Talha A. Malik

Inflammatory Bowel Disease: Historical Perspective, Epidemiology, and Risk Factors.

Inflammatory bowel disease (IBD) describes a group of closely related yet heterogeneous predominantly intestinal disease processes that are a result of an uncontrolled immune mediated inflammatory response. It is estimated that approximately one and a half million persons in North America have IBD. Pathogenesis of IBD involves an uncontrolled immune mediated inflammatory response in genetically predisposed individuals to a still unknown environmental trigger that interacts with the intestinal flora. There continues to be an enormous amount of information emanating from epidemiological studies providing expanded insight into the occurrence, distribution, determinants, and mechanisms of inflammatory bowel disease.

Autoimmune Hepatitis-Primary Sclerosing Cholangitis Overlap Syndrome Complicated by Crohn’s Disease

transhepatic cholangiography (PTC) with temporary biliary stenting was performed within a month of the new diagnosis for worsening cholestasis. Three months later, mycophenolate mofetil (Cellcept) was started for persistently increased transaminases. She finally began to respond with significant decrease in serum transaminase and alkaline phosphatase levels. After 3 years of successful management, she developed diarrhea and abdominal cramping. Colonoscopy revealed extensive patchy mucosal inflammation throughout the colon and terminal ileum. Mucosal biopsies demonstrated extensive crypt distortion, focal cryptitis, increased chronic inflammation, fibrino-inflammatory exudates and erosion establishing a diagnosis of Crohn’s disease (CD) ( fig. 1 ). Contrasted CT scan of the abdomen and pelvis revealed diffuse thickening of terminal ileum, cecum, ascending and transverse colonic wall and pericolic stranding consistent with active inflammatory bowel disease. It also demonstrated signs of liver cirrhosis (based on the increased caudate to right lobe ratio) as well as intraand extrahepatic biliary dilation ( fig. 2 a, b). Budesonide 9 mg daily was added to treat active CD and prednisone was discontinued. She remained symptomatic with continued diarrhea and further deterioraDear Sir Autoimmune hepatitis-primary sclerosing cholangitis (AIH-PSC) overlap syndrome is characterized by features of both conditions. Association of AIH-PSC overlap syndrome with ulcerative colitis (UC) is well recognized but is rarely seen with Crohn’s disease (CD). We report a case of a young African-American woman with AIH-PSC overlap syndrome complicated by CD that illustrates the approach to diagnosis and management of the condition. A brief discussion of the topic follows the case presentation.

Impact of Metabolic Syndrome on the Hospitalization Rate of Crohn's Disease Patients Seen at a Tertiary Care Center: A Retrospective Cohort Study

Background/Aims: Recent studies suggest that markers of mesenteric inflammation, such as increased adipose tissue, may be associated with poor outcomes in Crohns disease (CD). This studys hypothesis is that CD patients with metabolic syndrome (MetS) have more CD-related hospitalizations than CD patients without MetS. Methods: We conducted a retrospective cohort study of CD patients seen from 2000 to 2012 at our tertiary care center. We analyzed crude and age-, sex- and duration of CD-adjusted incidence rate ratio (IRR) of CD-related hospitalization of those with MetS versus those without MetS. We also investigated possible associations between individual component conditions of MetS and rate of CD-related hospitalization. Results: A total of 868 CD patients were included. There were 37 (4%) patients with MetS at initial observation. After multi-variable adjustment, patients with MetS had a CD-related hospitalization rate twice that of those who did not have MetS. High triglycerides (TG), low high density lipoprotein (HDL) cholesterol and diabetes mellitus (DM) were associated with increased risk of CD-related hospitalization. Conclusions: CD patients with MetS have a higher rate of CD-related hospitalization compared to those without MetS. Hypertriglyceridemia, low HDL cholesterol and DM may be good markers of local and systemic inflammation as seen in CD.

