Ulcerative Colitis: Dubinsky MC

Dubinsky MC. · Pediatric IBD Center, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. · Colorectal Dis. · Pubmed #16594959 No free full text.

Abstract: Inflammatory bowel disease (IBD) in childhood is often diagnosed at a vulnerable time of growth and development, and is recognized as one of the most significant chronic gastrointestinal diseases to affect children. Children and adolescents with IBD are at increased risk of complications as a result of malnutrition secondary to reduced appetite, increased metabolism and decreased absorptive capacity. The most common and serious complications are growth failure, bone demineralization and impaired psychosocial development. These issues add to the complexity of childhood IBD management and it is essential that adequate medical management is in place to prevent these long-term complications. Current treatment options include 5-aminosalicylic acid, antibiotics, corticosteroids, nutritional therapy and immunomodulators used to induce and maintain remission; some are specifically employed to maintain a steroid free long-term remission. As a general rule, long-term corticosteroid use should be avoided to reduce the risk of bone demineralization and growth failure. Newer treatment options such as infliximab have been shown to be effective for inducing and prolonging remission of Crohn's disease in children and paediatric use of infliximab is likely to increase in the near future. A recent case report, involving a 15-year old boy presenting with abdominal pain and bloody diarrhoea, illustrates the difficulty in correctly diagnosing IBD in children and the need for optimizing therapy to achieve treatment success.

Dubinsky MC. · Pediatric IBD Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Clin Gastroenterol Hepatol. · Pubmed #15354273 No free full text.

Abstract: 6-Mercaptopurine and its prodrug azathioprine remain the mainstay of immunomodulator therapy for the maintenance of a steroid-free remission in patients with IBD. Recent evidence suggests that the cytotoxic and immunosuppressive effects of azathioprine might be mediated via the induction of lymphocyte apoptosis by its active metabolites, 6-thioguanine nucleotides. The therapeutic benefits of thiopurines have been shown to correlate with the concentration of 6-thioguanine nucleotides. Inherited differences in drug metabolism and disposition can significantly impact the safety and efficacy of these drugs. The thiopurine methyltransferase enzyme plays an important role in the metabolism of 6-mercaptopurine and azathioprine and in the determination of thiopurine cytotoxicity. By gaining an understanding of the pharmacology and metabolism of thiopurine therapy and putting it into the clinical context, clinicians will be able to optimize thiopurine therapy in IBD.

Rubin DT, Siegel CA, Kane SV, Binion DG, Panaccione R, Dubinsky MC, Loftus EV, Hopper J. · Section of Gastroenterology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois, USA. · Inflamm Bowel Dis. · Pubmed #19067414 No free full text.

Abstract: BACKGROUND: Two national internet surveys were conducted to understand how patients perceive the impact of ulcerative colitis (UC) relative to gastroenterologists. METHODS: In total, 451 patients with UC (20% mild, 63% moderate, 13% severe, 4% unsure [patient self-assessment]) were recruited for one survey and 300 gastroenterologists (not associated with the patients) were recruited for the other survey. RESULTS: Patients reported, on average, 8 (self-defined) flares per year; this was more than the number anticipated by gastroenterologists. Sixty-two percent of patients with UC reported that their disease made it difficult to lead a normal life, compared with gastroenterologists' estimations of 36%. Only 42% of patients believed that being in remission could mean living without symptoms. Both patients and gastroenterologists reported that it is difficult for patients to take medication as prescribed every day (42% and 90%) and that managing UC medication is a struggle for patients (49% and 41%). Forty-six percent of patients admitted nonadherence to their therapy over the previous week, while gastroenterologists believed that 41% of their patients were not adherent. CONCLUSIONS: These surveys identified disparities between patients' and gastroenterologists' perceptions of the impact of UC on patients' lives. The results suggest that more patients than gastroenterologists estimated chose to adapt their lives to accommodate UC rather than act to optimize therapy and adherence. Improved communication between patients and gastroenterologists, as well as better management strategies and education are necessary.

Anonymous00166, Anonymous00167, Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glickman JN, Gold BD, Griffiths AM, Jevon GP, Higuchi LM, Hyams JS, Kirschner BS, Kugathasan S, Baldassano RN, Russo PA. · No affiliation provided · J Pediatr Gastroenterol Nutr. · Pubmed #17460505 No free full text.

