Vulvar Crohn's Disease: Clinical Features and Outcomes.

INTRODUCTION: Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown. METHODS: We conducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers. Clinical features and outcomes were studied. RESULTS: Fifty patients were identified. The most common vulvar symptoms were pain (74%), edema (60%), ulcerations (46%), nodules (36%), and abscess (34%). Medical management leading to symptomatic improvement varied, and 5 patients ultimately required surgery. DISCUSSION: Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases.

Association Between Serological Markers and Crohn's Disease Activity.

BACKGROUND: The aim was to study the association between six serological markers and Crohn's disease (CD) activity at an inflammatory bowel disease (IBD) referral center. METHODS: We designed a retrospective cohort study using adults (> 18 years) with CD followed for at least 1 year at University of Alabama at Birmingham. Baseline serological markers ASCA-IgA, ASCA-IgG, anti-OmpC IgA, anti-CBir1 IgG, anti-A4Fla2 IgG and anti-FlaX IgG were drawn at initial visit. Poisson regression was used to assess the longitudinal relationship between these markers drawn at baseline and rate of active clinical disease during follow-up. RESULTS: Each marker, from 135 patients, was categorized into high vs. low. A Poisson regression model adjusted for age, gender, race, duration of disease, obesity, proton pump inhibitor; steroid and thiopurine use, and disease location demonstrated that CD patients with high anti-CBir1 IgG at baseline were approximately twice more likely to have active clinical disease (incidence rate ratio (IRR) 2.06, 95% confidence interval (CI) 1.28 - 3.33, P = 0.0032). The unadjusted Poisson regression model for A4Fla2 IgG antibody level did suggest that a high A4Fla2 IgG at baseline was associated with a higher likelihood of active CD (IRR 1.64, 95% CI 1.07, 2.53, P = 0.0238) which however, upon adjustment based on effect size, was not significant. The other four antibodies did not appear to predict clinical course. CONCLUSIONS: High levels of anti-CBir1 IgG appear to be associated with a greater likelihood of active CD. Whether routine baseline testing for anti-CBir1 IgG to predict a more active clinical course is warranted needs more research.

Comparative Effectiveness of Ustekinumab Versus Adalimumab in Induction of Clinical Response and Remission in Crohn's Disease: Experience of a Real-World Cohort at a Tertiary Care Inflammatory Bowel Disease Referral Center.

BACKGROUND: There is paucity of head-to-head studies comparing the effectiveness of ustekinumab (UST) and adalimumab (ADA) in Crohn's disease (CD). Here we provide a real-world comparison of these two agents. METHODS: We conducted an ambidirectional cohort study. Each patient included had moderate to severe active CD. Clinical response and remission were assessed between 4 and 16 weeks after induction. RESULTS: Of a total of 163 patients, 97 were induced with ADA and 66 were induced with UST. Logistic regression model analysis adjusted based on effect size showed that ADA when compared to UST induced clinical response (73.2% vs. 50% (odds ratio (OR): 2.40; 95% confidence interval (CI): 1.14 - 5.07; P = 0.02)) and remission (44.3% vs. 27.7% (OR: 2.35; 95% CI: 1.07 - 5.16; P = 0.034) in a statistically significantly higher proportion of patients. Among tumor necrosis factor (TNF)-naive patients, when comparing ADA vs. UST, ADA was superior in inducing clinical response (69/89 (77.5%) vs. 4/10 (40%) (OR: 4.26; 95% CI: 1.08 - 16.84; P = 0.04)), but not remission (41/89 (46%) vs. 3/9 (33%) (OR: 1.64; 95% CI: 0.39 - 6.97; P = 0.503)). Among TNF-experienced patients, ADA was numerically inferior in inducing clinical response (2/8 (25%) vs. 29/56 (52%) (OR: 0.38; 95% CI: 0.07 - 1.94; P = 0.24)) and remission (2/8 (25%) vs. 15/56 (27%) (OR: 1.22; 95% CI: 0.22 - 6.81; P = 0.82)), but neither of these differences were statistically significant. CONCLUSIONS: In a real-world setting, the rate of clinical response and remission was higher among patients with CD who received ADA compared to UST. Of note, however, despite the small sample sizes of TNF-experienced patients who received ADA and TNF-naive patients who received UST, the higher effectiveness of ADA in inducing clinical response and indeed remission among patients with CD with active disease appears to primarily be driven by those who are TNF-naive. Among TNF-experienced patients, UST may be superior in inducing clinical response and equally effective in inducing clinical remission when compared to ADA. Based on this study, one may infer that among TNF-experienced patients with CD with active disease, one could consider switching to an agent such as UST instead of a second approved TNF blocker. However, larger studies comparing the two agents are required.

