PubMed was searched for reports published between Jan 1, 1990, and May 31, 2016, using the terms “CMV”, “Crohn's disease”, “ulcerative colitis”, and “IBD”. Articles were also identified through searches of the author's own files. Only papers published in English were considered. The final reference list was generated on the basis of originality and relevance to the broad scope of this Review.
ReviewCytomegalovirus infection associated with inflammatory bowel disease
Introduction
Although the repertoire of medical treatment options is continuously increasing, refractory colitis remains a clinical challenge. To avoid surgery, any additional complications, including cytomegalovirus infection, must be excluded. In theory, the diagnosis of cytomegalovirus-mediated colitis should be easy because various methods exist for detection of viral DNA with high sensitivity and specificity. However, the detection of virus replication alone is not sufficient for diagnosis. From a clinical perspective, it is highly relevant to distinguish between simple viral replication and virus-mediated disease.
Colitis can be caused by inflammatory bowel disease, cytomegalovirus infection, or a combination of both. Therefore, unlike other patients with compromised immune systems, the diagnosis of cytomegalovirus-mediated colitis in patients with inflammatory bowel disease is particularly challenging because the intestine is the organ of interest in both cases. In this Review, I propose a pragmatic approach to the diagnosis and treatment of cytomegalovirus-mediated colitis in clinical practice.
Section snippets
Epidemiology
Cytomegalovirus is a DNA virus that belongs to the Herpesviridae family. Human beings are the only reservoir, and salivary and sexual transmission are the dominant paths of cytomegalovirus infection, although congenital infection and infection via organ transplants are also known to occur.1, 2, 3, 4 As with any other herpes virus, cytomegalovirus persists after primary infection. Remarkably, the sites of latency remain largely undefined, but probably include peripheral blood mononuclear cells,
Diagnostic tests and clinical features
A number of diagnostic tests are used in the clinic routinely (table 2),14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 yet it is important to remember that cytomegalovirus can exist in a latent form and that viral reactivation can occur after primary infection. In view of the high prevalence of cytomegalovirus in the general population, serology tests are of limited value. Serology is useful for the identification of a primary cytomegalovirus infection when cytomegalovirus-specific IgG
Cytomegalovirus-mediated colitis or just cytomegalovirus replication: implications for clinical practice
Whereas the diagnosis of a primary cytomegalovirus infection and cytomegalovirus carrier is clearly important, it is crucial to distinguish between a simple cytomegalovirus replication, which is observed frequently, and real cytomegalovirus-mediated colitis, which should be treated with antiviral therapy. Whether or not cytomegalovirus replication in patients with colitis warrants antiviral treatment at all remains to be addressed in future studies.45, 46
Data from numerous studies suggest that
When to start antiviral therapy
A problem with most studies is that cytomegalovirus replication alone is not distinguished from cytomegalovirus-mediated colitis. My colleagues and I have addressed this problem with the development of a local algorithm.56 109 patients who had been admitted to hospital between 2006 and 2009 with moderate-to-severe or steroid-refractory inflammatory bowel disease were tested for cytomegalovirus infection. In patients with systemic or mucosal viral infection, immunosuppressive treatment was not
Treatment of cytomegalovirus-mediated colitis
Due to the low number of patients with cytomegalovirus-mediated colitis, no randomised controlled trials are available. Thus the current recommendations are based on data retrieved from transplantation medicine studies. In line with ECCO guidelines based on expert opinion and various case studies, ganciclovir (5 mg/kg bodyweight twice daily) for 2–3 weeks is the therapy of choice for cytomegalovirus infections. After 3–5 days, a switch to oral valganciclovir (900 mg twice daily) for the
Is it only cytomegalovirus, or is there more?
As cytomegalovirus belongs to the Herpesviridae family,1, 2, 3, 4 whether or not the effect of cytomegalovirus on refractory colitis applies to other family members is a relevant question. The results of a study62 confirmed that Epstein-Barr virus causes a similar effect. In this study, control patients, patients with inflammatory bowel disease and refractory disease, and responders were analysed separately, and the presence of either cytomegalovirus or Epstein-Barr virus was analysed on a
Immunosuppressive therapy and cytomegalovirus-mediated colitis
Real cytomegalovirus-mediated colitis is a rare event, and controlled trials have not been done; any therapeutic recommendations are based on weak evidence. The recommendation for use of antiviral therapy is based on data retrieved from transplantation medicine. However, this recommendation does not address how to proceed with the immunosuppressive strategy after or during treatment of cytomegalovirus-mediated colitis. The following considerations are entirely based on mechanistic thoughts and
Conclusion
Real cytomegalovirus-mediated colitis in patients with inflammatory bowel disease is rare. However, cytomegalovirus replication is often seen in patients with steroid-refractory colitis. Because cytomegalovirus-mediated colitis is rare, little evidence is available to support diagnosis and treatment methods. In view of the available scientific literature, this Review offers a diagnostic and therapeutic approach that will allow clinicians to distinguish between cytomegalovirus replication and
Search strategy and selection criteria
References (65)
- et al.
Summary of the II International Symposium on Cytomegalovirus
Antiviral Res
(1998) - et al.
Management of cytomegalovirus infection in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations
Transplant Rev (Orlando)
(2016) - et al.
Cytomegalovirus inclusions in patients with ulcerative colitis and toxic dilation requiring colonic resection
Gastroenterology
(1977) - et al.
