Sunil Samuel

Endoscopic Skipping of the Distal Terminal Ileum in Crohn's Disease Can Lead to Negative Results From Ileocolonoscopy

BACKGROUND & AIMS Crohns disease often involves the terminal ileum (TI), but skipping of the distal TI can occur. This can lead to negative results from ileocolonoscopy. We analyzed advanced cross-sectional images to determine how frequently this occurs. METHODS We analyzed data from 189 consecutive patients (55% women) with Crohns disease, evaluated in 2009 by computed tomography enterography (CTE) and ileocolonoscopy. The discharge impression of the gastroenterologist who treated the patients was used as the reference standard for Crohns disease activity. RESULTS Of the patients evaluated, 153 underwent TI intubation during endoscopy; 67 of these (43.8%) had normal results from ileoscopy, based on endoscopic appearance. Despite their normal results from ileoscopy, 36 of these patients (53.7%) had active, small-bowel Crohns disease. The ileum appeared normal at ileoscopy because the disease had skipped the distal ileum of 11 patients (30.6%), developed only in the intramural and mesenteric distal ileum of 23 patients (63.9%), and appeared only in the upper gastrointestinal region of 2 patients (5.6%). These patients had a shorter duration of disease (61.1% for less than 5 years) compared with those found to have Crohns disease based on ileoscopy (41.1% for less than 5 years; P < .05). CTE detected extracolonic Crohns disease in 26% of patients; 14% of patients were found to have disorders unrelated to inflammatory bowel disease that warranted further investigation or consultation (including 4 cancers). CONCLUSIONS Ileoscopy examination can miss Crohns disease of the TI because the disease can skip the distal ileum or is confined to the intramural portion of the bowel wall and the mesentery. CTE complements ileocolonoscopy in assessing disease activity in patients with Crohns disease.

Validation of the Ulcerative Colitis Colonoscopic Index of Severity and Its Correlation With Disease Activity Measures

BACKGROUND & AIMS Endoscopic healing is likely to become an important goal for treatment of patients with ulcerative colitis (UC). A simple validated endoscopic index is needed. We validated the previously developed UC Colonoscopic Index of Severity (UCCIS). METHODS In a prospective study, 50 patients with UC were examined by colonoscopy; we analyzed videos of rectum and sigmoid, descending, transverse, and cecum/ascending colon. Eight gastroenterologists blindly rated 4 mucosal lesions (for vascular pattern, granularity, friability, ulceration) and severity of damage to each segment and overall. The global assessment of endoscopic severity (GAES) was based on a 4-point scale and 10-cm visual analogue scale. Correlation of the UCCIS score with clinical indexes (clinical activity index and simple clinical colitis activity index), patient-defined remission, and laboratory measures of disease activity (levels of C-reactive protein, albumin, and hemoglobin and platelet counts) were estimated by using the Pearson (r) or Spearman (r(s)) method. RESULTS Interobserver agreement was good to excellent for the 4 mucosal lesions evaluated by endoscopy and the GAES. The UCCIS calculated for our data accounted for 74% (R(2) = 0.74) and 80% (R(2) = 0.80) of the variation in the GAES and visual analogue scores, respectively (P < .0001). The UCCIS also correlated with clinical activity index (r = 0.52, P < .001), simple clinical colitis activity index (r = 0.62, P < .0001), and patient-defined remission (r = 0.43, P < .01). The UCCIS also correlated with levels of C-reactive protein (r(s) = 0.56, P < .001), albumin (r = -0.55, P < .001), and hemoglobin (r = -0.39, P < .01). A rederivation of the equation for the UCCIS by using the data from a previous study combined with those of the current study (n = 101) yielded similar results. CONCLUSIONS The UCCIS is a simple tool that provides reproducible results in endoscopic scoring of patients with UC.

Cumulative incidence and risk factors for hospitalization and surgery in a population-based cohort of ulcerative colitis.

