Diagnosis Of UC Research Articles

T1166 Interobserver Agreement and Accuracy Among International Experts of Probe-Based Confocal Laser Microscopy (pCLE) in Predicting Colorectal Neoplasia

G A A b st ra ct s infliximab. We describe the first case of disseminated mucocutaneous granulomas in a patient with UC receiving infliximab. Case: 19-year-old female with UC in clinical remission, who had been treated with infliximab (10mg/kg/every 8 weeks) for 2 years, presented with multiple skin, nasal and oral lesions developing over the course of three months. The skin lesions were erythematous annular plaques on the right hip, inner thighs and forearms. Multiple ulcers were found in the nasal turbinates and one on the hard palate. Repeat esophagogastroduodenoscopy and colonoscopy at the time of evaluation for these lesions showed mild chronic esophagitis andmild chronic proctitis. She had a normal MRI enterography. Her IBD serology (pANCA positive; ASCA IgA, IgG negative) was also supportive of a diagnosis of UC. Histological examination of the skin biopsy revealed a diffuse interstitial granulomatous infiltrate with lymphocytes and histiocytes. Biopsy of the nasal and oral mucosa revealed a marked submucosal inflammatory infiltrate composed of lymphocytes, plasma cells and eosinophils with granulomas and foci of necrosis. Special stains and cultures for bacteria, fungus and mycobacteria were negative. Evaluation was negative for Cryptococcus, Bordetella henselae, Blastomyces and Histoplasma. Angiotensin I converting enzyme was normal. CT scan of the sinuses and chest radiograph were normal as well. Discussion: Metastatic Crohn's disease, opportunistic infections and granulomatous reaction to infliximab were considered in the differential diagnosis. IGD was the most likely cause of these lesions in our patient. Metastatic Crohn's disease was unlikely given the quiescence of her intestinal disease compared to the activity of the mucocutaneous involvement. Opportunistic infections, which can be fatal in the face of anti-TNF therapy were ruled out by negative cultures. Furthermore, in our patient, her skin and mucosal lesions had significantly improved with no other intervention except for the discontinuation of her anti-TNF therapy. Conclusion: Granulomatous diseases, including IGD, should be considered in the differential diagnosis of annular or ulcerated lesions in the setting of anti TNFtherapy in a patient with IBD.

Predicting a Change in Diagnosis From Ulcerative Colitis to Crohn’s Disease: A Nested, Case-Control Study

Some patients diagnosed with UC undergo a change in diagnosis to CD. Identification of predictors of a diagnostic change could potentially impact the management of patients with colonic inflammation. Our aim was to characterize clinical and serologic predictors of a change in diagnosis from UC to CD. A nested, case-controlled study was performed to compare individuals with a change in diagnosis from UC to CD (cases) with age-matched UC and CD controls; primary analysis compared cases with UC controls. Subjects underwent chart review for clinical "red flags" identified by gastroenterologists with expertise in IBD. Serum collected at the time of database enrollment was tested for antibodies to oligomannan (anti-Saccharomyces cerevisiae), Pseudomonas fluorescens-related protein, Escherichia coli outer membrane porin C, CBir1 flagellin, and perinuclear antineutrophil cytoplasmic antibodies. Twenty-one cases, 52 UC controls, and 56 CD controls were assessed. Three red flags, but no serologic markers, differed between cases and UC controls. At initial colonoscopy, cases were more likely to have extensive colonic involvement than UC controls (P = .008). Multivariate regression identified non-bloody diarrhea at initial presentation (P = .01) and weight loss >10% at presentation (P = .007) as independent predictors of diagnostic change. Serologic markers did not add to the contribution of these 2 clinical factors in predicting a change in diagnosis from UC to CD. Diagnostic change was evident in 6 of 6 (100%) patients with both predictors, compared with 8 of 50 (16%) with neither of these factors (P < .0001). Patients with a diagnosis of UC with initial non-bloody diarrhea or weight loss have an increased likelihood of subsequent change in diagnosis to CD and might thus warrant further diagnostic work-up.

