Factors Associated with Cytomegalovirus (CMV) Procto-Colitis in Immunocompetent Adults: A Systematic Review

Timothy Bromley; Keziah Lewis; Colin Fitzpatrick; Daniel Richardson

doi:10.58600/eurjther2148

Authors

Timothy Bromley Department of Sexual Health and HIV, University Hospitals Sussex NHS Foundation Trust, Brighton, UK https://orcid.org/0000-0002-3423-4118
Keziah Lewis Department of Sexual Health and HIV, University Hospitals Sussex NHS Foundation Trust, Brighton, UK https://orcid.org/0009-0001-7638-6697
Colin Fitzpatrick Department of Sexual Health and HIV, University Hospitals Sussex NHS Foundation Trust, Brighton, UK https://orcid.org/0000-0001-5764-5860
Daniel Richardson Department of Sexual Health and HIV, University Hospitals Sussex NHS Foundation Trust, Brighton, UK https://orcid.org/0000-0003-0955-6307

DOI:

https://doi.org/10.58600/eurjther2148

Keywords:

Cytomegalovirus, CMV, Immunocompetent, colitis, proctitis, functional gastrointestinal system disorders

Abstract

Objective: The pathophysiology of CMV procto-colitis in immunocompetent adults is poorly understood. We aimed to systematically review the literature to explore factors, presenting symptoms and endoscopy findings associated with CMV procto-colitis in immunocompetent adults.

Methods: Following PRISMA guidelines, we conducted a narrative systematic review by searching MEDLINE, EMBASE, EMCARE and CINAHL for manuscripts published up to August 2023. One author screened manuscript abstracts; two authors independently conducted a full text review. We included manuscripts which included primary data of immunocompetent adults with CMV procto-colitis except case reports. Quality and risk of bias was assessed independently by two authors using the Joanna Briggs institute critical appraisal tools.

Results: 8 manuscripts were included in the final review from the USA (n=2), China (n=2), Korea (n=2), India (n=1) and Brazil (n=1) and consisted of 6 case series, one case-control study and one cross-sectional study published between 1988-2022. We identified demographic and behavioural factors (older age, lower BMI, receptive anal sex), infection factors (urinary tract infections, shigellosis, Hepatitis C, COVID-19, sepsis, antimicrobial use), medical conditions (cardiovascular disease, respiratory disease, renal disease, auto-immune disease, diabetes) and hospitalisation factors (intensive care admission, longer length of hospital stay) associated with CMV procto-colitis in immunocompetent adults. Patients presented with rectal bleeding, diarrhoea, melaena, fever, nausea/vomiting, abdominal pain/bloating and constipation. Large bowel endoscopy findings were ulcers, erosions, and erythema and polyp/mass lesions.

Conclusion: We have highlighted factors, presenting symptoms and endoscopy findings associated with CMV procto-colitis in immunocompetent patients which provides insight for clinical guideline development and future research.

Metrics

Metrics Loading ...

References

Cannon M, Schmid D, Hyde T (2010) Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 30:202-213. https://doi.org/10.1002/rmv.655

Gandhi M, R K (2004) Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. The Lancet Infectious Diseases 4:725-738. https://doi.org/10.1016/S1473-3099(04)01202-2

Hodson E, Barclay P, Craig J, Jones C, Kable K, Strippoli G, Vimalachandra D, Webster A (2005) Antiviral medications for preventing cytomegalovirus disease in solid organ transplant receipients. Cochrane Database Syst Rev 19. https://doi.org/10.1002/14651858.CD003774.pub2

Gronborg H, Jespersen S, Honge B, Jensen-Fangel S, Wejse C (2017) Review of cytomegalovirus coinfection in HIV-infected individuals in Africa. Rev Med Virol 27. https://doi.org/10.1002/rmv.1907

Shukla T, Singh S, Tandon P, McCurdy J (2017) Corticosteroids and thiopurines, but not tumor necrosis factor antagonists, are associated with cytomegalovirus reactivation in inflammatory bowel disease: A systematic review and meta-analysis. J Clin Gastroenterol 51:394-401. https://doi.org/10.1097/MCG.0000000000000758

