Venous thrombosis and prothrombotic factors in inflammatory bowel disease

Patients with inflammatory bowel disease(IBD)may have an increased risk of venous thrombosis(VTE).PubMed,ISI Web of Knowledge and Scopus were searched to identify studies investigating the risk of VTE and the prevalence of acquired and genetic VTE risk factors and prothrombotic abnormalities in IBD.Overall,IBD patients have a two-to fourfold increased risk of VTE compared with healthy controls,with an overall incidence rate of 1%-8%.The majority of studies did not show significant differences in the risk of VTE between Crohn’s disease and ulcerative colitis.Several acquired factors are responsible for the increased risk of VTEin IBD:inflammatory activity,hospitalisation,surgery,pregnancy,disease phenotype(e.g.,fistulising disease,colonic involvement and extensive involvement)and drug therapy(mainly steroids).There is also convincing evidence from basic science and from clinical and epidemiological studies that IBD is associated with several prothrombotic abnormalities,including initiation of the coagulation system,downregulation of natural anticoagulant mechanisms,impairment of fibrinolysis,increased platelet count and reactivity and dysfunction of the endothelium.Classical genetic alterations are not generally found more often in IBD patients than in nonIBD patients,suggesting that genetics does not explain the greater risk of VTE in these patients.IBD VTE may have clinical specificities,namely an earlier first episode of VTE in life,high recurrence rate,decreased efficacy of some drugs in preventing further episodes and poor prognosis.Clinicians should be aware of these risks,and adequate prophylactic actions should be taken in patients who have disease activity,are hospitalised,are submitted to surgery or are undergoing treatment.

Nocardia infections among immunomodulated inflammatory bowel disease patients:A review

Human nocardiosis,caused by Nocardia spp.,an ubiquitous soil-borne bacteria,is a rare granulomatous disease close related to immune dysfunctions.Clinically can occur as an acute life-threatening disease,with lung,brain and skin being commonly affected.The infection was classically diagnosed in HIV infected persons,organ transplanted recipients and long term corticosteroid treated patients.Currently the widespread use of immunomodulators and immunossupressors in the treatment of inflammatory diseases changed this scenario.Our purpose is to review all published cases of nocardiosis in immunomodulated patients due to inflammatory diseases and describe clinical and laboratory findings.We reviewed the literature concerning human cases of nocardiosis published between 1980 and 2014 in peer reviewed journals.Eleven cases of nocardiosis associated with anti-tumor necrosis factor(TNF) prescription(9 related with infliximab and 2 with adalimumab) were identified; 7 patients had inflammatory bowel disease(IBD),4 had rheumatological conditions; nocardia infection presented as cutaneous involvement in 3 patients,lung disease in 4 patients,hepatic in one and disseminated disease in 3 patients.From the 10 cases described in IBD patients 7 were associated with anti-TNF and 3 with steroids and azathioprine.In conclusion,nocardiosis requires high levels of clinical suspicion and experience of laboratory staff,in order to establish a timely diagnosis and by doing so avoid worst outcomes.Treatment for long periods tailored by the susceptibility of the isolated species whenever possible is essential.The safety of restarting immunomodulators or anti-TNF after the disease or the value of prophylaxis with cotrimoxazole is still debated.

Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy:A single center report of 8 cases

This article describes cases of anti-tumor necrosis factor(TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis(AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.

Clinical prognostic factors for disabling Crohn's disease: A systematic review and meta-analysis