Chlamydia, cytomegalovirus, and Yersinia in inflammatory bowel disease
Lancet
(1979) - et al.
Prevalence, detection rate and outcome of cytomegalovirus infection in ulcerative colitis patients requiring colonic resection
Dig Liver Dis
(2005) Broadsheet. Number 50: diagnosis of human cytomegalovirus infection and disease
Pathology
(1999)- et al.
Screening of blood donors for human cytomegalovirus (HCMV) IgG antibody with an enzyme immunoassay using recombinant antigens
J Clin Virol
(1999) - et al.
Human cytomegalovirus infection: diagnostic potential of recombinant antigens for cytomegalovirus antibody detection
J Virol Methods
(2001) - et al.
Severe acute colitis associated with CMV: a prevalence study
Dig Liver Dis
(2004) - et al.
Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease
J Crohns Colitis
(2014)
Cytomegalovirus infection in inflammatory bowel disease patients undergoing anti-TNFalpha therapy
J Clin Virol
Management of cytomegalovirus infection in inflammatory bowel diseases
Dig Liver Dis
American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation
Am J Transplant
Outcome of cytomegalovirus infections in patients with inflammatory bowel disease
Am J Gastroenterol
A model for identifying cytomegalovirus in patients with inflammatory bowel disease
Clin Gastroenterol Hepatol
Effects of antiviral therapy for patients with inflammatory bowel disease and a positive intestinal biopsy for cytomegalovirus
Clin Gastroenterol Hepatol
Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn's colitis
Am J Gastroenterol
Prevention of congenital cytomegalovirus complications by maternal and neonatal treatments: a systematic review
Rev Med Virol
Seroprevalence of cytomegalovirus infection in the United States, 1988–1994
Clin Infect Dis
Epidemiology of cytomegalovirus infections
Rev Infect Dis
Complement-fixing antibodies against cytomegalovirus in different parts of the world
Bull World Health Organ
Incidence and clinical significance of colonic cytomegalovirus infection in idiopathic inflammatory bowel disease requiring colectomy
Gut
Cytomegaloviral enterocolitis: clinical associations and outcome
Dis Colon Rectum
Infection by cytomegalovirus in patients with ulcerative colitis requiring colonic resection
Med Clin (Barc)
Cytomegalovirus infection in patients who required colectomy for toxic megacolon or severe steroid-refractory ulcerative colitis
Dig Dis Sci
Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant
Clin Microbiol Rev
Clinical and immunologic aspects of cytomegalovirus infection in solid organ transplant recipients
Transplantation
Multicenter comparison of the digene hybrid capture CMV DNA assay (version 2.0), the pp65 antigenemia assay, and cell culture for detection of cytomegalovirus viremia
J Clin Microbiol
Prevention and treatment of cytomegalovirus infection in solid organ transplant recipients
Curr Opin Infect Dis
Evaluation of the AMPLICOR cytomegalovirus test with specimens from human immunodeficiency virus-infected subjects
J Clin Microbiol
Cytomegalovirus excretion as a predictor of cytomegalovirus disease after marrow transplantation: importance of cytomegalovirus viremia
J Infect Dis
Recent advances in the diagnosis of cytomegalovirus infection
Ann Biol Clin (Paris)
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Epstein-Barr Virus-Positive Mucocutaneous Ulcers Complicate Colitis Caused by Immune Checkpoint Regulator Therapy and Associate With Colon Perforation
2020, Clinical Gastroenterology and HepatologyCitation Excerpt :Regarding the presence of CMV, similar macroscopic appearance of punched-out ulcers could be observed in CMV-mediated colitis in the context of ulcerative colitis. However, CMV infection in these circumstances does not result in a characteristic pattern of circumscribed lymphoproliferation, as seen with EBVMCUs.32,33 Although aspects of immunosurveillance over EBV and CMV, both latent herpesviruses, are similar, the pathogenesis of tissue damage, respectively, is different and beyond the scope of this study.
Management of acute severe ulcerative colitis in Spain: A nationwide clinical practice survey
2019, Gastroenterologia y HepatologiaDifferential diagnosis of inflammatory bowel disease: imitations and complications
2018, The Lancet Gastroenterology and HepatologyCitation Excerpt :After 3–5 days, a switch to oral valganciclovir can be considered for the rest of the 2–3 week course. Alternatively, in cases of resistance or myelotoxicity, foscarnet can be used20 in patients with or without IBD.73 During the course of Crohn's disease, approximately 30% of patients develop at least one fistulising episode.74
Novel score predicts risk for cytomegalovirus infection in ulcerative colitis
2018, Journal of Clinical VirologyCitation Excerpt :In UC patients, loss of successful immune surveillance can lead to symptomatic end-organ involvement, such as CMV colitis. The diagnostic challenge to distinguish between clinically irrelevant (bystander) CMV reactivation and CMV mediated disease is further complicated by the fact that a multitude of techniques have been proposed to monitor CMV infections [7–11]. Current guidelines suggest histology and immunohistochemistry for CMV antigens or polymerase chain reaction (DNA PCR) for detection of CMV in the blood, however, the optimal method for detecting clinically relevant CMV infection in patients with colitis has not been established yet [12,13].
An Intestinal Th17 Subset is Associated with Inflammation in Crohn's Disease and Activated by Adherent-invasive Escherichia coli
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