Mazen Issa

Clostridium difficile and inflammatory bowel disease.

Clostridium difficile colitis has doubled in North America over the past 5 years and recent reports have demonstrated an increase in incidence and severity of these infections in patients with inflammatory bowel disease (IBD; Crohns disease, ulcerative colitis). Studies from single institutions as well as trends identified in nationwide inpatient databases have shown that IBD patients with concomitant C. difficile infection experience increased morbidity and mortality. Results from our center have shown that over half of C. difficile-infected IBD patients will require hospitalization and the colectomy rate may approach 20%. Because C. difficile colitis will both mimic and precipitate an IBD flare, it is essential that clinicians be vigilant to identify and address this infectious complication, as empiric treatment with corticosteroids without appropriate antibiotics may precipitate deterioration. The majority of IBD patients appear to contract C. difficile as outpatients, and a prior history of colitis appears to be the most significant risk factor for acquiring this infection. In addition to C. difficile colitis, IBD patients are now known to be at risk for C. difficile enteritis as well as infections in reconstructed ileoanal pouches. An additional challenge facing C. difficile infections in IBD patients is the decreased efficacy of metronidazole, and the need for oral vancomycin in patients requiring hospitalization. In this review we summarize the present knowledge regarding C. difficile infection in the setting of IBD, including unique clinical scenarios facing IBD patients, diagnostic algorithms, and treatment approaches.

Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life.

BACKGROUND Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aim of the study was to determine the prevalence and predictors of vitamin D deficiency in an IBD cohort. It was hypothesized that vitamin D deficiency is associated with increased disease activity and lower health-related quality of life (HRQOL). METHODS This was a retrospective cohort study. Harvey-Bradshaw index and ulcerative colitis disease activity index were used to assess disease activity. Short Inflammatory Bowel Disease Questionnaire scores were used to assess HRQOL. Multivariate logistic regression was used to identify independent predictors of vitamin D deficiency and its association with disease activity and HRQOL. RESULTS The study included 504 IBD patients (403 Crohns disease [CD] and 101 ulcerative colitis [UC]) who had a mean disease duration of 15.5 years in CD patients and 10.9 years in UC patients; 49.8% were vitamin D deficient, with 10.9% having severe deficiency. Vitamin D deficiency was associated with older age (P = .004) and older age at diagnosis (P = .03). Vitamin D deficiency was associated with lower HRQOL (regression coefficient -2.21, 95% confidence interval [CI], -4.10 to -0.33) in CD but not UC (regression coefficient 0.41, 95% CI, -2.91 to 3.73). Vitamin D deficiency was also associated with increased disease activity in CD (regression coefficient 1.07, 95% CI, 0.43 to 1.71). CONCLUSIONS Vitamin D deficiency is common in IBD and is independently associated with lower HRQOL and greater disease activity in CD. There is a need for prospective studies to assess this correlation and examine the impact of vitamin D supplementation on disease course.

Budesonide induction and maintenance therapy for Crohn's disease during pregnancy

Background: There is no standard approach for the medical management of Crohns disease (CD) during pregnancy and there is limited data regarding safety and efficacy of the treatments. Budesonide (Entocort® EC, AstraZeneca) is an enteric coated locally acting glucocorticoid preparation whose pH‐ and time‐dependent coating enables its release into the ileum and ascending colon for the treatment of mild to moderate Crohns disease. There is no available data on the safety of using oral budesonide in pregnant patients. Methods: We reviewed our Inflammatory Bowel Disease (IBD) center database to identify patients with CD who received treatment with budesonide for induction and/or maintenance of remission during pregnancy and describe the maternal and fetal outcomes in a series of eight mothers and their babies. Results: The mean age of the patients was 27.7 years. All patients had small bowel involvement with their CD. The disease pattern was stricturing in 6 patients, fistulizing in 1 and inflammatory in 1 patient. Budesonide was used at the 6 mg/day dose in 6 patients and 9 mg/day dose in 2 patients. The average treatment duration ranges from 1‐8 months. There were no cases of maternal adrenal suppression, glucose intolerance, ocular side effects, hypertension or fetal congenital abnormalities. Conclusion: Budesonide may be a safe option for treatment of CD during pregnancy.