Crohn's colitis with perianal disease complicated by collagenous colitis: discourse on management options.

disease. She also had a history of depression and had undergone trials of several mood stabilizers over the years. The patient was being maintained in clinical remission on a TNF blocker when she developed new onset perianal pain with discharge as well as increased diarrhea for which endoscopic and surgical evaluation was scheduled. An active perianal fistula was confirmed with a probe ( fig. 1 ). Flexible sigmoidoscopy performed after seton placement into the fistula revealed a completely normal colonic mucosa to the level of the splenic flexure except for a minute area of inflammation at the anorectal junction where biopsies were taken. The pathology report suggested evidence of subepithelial accentuation of collagen band with increased chronic inflammation ( fig. 2 a, b). A subsequent colonoscopy performed for complete colonic mucosal evaluation also did not reveal any endoscopic disease, however, random colonic biopsies taken during the procedure confirmed the subepithelial accentuation of collagen band with increased chronic inflammation throughout the colon, therefore establishing a diagnosis of concomitant CC in the patient ( fig. 3 ). The patient had a history of severe acute steroid psychosis in the past and Dear Sir, Crohn’s disease (CD) and collagenous colitis (CC) are rarely seen together in clinical practice and when they are, they may present a management challenge. We describe the case of a patient with perianal CD unable to take steroids whose clinical course was complicated by the development of CC. A brief review of the topic follows the case presentation.

Rates of hospitalization among African American and Caucasian American patients with Crohn's disease seen at a tertiary care center

Abstract Background There is equivocal evidence regarding differences in the clinical course and outcomes of Crohn’s disease (CD) among African Americans compared with Caucasian Americans. We sought to analyze whether African Americans with CD are more likely to be hospitalized for CD-related complications when compared with Caucasian Americans with CD. Methods We conducted a retrospective cohort study including 909 African Americans and Caucasian Americans with CD who were seen at our tertiary care Inflammatory Bowel Disease (IBD) referral center between 2000 and 2013. We calculated the rate of hospitalization for CD-related complications among African Americans and Caucasian Americans separately. Zero-inflated Poisson regression models with robust variance estimates were used to estimate crude and multivariable adjusted rate ratios (RR) for CD-related hospitalizations. Multivariable adjusted models included adjustment for age, sex, duration of CD, smoking and CD therapy. Results The cumulative rate of CD-related hospital admissions was higher among African American patients compared with Caucasian American patients (395.6/1000 person-years in African Americans vs. 230.4/1000 person-years in Caucasian Americans). Unadjusted and multivariable adjusted rate ratios for CD-related hospitalization comparing African Americans and Caucasian Americans were 1.59 (95% confidence interval [95%CI]: 1.10–2.29; P=0.01) and 1.44 (95%CI: 1.02–2.03; P=0.04), respectively. Conclusions African Americans with CD followed at a tertiary IBD-referral center had a higher rate for CD-related hospitalizations compared with Caucasian Americans. Future studies should examine whether socioeconomic status and biologic markers of disease status could explain the higher risk observed among African Americans.

Socioeconomic Status and Race are both Independently associated with Increased Hospitalization Rate among Crohn’s Disease Patients

Racial disparities are observed clinically in Crohn’s Disease (CD) with research suggesting African Americans (AA) have worse outcomes than Caucasian Americans (CA). The aim of this study is to assess whether socioeconomic status (SES) rather than race is the major predictor of worse outcomes. We designed a retrospective cohort study of 944 CD patients seen at our center. Patients’ billing zip codes were collected and average income and percent of population living above or below poverty level (PL) for each zip code calculated. Patients were separated by quartiles using average state income level and federal PL. Demographics and hospitalization rates were collected. Poison regression models estimated incidence rate ratios (IRR) for CD-related hospitalizations. Incidence rate (IR) of hospitalization per 100-person years for the lowest income group was 118 (CI 91.4–152.3), highest income group was 29 (CI 21.7–38.9), Above PL was 26.9 (25.9–28.9), Below PL was 35.9 (33.1–38.9), CA was 25.3 (23.7–27), and AA was 51.4 (46.8–56.3). IRR for a CD-related hospitalization for lowest income group was 2.01 (CI 1.34–3.01), for Below PL was 1.26 (CI 1.12–1.42), and for AAs was 1.88 (CI 1.66–2.12). SES and race are both associated with hospitalization among CD patients and need further investigation.