Background:We sought to identify clinical and demographic features influencing hospitalization and colectomy in a population-based inception cohort of ulcerative colitis. Methods:Between 1970 and 2004, a total of 369 patients (58.5% males) from Olmsted County, MN, were followed from diagnosis for 5401 person-years. The cumulative probability of hospitalization and colectomy were estimated using the Kaplan–Meier method. Cox proportional hazards regression was used to identify factors associated with hospitalization and colectomy. Results:The cumulative probability of first hospitalization was 29.4% at 5 years (95% confidence interval [CI], 24.5%–34.1%), 38.7% at 10 years (33.1%–43.8%), 49.2% at 20 years (42.7%–55.2%), and 52.3% at 30 years (45.1%–59.7%). The incidence rate of hospitalizations decreased over the last 4 decades, although cumulative probability of first hospitalization increased with successive decades of diagnosis. Early need for corticosteroids (hazard ratio [HR], 1.8; 95% CI, 1.1%–2.7%) and early need for hospitalization (HR, 1.5; 95% CI, 1.02–2.4) were independent predictors of hospitalization after 90 days of illness. The cumulative probability of colectomy from the time of diagnosis was 13.1% at 5 years (95% CI, 9.4%–16.6%), 18.9% at 10 years (95% CI, 14.4%–23.2%), and 25.4% at 20 years (95% CI, 19.8%–30.8%). Male gender (HR, 2.1; 95% CI, 1.3–3.5), diagnosis in the 1990s (HR, 2.0; 95% CI, 1.01–4.0), and diagnosis in 2000 to 2004 (HR, 3.7; 95% CI, 1.7–8.2) were significantly associated with colectomy risk. Conclusions:Colectomy rates were comparable to reports from northern Europe. The numbers of hospitalizations show a decreasing trend. Male gender and being diagnosed in the 2000 to 2004 period predicted colectomy while extensive colitis predicted future hospitalizations.

Inflammatory bowel disease in primary sclerosing cholangitis: a robust yet changing relationship.

Background:Primary sclerosing cholangitis (PSC) has a well-established association with inflammatory bowel disease (IBD) and may represent a distinctive phenotype. It is unknown whether changes in the clinical and endoscopic presentation of newly diagnosed IBD among patients with PSC might have occurred over time. Methods:Initial clinical and endoscopic presentations of IBD in PSC were studied for 2 different time periods: 1993 to 1997 (early cohort) compared with 2003 to 2007 (recent cohort). Results:The baseline characteristics were similar in the 57 early cohort and 72 recent cohort patients. Compared with the recent cohort, alkaline phosphatase concentrations were higher in the early cohort (7.1 versus 2.6 × upper limit of normal, P = 0.0001). PSC was diagnosed before IBD in the recent cohort compared with the early cohort (50% versus 35%, P = 0.0009). The initial clinical and endoscopic presentations of IBD were similar in the 2 cohorts. The majority of patients had mild pancolitis, whereas rectal sparing and backwash ileitis were detected in one third and one fourth of patients, respectively. In addition, no differences in IBD outcomes or PSC characteristics were revealed. Immunomodulators and biological treatments were more commonly used in the recent cohort when compared with the early cohort (90% versus 56%, P = 0.03, and 13% versus 4%, P = 0.08, respectively). Conclusions:IBD in PSC has unique characteristics, and the clinical features of this unique presentation have remained stable over time. A shift in the timing of diagnosis of the 2 diseases has occurred in recent years, with PSC being more often diagnosed first.

Henoch–Schönlein Purpura in an Adult Mimicking Crohn’s Disease and Pyoderma Gangrenosum

To the Editor We read with interest the article from Saps et al. on their study of the occurrence of FGIDs (functional gastrointestinal disorders) in children after Henoch–Schönlein purpura (HSP) [1]. This study had included only those children who recovered from HSP. However, in contrast with children, HSP in adults runs a much more aggressive course and is unlikely to resolve spontaneously. We would like to emphasize this by reporting an adult case of HSP that we recently encountered and caused diagnostic difficulties by mimicking Crohn’s disease and pyoderma gangrenosum. A 26-year-old teacher was referred to our department with intermittent episodes of abdominal pain, vomiting, diarrhea, and polyarthralgia for the last 6 years. Previous colonoscopy and CT abdomen had shown evidence of terminal ileal inflammation suggesting diagnosis of Crohn’s disease. Twelve months before her presentation to us, she had also noted a rash on her lower limbs. Examination was significant for numerous wellcircumscribed, ulcerated lesions on her shins and a fading rash on both her feet (Fig. 1a, b). Repeat ileocolonoscopy with biopsies was normal. Capsule endoscopy revealed multiple clean-based ulcerations in the ileum. CT enterography showed patchy hyper-enhancement and fat deposition in the distal ileum consistent with acute and chronic inflammation. Laboratory tests showed raised C-reactive protein of 7.7 mg/l, positive antibodies to Saccharomyces cerevisiae (ASCA), and 3–10 red cells and 11–20 white cells/HPF on urine microscopy. Vasculitis panel and various other immunologic tests were negative. Skin biopsy showed evidence of leukocytoclastic vasculitis and direct immunofluorescence showed IgA class antibody deposition within the dermal capillaries. These findings were suggestive of Henoch–Schönlein purpura (HSP). Renal biopsy showed IgA nephropathy with mesangial IgA deposits on immunofluorescence, consistent with a diagnosis of HSP (Fig. 2). Mycophenolate mofetil 1 g twice a day led to complete resolution of skin rashes within 6 months, and significant improvement in her bouts of abdominal pain and arthralgia after 12 months of therapy. HSP is a small vessel vasculitis that in adults carry a much higher risk of end-stage renal failure and malignancy, emphasizing the importance of making this diagnosis in this group [2]. As seen in our patient, adults with HSP can have chronic intermittent abdominal pain for many years and diagnosis can remain a challenge. The classical purpuric skin rash seen in children tends to necrose in adults, and can be indistinguishable from pyoderma gangrenosum [2]. The gastrointestinal small vessels are affected commonly in HSP (50–75%), because of vasculitis, with abdominal pain and bleeding being the most common presenting symptoms [3, 4]. The small intestine is the most frequently involved site in the GI tract because of its tendency to ischemic injury [5]. Small bowel ischemic ulcerations and thickening of the intestinal wall (particularly of the ileum) because of mucosal edema, apparent on radiological testing, can pose diagnostic difficulties with Crohn’s disease. S. Samuel E. V. Loftus Jr. W. J. Sandborn Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