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.

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.

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.

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

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.

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.

Budesonide Use and Hospitalization Rate in Crohn's Disease: Results From a Cohort at a Tertiary Care IBD Referral Center.

BACKGROUND: Budesonide is generally not used for periods > 90 days in Crohn's disease (CD). We sought to study the association between cumulative outpatient budesonide use in days and hospitalization rate in CD patients seen at our institution. METHODS: Using a retrospective cohort study design, we selected CD patients > 19 years old and followed for at least 1 year. Days of outpatient budesonide use were calculated by reviewing outpatient clinic notes. Treatment groups included patients who were not given budesonide, received budesonide from 1 to 90 days, and received budesonide > 90 days. We performed univariate analyses and developed generalized Poisson regression models for rate data to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) for CD-related hospitalization. RESULTS: Of 767 CD patients, 664 did not receive budesonide, 45 received budesonide from 1 to 90 days, and 58 received budesonide for > 90 days. Incidence rates of hospitalization in patients who received no budesonide vs. 1 - 90 days of budesonide vs. > 90 days of budesonide were 31, 26, and 19 per 100 person-years, respectively. Adjusted models demonstrated that receiving outpatient budesonide from 1 to 90 days and for > 90 days was associated with a lower likelihood of being admitted for a CD exacerbation (1 - 90 days: IRR 0.85; 95% CI 0.65 - 1.10; > 90 days: IRR 0.71; 95% CI 0.56 - 0.91). CONCLUSIONS: Outpatient budesonide use appears to be associated with a lower likelihood of a CD-related hospitalization, notably when used for > 90 days. This association needs to be further assessed before recommending this agent for routine use for > 90 days.

Racial Disparities in Readmissions for Patients with Inflammatory Bowel Disease (IBD) After Colorectal Surgery.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) in minorities is increasing, and health outcome disparities are becoming more apparent. Our aim was to investigate the contribution of race to readmissions in IBD patients undergoing colorectal surgery. DESIGN: The National Surgical Quality Improvement Program database from 2012 to 2013 was queried for all patients with IBD undergoing elective colorectal surgery. After stratifying by race, unadjusted univariate and bivariate comparisons were made. Primary outcome was all-cause 30-day readmission. Predictors of readmission were identified using multivariable logistic regression. RESULTS: Of the 2523 patients with IBD who underwent elective colon surgery, 15.0 % were readmitted within 30 days of index operation. Black patients constituted 7.7 % of the entire cohort. Black patients were significantly different in smoking status (27 vs. 22 %) and Crohn's diagnosis (84 vs. 73 %) (p < 0.05). Black patients had significantly higher readmission rates (20 vs. 15 %) and longer length-of-stays (8 vs. 6 days) after surgery (p < 0.05). On multivariable analysis, black race remained a significant predictor for 30-day readmissions in patients with IBD (odds ratio 1.6, 95 % confidence interval 1.1-2.5). CONCLUSIONS: Black patients with IBD have an increased risk for readmission after colorectal surgery. Efforts to reduce readmissions need to target not only well-studied risk factors such as postoperative complications, but also investigate non-NSQIP-measured elements such as social and behavioral determinants of health.

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.

Obesity and Outcome of Crohn's Associated Perianal Fistula Surgery: A Case-Control Study.

BACKGROUND: Evidence suggests that obesity (body mass index (BMI) > 30 kg/m2) adversely affects several outcomes in Crohn's disease (CD). CD-associated perianal fistula (CDPF) represents a debilitating phenotype with a clinical course that may be affected by obesity. We hypothesized that obese CD patients would be more likely to have poor outcomes following CDPF surgery. METHODS: We designed a case-control study of CD patients who underwent surgery for CDPF between 2000 and 2013 with documented pre-operative BMI and post-operative outcome. Cases and controls were defined based on the outcome of CDPF surgery. Poor outcomes were designated as cases. RESULTS: Of the 317 patients diagnosed with CDPF, 73 patients underwent 120 surgeries for CDPF. Eighty-nine (74%) of the surgeries comprised fistulotomy with or without Seton placement, whereas 31 (26%) were mucosal flap procedures. Twenty-five (21%) cases and 95 (79%) controls were identified. Unadjusted odds ratio (OR) for the association between obesity and outcome demonstrated a trend towards a poor surgical outcome among obese patients that did not reach statistical significance (OR: 1.86; 95% confidence interval (CI): 0.58 - 5.98; P = 0.295). Multivariable logistic regression analysis demonstrated an even stronger trend towards a poor outcome among obese CD patients, albeit without reaching statistical significance (OR: 2.83; 95% CI: 0.64 - 12.49; P = 0.169). CONCLUSION: In patients undergoing Seton placement, fistulotomy or mucosal flap procedure for CDPF, there is a trend towards poor outcomes in the obese; however, as this trend did not reach statistical significance, this association should be examined further.

