Kelly C. Cushing

Depression Is Associated With More Aggressive Inflammatory Bowel Disease

Objectives:Depression is prevalent in inflammatory bowel disease (IBD) patients. The impact of depression on IBD is not well-studied. It is unknown how providers should assess depression.Methods:We used data from the Sinai–Helmsley Alliance for Research Excellence cohort, to assess methods of diagnosing depression and effects of baseline depression on disease activity at follow-up. A patient health questionnaire (PHQ-8) score ≥5 was consistent with mild depression. Relapse was defined as a modified Harvey–Bradshaw Index ≥5 or Simple Clinical Colitis Activity Index >2. We performed binomial regression to calculate adjusted risk ratios (RRs).Results:We included 2,798 Crohn’s disease (CD) patients with 22-month mean follow-up and 1,516 ulcerative colitis (UC) patients with 24-month mean follow-up. A total of 64% of CD patients and 45% of UC patients were in remission at baseline. By self-report, 20% of CD and 14% of UC patients were depressed. By PHQ-8, 38% of CD and 32% of UC patients were depressed (P<0.01). Adjusted for sex, remission, and disease activity, CD patients with baseline depression were at an increased risk for relapse (RR: 2.3; 95% confidence interval (CI): 1.9–2.8), surgery, or hospitalization (RR: 1.3 95% CI: 1.1–1.6) at follow-up. UC patients with baseline depression were also at increased risk for relapse (RR: 1.3; 95% CI: 0.9–1.7), surgery, or hospitalization (RR: 1.3; 95% CI: 1.1–1.5) at follow-up.Conclusions:Baseline depression is associated with a higher risk for aggressive IBD at follow-up. A single question is not a sensitive method of assessing depression. Providers should consider administering the PHQ-8 to capture those at greater risk for aggressive disease.

Vedolizumab as a Novel Treatment for Refractory Collagenous Colitis: A Case Report

time of her initial evaluation. Th e decision was made to discontinue Uceris and begin a 3-month taper of standard formulation budesonide (Entocort EC). She did not experience symptom relief at the starting dose of 9 mg budesonide daily. Infectious workup, with stool culture and Clostridium diffi cile studies, was negative. Th e budesonide dose was increased to 12 mg daily without signifi cant improvement in her symptoms. Colonoscopy was performed to confi rm the previous diagnosis of CC and rule out alternative etiologies of her symptoms. Th is demonstrated normal ileal and colonic mucosa with diverticulosis. Th e biopsies revealed increased lymphoplasmacytic and eosinophilic infi ltration in the lamina propria ( Figure 1a ) and thickened subepithelial collagen table that was highlighted by a trichrome stain ( Figure 1b ) confi rming the diagnosis of CC. Prednisone 40 mg daily was initiated with good response, but she experienced relapse of her symptoms aft er tapering prednisone. A second course of prednisone was given with the addition of colestipol, which was not tolerated owing to side eff ects. Biological therapy with anti-tumor necrosis factor or vedolizumab was discussed with the patient. Given her age and preference to avoid systemic immunosupTo the Editor: Microscopic colitis is a debilitating and increasingly recognized infl ammatory bowel disorder, characterized by watery, non-bloody diarrhea with increased number of intraepithelial lymphocytes in the colon and absence of macroscopic mucosal abnormalities. Two separate entities fall within the umbrella of microscopic colitis: collagenous colitis (CC) and lymphocytic colitis (LC). In CC, there is evidence of a thickened subepithelial collagen band on mucosal biopsy. Th e incidence of CC is 4.14 per 100,000 person-years with an increased risk among older females ( 1 ). Treatment options include antidiarrheal medications such as cholestyramine, bismuth or loperamide and systemic corticosteroid medications, such as budesonide. Immunomodulators and anti-tumor necrosis factor therapy have been used in the treatment of refractory cases ( 2 ). Here we report a case of CC successfully treated with vedolizumab. Informed consent from the patient was obtained. A 75-year-old woman with a 4-year history of CC presented to our center with persistent symptoms of watery diarrhea and abdominal cramping. She had previously been treated with oral budesonide and was on an extended release form (Uceris) at the in immuncompromised patients, especially if the patient has a history of other Parvovirus B19-related infections including PRCA.

Response to Dai et al. and Gracie et al.

