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Acute Cytomegalovirus Infection Is a Risk Factor in Refractory and Complicated Inflammatory Bowel Disease

  • Maha M. MaherEmail author
  • Mahmoud I. Nassar
Original Article

Abstract

The role of cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is controversial. Although CMV has been specifically associated with refractory disease, the strength and nature of this association have been a subject of debate. The aim of this study was to evaluate the prevalence and outcome of acute cytomegalovirus infection in patients with severe refractory and complicated inflammatory bowel disease. Seventy-two patients with active IBD (both ulcerative colitis [UC] and Crohn’s diseases [CD]) were included in this study. Thorough history taking and physical examination of all patients was made with special emphasis on symptoms and signs of CMV disease. Colonoscopic assessment was made for the extent and activity of IBD and collection of specimen. Prevalence of CMV infection was estimated by serology; anti-CMV IgM and IgG antibodies, and pathologic studies of colonic biopsies used conventional haematoxylin and eosin (H & E) and immunohistochemistry (IHC) with monoclonal antibodies. Complete blood count and liver function tests were done for all patients. Among 72 patients with active inflammatory bowel disease, 23 (31.9%) were resistant to intravenous steroids. CMV was detected in eight (six with UC and two with CD) of the 23 (34.8%) steroid-resistant patients and in only one (3.2%) patient in the remaining 31 patients under steroid treatment and was not detected in 18 IBD patients not using steroids. Among nine CMV-positive IBD patients, six (66.6%) were female and six had fever; cervical lymphadenopathy was found in five patients and splenomegaly in two, compared to no patients in the CMV-negative group (P = 0.01 and 0.03, respectively). Leucopenia and thrombocytopenia were predominantly seen in the CMV-positive versus CMV-negative patients (2.1±0.3 vs. 5.9±3.4 and 98±34 vs. 165±101, respectively). Pancolitis was found in five of nine CMV-positive IBD patients whereas in only two patients out of 63 in the CMV-negative group (P = 0.005). Acute CMV infection in patients with IBD is not rare and is often underestimated. CMV infection in patients with refractory or complicated IBD should be ruled out before aggressive immunosuppressive therapy. High clinical index of suspicion for the association of CMV infection with IBD should be directed towards female IBD patients presenting with fever, lymphadenopathy, splenomegaly, leucopenia, and mild hepatitis. CMV IHC is significantly more sensitive than routine H & E stain and should be considered as part of the routine evaluation of IBD patients with severe exacerbation or steroid-refractory disease before proceeding with other medical or surgical therapy that may not be necessary once the CMV is treated.