The effects of itraconazole on inflammatory bowel disease activity in patients treated for histoplasmosis

1. Ford A. Reporting of relapse rates in a trial of mesalazine for ulcerative colitis. Aliment Pharmacol Ther 2010; 32: 1205–6. 2. Lichtenstein GR, Gordon GL, Zakko S, et al. Clinical trial: once-daily mesalamine granules for maintenance of remission of ulcerative colitis – a 6-month placebo-controlled trial. Aliment Pharmacol Ther 2010; 32: 990–9. 3. Apriso (mesalamine) extended-release capsules; prescribing information: Salix Pharmaceuticals Inc., Morrisville, NC.

Chromoendoscopy versus autofluorescence imaging for neoplasia detection in patients with longstanding ulcerative colitis (FIND-UC): an international, multicentre, randomised controlled trial

BACKGROUND Patients with longstanding ulcerative colitis undergo regular dysplasia surveillance because they have an increased colorectal cancer risk. Autofluorescence imaging and chromoendoscopy improve dysplasia detection. The aim of this study was to determine whether autofluorescence imaging should be further studied as an alternative method for dysplasia surveillance in patients with longstanding ulcerative colitis. METHODS This prospective, international, randomised controlled trial included patients from an ulcerative colitis-dysplasia surveillance cohort from five centres in the Netherlands and the UK. Eligible patients were aged 18 years or older who were undergoing dysplasia surveillance after being diagnosed with extensive colitis (Montreal E3) at least 8 years before study start or with left-sided colitis (Montreal E2) at least 15 years before study start. Randomisation (1:1) was minimised for a previous personal history of histologically proven dysplasia and concomitant primary sclerosing cholangitis. The coprimary outcomes were the proportion of patients in whom at least one dysplastic lesion was detected and the mean number of dysplastic lesions per patient. The relative dysplasia detection rate, calculated as the ratio of the detection rates by autofluorescence imaging and chromoendoscopy, needed to be more than 0·67 (using an 80% CI) for both primary outcomes to support a subsequent large non-inferiority trial. Outcomes were analysed on a per-protocol basis. The trial is registered at the Netherlands Trial Register, number NTR4062. FINDINGS Between Aug 1, 2013, and March 10, 2017, 210 patients undergoing colonoscopy surveillance for longstanding ulcerative colitis were randomised for inspection with either autofluorescence imaging (n=105) or chromoendoscopy (n=105). Dysplasia was detected in 13 (12%) patients by autofluorescence imaging and in 20 patients (19%) by chromoendoscopy. The relative dysplasia detection rate of autofluorescence imaging versus chromoendoscopy for the proportion of patients with ulcerative colitis with at least one dysplastic lesion was 0·65 (80% CI 0·43-0·99). The mean number of detected dysplastic lesions per patient was 0·13 (SD 0·37) for autofluorescence imaging and 0·37 (1·02) for chromoendoscopy (relative dysplasia detection rate 0·36, 80% CI 0·21-0·61). Adverse events were reported for two patients in the autofluorescence imaging group (one patient had intraprocedural mild bleeding, and one patient had abdominal pain) and for three patients in the chromoendoscopy group (two patients had intraprocedural mild bleeding, and one patient had perforation). INTERPRETATION Autofluorescence imaging did not meet criteria for proceeding to a large non-inferiority trial. Therefore, existing autofluorescence imaging technology should not be further investigated as an alternative dysplasia surveillance method. FUNDING Olympus Europe and Olympus Keymed.

Validation of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Its Correlation With Clinical Indices and Laboratory Measures of Disease Activity

Validation of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Its Correlation With Clinical Indices and Laboratory Measures of Disease Activity Sunil Samuel, Edward V. Loftus, David H. Bruining, Kelvin T. Thia, William J. Tremaine, Kenneth W. Schroeder, William A. Faubion, Sunanda V. Kane, Darrell S. Pardi, Piet C. de Groen, William S. Harmsen, Alan R. Zinsmeister, William J. Sandborn