Cytomegalovirus positive ulcerative colitis:A single center experience and literature review

AIM:To compare the clinical outcome of cytomegalovirus(CMV)-positive ulcerative colitis(UC) patients with and without antiviral therapy.METHODS:This was a retrospective case-controlled study.The database of UC patients in our institution was scanned for documented presence of CMV on colonic biopsies.Demographics,clinical data,endoscopy findings and pathology reports were extracted from the patients' charts and electronic records.When available,the data from colonoscopies preceding and following the diagnosis of colonic CMV infection were also ex-tracted.The primary outcomes of the study were colectomy/death during hospitalization and the secondary outcomes were colectomy/death through the course of the follow-up.RESULTS:Thirteen patients were included in the study,7(53.5%) of them were treated with gancyclovir and 6(46.5%) were not.Patients treated with antivirals presented with a more severe disease and 57% of them were treated with cyclosporine or infliximab before initiation of gancyclovir,while none of the patients without antivirals required rescue therapy.One patient died and another patient underwent urgent colectomy during hospitalization,both of them from the gancyclovir-treatment group.For the entire follow-up time(13 ± 13 mo),a total of 3 colectomies and one death occurred,all among the antiviral-treated patients(for colectomy:3/7 vs 0/6 patients,P = 0.19;for combined adverse outcome:4/7 vs 0/6 patients,P = 0.07).In 9/13 patients,immunohistochemistry for CMV was performed on biopsies obtained during a subsequent colonoscopy and was positive in one patient only.CONCLUSION:Gancyclovir-treated patients had a more severe disease and outcome,probably unrelated to antiviral therapy.Immunohistochemistry-CMV-positive patients with mild disease may recover without antiviral therapy.

Antiviral therapy in cytomegalovirus-positive ulcerative colitis:A systematic review and meta-analysis

AIM:To evaluate the impact of antiviral treatment on cytomegalovirus(CMV)-positive ulcerative colitis patients.METHODS:We performed a systematic review and meta-analysis(MA)of comparative cohort and casecontrol studies published between January 1966 and March 2013.Studies focusing on colectomy series and studies including only less than 3 patients in the treated or non-treated arm were excluded.The primary outcome was colectomy within 30 d of diagnosis.Secondary outcomes included colectomy during the follow-up period Subgroup analyses by method of detection of CMV,study design,risk of bias and country of origin were performed.Quality of studies was evalu-ated according to modified New-Castle Ottawa Scale.RESULTS:After full-text review,nine studies with a total of 176 patients were included in our MA.All the included studies were of low to moderate quality.Patients who have received antiviral treatment had a higher risk of 30-d colectomy(OR=2.40;95%CI:1.05-5.50;I2=37.2%).A subgroup analysis including only patients in whom CMV diagnosis was based did not demonstrate a significant difference between the groups(OR=3.41;95%CI:0.39-29.83;I2=56.9%).Analysis of long-term colectomy rates was possible for 6 studies including110 patients.No statistically significant difference was found between the treated and untreated groups(OR=1.71;95%CI:0.71-4.13;6 studies,I2=0%).Analysis of mortality rate was not possible due to a very limited number of cases.Stratification of the outcomes by disease severity was not possible.CONCLUSION:No positive association between antiviral treatment and a favorable outcome was demonstrated.These findings should be interpreted cautiously due to primary studies’quality and potential biases.

Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis:A global survey of physicians'practice

AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.

Flare-up of ulcerative colitis after systemic corticosteroids: A strong case for Strongyloides

Super-imposed infection with intestinal organisms can mimic a flare-up of underlying disease in patients with inflammatory bowel disease (IBD). We report a case of patient with long standing ulcerative colitis (UC), who presented with abdominal pain, diarrhea and low- grade fever after receiving systemic corticosteroids for an unrelated disorder. Despite a negative stool examination, a peripheral eosinophilia reappeared upon tapering down of a corticosteroid dose. Subsequently, duodenal biopsies showed evidence for Strongyloides, presumably acquired 20 years ago when the patient was residing in Brazil. The patient fully recovered following anti-helmintic therapy. This case underscores the importance of considering Strongyloides in the work-up of flaring-up IBD patients, even if a history of residing or traveling to endemic areas is in the distant past.

Significance of low level infliximab in the absence of anti-infliximab antibodies

AIM:To evaluate the prevalence of double negative(DN)sera and the mechanisms responsible for DN status.METHODS:Sera of inflammatory bowel disease patients treated with infliximab(IFX)were tested for drug/antibodies to infliximab(ATI)trough levels and the proportion of DN results was compared between a commercially available double antigen ELISA(with labeled IFX as the detection antibody)and an antilambda ELISA(with anti-human lambda chain detection antibody).Repeat testing with lower than customary serum dilution(1:10)was performed.Patients with DN status were matched with IFX+/ATI-controls and were followed-up for subsequent development of nontransient ATI to investigate if DN status precedes ATI.RESULTS:Of 67 sera obtained at time of loss of response,only 6/67(9%)were DN by anti-lambda ELISA compared to 27/67(40%)with double antigen ELISA(P<0.001,Fisher’s Exact test).Of the latter27 sera,22%were also DN by anti-lambda ELISA,whereas 44%were actually IFX positive(IFX+ATI-),30%were ATI positive(IFX-ATI+)and 4%were double positive(IFX+ATI+).Re-testing using a 1:10 dilution converted most DN results into IFX+and/or ATI+status.Patients with DN status had shorter survival free of non-transient ATI compared with matched controls(log rank test,P<0.001).In 9/30(30%)of these patients,non transient ATI occurred before and after the event at which the DN serum was obtained,supporting the view that a DN result may represent aparticular time-point along the two curves of ATI titer rise and infliximab drug level decline.CONCLUSION:DN status may result from false negative detection of IFX or ATI by double antigen ELISA,suggesting a transitional state of low-level immunogenicity,rather than non-immunological clearance.