Abstract: BACKGROUND: Studies of pediatric inflammatory bowel disease (IBD) have varied in the criteria used to classify patients as having Crohn disease (CD), ulcerative colitis (UC), or indeterminate colitis (IC). Patients undergoing an initial evaluation for IBD will often undergo a series of diagnostic tests, including barium upper gastrointestinal series with small bowel follow-through, abdominal CT, upper endoscopy, and colonoscopy with biopsies. Other tests performed less frequently include magnetic resonance imaging scans, serological testing, and capsule endoscopy. The large amount of clinical information obtained may make a physician uncertain as to whether to label a patient as having CD or UC. Nevertheless, to facilitate the conduct of epidemiological studies in children, to allow the entry of children into clinical trials, and to allow physicians to more clearly discuss diagnosis with their patients, it is important that clinicians be able to differentiate between CD and UC. METHODS: A consensus conference regarding the diagnosis and classification of pediatric IBD was organized by the Crohn's and Colitis Foundation of America. The meeting included 10 pediatric gastroenterologists and 4 pediatric pathologists. The primary aim was to determine the utility of endoscopy and histology in establishing the diagnosis of CD and UC. Each member of the group was assigned a topic for review. Topics evaluated included differentiating inflammatory bowel disease from acute self-limited colitis, endoscopic and histological features that allow differentiation between CD and UC, upper endoscopic features seen in both CD and UC, ileal inflammation and "backwash ileitis" in UC, patchiness and rectal sparing in pediatric IBD, periappendiceal inflammation in CD and UC, and definitions of IC. RESULTS: Patients with UC may have histological features such as microscopic inflammation of the ileum, histological gastritis, periappendiceal inflammation, patchiness, and relative rectal sparing at the time of diagnosis. These findings should not prompt the clinician to change the diagnosis from UC to CD. Other endoscopic findings, such as macroscopic cobblestoning, segmental colitis, ileal stenosis and ulceration, perianal disease, and multiple granulomas in the small bowel or colon more strongly suggest a diagnosis of CD. An algorithm is provided to enable the clinician to differentiate more reliably between these 2 entities. CONCLUSIONS: The recommendations and algorithm presented here aim to assist the clinician in differentiating childhood UC from CD. We hope the recommendations in this report will reduce variability among practitioners in how they use the terms "ulcerative colitis," "Crohn disease," and "indeterminate colitis." The authors hope that progress being made in genetic, serological, and imaging studies leads to more reliable phenotyping.

Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, Dutridge D, Wahbeh G, Silber G, Bahar R, Mengesha E, Targan SR, Taylor KD, Rotter JI, Anonymous00160. · Department of Pediatrics, Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Inflamm Bowel Dis. · Pubmed #17309073 links to  free full text

Abstract: BACKGROUND: The IL-23 receptor (IL-23R) has been found to be associated with small bowel Crohn's disease (CD) in a whole genome association study. Specifically, the rare allele of the R381Q single nucleotide polymorphism (SNP) conferred protection against CD. It is unknown whether IL-23R is associated with IBD in children. The aim was to examine the association of IL-23R with susceptibility to IBD in pediatric patients. METHODS: DNA was collected from 609 subjects (151 CD and 52 ulcerative colitis [UC] trios). Trios were genotyped for the R381Q SNP of the IL-23R gene and SNP8, SNP12, SNP13, of the CARD15 gene using Taqman. The transmission disequilibrium test (TDT) was used for association to disease using GENEHUNTER 2.0. RESULTS: The rare allele of R381Q SNP was present in 2.7% of CD and 2.9% UC probands. The CARD15 frequency was 31.5% (CD) and 18% (UC). The IL-23R allele was negatively associated with inflammatory bowel disease (IBD): the R381Q SNP was undertransmitted in children with IBD (8 transmitted [T] versus 27 untransmitted [UT]; P = 0.001). This association was significant for all CD patients (6 T versus 19 UT; P = 0.009), especially for non-Jewish CD patients (2 T versus 17 UT; P = 0.0006). TDT showed a borderline association for UC (2 T versus 8 UT; P = 0.06). As expected, CARD15 was associated with CD in children by the TDT (58 T versus 22 UT P = 0.00006), but not with UC. CONCLUSIONS: The protective IL-23R R381Q variant was particularly associated with CD in non-Jewish children. Thus, the initial whole genome association study based on ileal CD in adults has been extended to the pediatric population and beyond small bowel CD.