Permanent Work Disability in Crohn's Disease

OBJECTIVE:Crohns disease (CD) frequently presents during early adulthood, a peak time of work productivity. There are limited data from the United States on work disability from CD. We performed this study to identify clinical factors associated with permanent work disability in a CD tertiary referral cohort.METHODS:Cases were identified as patients who received permanent work disability compensation from the social security administration (SSA) related to CD. Four control patients who were not receiving work disability were selected for each case. Multivariate logistic regression was performed to identify characteristics that were independently associated with work disability.RESULTS:A total of 737 patients with CD were seen in our center, and 185 CD patients were included in our study (37 disability cases, 148 controls). On multivariate analysis, an SIBDQ score ≤50 (OR 12.44, 95% CI 4.45–34.79), undergoing two or more GI surgeries (OR 7.09, 95% CI 2.63–19.11), and two or more medical hospitalizations (OR 2.76, 95% CI 1.03–7.37) were significantly associated with work disability in CD. Disease location (small bowel vs colon), type (inflammatory, stricturing, or fistulizing), or specific treatment strategies were not associated with work disability in our analysis.CONCLUSION:Permanent work disability administered through social security was encountered in 5.3% of the Crohns patients followed in our cohort. Patients who consistently report low quality of life, or have frequent flares requiring surgical intervention or hospitalization for medical management, may be at risk for CD-related work disability.

History of Medical Hospitalization Predicts Future Need for Colectomy in Patients with Ulcerative Colitis

Background: Patients who require hospitalization for the management of ulcerative colitis (UC) may represent a subset with severe disease. These patients may be more likely to require future colectomy. There are limited data examining whether medical hospitalization is predictive of subsequent colectomy. Methods: This was a retrospective case–control study utilizing the inflammatory bowel disease center database at our academic referral center. Cases comprised UC patients who underwent colectomy for disease refractory to medical management. The control population was comprised of all patients with UC who had not undergone colectomy. Multivariate logistic regression was used to identify independent predictors of requiring colectomy. Results: There were a total of 246 UC patients included in our study, with 103 being hospitalized sometime in their disease course (41.9%). A total of 27 patients underwent colectomy (11%). Colectomy patients were significantly more likely to have been on infliximab therapy (51.8% versus 22.4%, P = 0.001) but no more likely to have been on immunomodulator therapy (74.1% versus 59.4%, P = 0.14). Patients who required medical hospitalization for UC were more likely to require future colectomy (20.4% versus 4.2%, P < 0.001) than those who had not required hospitalization. On multivariate analysis, requiring medical hospitalization for management of UC (odds ratio [OR] 5.37, 95% confidence interval [CI] 2.00–14.46) and ever requiring infliximab therapy (OR 3.12, 95% CI 1.21–8.07) were independent predictors of colectomy. Conclusions: Requiring medical hospitalization for the management of disease activity in UC is an independent predictor of the need for colectomy. Future studies will determine whether aggressive medical management may modify the need for colectomy in this cohort.

QuantiFERON TB gold testing for tuberculosis screening in an inflammatory bowel disease cohort in the United States.

Background: Reactivation of latent Mycobacterium tuberculosis (TB) is a rare, yet devastating infectious complication associated with anti‐tumor necrosis factor alpha (TNF‐&agr;) therapy. We evaluated the performance of the QuantiFERON TB Gold test (QFT‐G) for TB screening in a cohort of inflammatory bowel disease (IBD) patients in the United States. Methods: We performed a retrospective, observational study of patients initiated and/or maintained on an anti‐TNF‐&agr; agent in a single IBD referral center and recorded the frequency and the test results of QFT‐G testing and the rate of TB reactivation. Results: 512 QFT‐G tests were done in 340 patients. Five patients (1.5%) had a positive, nine (2.7%) indeterminate, and 326 patients (95.8%) had a negative QFT‐G. After a mean follow‐up of 17 months there was one case of TB reactivation (0.3%). The use of immunosuppressive therapy or anti‐TNF therapy at the time of testing did not affect the results of the QFT‐G testing. Test–retest had substantial concordance (&kgr; = 0.72). 25% of patients (n = 85) had TST testing. Concordance between the TST and QFT‐G was found to be moderate (&kgr; = 0.4152, P = 0.0041). Conclusions: Most patients with negative QFT‐G tolerated anti‐TNF therapy with no evidence of TB reactivation. Concomitant use of immunosuppressive therapy or anti‐TNF did not seem to affect QFT‐G results. One patient had an indeterminate QFT‐G while on infliximab and later developed miliary TB. Concordance with TST is moderate. (Inflamm Bowel Dis 2011;)

Clostridium Difficile and Inflammatory Bowel Disease

The past decade has seen an alarming increase in the burden of disease associated with Clostridium difficile. Several studies have now demonstrated an increasing incidence of C difficile infection in patients with inflammatory bowel disease (IBD) with a more severe course of disease compared with the non-IBD population. This article summarizes the available literature on the impact of C difficile infection on IBD and discusses the various diagnostic testing and treatment options available. Also reviewed are clinical situations specific to patients with IBD that are important for the treating physician to recognize.