Keywords

Inflammatory bowel disease Ulcerative colitis Crohn’s Cytomegalovirus 

References

  1. 1.
    Papadakis KA, Tung JK, Binder SW, et al. Outcome of cytomegalovirus infections in patients with inflammatory bowel disease. Am J Gastroenterol. 2001;96:2137–2142. doi: 10.1111/j.1572-0241.2001.03949.x.CrossRefPubMedGoogle Scholar
  2. 2.
    de la Hoz RE, Stephens G, Sherlock C. Diagnosis and treatment approaches of CMV infections in adult patients. J Clin Virol. 2002;25(Suppl 2):S1–S12. doi: 10.1016/S1386-6532(02)00091-4.PubMedGoogle Scholar
  3. 3.
    Pereyra F, Rubin RH. Prevention and treatment of cytomegalovirus infection in solid organ transplant recipients. Curr Opin Infect Dis. 2004;17:357–361. doi: 10.1097/01.qco.0000136933.67920.dd.CrossRefPubMedGoogle Scholar
  4. 4.
    Kishore J, Ghoshal U, Ghoshal UC, et al. Infection with cytomegalovirus in patients with inflammatory bowel disease: prevalence, clinical significance and outcome. J Med Microbiol. 2004;53:1155–1160. doi: 10.1099/jmm.0.45629-0.CrossRefPubMedGoogle Scholar
  5. 5.
    Pfau P, Kochman ML, Furth EE, et al. Cytomegalovirus colitis complicating ulcerative colitis in the steroid-naive patient. Am J Gastroenterol. 2001;96:895–899. doi: 10.1111/j.1572-0241.2001.03672.x.CrossRefPubMedGoogle Scholar
  6. 6.
    Hommes DW, Sterringa G, van Deventer SJ, et al. The pathogenicity of cytomegalovirus in inflammatory bowel disease: a systematic review and evidence-based recommendations for future research. Inflamm Bowel Dis. 2004;10:245–250. doi: 10.1097/00054725-200405000-00011.CrossRefPubMedGoogle Scholar
  7. 7.
    Rahbar A, Bostrom L, Lagerstedt U, et al. Evidence of active cytomegalovirus infection and increased production of IL-6 in tissue specimens obtained from patients with inflammatory bowel diseases. Inflamm Bowel Dis. 2003;9:154–161. doi: 10.1097/00054725-200305000-00002.CrossRefPubMedGoogle Scholar
  8. 8.
    Alcala MJ, Casellas F, Pallares J, et al. Infection by cytomegalovirus in patients with ulcerative colitis requiring colonic resection. Med Clin (Barc). 2000;114:201–204.Google Scholar
  9. 9.
    Truelove SC, Witts LJ. Cortisone in ulcerative colitis. Final report on a therapeutic trial. BMJ. 1955;2:1041–1048.Google Scholar
  10. 10.
    Best WR, Becktel JM, Singleton JW, et al. Development of a Crohn’s disease activity index. National cooperative Crohn’s disease study. Gastroenterology. 1976;70:439–444.PubMedGoogle Scholar
  11. 11.
    Marion JF, Present DH. The modern medical management of acute, severe ulcerative colitis. Eur J Gastroenterol Hepatol. 1997;9:831–835.PubMedGoogle Scholar
  12. 12.
    Criscuoli V, Casa A, Orlando A, et al. Severe acute colitis associated with CMV: a prevalence study. Dig Liver Dis. 2004;36:818–820. doi: 10.1016/j.dld.2004.05.013.CrossRefPubMedGoogle Scholar
  13. 13.
    Beaugerie L, Cywiner-Golenzer C, Monfort L, et al. Definition and diagnosis of cytomegalovirus colitis in patients infected by human immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14:423–429.PubMedGoogle Scholar
  14. 14.
    Chemaly RF, Yen-Lieberman B, Castilla EA, et al. Correlation between viral loads of cytomegalovirus in blood and bronchoalveolar lavage specimens from lung transplant recipients determined by histology and immunohistochemistry. J Clin Microbiol. 2004;42:2168–2172. doi: 10.1128/JCM.42.5.2168-2172.2004.CrossRefPubMedGoogle Scholar
  15. 15.
    Truelove SC, Richards WC. Biopsy studies in ulcerative colitis. BMJ. 1956;4979:1315–1318.CrossRefGoogle Scholar
  16. 16.
    Goodgame RW. Gastrointestinal cytomegalovirus disease. Ann Intern Med. 1993;119:924–935.PubMedGoogle Scholar
  17. 17.
    Cheung ANY, Path MRC, Olng I. Cytomegalovirus infection of the gastrointestinal tract in non-AIDS patients. Am J Gastroenterol. 1993;88:1882–1886.PubMedGoogle Scholar
  18. 18.
    Vega R, Bertran X, Menacho M, et al. Cytomegalovirus infection in patients with inflammatory bowel disease. Am J Gastroenterol. 1999;94:1053–1056. doi: 10.1111/j.1572-0241.1999.01013.x.CrossRefPubMedGoogle Scholar
  19. 19.
    Cottone M, Pietrosi G, Martorana G, et al. Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn’s colitis. Am J Gastroenterol. 2001;96:773–775. doi: 10.1111/j.1572-0241.2001.03620.x.CrossRefPubMedGoogle Scholar
  20. 20.
    Hamlin PJ, Shah MN, Scott N, et al. Systemic cytomegalovirus infection complicating ulcerative colitis: a case report and review of the literature. Postgrad Med J. 2004;80:233–235. doi: 10.1136/pgmj.2003.007385.CrossRefPubMedGoogle Scholar
  21. 21.
    Waya Y, Matsui T, Mataki H, et al. Intractable ulcerative colitis caused by cytomegalovirus infection: a prospective study on prevalence, diagnosis and treatment. Dis Colon Rectum. 2003;46:S59–S65. doi: 10.1007/s10350-004-6497-1.CrossRefGoogle Scholar
  22. 22.
    Revello MG, Gerna G. Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev. 2002;15:680–715. doi: 10.1128/CMR.15.4.680-715.2002.CrossRefPubMedGoogle Scholar
  23. 23.
    Hinnant KL, Rotterdam HZ, Bell ET, Tapper ML. Cytomegalovirus infection of the alimentary tract: a clinicopathological correlation. Am J Gastroenterol. 1986;81:944–950.PubMedGoogle Scholar
  24. 24.
    Goodman ZD, Boitnott JK, Yardley JH. Perforation of the colon associated with cytomegalovirus infection. Dig Dis Sci. 1979;24:376–380. doi: 10.1007/BF01297124.CrossRefPubMedGoogle Scholar
  25. 25.
    Kambham N, Vij R, Cartwright CA, et al. Cytomegalovirus infection in steroid-refractory ulcerative colitis: a case-control study. Am J Surg Pathol. 2004;28:365–373. doi: 10.1097/00000478-200403000-00009.CrossRefPubMedGoogle Scholar
  26. 26.
    Rowshani AT, Bemelman FJ, van Leeuwen EM, et al. Clinical and immunologic aspects of cytomegalovirus infection in solid organ transplant recipients. Transplantation. 2005;79:381–386. doi: 10.1097/01.TP.0000148239.00384.F0.CrossRefPubMedGoogle Scholar
  27. 27.
    De Saussure P, Lavergne-Slove A, Mazeron MC, et al. A prospective assessment of cytomegalovirus infection in active inflammatory bowel disease. Aliment Pharmacol Ther. 2004;20:1323–1327. doi: 10.1111/j.1365-2036.2004.02273.x.CrossRefPubMedGoogle Scholar
  28. 28.
    Takahashi Y, Tange T. Prevalence of cytomegalovirus infection in inflammatory bowel disease patients. Dis Colon Rectum. 2004;47:722–726. doi: 10.1007/s10350-003-0117-3.CrossRefPubMedGoogle Scholar
  29. 29.
    Chang HR, Lian JD, Chan CH, et al. Cytomegalovirus ischemic colitis of a diabetic renal transplant recipient. Clin Transplant. 2004;18:100–104. doi: 10.1046/j.0902-0063.2003.00108.x.CrossRefPubMedGoogle Scholar
  30. 30.
    Nucci M, Andrade F, Vigorito A, et al. Infectious complications in patients randomized to receive allogeneic bone marrow or peripheral blood transplantation. Transpl Infect Dis. 2003;5:167–173. doi: 10.1111/j.1399-3062.2003.00033.x.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Internal MedicineMansoura UniversityMansouraEgypt
  2. 2.Department of PathologyAssuit UniversityAssuitEgypt

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