfected KO mice, histological examination revealed severe hyperplasia of the epithelial cells, infiltration of inflammatory cells, and crypt loss in infected TCR-α KO mice at 12 weeks (H&E, ×200).

• 

  Fig. 3 Proposed mechanisms of human cytomegalovirus (HCMV) reactivation in UC. Tissue PCR is useful and accurate modality for diagnosis of CMV infection in patients with UC.

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