To the Editor: Dai et al. [1] make an important point about the association between steroids and mood. Only 11% of our Crohn’s cohort and 17% of our ulcerative colitis cohort were on steroids at baseline. After eliminating the 300 subjects who were on steroids at baseline, the point estimates for the adjusted risk ratios for worsening disease at follow-up (worsening disease activity index, relapse by disease activity index, new biologic prescription, new steroid prescription, hospitalization, and surgery) did not change dramatically. Therefore, our original conclusions are still valid. As we note in the study limitations, this large prospective cohort of IBD patients across the United States did not collect information on psychiatric treatment. Therefore, the association between depression at baseline and more aggressive inflammatory bowel disease at follow-up should be investigated in a prospective manner. Gracie and Ford [2] point out that we did not base disease activity on serologic data. Serological markers are used to measure inflammation. Clinical disease activity indices, on the other hand, are widely accepted standard of measuring symptomatic disease activity for research purposes [3–6]. Importantly, in our analyses, clinical disease activity indices were not the sole determinant of disease activity. We also use new biologic or steroid prescriptions, as well as new hospitalizations or surgeries since baseline. These are objective measures of more aggressive disease at follow-up.

Response to Levenstein and Prantera

To The Editor: Levenstein and Prantera point out correctly that we do not establish causation in this study of depression in inflammatory bowel disease (IBD) patients [1, 2]. We certainly acknowledge that this is an association study. However, in our discussion we described a range of biologically and instrumentally plausible explanations for the association we observed, that of depression being associated with a worsening of disease over time. They also raise the question of whether stricter definitions of remission should have been used. At their suggestion, we re-defined remission using their proposed criteria for remission and repeated our analyses. The adjusted risk ratios had similar point estimates, but wider confidence intervals, as expected. Using a stricter definition of remission did not change our conclusions.

Smoking Interacts With CHRNA5, a Nicotinic Acetylcholine Receptor Subunit Gene, to Influence the Risk of IBD-Related Surgery

Abstract Background Inflammatory bowel disease (IBD) is a chronic luminal disease with genetic and environmental factors affecting phenotype. This study evaluated the relationship between CHRNA5, a nicotinic receptor subunit gene, and smoking in predicting IBD-related surgery as well as the relationship between CHRNA5 and nicotine dependence. Methods Participants completed a smoking questionnaire and were genotyped for CHRNA5 rs16969968. Demographic and clinical data were obtained from medical records. Wilcoxon, ANOVA, Chi square, and Fisher’s exact tests were used for comparisons. Logistic regression was used to evaluate the effect of clinical and genetic predictors on surgery, stratified by disease subtype given paradoxical effects of smoking. Kaplan-Meier curves were used to examine the effect of smoking and genotype on time to surgery. (Significance: P < 0.05 for main effects; P < 0.2 for interaction terms) Results 400 (65.8%) patients had Crohn’s disease (CD) and 208 (34.2%) had ulcerative colitis (UC). 298 (49%) underwent an IBD-related surgery. There was a trend towards significance between rs16969968 and smoking behavior (smoking status [P = 0.05], nicotine dependence [AA > AG > GG; P = 0.08]). Smoking and genotype were not independently associated with surgery in UC or CD. However, interaction between rs16969968 and smoking in predicting surgery was observed for both UC (OR = 2.72; P = 0.05) and CD (OR = 2.88; P = 0.1). CHRNA5 genotype, but not smoking, predicted time to surgery in patients with UC (P = 0.007) but not in patients with CD. The interaction between smoking and genotype was not significantly associated with time to surgery in UC or CD. Conclusions The CHRNA5 rs16969968 A variant interacts with smoking to influence IBD-related surgery.

Smoking Interacts with CHRNA5, a Nicotine Acetylcholine Receptor Subunit Gene, to Influence the Risk of IBD Related Surgery

Background Inflammatory bowel disease (IBD) is a chronic luminal disease with genetic and environmental factors affecting phenotype. This study evaluated the relationship between CHRNA5, a nicotinic receptor subunit gene, and smoking in predicting IBD-related surgery as well as the relationship between CHRNA5 and nicotine dependence. Methods Participants completed a smoking questionnaire and were genotyped for CHRNA5 rs16969968. Demographic and clinical data were obtained from medical records. Wilcoxon, ANOVA, Chi square, and Fishers exact tests were used for comparisons. Logistic regression was used to evaluate the effect of clinical and genetic predictors on surgery, stratified by disease subtype given paradoxical effects of smoking. Kaplan-Meier curves were used to examine the effect of smoking and genotype on time to surgery. (Significance: P AG > GG; P = 0.08]). Smoking and genotype were not independently associated with surgery in UC or CD. However, interaction between rs16969968 and smoking in predicting surgery was observed for both UC (OR = 2.72; P = 0.05) and CD (OR = 2.88; P = 0.1). CHRNA5 genotype, but not smoking, predicted time to surgery in patients with UC (P = 0.007) but not in patients with CD. The interaction between smoking and genotype was not significantly associated with time to surgery in UC or CD. Conclusions The CHRNA5 rs16969968 A variant interacts with smoking to influence IBD-related surgery. 10.1093/ibd/izx094_video1izx094.video15775248538001.