Impact of Age on Annual Costs of Care and Resource Utilization in Patients with Ulcerative Colitis from a Payer Perspective

Purpose: To assess the impact of age on annual costs of care and resource utilization for pts with UC using a medical claims database. Methods: A retrospective analysis, using the PharMetrics database, of pts with a diagnosis of UC (ICD-9 code 556.x) from January 1, 2000 through June 30, 2005 was conducted. Pts had to be continuously enrolled for 6 months pre-and 12 months post-UC diagnosis, and have 2 distinct claims for UC. Mean per pt healthcare resource utilization and costs were calculated for pts in the yr following their initial UC diagnosis. Outcomes are presented for UC pts by age groups: pediatric ≤ 18 yrs of age; adults 18 to 64 yrs; and adults ≥ 65 yrs of age. Results: The study cohort consisted of 15105 pts with UC. Almost 50% of the pts were males. Mean annual total cost for all UC pts in the study were $13233. Pediatric UC pts incurred the highest mean cost ($23113), followed by adults ≥ 65 yrs $15811, and adults 18 to 64 yrs $12693. Inpt hospitalization costs constituted the largest component ($5771, 44%) of the mean annual total costs for all pts. The next highest cost components were prescription medications ($2423, 18%), outpts ($1310, 10%), physician office visits ($899, 6.8%), and lab procedures ($470, 3.6%). Resource utilization was highest in the adults ≥ 65 yrs followed by pediatric, and adults 18 to 64 yrs (Table).Table: Mean Healthcare Costs and Resource Utilizations.Conclusions: UC in pediatric pts is associated with a high cost of care that is almost twice the cost for the adults UC pts. New therapies that can reduce hospitalizations have the potential to decrease overall cost of care for pts with UC.

Pre‐pouch ileitis: a disease of the ileum in ulcerative colitis after restorative proctocolectomy

Ileal inflammation in ulcerative colitis can occur as backwash ileitis or prestomal ileitis. After restorative proctocolectomy (RPC), ileal inflammation may be present in the pouch (pouchitis) but inflammation proximal to the pouch in the neo-terminal ileum, so called pre-pouch ileitis (PI), has also been observed. As pouchitis is increasingly common and PI can mimic it, our aim was to characterize this condition. A review of prospectively collected data on 571 inflammatory bowel disease patients undergoing follow-up after RPC in a single centre over 22 years was performed. The histology of biopsy material was reviewed and staining for colonic mucosal phenotypic changes was undertaken. It was not routine practice to prospectively assess all patients for pre-pouch ileitis when the database was constructed. Of 19 patients with inflammation of the pre-pouch neo-terminal ileum (NTI) identified three had Crohn's disease and one a NSAID stricture. The remaining 15 had a characteristic diffuse inflammation extending from the NTI-pouch junction proximally: pre-pouch ileitis. The inflammation extended proximally for up to 50 cm. Fistula formation was seen in only one. Seven (47%) of 15 had pouchitis but only two had suffered backwash ileitis pre-operatively. Seven responded to medical therapy and four to surgery. The histological appearances including staining for colonic phenotypic change were similar in PI and pouchitis. Pre-pouch ileitis is uncommon. As the patients' previous diagnosis of UC was confirmed and there was no radiological or histological evidence of Crohn's disease, PI appears to have a distinct pathogenesis from Crohn's disease.

