Jeanne Emmons

Infliximab retreatment in adults and children with Crohn's disease: risk factors for the development of delayed severe systemic reaction.

Infliximab retreatment in adults and children with Crohns disease: risk factors for the development of delayed severe systemic reaction

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.

Intestinal strictures complicating initially successful infliximab treatment for luminal Crohn’s disease

Intestinal strictures complicating initially successful infliximab treatment for luminal Crohns disease

Terminal ileum resection is associated with higher plasma homocysteine levels in Crohn's disease.

Background Elevated plasma total homocysteine (tHcy) is associated with a higher risk of thrombosis. Crohns disease (CD) is associated with hypercoagulability of undefined etiology. We investigated tHcy in patients with CD and its relationship with vitamin status, disease activity, location, duration, and history of terminal ileum (TI) resection. Study We examined fasting plasma tHcy, folate, serum vitamin B 12 levels, and sedimentation rate in consecutive adult patients with CD. Harvey–Bradshaw index of CD activity and history of TI resection and thromboembolism were recorded. Results Median plasma tHcy was 10.2 &mgr;mol/L in 125 patients with CD. Men (n = 60) had higher plasma tHcy than women (n = 65) (11.2 vs. 9.1 &mgr;mol/L;p = 0.004). Patients with a history of TI resection showed lower serum B 12 levels (293 vs. 503 pg/mL;p < 0.001) and higher plasma tHcy levels (11.0 vs. 9.35 &mgr;mol/L;p = 0.027) than patients without such history. Multivariate analysis showed history of TI resection, serum B 12 , and creatinine levels to be significant predictors of elevated plasma tHcy. Fourteen patients with CD with a history of thrombosis had an elevated median plasma tHcy of 11.6 &mgr;mol/L. Conclusions Terminal ileum resection contributes to elevated plasma tHcy levels in CD cases. We recommend tHcy screening in patients with CD, especially in those with prior history of TI resection, and the initiation of vitamin supplementation when appropriate.

Leflunomide treatment of Crohn's disease patients intolerant to standard immunomodulator therapy.

Background Immunomodulator therapy with the purine analogs azathioprine and 6-mercaptopurine (6-MP), is efficacious in the treatment of moderate to severe Crohns disease (CD), but is not tolerated by a significant minority of patients. The pyrimidine analog, leflunomide, has demonstrated efficacy in the treatment of rheumatoid arthritis (RA) patients. Because established RA immunomodulator agents may demonstrate success in the treatment of CD, we reviewed our clinical open-label experience with leflunomide in a refractory CD population. Goals Assess the effect of leflunomide 20 mg daily, on disease activity, steroid requirement and serologic measures of inflammatory activity in our series of CD patients intolerant to azathioprine/6-MP. Study CD patients intolerant of azathioprine/6-MP were offered leflunomide treatment. The Harvey-Bradshaw (H-B) disease activity index, global assessment, serologic parameters and ability to taper corticosteroids of those who accepted were retrospectively assessed. Results Leflunomide was well tolerated and resulted in a significant reduction in the H-B score, global assessment and serologic parameters in 8/12 patients. Average follow-up was 38 weeks and a majority of steroid-dependent patients were able to successfully taper following leflunomide initiation. Conclusions Our case series demonstrates that the pyrimidine analog leflunomide may be effective for treating moderate to severe CD patients intolerant to standard immunomodulator therapy and warrants further investigation in a randomized controlled trial.

Successful treatment of an acute flare of steroid-resistant Crohn's colitis during pregnancy with unfractionated heparin.

Recent reports suggest that unfractionated heparin may be a useful adjunct in the treatment of inflammatory bowel disease (IBD). We report the successful use of subcutaneous unfractionated heparin to treat a moderate-to-severe flare of Crohns disease during pregnancy, which was refractory to standard therapy. The patient received 10,000 units of unfractionated heparin subcutaneously twice a day after her Crohns colitis failed to come under remission with intravenous corticosteroids. Heparin was continued throughout her pregnancy. Following initiation of adjunctive heparin therapy, the patient experienced a rapid clinical response, was able to discontinue intravenous steroids, discharge from the hospital, and ultimately deliver a healthy term newborn. Although there is extensive obstetric experience with heparin in the treatment of thrombosis associated with pregnancy, there is limited information regarding its use in IBD patients during pregnancy. Because heparin has an established track record in maternal-fetal medicine, this agent may be considered in women who suffer an inflammatory flare of IBD during pregnancy who have not responded to standard treatment.

Increased rates of drug allergy in inflammatory bowel disease (IBD) patients compared to irritable bowel syndrome (IBS) patients and normal controls

Background and Aims: Drug allergy (rash, angioedema, anaphylactic, anaphylactoid reactions) is a frequently encountered clinical problem, and published reports suggest that it is present in up to 20% of hospitalized patients. The rate of drug allergy among patients with 1BD (Crohns disease (CD), ulcerative colitis (UC)) has not been previously described. We hypothesized that adult patients with chronic gut inflammation would have increased rates of drug allergy compared to controls. Methods: Retrospective observational analysis was performed on all 1BD patients followed at a tertiary referral center. All intake visits were reviewed for histories of drug allergy, defined as emergence of rash, angnoedema, anaphytactic/ anaphylactoid reaction following challenge with the offending agent. Demographic information regarding patients as well as classes of agents inducing allergic reactions were recorded, as was the duration of the IBD. Controls included patients with irritable bowel syndrome as well as healthy volunteers without clinical evidence of gastrointestinal disease. Results: Records of 410 IBD patients (297 CD, 107 UC, 6 indeterminate colitis) were reviewed, as weft as 230 control patients (IBS 50, normal 180). 33.2% of IBD patients and 19% of controls demonstrated drug allergy ( p = < 0.001 Chi-square). There was no difference between the prevalence of drug allergy between CD and UC patients. The duration of disease did not impact on the prevalence of drug allergy. There were significantly more female IBD patients with drug allergy when compared to males (36% vs. 25%; p = < 0 . 0 3 ) which corresponded with an increased rate of drug allergy noted in the female control population. The classes of drugs associated with allergic reactions in IBD patients included penicillin (13.9%), sulfa (8.3%), narcotics (7.1%). The prevalence of antibiotic allergy in the IBD patients was 22% compared with 11% of controls (p = <O.001). Conclusions: The prevalence of drag allergy is significantly higher in patients with IBD compared to patients with IBS or healthy volunteers. Female IBD patients have a higher prevalence of allergic reactions compared to males, but there is no difference in the prevalence of the reactions between UC and CD Drug allergnc IBD patients are a commonly encountered phenotype which pose added clinical challenges in management.

Remediable underlying factors associated with steroid dependency in Crohn's disease (CD)

Purpose: Although corticosteroids are highly effective in the treatment of CD intestinal inflammation, these medications are associated with frequent short and long term adverse reactions. CD pts with steroid dependency are considered to have refractory disease that is difficult to treat. In addition, steroid dependency is often used to define a subset of CD pts that is frequently targeted for clinical trials. We investigated steroid dependent CD pts refered to a tertiary center for underlying remediable factors.