Comparative Effectiveness of Vedolizumab vs. Infliximab Induction Therapy in Ulcerative Colitis: Experience of a Real-World Cohort at a Tertiary Inflammatory Bowel Disease Center

Background Vedolizumab (VDZ), an adhesion molecule inhibitor and infliximab (IFX), a tumor necrosis factor (TNF) blocker, are both approved as first-line induction agents in moderately to severely active ulcerative colitis (UC). However, there are no head-to-head studies comparing the relative effectiveness of the two agents. Here we provide a real-world comparison of these two agents. Methods We conducted an ambidirectional cohort study of adult UC patients seen at our tertiary inflammatory bowel disease (IBD) center from 2012 to 2017. Each patient had moderately to severely active UC via partial Mayo score and was induced with IFX or VDZ. They were followed until assessment of clinical response. Poisson regression was used to calculate clinical response rates and rate ratios. Results Of 59 patients who met inclusion criteria, 27 and 32 patients were induced with IFX and VDZ, respectively. Totally, 18/27 (66.7%) patients induced with IFX vs. 24/32 (78.1%) patients induced with VDZ were clinical responders. Response rates per 100 person-weeks (PW) were similar for VDZ (5.21) and IFX (5.38). The effectiveness in terms of induction of clinical response (incidence rate ratio, IRR) was not statistically significant for VDZ vs. IFX (IRR 0.97, 95% confidence interval (CI) 0.53 - 1.77). Among TNF blocker naive patients, IRR was also not statistically significant between VDZ (6.74/100 PW) and IFX (6.48/100 PW) (IRR 1.04, 95% CI 0.47 - 2.29). Among TNF blocker experienced patients, there was a higher response rate for VDZ (4.52) vs. IFX (2.29) per 100 PW, but the IRR did not reveal statistical significance (IRR 1.97, 95% CI 0.45 - 8.63) due to small sample size of TNF blocker experienced patients who received IFX. Five patients developed severe infection or adverse reaction during IFX induction requiring exclusion, whereas no VDZ patients were excluded for this reason. Conclusions Our study revealed a higher proportion of patients who responded to VDZ vs. IFX; however when accounting for period between induction and assessment of clinical response, rates of clinical response were similar. A key difference between the two groups was the higher response rate in the VDZ group among TNF blocker experienced patients; however, a larger cohort is needed to further elaborate on this difference. VDZ held its own against IFX and this study strengthens its standing as a first-line agent among TNF blocker naive as well as TNF blocker experienced UC patients.

Impact of vitamin D on the hospitalization rate of Crohn's disease patients seen at a tertiary care center

AIM To study the association between vitamin D level and hospitalization rate in Crohn’s disease (CD) patients. METHODS We designed a retrospective cohort study using adult patients (> 19 years) with CD followed for at least one year at our inflammatory bowel disease center. Vitamin D levels were divided into: low mean vitamin D level (< 30 ng/mL) vs appropriate mean vitamin D level (30-100 ng/mL). Generalized Poisson Regression Models (GPR) for Rate Data were used to estimate partially adjusted and fully adjusted incidence rate ratios (IRR) of hospitalization among CD patients. We also examined IRRs for vitamin D level as a continuous variable. RESULTS Of the 880 CD patients, 196 patients with vitamin D level during the observation period were included. Partially adjusted model demonstrated that CD patients with a low mean vitamin D level were almost twice more likely to be admitted (IRR = 1.76, 95%CI: 1.38-2.24) compared to those with an appropriate vitamin D level. The fully adjusted model confirmed this association (IRR = 1.44, 95%CI: 1.11-1.87). Partially adjusted model with vitamin D level as a continuous variable demonstrated, higher mean vitamin D level was associated with a 3% lower likelihood of admission with every unit (ng/mL) rise in mean vitamin D level (IRR = 0.97, 95%CI: 0.96-0.98). The fully adjusted model confirmed this association (IRR = 0.98, 95%CI: 0.97-0.99). CONCLUSION Normal or adequate vitamin D stores may be protective in the clinical course of CD. However, this role needs to be further characterized and understood.

