Abstract
Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.
Highlights
Inflammatory bowel diseases (IBDs) primarily involve two main entities: Crohn disease (CD) and ulcerative colitis (UC)
We showed that tissue CMV viral load predicts the response to several lines of immunosuppressive treatment: A viral load greater than 250 copies/mg of tissue or 370 international units (IU)/100,000 cells (sensitivity 95.2% and specificity 97.2%) is associated with resistance to more than two successive lines of treatment [44,81]
Algorithms have recently been published to better rationalize this management [7,12,46,156,165,166]. In addition to these recommendations, we suggest that anti-TNF biotherapy, combined with a ganciclovir-type antiviral agent, should be preferred in the case of a moderate or high viral load
Summary
Inflammatory bowel diseases (IBDs) primarily involve two main entities: Crohn disease (CD) and ulcerative colitis (UC). IBDs affect mainly young and active subjects with a diagnosis generally made between 20 and 30 years old Their annual incidence is increasing overall, with a relative stabilization in Western countries [1], but an accelerating incidence in newly industrialized countries, where the way of life is becoming “Westernized” [2]. The incidence is increasing in adolescents, as reported by a recent French study [3] These chronic diseases are incurable and disabling with a major impact on the socio-professional life of patients. Their pathophysiology is complex and dominated by chronic inflammation of the digestive tract, and involves genetic factors affecting innate and adaptive immune responses of the digestive mucosa together with environmental factors (Figure 1) [4,5,6]. HumanHucmytaonmcyetgoamloegvailrouvsiru(Cs M(CMV)V,),alaslsoo tteerrmeeddhhuummananbebtaehtearhpesrvpierussvi5r,uis a5n, iosppanortoupnipstoicrtunistic pathogepnatihnovgoelnveindvoinlvmedaninyminaflnayminmflaamtomryatporryocpersosceesss[e1s0][.10T].heThdeiadgiangonsoissisofoCf MCMVVcocloiltiitsisininIBIBDDpatients is difficpualttiednutse itsodtihffeicualbtsdeunecetootfheclainbsiceanlceoorfecnlidnoicsacloopriecnsdyomscopptoicmsysmthpatotmdsifftheartenditfifaetreenCtiMateVCcMoVlitis from colitis from colitis associated with the inflammatory disease itself; it is based exclusively on the colitis adsestoecctiiaonteodf hwisittohlotghicealionrflvairmalmmaatrokerrys idnitsheeaisneteisttsinealfl;miut ciossaba[1s1e,1d2]e. xTchleuasiimveolfythoisnretvhieewdwetaesction of histologtiochailgohrlivghirtatlhme palrakceerosf cinolothneiciCnMteVstiinnfaelctmiouncdousrain[g11IB,1D2b].yTemhephaiamsizoinfgththise rreelvaiteiownswhiapss btoethwiegehnlight the place ofCcMoVloninicfeCctMionV oinf ftehcetioconlodnuicrinmgucIBosDa bayndeminpflhamasmizaitnorgythflearree-luaptioonf sUhCip, stbheetwvireuesn aCnMd Vthienfection of the cionlfolanmicmmatiuocnoisnatearnacdtiningflwaimthmeaacthoroythflear,rew-uhipchorfeUsuClt,s tihnepveirrpuestuaantidngthaendinwfloarmsemninagtioconloinnitceracting with eaclehsioonths.eWr, ewwhililcahlsroesshuolwts hinowp,einrpUeCtu, iamtimnugnaonsudpwproersssievneianngdcaonltoivniriacllteresaiotmnse.ntWs ceanwhielllpaclsoontsrholow how, in UC, itmhemcoulonnoiscuinpfplarmemssaivtioena.nd antiviral treatments can help control the colonic inflammation
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