Impact of autonomic dysfunction on inflammatory bowel disease.

UNLABELLED: 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.

Bowel rest and nutrition therapy in the management of active Crohn's disease.

Nutrition and Crohn's disease (CD) are intertwined because of the central role of nutrition in the care of patients with CD, specifically the theories regarding a dietary contribution to pathogenesis and formal studies investigating the primary role of nutrition as therapy for CD. Perhaps one of the most important studies evaluating the role of nutrition therapy and bowel rest in the management of CD was performed by Greenberg and colleagues in 1988. This pivotal study attempted to define the role of bowel rest as an independent variable in the management of hospitalized patients with active CD unresponsive to the traditional medical therapy that was available at the time. As the first randomized controlled trial evaluating nutrition intervention in CD, it showed that bowel rest was not a major factor in achieving remission during nutrition support and did not affect outcome during 1-year follow-up. Although these discouraging findings would be subsequently replicated, the role of enteral and parenteral nutrition therapy would evolve during the following years as a result of insight into CD pathogenesis, the emergence of more effective medical therapies, and improved understanding of the role of nutrition in the care of patients with CD.

Impact of Clostridium difficile on inflammatory bowel disease.

BACKGROUND & AIMS: Clostridium difficile-associated disease has increased significantly in North American medical centers. The impact of C difficile on patients with IBD (Crohn's disease, ulcerative colitis) at the present time is unknown. METHODS: A retrospective, observational study evaluating IBD patients followed in a referral center to evaluate the impact of C difficile was performed. Diagnosis was confirmed with stool toxin analysis. Demographic information, diagnosis, anatomic location, IBD therapy, antibiotic exposure, hospitalizations, and surgeries were recorded. Available endoscopic and histologic data were evaluated. RESULTS: Rate of C difficile infection increased from 1.8% of IBD patients in 2004 to 4.6% in 2005 (P < .01). Proportion of IBD patients within the total number of C difficile infections at our institution increased from 7% in 2004 to 16% in 2005 (P < .01). IBD colonic involvement was found in the majority of C difficile-infected patients in 2005 (91%), and the majority contracted infection as an outpatient (76%). Antibiotic exposure was identified in 61% of IBD patients with C difficile infection in 2005. Pseudomembranes and fibrinopurulent eruptions were not seen endoscopically or histologically. During 2004-2005 more than half of the infected IBD patients required hospitalization, and 20% required colectomy. Univariate and multivariate analysis identified maintenance immunomodulator use and colonic involvement as independent risk factors for C difficile infection in IBD. CONCLUSIONS: C difficile infection has increased significantly in IBD patients and negatively impacts clinical outcome. Increased vigilance regarding this infection in IBD patients with colitis activity is warranted.

Impact of pregnancy on health-related quality of life of patients with inflammatory bowel disease.

OBJECTIVE: To examine the impact of pregnancy on health-related quality of life (HRQoL) of women with inflammatory bowel disease (IBD). METHODS: This was a retrospective study in a tertiary referral center and included women with ≥2 short inflammatory bowel disease questionnaire (SIBDQ) scores obtained during their pregnancy. Regression models were used to identify independent factors influencing SIBDQ scores and changes of SIBDQ scores at different time points. RESULTS: A total of 32 women (23 CD, 9 UC) with a mean age at pregnancy of 29.4 years and a mean disease duration of 7.8 years were included in the study. The mean pre-pregnancy SIBDQ score in our cohort was 49, which was significantly lower than the values during (55, P < 0.001) and post-pregnancy (53, P = 0.01). The score during pregnancy directly correlated with the pre-pregnancy SIBDQ score (correlation co-efficient 0.50, P = 0.003). Half of the patients had a ≥7-point increase in SIBDQ scores during pregnancy. Change in SIBDQ scores during pregnancy was inversely related to the pre-pregnancy score (-0.47, 95% CI -0.75 to -0.20) and changes in disease activity during pregnancy (-1.80, 95% CI -0.75 to -0.20). CONCLUSIONS: Half of the pregnant women with IBD in our cohort experienced improvement in their HRQoL. Pre-pregnancy HRQoL is predictive of HRQoL during pregnancy, supporting the need for optimizing disease activity prior to conception.

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.

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 Crohn's 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.

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-α) 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-α 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 (κ = 0.72). 25% of patients (n = 85) had TST testing. Concordance between the TST and QFT-G was found to be moderate (κ = 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.

Clinical course of Crohn's disease following treatment of lymphoma.