AIM: To identify demographic and clinical factors asso-ciated with disabling Crohn's disease (CD). METHODS: A systematic review and meta-analysisof observational studies, focusing on the factors that can predict the prognosis of different outcomes of CD was undertaken. PubMed, ISI Web of Knowledge and Scopus were searched to identify studies investigat-ing the above mentioned factors in adult patients with CD. Studies were eligible for inclusion if they describe prognostic factors in CD, with inclusion and exclusion criteria defined as follows. Studies with adult patients and CD, written in English and studying association between clinical factors and at least one prognosis out-come were included. Meta-analysis of effects was un-dertaken for the disabling disease outcome, using odds ratio (OR) to assess the effect of the different factors in the outcome. The statistical method used was Mantel-Haenszel for fixed effects. The 16-item quality assess-ment tool (QATSDD) was used to assess the quality of the studies (range: 0-42). RESULTS: Of the 913 papers initially selected, sixty studies were reviewed and three were included in the systematic review and meta-analysis. The global QA-TSDD scores of papers were 18, 21 and 22. Of a total of 1961 patients enrolled, 1332 (78%) were classified with disabling disease five years after diagnosis. In two studies, age at diagnosis was a factor associated with disabling disease five years after diagnosis. Individu-als under 40 years old had a higher risk of developing disabling disease. In two studies, patients who were treated with corticosteroids on the first flare developed disabling disease five years after diagnosis. Further, perianal disease was found to be relevant in all of the studies at two and five years after diagnosis. Finally, one study showed localization as a factor associated with disabling disease five years after diagnosis, with L3 being a higher risk factor. This meta-analysis showed a significantly higher risk of developing disabling dis-ease at five years after initial diagnosis among patients younger than 40 years of age (OR=2.47, 95%CI: 1.74-3.51), with initial steroid treatment for first flare (OR=2.42, 95%CI: 1.87-3.11) and with perianal dis-ease (OR = 2.00, 95%CI: 1.41-2.85).CONCLUSION: Age at diagnosis, perianal disease, ini-tial use of steroids and localization seem to be indepen-dent prognostic factors of disabling disease.

Fecal marker levels as predictors of need for endoscopic balloon dilation in Crohn's disease patients with anastomotic strictures

AIM To evaluate the accuracy and best cut-off value of fecal calprotectin(FC) and fecal lactoferrin(FL) to predict disease recurrence in asymptomatic patients presenting with anastomotic strictures. METHODS This was a longitudinal single tertiary center study based on prospectively collected data(recorded in a clinical database created for this purpose) performed between March 2010 and November 2014. Crohn's disease(CD) patients with anastomotic stricture who submitted to postoperative endoscopic evaluation were included. Stools were collected on the day before bowel cleaning for FC and FL. Endoscopic balloon dilation(EBD) was performed if the patient presented an anastomotic stricture not traversed by the colonoscope, regardless of patients' symptoms. Successful dilation was defined as passage of the colonoscope through the dilated stricture into the neotermimal ileum.Postoperative recurrence was defined as a modified Rutgeerts score of ≥ i2 b. RESULTS In a total of 178 patients who underwent colonoscopy, 58 presented an anastomotic stricture, 86% were asymptomatic, and 48(54% male; median age of 46.5 years) were successfully dilated. Immediate success rate was 92% and no complications were recorded. FC and FL levels correlated significantly with endoscopic recurrence(P < 0.001) with an optimal cut-off value of 90.85 μg/g(sensitivity of 95.5%, specificity of 69.2%, positive predictive value(PPV) of 72.4%, negative predictive value(NPV) of 94.7% and accuracy of 81%] for FC and of 5.6 μg/g(sensitivity of 77.3%, specificity of 69.2%, PPV of 68%, NPV of 78.4% and accuracy of 72.9%) for FL.CONCLUSION Fecal markers are good predictors of CD endoscopic recurrence in patients with asymptomatic anastomotic stricture. FC and FL may guide the need for EBD in this context.

Endoscopic balloon dilation of crohn's disease stricturessafety,efficacy and clinical impact

AIM To evaluate the incidence of anastomotic strictures after intestinal resection in Crohn's disease(CD), demonstrate long-term efficacy and safety of endoscopic balloon dilation(EBD) in CD strictures and its impact on the diagnosis of subclinical postoperative endoscopic recurrence. METHODS Retrospective single tertiary center study based on prospectively collected data between 2010 and 2015including anastomotic and non-anastomotic strictures. RESULTS29% of 162 CD patients included developed an anastomotic stricture. 43 patients with anastomotic strictures and 37 with non-anastomotic strictures underwent EBD; technical success was 97.7% and 100%, respectively, however, 63% and 41% needed repeat dilation during the 4.4-year follow-up. Longer periods between surgery and index colonoscopy and higher lactoferrin levels were associated with the presence of stricture after surgery. Calprotectin levels > 83.35 μg/g and current or past history of smoking were associated with a shorter time until need for dilation(HR = 3.877, 95%CI: 1.480-10.152 and HR = 3.041, 95%CI: 1.213-7.627). Anastomotic strictures had a greater need for repeat dilation(63% vs 41%, P = 0.047). No differences were found between asymptomatic and symptomatic cohorts. Disease recurrence diagnosis was only possible after EBD in a third of patients. CONCLUSION EBD is an effective and safe alternative to surgery, with a good short and long-term outcome, postponing or even avoiding further surgery. EBD may allow to diagnose disease recurrence in patients with no clinical signs/biomarkers of disease activity.