Body Mass Index Is Associated With Mucosal Disease in Crohn's: Results of a Case-Control Study.

BACKGROUND: Recent studies have suggested that increased body mass index (BMI) may have an adverse effect on treatment outcomes and natural history in Crohn's disease (CD). We aimed to test the hypothesis that CD patients with higher BMI would be more likely than those with lower BMI to have persistent active mucosal disease. METHODS: We designed a case-control study. Sample population comprised CD patients with active disease at the beginning of observation. At the end of observation, cases had persistent active mucosal disease and controls had entered remission. With multivariable logistic regression models, we evaluated the effect of baseline BMI as a continuous variable and a categorical variable on persistent active mucosal disease. RESULTS: We analyzed data from 104 patients (36 cases and 68 controls). In a model containing BMI as a continuous variable, higher BMI was significantly associated with persistent active mucosal disease (odds ratio (OR) = 1.09 per unit increase; 95% confidence interval (CI), 1.02 - 1.17; P = 0.012). In a model containing BMI as a categorical variable, obese patients were 2.7 times more likely to have persistent active mucosal disease compared to non-obese patients (OR = 2.72; 95% CI, 1.00 - 7.35; P = 0.049). CONCLUSION: Excessive weight measured both quantitatively as BMI and categorically as obesity in CD patients is associated with persistent active mucosal disease.

Obesity is Associated With Poor Surgical Outcome in Crohn's Disease.

BACKGROUND: Published data suggest a link between obesity and adverse outcomes in Crohn's disease (CD). We aimed to test the hypothesis that obese CD patients would be more likely than non-obese CD patients to have poor surgical outcome when undergoing surgery for a complication of CD. METHODS: We designed a retrospective cohort study to test our hypothesis. The population comprised of adult CD patients who underwent CD related surgery at a tertiary referral center. The exposed and unexposed cohorts were represented by patients who were obese vs. non-obese at the pre-op visit respectively. Outcome was represented by successful vs. unsuccessful surgical outcome as deemed by the treating clinician. RESULTS: Ninety CD patients were eligible for inclusion into this cohort study of which 36 were obese (exposed cohort) and 54 were non-obese (unexposed cohort). Among obese CD patients, 64% had an unsuccessful surgical outcome vs. 41% with unsuccessful surgical outcome among the non-obese. Based on unadjusted bivariate analysis, potential confounders identified included age and type of surgery. Gender distribution, disease duration, ethnicity, tobacco use, steroid use, traditional and biological immune modulator use and clinical disease activity were similar between the two groups. Logistic regression adjusted for age and type of surgery revealed that obese CD patients were approximately 2.5 times more likely to have a poor surgical outcome than patients with CD who were not obese (P = 0.05 OR 2.53 95% CI 0.99 - 6.52). BMI as a continuous variable (adjusted for age and type of surgery) appeared to be associated with poor surgical outcome (P = 0.06 OR 1.07 95% CI 0.99 - 1.15). CONCLUSIONS: Obesity may be associated with poor surgical outcome in CD patients.

Chronic Recurrent Esophageal Diverticulitis - A Rare Entity.

In this report, we seek to shed light on a 44-year-old Caucasian male with a known history of an esophageal diverticulum, who was transferred to our facility after an upper endoscopy at an outside hospital suggested a purulent discharge emanating from the mouth of a mid-esophageal diverticulum. A barium swallow done at the outside institution had reportedly demonstrated an 8 cm long barium collection parallel to and anterolateral to the mid-and distal esophagus which terminated several centimeters proximal to the gastroesophageal junction. At our facility, antibiotics (piperacillin/tazobactam) were continued, and a double-contrast esophagram was performed. The presence of an unusual mid-esophageal diverticulum was confirmed. He clinically improved after a 3-day course of intravenous broad-spectrum antibiotics. No surgical or endoscopic repair was elected as the patient opted for continued medical management. While esophageal diverticula are not rare in humans, to our knowledge, this is the first report of development of esophageal diverticulitis in humans. We believe that antibiotic coverage in addition to dietary restriction is the logical mainstay of acute therapy. Optimal antibiotic coverage should likely include oral flora aerobes and anaerobes. Once symptoms resolve, diverticula may be managed expectantly.