BACKGROUND: Crohn's disease (CD) patients may be at increased risk for the development of Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL), either through exposure to immunosuppressive medications or due to their underlying chronic inflammatory illness. There are limited data regarding the natural history of CD following treatment of lymphoma. We present a series of CD patients who were treated for lymphoma and describe the natural history of their CD following lymphoma treatment. METHODS: Retrospective case series from three academic referral centers was used. All CD patients with a history of lymphoma were identified. Demographic data, CD medication exposure, and surgical procedures before and after lymphoma treatment were recorded. RESULTS: Nine CD patients with a history of lymphoma were identified. Eight individuals received chemotherapy, while one patient was observed without treatment. Eight patients remained free of lymphoma for a mean of 72.8 months (range 1-276 months). The ninth patient had recurrence of his HL 3 years after lymphoma diagnosis. Following lymphoma treatment, two patients had quiescent CD with no specific therapy. Three patients demonstrated significant clinical relapse of their CD and a fourth patient developed CD after treatment of her lymphoma, which ultimately required long-term immunomodulator therapy with 6-mercaptopurine or methotrexate in the first three patients, and azathioprine in the fourth. Four patients required CD surgery after lymphoma treatment. CONCLUSION: We report on the clinical course of CD in patients who develop lymphoma. Significant clinical relapse of CD following successful medical treatment of lymphoma occurred frequently in patients with a history of this neoplasm.

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.

Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease?

BACKGROUND: Impairment of health-related quality of life (HRQoL) is an important concern in inflammatory bowel disease (IBD; ulcerative colitis [UC], Crohn's disease [CD]). Between 2%-10% of patients with IBD have primary sclerosing cholangitis (PSC). There has been limited examination of the disease-specific HRQoL in this population compared to non-PSC IBD controls. METHODS: This was a retrospective, case-control study performed at a tertiary referral center. Cases comprised 26 patients with a known diagnosis of PSC and IBD (17 UC, 9 CD). Three random controls were selected for each case after matching for IBD type, gender, age, and duration of disease. Disease-specific HRQoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Disease activity for CD was measured using the Harvey-Bradshaw index (HB) and using the UC activity index for UC. Independent predictors of HRQoL were identified. RESULTS: There was no significant difference in the age, gender distribution, or disease duration between PSC-IBD and controls. There was no difference in use of immunomodulators or biologics between the 2 groups. Mean SIBDQ score was comparable between PSC-IBD patients (54.5) and controls (54.1), both for UC and CD. Likewise, the disease activity scores were also similar (2.8 versus 3.1, P = 0.35). On multivariate analysis, higher disease activity score (-1.33, 95% confidence interval [CI] 95% CI -1.85 to -0.82) and shorter disease duration were predictive of lower HRQoL. Coexisting PSC did not influence IBD-related HRQoL. There was a higher proportion of permanent work disability in PSC-IBD (7.7%) compared to controls (0%). CONCLUSIONS: PSC does not seem to influence disease-specific HRQoL in our patients with IBD but is associated with a higher rate of work disability.

Impact of prior irregular infliximab dosing on performance of long-term infliximab maintenance therapy in Crohn's disease.

BACKGROUND: Infliximab is efficacious in the management of moderate to severe Crohn's disease (CD). There are limited data regarding performance of infliximab in patients who require reinitiation of maintenance dosing following previous irregular exposure. METHODS: This was a retrospective, observational study of CD patients treated with maintenance infliximab beyond 3 years. Maintenance infliximab infusion regimens were categorized as scheduled maintenance (SM) (maintenance infusions q < or =8 weeks after loading) or prior irregular (PI) (no loading, gap in therapy >8 weeks prior to or during maintenance therapy). We examined differences in need for medical and surgical hospitalizations as well as associated healthcare costs between the 2 groups. RESULTS: In all, 104 CD patients met criteria for 3-year maintenance infliximab treatment (SM n = 64; PI n = 40). The rates of CD-related surgeries (60.9% and 55.0%, P = not significant [N.S.]) and medical hospitalizations (35.9% and 37.5%, P = N.S.) prior to infliximab initiation was similar between the 2 groups. However, the rate of medical (26.5% versus 47.5%, P = 0.035) and surgical hospitalizations (21.8% versus 48.7%, P = 0.009) were significantly lower in the SM compared to the PI group. During the third year of treatment the excess costs per patient for the PI group compared to the SM group amounted to $11,464 in spite of both cohorts being on SM therapy. CONCLUSIONS: Patients who begin and continue an uninterrupted maintenance dosing regimen had a lower incidence of hospitalization and surgery than those who received an irregular or interrupted regimen prior to beginning an SM regimen.

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.

Durability of infliximab in Crohn's disease: a single-center experience.

BACKGROUND: Infliximab is effective maintenance for moderate to severe Crohn's 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.

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

BACKGROUND: There is no standard approach for the medical management of Crohn's 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 Crohn's 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.

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.

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; Crohn's 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.

Permanent work disability in Crohn's disease.

OBJECTIVE: Crohn's 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