Impact of Autonomic Dysfunction on Inflammatory Bowel Disease

Functional symptoms are common in patients with inflammatory bowel disease (IBD). The autonomic nervous system has been proposed to be involved in the pathogenesis of IBD. Autonomic dysfunction (AD) is associated with systemic manifestations and altered gut motility that may contributed to functional symptoms. Aim To examine the impact of clinically manifest AD on patients with IBD. Methods This was a retrospective case-control study from a single tertiary referral IBD center. The cases comprised 43 IBD patients with AD diagnosed using a standardized battery of tests. Three disease-matched controls were selected for each case. We performed multivariate regression to compare health-related quality of life (SIBDQ), disease activity scores, and healthcare utilization. Results Female sex (83.7% vs. 53.5%, P<0.001) and psychiatric comorbidity (41.9% vs. 10.9%, P<0.001) were more common among IBD patients with AD than IBD controls. Small bowel transit times were significantly longer in cases (92.7 min) compared with controls (62.9 min, P=0.02). On multivariate analysis, AD was associated with a 7-point lower adjusted SIBDQ score compared with IBD controls [odds ratio (OR)−7.50; 95% confidence interval (CI), −12.0-−3.03]. AD was also significantly associated with having more than 3 annual gastroenterology office visits (OR 2.84; 95% CI, 1.09-7.35), and 1 or more IBD-related medical hospitalizations (OR 2.49; 95% CI, 1.09-5.71). Conclusions Clinically manifest AD is associated with lower quality of life and higher healthcare utilization in IBD patients. They may represent a cohort at risk for worse outcomes.

Durability of Infliximab in Crohn's Disease: A Single-Center Experience

Background: Infliximab is effective maintenance for moderate to severe Crohns disease (CD); however, problems with immunogenicity and decreased efficacy often complicate long‐term use. Durability of infliximab maintenance therapy over multiple years has not been defined. Methods: This was a retrospective, observational study of CD patients who received maintenance infliximab for ≥1 year with the intention of ongoing maintenance. Patients were categorized into those who either discontinued treatment or continued maintenance therapy. We examined the impact of demographic, clinical characteristics, and prior episodic exposure on long‐term durability of infliximab therapy and also examined the reasons for discontinuation of therapy. Results: A total of 153 CD patients received maintenance infliximab treatment beyond 1 year and 42 (27%) ultimately discontinued treatment. The mean duration of maintenance treatment at the time of discontinuation was 42.4 ± 19.1 months compared to a follow‐up period of 49.4 ± 19.8 months in the cohort continuing therapy (P = 0.049). The main reasons for discontinuation were allergy/adverse reaction (44.2%) and decreased efficacy (38.2%). Use of concomitant immunosuppression was similar between the 2 groups (78.6% versus 83.8%, P = NS). However, the discontinued group had a higher rate of prior episodic dosing compared to CD patients who continued maintenance (28.8% versus 11.7%, P = 0.025), while there was no difference in the rate of intensified dosing (57.2% versus 50.5%, P = NS). Conclusions: One‐quarter of CD patients on long‐term infliximab maintenance discontinued treatment. A history of prior episodic dosing was significantly associated with infliximab discontinuation, despite concomitant immunosuppression. These data emphasize the need for optimization of infliximab for successful long‐term management. Inflamm Bowel Dis 2009

Diet in Inflammatory Bowel Disease

The past few years have seen a great expansion of our understanding of the pathophysiology of inflammatory bowel disease (IBD). Much of the progress has been on the genetic basis of disease as well as the role of microbiota. These findings have magnified the role of the environmental component of this rather complex process. Recent advances have emanated from more in-depth, comprehensive, and at times nontraditional inquiry into the potential role of diet through its anti-inflammatory properties and modulation of microbiota. This concise review focuses on the novel aspects of research related to the potential role of diet in IBD.