Marchesi F, Pimpinelli F, Ensoli F, Mengarelli A (2018) Cytomegalovirus infection in hematologic malignancy settings other than the allogenic transplant. Hematol Oncol 36:381-391. https://doi.org/10.1002/hon.2453

Yoo S, Han K, Lee K, Lim J, La Y, Kwon D, Han S (2021) Epidemiological changes in cytomegalovirus end-organ diseases in a developed country: A nationwide, general-population-based study. J Micro, Imm and Infect 55:812-819. https://doi.org/10.1016/j.jmii.2021.08.004

Tang Y, Guo J, Li J, Zhou J, Mao X, Qiu T (2022) Risk factors for cytomegalovirus infection and disease after kidney transplantation. Transpl Immunol 74. https://doi.org/10.1016/j.trim.2022.101677

Rafailidis P, Mourtzoukou E, Varbobitis I, Falagas M (2008) Severe cytomegalovirus infection in apparently immunocompetent patients: A systematic review. Virology Journal 5. https://doi.org/10.1186/1743-422X-5-47

Hoehl S, Berger A, Ciesek C, Rabenau H (2020) Thirty years of CMV seroprevalence-a longitudinal analysis in a German university hospital. Eur J Clin Microbiol Infect Dis 39:1095-1102. https://doi.org/10.1007/s10096-020-03814-x

Guo L, DeRoche T, Salih Z, Qasem S (2018) Routine hematoxylin and eosin stain in specific for the diagnosis of cytomegalovirus infection in gastrointestinal biopsy specimens. International Journal of Surgical Pathology 26:500-506. https://doi.org/10.1177/1066896918761601

Goyal G, Zinger T, Warfield D, Cao W (2022) The trends of immunohistochemistry for tissue-invasive cytomegalovirus in gastrointestinal mucosal biopsies: a large single academic centre study. Archives of Pathology and Laboratory Medicine 146:360-365. https://doi.org/10.5858/arpa.2020-0425-OA

Suarez-Lledo M, Marcos M, Cuatrecasas M, Bombi J, Fernandez-Aviles F, Magnano L, Martinez-Cibrian N, Llobet N, Rosinol L, Gutierrez-Garcia G, Jorge S, Martinez C, Rovira M, Ubrano-Ispizua A (2019) Quantiative PCR is faster, more objective, and more reliable than immunohistochemistry for the diagnosis of cytomegalovirus gastrointestinal disease in allogenic stem cell transplant. Biol Blood Marrow Transplant 25:2281-2286. https://doi.org/10.1016/j.bbmt.2019.07.016

Bontà J, Zeitz J, Frei P, Biedermann L, Sulz MC, Vavricka SR, Scharl S, Fried M, Rogler G, Scharl M (2016) Cytomegalovirus disease in inflammatory bowel disease: epidemiology and disease characteristics in a large single-centre experience. Eur J Gastroenterol Hepatol 28:1329-1334. https://doi.org/10.1097/meg.0000000000000716

Gauss A, Rosenstiel S, Schnitzler P, Hinz U, Rehlen T, Kadmon M, Ehehalt R, Stremmel W, Zawierucha A (2015) Intestinal cytomegalovirus infection in patients hospitalized for exacerbation of inflammatory bowel disease: a 10-year tertiary referral center experience. Eur J Gastroenterol Hepatol 27:712-720. https://doi.org/10.1097/meg.0000000000000361

Shukla T, Singh S, Loftus EV, Jr., Bruining DH, McCurdy JD (2015) Antiviral Therapy in Steroid-refractory Ulcerative Colitis with Cytomegalovirus: Systematic Review and Meta-analysis. Inflamm Bowel Dis 21:2718-2725. https://doi.org/10.1097/mib.0000000000000489

Rafailidis PI, Mourtzoukou EG, Varbobitis IC, Falagas ME (2008) Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. Virol J 5:47. https://doi.org/10.1186/1743-422x-5-47

Moola S, Munn Z, Sears K, Sfetcu R, Currie M, Lisy K, Tufanaru C, Qureshi R, Mattis P, Mu P (2015) Conducting systematic review of association (etiology): The Joanna Briggs Institute’s approach. Int J Evid Based Healthc 13:163-169. https://doi.org/10.1097/XEB.0000000000000064