PULMONARY VASCULITIS

Case: A 26year old Caucasian female, never smoker, presented to an outside medical facility with right-sided pleuritic chest pain. She denied any other systemic complaints. She was not taking any medications. Chest radiograph followed by CT identified multiple bilateral ill-defined pulmonary nodules and infiltrates. Her past medical history was remarkable for a biopsy proven diagnosis of UC almost a year prior to this presentation. It was treated with sulfasalazine for initial six months and was in remission. Apart from a high sedimentation rate of 42 mm/hr & C-reactive protein of 28.2 mg/dl, her laboratory evaluation was normal including urine analysis, CBC, hypersensitivity panel, p-ANCA, c-ANCA, infectious etiology workup including PPD, fungal & HIV serologies & serologies for connective tissue diseases. CT guided biopsy of a nodule was suspicious for non-small cell carcinoma. Her cancer screening including mammogram, Pap smear, colonoscopy, EGD & CT scan of abdomen and pelvis were unremarkable. Thorascopic lung biopsy was done and she was referred to us. Her physical examination was normal. Repeat tests revealed positive p-ANCA & antibody to proteinase 3 at 154.7 EU/ml (NL <5) but negative antibody to myeloperoxidase & c-ANCA. Her initial colon biopsy was reviewed again at our institute and the diagnosis of UC was confirmed. Her pulmonary pathology showed necrotizing granulomatous vasculitis. She was started on tapering dose of corticosteroid. At three month follow- up, she remained asymptomatic and the pulmonary nodules had resolved on subsequent chest radiograph. Discussion: Extraintestinal manifestations of UC are common, however, pulmonary complications of UC are very rare. The etiology of pulmonary vasculitis is unknown and it appears to be unrelated to the underlying UC activity. Most of the patients described in seven case reports so far, presented with cough, pleuritic chest pain and dyspnea on exertion with evidence of bilateral infiltrates or nodular densities on chest radiograph. The significance of ANCA in the pathogenesis of the IBD remains unclear. Lung biopsy is essential to make the diagnosis. Conclusion: Pulmonary vasculitis is a rare complication of UC, but emphasizes the systemic nature of the disease. This case reiterates the fact that pulmonary manifestations of this entity can occur in the absence of overt bowel inflammation. Corticosteroid therapy appears to be the mainstay in the management of this condition.

P0654 LONGITUDINAL STUDIES OF ANTIBODIES TO SACCHAROMYCES CEREVISIAE (ASCA) AND PERINUCLEAR ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (P-ANCA) IN CROHN???S DISEASE (CD)

Introduction: To evaluate ASCA and pANCA as diagnostic tools in paediatric CD and UC patients and investigate the role of serial ASCA in treatment. Methods: Clotted blood samples were collected from children with CD (n=33). UC (n=17) and controls (n=17). IgG ASCA was assayed using a commercial ELISA kit. ANCA was detected by indirect immunofluorescence. Follow-up blood samples were obtained from 9 patients and ASCA titres measured. Statistical analysis was performed using a Mann Whitney U test. Results: ASCA was positive in 66 % of patients with CD, compared with 15% of patients with UC (p<0.05) or controls (p<0.05). There was no difference in ASCA levels between controls and UC patients. In our longitudinal studies, 6/9 CD patients were positive for ASCA at the first sample and remained positive on subsequent samples taken up to a year later. Of the remaining three patients, one was ASCA positive and became negative after 6 months while another was ASCA negative and became positive over a 4 month period, the third was negative and remained negative at the second blood test 3 weeks later. Four specific serologic profiles were identified. ASCA+/pANCA-, ASCA-/pANCA+, ASCA+/pANCA+, and ASCA-/pANCA-. The majority of CD patients (67%) were ASCA +/ANCA- while UC patients ( 60%) were ANCA+/ASCA-. Conclusion: These two groupings (ASCA+/pANCA-, ASCA-/pANCA+) may be helpful in the diagnosis of UC and CD phenotypes. Preliminary studies suggest that serial ASCA antibody positivity were not affected by treatment.

Epidemiología de la enfermedad inflamatoria intestinal crónica en cinco áreas de Asturias: España

The epidemiologic analysis inflammatory bowel disease (IBD) is a powerful research tool to assess the contribution of environmental factors to its etiology. IBD has been reported to have varying frequencies in different parts of the world, and there seem to be significant differences in the disease pattern and clinical course. The aim of the present study was to assess the disease pattern of IBD in Asturias (Spain). A descriptive epidemiological population based study, retrospective (1954-1993) and prospective (1994-97), was performed to study 1018 patients found, bigger than 14 years, to have IBD, in five areas of Asturias (Spain) (461.965 inhabitants). During the period of time studied, we diagnosed 1018 IBD [565 ulcerative colitis (55.5%), 415 (40.8%) Crohn's disease and 38(3.7%) indeterminate colitis], with 482 females (47.2%), 536 males (52.8%), and male/female: 1.11. Age at diagnosis were 39.49 +/- 1.08 (95% CI : 38.41 +/- 40.57); (UC: 43.95 +/- 1.47; CD: 33.53 +/- 1.51; IC: 38.26 +/- 5.14. p = 0.000. Age at onset previously at diagnosis for UC: 42.84 +/- 1.34; CD: 30.68 +/- 1.40; IC: 36.74 +/- 4.86 (p = 0.000). Diagnosis criteria: UC: syntomatic 97.34% (p = ns), endoscopy 96.63% (p = 0.000 pathology 90.26% (p = 0.000). CD: radiology 83.61% (p =0.000). Study level in CD: 57.57 (p = 0.0005). Family history: 8.4%. The most frequent involvement at diagnosis of UC was proctitis only, in 13.6%, 269% rectum and sigmoid 26% let colitis, 20% pancolitis, and in CD colon only, in 16.7%, 30.3% terminal ileum, 41.3% ileo-colon of the patients. This also helps to explain the differences in severity, need for surgery, and survival noted between community based studies. We highlight the uniformity of distribution of the inflammatory bowel disease in relation to types and sex. The high frequency of familial Crohn's disease suggests a genetic predisposition. Highlighting a bigger morbilidad for the Crohn's Disease reflected in the surgical requirements, but however with smaller mortality that in ulcerative colitis.