Inflammatory Bowel Disease: Epidemiology

Inflammatory bowel disease (IBD) is characterized by two partially distinct alimentary disease processes, namely Crohn’s disease (CD) and ulcerative colitis (UC), affecting genetically predisposed individuals. CD and UC were first described in 1932 and 1859, respectively. It is estimated that 1.5 million in North America and 2.5 million persons in Europe have IBD. The peak incidence of CD and UC is between 20–30 years and 30–40 years of age, respectively. Both incidence and prevalence of CD and UC are similar across males and females. However, several studies suggest a female predominance in CD and a male predominance in UC. The pathogenesis of IBD is attributed to an uncontrolled immune-mediated inflammatory response to an unrecognized environmental trigger that interacts with the intestinal flora. Various determinants of IBD include the following: peculiar environmental triggers, intestinal immune mechanisms, heritable factors, gut flora, diet, mesenteric fat, medications, nicotine, infectious agents, immunization, hygiene, pregnancy, breastfeeding, stress and lifestyle. Predominant complications in IBD are surgery, malnutrition, disease exacerbations and cancer. Patients with CD have a higher mortality compared to general population. Epidemiological studies continue to expand our understanding of the distribution, determinants and mechanisms of IBD. This has enabled us to recognize safer and effective approaches to management.

Predictors of Outcome of Rectovaginal Fistula Surgery in Women With Crohn’s Disease

Background Despite measures taken to control traditional risk factors like increased rectal disease activity, anorectal stenosis, and, to a lesser extent, obesity, rates of poor outcomes after rectovaginal fistula (RVF) surgery in women with Crohn’s disease (CD) are still high and require further elucidation. To bridge the gap, we sought to identify risk factors beyond the aforementioned determinants that may be associated with poor outcomes in these patients. Methods We designed a retrospective, unmatched, case-control study to test our hypothesis. The population comprised women with CD who underwent RVF surgery between the years of 2000 and 2013. Cases were defined as surgeries with an unsuccessful outcome at 4 weeks post-surgery, and controls represented those with a successful outcome at 4 weeks post-surgery. With multivariable logistic regression models, we sought to identify pertinent risk factors for poor outcomes after RVF surgery in these women. Results Of the 108 women with CD who were referred to our institution for evaluation of RVFs between 2000 and 2013, 39 underwent a total of 63 surgeries, of which 16 were cases and 47 were controls. There were no significant differences between them with regard to medications and clinical or mucosal disease severity, but a significantly higher proportion of poor outcomes arose from the group of women who underwent a mucosal flap procedure (88%) compared to those who had a seton placed (13%; P = 0.0004). The final adjusted logistic regression model demonstrated that women who underwent a mucosal flap procedure instead of a seton placement were 17.5 times more likely to have a poor surgical outcome (odds ratio (OR): 17.51; 95% confidence interval (CI): 3.12 - 98.43; P = 0.0012). Moreover, it was seen that women with active colonic mucosal disease, independent of rectal disease activity, were 4.4 times more likely to have a poor outcome (OR: 4.40; 95% CI: 1.06 - 18.26). Conclusion Mucosal flap procedures, representing the second, or definitive, stage in surgical treatment of RVF are associated with much worse outcomes and therefore should be preceded by aggressive medical optimization of the patient.