Cytomegalovirus and mixed viral infections in patients with inflammatory bowel disease
Background. The issue of the prevalence of opportunistic infections in persons with inflammatory bowel disease (IBD) remains relevant. Among opportunistic infections, in particular, we would like to note Herpesviridae family (herpes simplex virus type 1 and 2), human herpesvirus type 3 (varicella zoster virus), human herpesvirus type 4 (Epstein-Barr virus), cytomegalovirus (CMV), or human herpesvirus type 5, human herpesvirus type 6 and parvovirus B19. Clinically marked herpes and parvovirus infections are frequent causes of systemic inflammation of the gastrointestinal tract. This is a serious problem, especially for persons with long-term immunosuppression, who have IBD, and special attention in this aspect is paid to cytomegalovirus infection. Clinical activity of CMV-associated IBD, its duration and severity, as well as the use of steroids and anti-TNF-α agents were identified as risk factors for adverse outcomes. It is important not only to detect the presence of viruses in the patient’s body, but also to clarify their etiological role in the development of the disease. According to the current European Crohn’s and Colitis Organisation (ECCO) protocols, all patients with IBD are recommended to be screened in hormone resistance, loss of effect from maintenance therapy and severe attacks of the disease. The addition of active CMV infection to IBD may likely be one of the causes of resistance to hormone and immunosuppressive therapy, as well as biological drugs, but this issue requires further researches. The purpose was to evaluate the frequency of detecting isolated cytomegalovirus infection and mixed (herpes and parvovirus B19) viral infections in patients with IBD and their influence on the disease activity. Materials and methods. One hundred and eighty-nine patients (98 women and 91 men) with IBD (102 with ulcerative colitis (UC) and 87 with Crohn’s disease (CD)) were examined. The age of patients was from 16 to 63 years (mean age (41.4 ± 4.8) years). In addition to standard clinical endoscopic examinations according to ECCO guidelines, disease activity was assessed by indicators of highly sensitive C-reactive protein, homocysteine, vitamin D in blood serum, albumin in urine, calprotectin and lactoferrin in feces. All patients underwent serological blood test by enzyme-linked immunosorbent assay for specific antibodies to herpesviruses and IgG/IgM antibodies to parvovirus B19, determination of DNA of herpes simplex viruses types 1, 2, 6, Epstein-Barr virus, cytomegalovirus, herpes zoster by a polymerase chain reaction in blood and tissues. All patients underwent determination of blood cytokines (tumor necrosis factor α, interleukins 1β, -2, -4, -6, -8, -10, -18). Results. Viral (herpes and parvovirus B19) infections in patients with IBD occurred in 81 cases (42.8 %): in 35 (40.2 %) of 87 patients with CD and in 46 (45.0 %) of 102 — with UC. Among patients with cytomegalovirus infection alone, 21 (11.1 % of the total number and 25.9 % of infected persons) suffered from UC and 16 (8.5 % of the total number and 19.7 % of infected persons) — from CD. In 26 (13.8 % of the total number and 32.1 % of infected persons) cases, mixed viral infections were detected — in 13 patients with CD and 13 with UC (6.9 % of the total number and 16.0 % of infected persons). In patients with IBD, the frequency of detecting isolated cytomegalovirus infection is 19.5 % of the total number and 45.6 % of infected persons; mixed viral infection was found in 13.8 % of the total number and 32.1 % of infected patients. The clinical endoscopic picture (resistance to basic therapy, the mismatch between the endoscopic picture and the pathomorphological conclusion), as well as laboratory data, indicate a more severe course of diseases in the presence of cytomegalovirus infection. Conclusion. The data obtained allow us to recommend, in addition to ECCO protocols, the determination of the presence of opportunistic (herpes and parvovirus B19) infections in patients with newly diagnosed IBD before starting basic therapy, without waiting for the development of disease forms refractory to therapy.
Shestakova IV, editor. Tsitomegalovirusnaia infektsiia u vzroslykh (iskliuchaia bol'nykh VICh-infektsiei): klinicheskie rekomendatsii [Cytomegalovirus in adults (excluding patients with HIV infection): clinical guidelines]. Moscow; 2014. 74 p. (in Russian).
Li Y, Xu H, Xu T, et al. Case-Control Study of Inflammatory Bowel Disease Patients with and without Clostridium difficile Infection and Poor Outcomes in Patients Coinfected with C. difficile and Cytomegalovirus. Dig Dis Sci. 2018 Nov;63(11):3074-3083. doi: 10.1007/s10620-018-5230-1.
Rowan C, Judge C, Cannon MD, et al. Severe Symptomatic Primary CMV Infection in Inflammatory Bowel Disease Patients with Low Population Seroprevalence. Gastroenterol Res Pract. 2018 Jun 28;2018:1029401. doi: 10.1155/2018/1029401.
Tsuchido Y, Nagao M, Matsuura M,et al. Real-time quantitative PCR analysis of endoscopic biopsies for diagnosing CMV gastrointestinal disease in non-HIV immunocompromised patients: a diagnostic accuracy study. Eur J Clin Microbiol Infect Dis. 2018 Dec;37(12):2389-2396. doi: 10.1007/s10096-018-3387-3.
Ciccocioppo R, Racca F, Scudeller L, et al. Differential cellular localization of Epstein-Barr virus and human cytomegalovirus sin the colonic mucosa of patients with active or quiescent inflammatory bowel disease. Immunol Res. 2016 Feb;64(1):191-203. doi: 10.1007/s12026-015-8737-y.
Ford AC, Peyrin-Biroulet L. Opportunistic infections with anti-necrosis factor-α therapy in inflammatory bowel disease: meta-analysis of randomized controlled trials. Am J Gastroenterol. 2013 Aug;108(8):1268-76. doi: 10.1038/ajg.2013.138.
Johnson J, Affolter K, Boynton K, Chen X, Valentine J, Peterson K. CMV Disease in IBD: Comparison of Diagnostic Tests and Correlation with Disease Outcome. Inflamm Bowel Dis. 2018 Jun 8;24(7):1539-1546. doi: 10.1093/ibd/izy045.
Rahier JF, Magro F, Abreu C, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2014 Jun;8(6):443-68. doi: 10.1016/j.crohns.2013.12.013.
Galegov GA, Andronova VL. Chemotherapy for viral infections. In: L'vov DK, editor. Meditsinskaia virusologiia [Medical virsology]. Moscow: MIA; 2008. 87-92 pp. (in Russian).
Inflammatory Bowel Disease Group, Chinese Society of Gastroenterology, Chinese Medical Association. Evidence-based consensus on opportunistic infections in inflammatory bowel disease (republication). Intest Res. 2018 Apr;16(2):178-193. doi: 10.5217/ir.2018.16.2.178.
Copyright (c) 2019 GASTROENTEROLOGY
This work is licensed under a Creative Commons Attribution 4.0 International License.
© Publishing House Zaslavsky, 1997-2020