Surawicz C, Myerson D (1988) Self-limited cytomegalovirus colitis in immunocompetent individuals. Gastroenterology 94:194-199. https://doi.org/10.1016/0016-5085(88)90630-0

Klauber E, Briski LE, Khatib R (1998) Cytomegalovirus colitis in the immunocompetent host: an overview. Scand J Infect Dis 30:559-564. https://doi.org/10.1080/00365549850161098

Ng F, Chau T, Cheung T, Kng C, Wong S, Ng W, Lee K, Chan E, Lai S, Yuen W, Chang C (1999) Cytomegalovirus colitis in individuals without apparent cause of immunodeficiency. Digestive Diseases and Sciences 44:945-952. https://doi.org/10.1023/a:1026604529393

Seo T, Kim J, Ko S, Hong S, Lee S, Sung I, Park H, Shim C, Ha H (2012) Cytomegalovirus colitis in immunocompetent patients: A clinical and endoscopic study. Hepato-gastroenterology 59:2137-2141. https://doi.org/10.5754/hge10825

Siciliano R, Castelli J, Randi B, Vieira R, Strabelli T (2014) Cytomegalovirus colitis in immunocompetent critically ill patients. Int J Infect Dis 20:71-73. https://doi.org/10.1016/j.ijid.2013.11.008

Ko J, Peck K, Lee W, Lee J, Cho S, Ha Y, Kang C, Chung D, Kim Y, Lee N, Kim K, Song J (2015) Clinical presentation and risk factors for cytomegalovirus colitis in immunocompetent adult patients. Clin Infect Disease 60:e20-e26. https://doi.org/10.1093/cid/ciu969

Le P, Lin W, Kuo C, Wu R, Hsu J, Su M, Lin C, Chiu C (2017) Clinical characteristics of cytomegalovirus colitis: A 15-year experience from a tertiary reference center. Therapeutics and CLinical Risk Management 13:1585-1593. https://doi.org/10.2147/TCRM.S151180

Verma A, Girish M, Dahale A, Dalal A, Sachdeva S (2021) CMV colitis in immunocompetent patients - a case series. J Dig Endo 12:245-246. https://doi.org/10.1055/s-0041-1742134

Dobner J, Kaser S (2018) Body mass index and the risk of infection - from underweight to obesity. Clin Microbiol Infect 24:24-28. https://doi.org/10.1016/j.cmi.2017.02.013

Castle SC (2000) Impact of age-related immune dysfunction on risk of infections. Z Gerontol Geriatr 33:341-349. https://doi.org/10.1007/s003910070030

Handsfield HH, Chandler SH, Caine VA, Meyers JD, Corey L, Medeiros E, McDougall JK (1985) Cytomegalovirus infection in sex partners: evidence for sexual transmission. J Infect Dis 151:344-348. https://doi.org/10.1093/infdis/151.2.344

Russell A, Siddiq M, Fitzpatrick C, Richardson D (2023) Anorectal Mpox in men who have sex with men associated with sexually transmitted co-infections: a case series. Sex Transm Infect. https://doi.org/10.1136/sextrans-2023-055906

Richardson D, Pakianathan M, Ewens M, Mitchell H, Mohammed H, Wiseman E, Tweed M, Nichols K, Rawdah W, Cooper R, Macrowan R, Irish M, Evans A, Godbole G (2023) British Association of Sexual Health and HIV (BASHH) United Kingdom national guideline for the management of sexually transmitted enteric infections 2023. Int J STD AIDS:9564624231168217. https://doi.org/10.1177/09564624231168217

Richardson D, Siddiqi A, Parashar K, Fitzpatrick C, Pinto-Sander N, Goldmeier D (2023) A Pilot Study Evaluating Antimicrobial Antagonism in Syphilis/Chlamydia trachomatis Co-Infection in Men Who Have Sex with Men. European Journal of Therapeutics 27:327-328. https://doi.org/10.5152/eurjther.2021-21062

Popa C, Netea MG, van Riel PL, van der Meer JW, Stalenhoef AF (2007) The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res 48:751-762. https://doi.org/10.1194/jlr.R600021-JLR200