Cytomegalovirus and inflammatory bowel disease: is there a link?

The objective of this report is to give an overall view of the epidemiological, clinical, diagnostic and therapeutic features of Cytomegalovirus (CMV) infection in inflammatory bowel disease (IBD). A review of published reports on this topic was carried out, with particular attention paid to the selection of patients included in studies and the diagnostic methods employed. CMV is frequently associated with IBD. In some cases, CMV infection is associated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. The use of anti-viral therapy in IBD is controversial and an empirical study with controls is needed. The natural history of CMV infection related to the development and treatment of IBD has not been clarified but it is important to take it in consideration because of the possibility of viral persistence in the immunocompromised host and viral interaction with the immune system.

Toxic megacolon and human Cytomegalovirus in a series of severe ulcerative colitis patients.

BACKGROUND: Human Cytomegalovirus (HCMV) infection has been reported to be a cause of refractory ulcerative colitis (UC). Toxic megacolon (TM) is a rare but severe complication of an acute attack of UC. OBJECTIVES: Aim of this study is to evaluate in a case-control study the association between HCMV and TM. STUDY DESIGN: All patients who were admitted at Medicine Department of V. Cervello Hospital in Palermo (tertiary referral center) for a severe UC flare-up complicated by the onset of TM (diameter of the transverse colon>6 cm) between January 1990 and November 2011 were identified through the electronic database. A total of 24 consecutive patients (16 male/8 female) with TM were identified. Each case of TM were individually matched by sex, age, extent of the underlying disease to 24 severe UC controls who did not develop TM. A further non matched control population of 48 severe UC was included. Haematoxilin and eosin stain, immunohistochemical procedure and nested polymerase chain reaction were performed to detect HCMV genes and proteins on rectal biopsies or surgical specimens. Pp65 antigenemia was performed in order to diagnose any possible systemic infection. HCMV frequency was compared between patients with and without TM during follow-up, using Fisher's Exact test. RESULTS AND CONCLUSIONS: HCMV was detected in histological specimens of 11 patients (46%) with TM compared to 2 (9%) severe UC matched controls (P = 0.0078) and 7 (14%) unmatched controls (p = 0,003). In severe colitis the presence of HCMV is more frequently associated with TM.

Mesalazine for the treatment of inflammatory bowel disease.

INTRODUCTION: Ulcerative colitis (UC) and Crohn's disease (CD) represent a chronic inflammatory condition of the bowel that often require lifelong medical therapy for the induction and maintenance of the remission. Mesalazine therapies are available both as oral delayed-release and sustained-release formulation, topical formulations and as prodrug. AREAS COVERED: Available literature regarding mesalazine is extensively reviewed in this article, covering its mechanism of action, pharmaceutics and pharmacokinetics, clinical efficacy, safety and tolerability in different settings. EXPERT OPINION: Mesalazine has a well-established role in the management of UC. It is the treatment of choice in active and inactive mild-to-moderate UC combining oral and topical drug. No clear role of mesalazine in prevention of colon cancer has been demonstrated because of the contradictory results coming from case-control and prospective studies. The role of mesalazine in the management of CD is less clear; some studies suggest a potential efficacy of 5-ASA in preventing relapse of CD after surgical resection but more convincing results are needed.

Is really megacolon a contraindication to infliximab in Crohn's disease?

Toxic megacolon (TM) is a rare complication of severe ulcerative colitis (UC) and colonic Crohn's disease (CD), defined as a clinical syndrome accompanied by radiographic evidence of colonic dilatation that in many cases must be treated aggressively with surgical intervention (1). We report two cases of steroid and antibiotic-refractory fulminant Crohn's colitis, complicated by toxic megacolon, who were successfully treated with infliximab (IFX), thus avoiding surgical intervention. Although there are no well defined recommendation about the correct timing of colectomy in CD-associated TM, and despite the fact that it may be imprudent to advocate delaying surgery in favour of anti-tumor necrosis (anti-TNF) factor therapy in these cases, we think that a medical "rescue therapy" can be considered in a subset of patients with stable clinical condition during corticosteroid treatment.

The role of portal vein thrombosis in the clinical course of inflammatory bowel diseases: report on three cases and review of the literature.

Inflammatory bowel diseases are associated with an increased risk of vascular complications. The most important are arterial and venous thromboembolisms, which are considered as specific extraintestinal manifestations of inflammatory bowel diseases. Among venous thromboembolism events, portal vein thrombosis has been described in inflammatory bowel diseases. We report three cases of portal vein thrombosis occurring in patients with active inflammatory bowel disease. In two of them, hepatic abscess was present. Furthermore, we performed a systematic review based on the clinical literature published on this topic.

Natural history of cytomegalovirus infection in a series of patients diagnosed with moderate-severe ulcerative colitis.

AIM: To evaluate the natural history of human cytomegalovirus (HCMV) infection in a series of 28 ulcerative colitis patients in whom the search for HCMV was positive. METHODS: A series of 85 patients with moderate-severe ulcerative colitis flare-up were evaluated for a HCMV search by performing a haematoxylin and eosin stain, immunohistochemical assay and nested polymerase chain reaction on rectal biopsies. Among 85 screened patients (19 of whom were steroid resistant/dependent), 28 were positive for HCMV; after remission the patients were followed up clinically and histologically. RESULTS: Among the 22 patients with complete follow-up, in 8 (36%) patients HCMV-DNA persisted in the intestinal specimens. Among the HCMV positive patients, 4 (50%) experienced at least one moderate-severe flare-up of colitis without evidence of peripheral HCMV. Among the 14 HCMV negative patients, 3 with pouches developed pouchitis and 5 out of 11 (45%) experienced a colitis flare-up. CONCLUSION: Our preliminary results suggest that HCMV may remain in the colon after an acute colitis flare-up despite remission; it seems that the virus is not responsible for the disease relapse.

The role of CARD15 mutations and smoking in the course of Crohn's disease in a Mediterranean area.

AIM: To evaluate the role of CARD15 mutations and smoking in the main events of Crohn's disease (CD). PATIENTS AND METHODS: A total of 182 patients with CD were included in a prospective study in order to evaluate the role of CARD15 mutations and smoking in the main outcomes of disease course: first operation and surgical recurrence. The following variables were evaluated in a univariable and multivariable analysis: age, sex, site of disease, pattern, smoking habit, extraintestinal manifestations, duration of disease, and CARD15 mutation. The Kaplan-Meier method for survival curves and Cox model for multivariable analysis were, respectively, used. RESULTS: A total of 110 patients were operated on and 32 were reoperated on. The 7-yr cumulative free rate of surgery was 42% (95% CI 34-51%). At multivariate analysis only stricturing and penetrating pattern were predictors of surgery (HR 1.7, 95% CI 1-2.8; HR 3.2, CI 1.8-5.5, respectively). The 7-yr cumulative free rate of reoperation was 75% (95% CI 0.52-0.88). At multivariable analysis in the model with any CARD15 mutation, only smoking habit at diagnosis (HR 3.6, 95% CI 1.4-9.1) was predictive of surgical recurrence. When single mutations were considered in the model smoking (HR 4.2, 95% CI 1.8-10.1) and L1007fs mutation (HR 2.9, 95% CI 1.1-7.3) were predictive of reoperation. CONCLUSIONS: In CD, smoking predicts recurrence after surgery. The role of CARD15 mutations in the clinical course of CD remains undefined.