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

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.

Cytomegalovirus Infection in Patients with Active Inflammatory Bowel Disease

“…For example, univariate analysis showed significant associations of CMV infection with elevated white blood cell count, hospitalization at the time of index endoscopy, and hospitalization C7 days. In contrast to some prior reports, our study did not show a significant association of steroid or other immunosuppressive therapy with CMV infection [17,30]. However, steroids were used twice as often in patients with CMV infection in our study, raising the possibility of a type II error.…”

Low frequency of cytomegalovirus infection during exacerbations of inflammatory bowel diseases

“…The prevalence rates of CMV infection among IBDs populations reported previously ranged from 0.5% to 72% [Wakefield et al, 1992;Papadakis et al, 2001]. Studies including patients presenting acute severe colitis or steroidrefractory colitis described the highest CMV prevalence [Cottone et al, 2001;Criscuoli et al, 2004;Minami et al, 2007;Yoshino et al, 2007;Maher and Nassar, 2009]. Only three studies could be legitimately compared with the present work.…”

“…Since then, some reports have assumed a triggering role of CMV infection in the onset or the worsening of IBDs [Cooper et al, 1977;Eyre Brook and Dundas, 1986;Orloff et al, 1989;Criscuoli et al, 2006;Kandiel and Lashner, 2006]. CMV was thus found to cause immunosuppression and to increase the severity of inflammatory diseases [Pofelski et al, 2007;Maher and Nassar, 2009]. Furthermore, CMV detection was associated with poor prognosis and steroid refractoriness [Cottone et al, 2001;Kambham et al, 2004;Maconi et al, 2005].…”

Diagnosis of Cytomegalovirus Infection during Exacerbation of Ulcerative Colitis

“…The association of CS treatment with the presence of CMV in colonic biopsies is well recognized, though it is still unclear whether CMV is only a surrogate marker of resistance and disease severity or a causative factor [1,2,14,15,16]. In accordance with our findings, there is previous evidence that UC patients whose disease course is complicated by CMV infection, have more severe systemic inflammatory signs, such as high fever, increased C-reactive protein and lower albumin levels [6,15]. On the other hand, one recently published prediction model found no statically significant association between fever and CMV infection risk [6].…”