Surgery for ulcerative colitis

The type of surgery performed for UC varies from patient to patient and must take into account the nutritional status and health of the patient, the presence of dysplasia or cancer, the desire of the patient to maintain continence, the preoperative anorectal function, the degree of confidence in the diagnosis of UC, and the technical constraint because of certain body habituses. A total proctocolectomy is the surgical procedure of choice for UC. A restorative proctocolectomy is the preferred surgical approach that not only cures the patient of the disease and prevents the development of colorectal cancer, but also maintains continence with an improved quality of life.

APPENDICECTOMY, PRIMARY SCLEROSING CHOLANGITIS (PSC) and ULCERATIVE COLITIS (UC)

The relationship between PSC and inflammatory bowel disases (IBD) remains largely unexplained. The most usual IBD phenotype reported with PSC is clinically mild UC pancolitis. Primary sclerosing cholangitis is not improved by colectomy (+ contemporaneous appendicectomy). We have shown that appendicectomy has a strong negative association with UC and a more benign UC phenotype. In animal models, early appendicectomy results in a significant reduction in mucosal Ig production, and in models of colitis the same early intervention protects the animal from the disease. The human appendix has a large complement of activated B cells which may seed the intestine with IgA‐secreting plasma cells in a similar way to these models. IgA will exclude bacteria from the gut epithelium. If there is impaired IgA‐mediated bacterial exclusion, then there may be not only a diluted intestinal mucosal immune response but an increased bacterial load in the portal circulation that requires a second‐line immune response by the liver. Thus, removal of an appendix in patients who are susceptible to UC may predispose to a more benign UC phenotype and PSC.Hypothesis Appendicectomy is associated with PSC.Materials and methods Review the Brisbane IBD database and interrogation of the Brisbane PSC transplant patient database for appendicectomy, age at surgery, age at diagnosis of UC and PSC, disease phenotype, smoking status (known to influence UC). Appendicectomy prevalence compared with age‐ and cohort‐matched controls randomly selected from a large population‐based twin registry (one twin selected from each pair). At this stage, the control population has been age‐ and cohort‐matched to the Brisbane IBD database only.Results The frequency of appendicectomy in patients with PSC prior to diagnosis of either the PSC or IBD is 17 of 67 (25.4%). This is significantly higher than the appendicectomy rate in UC alone 19 of 300 (6.3%), Fisher's exact test, P &lt; 0.0001. The 25.4% rate in PSC is similar to the controls, 235 of 897 (26%), P = 1.0.Conclusions The preliminary data support the hypothesis that appendicectomy is more likely in UC patients with PSC. Reported prevalences of appendicectomy in PSC vs. UC without PSC (Erpecum, Gastroenterology 2000, 110:1503 and Griffin &amp; Selby JGH 1999 Supp A121) support our findings. The appendicectomy prevalence may not be different from a matched control population. Further analysis controlling for smoking habit and a control group matched with the combined databases are ongoing.

ULCERATIVE COLITIS AND CROHN’S DISEASE IN CHILDREN

The foregoing discussion emphasizes the broad range of problems experienced by children and adolescents with chronic IBD. Approaches to the diagnosis and treatment of UC and CD in this distinctive population were provided herein.