Dubinsky MC, Seidman EG. · Division of Gastroenterology and Nutrition, Sainte Justine Hospital, Department of Pediatrics, University of Montreal, Montreal, Québec, Canada. · Curr Opin Gastroenterol. · Pubmed #17031098 No free full text.

Abstract: The diagnosis of inflammatory bowel disease is usually straightforward, based on a detailed history and physical examination, along with standard radiographic and endoscopic investigations, biopsies, and laboratory parameters. More challenging is the search for clinically useful, noninvasive markers for Crohn disease and ulcerative colitis to accurately screen cases with nonspecific and indolent symptoms. Equally required are diagnostic markers that discriminate between these two disorders in cases with indeterminate colitis. Another dilemma for clinicians is that there are no simple measures to observe disease activity and predict relapses. This review describes the recent advances in diagnostic markers that afford the ability to screen for inflammatory bowel disease, discriminate between its types, and monitor disease activity. These include serological, fecal, and tissue markers; permeability tests; and diagnostic imaging using color Doppler ultrasonography.

Bousvaros A, Sylvester F, Kugathasan S, Szigethy E, Fiocchi C, Colletti R, Otley A, Amre D, Ferry G, Czinn SJ, Splawski JB, Oliva-Hemker M, Hyams JS, Faubion WA, Kirschner BS, Dubinsky MC, Anonymous00395. · Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA. · Inflamm Bowel Dis. · Pubmed #16954808 links to  free full text

Abstract: It is estimated that of the >1 million individuals in the United States with inflammatory bowel disease (IBD), approximately 100,000 are children. IBD that begins in childhood affects the individual at a critical period of growth and development. Children with Crohn's disease and ulcerative colitis may experience complications such as growth failure, school absence, and depression. In addition, because children with IBD have fewer environmental confounders such as smoking, children may be an excellent population to study microbial and immune interactions. Despite these opportunities, the discipline of pediatric IBD investigation is still in its infancy. In September of 2005, a group of investigators with expertise in pediatric IBD met in Boston (Massachusetts) to review the current status of childhood IBD research and to develop research priorities that warranted funding from the Crohn's and Colitis Foundation of America. The group included pediatricians, internists, basic scientists, clinical investigators, and members of the administrative staff and board of the Crohn's and Colitis Foundation of America. The research needs in respective areas were outlined by the heads of 10 focus groups, each with expertise in their respective fields (genetics, psychosocial issues, epidemiology, microbiology, immunology, quality improvement, pharmacogenomics, nutrition, growth and skeletal health, and clinical trials). Before the conference, heads of the research focus groups developed their proposals with experts in the field. At the end of the conference, members of the focus groups and members of the steering committee rated the proposed areas of study in terms of feasibility and importance. It was recommended that the Crohn's and Colitis Foundation of America focus its initial efforts in pediatric IBD in 5 areas: the effects of inflammation on growth and skeletal development, the genetics of early-onset IBD, the development of quality improvement interventions to standardize and improve clinical care of children with IBD, the immunology of childhood IBD, and the diagnosis and treatment of psychosocial sequelae of childhood IBD. At the conclusion of the meeting, investigators discussed the formation of a multicenter collaborative network to advance clinical and basic research in the field.

Mow WS, Lo SK, Targan SR, Dubinsky MC, Treyzon L, Abreu-Martin MT, Papadakis KA, Vasiliauskas EA. · Inflammatory Bowel Disease Center, Los Angeles, California, USA. · Clin Gastroenterol Hepatol. · Pubmed #15017630 No free full text.

Abstract: BACKGROUND AND AIMS: Wireless capsule enteroscopy (WCE) offers the potential to directly visualize the entire small bowel and identify superficial lesions not detected by traditional endoscopy and radiography. The aim of this study is to assess the clinical utility of WCE in the evaluation of patients with known or suspected inflammatory bowel disease (IBD). METHODS: Fifty patients with ongoing symptoms underwent Given M2A endoscopic capsule examinations. Indications included: (1) evaluation for small-bowel involvement in patients with IBD with isolated colitis (n = 22), (2) determination of the extent of small-bowel disease in patients with Crohn's disease (CD; n = 20), and (3) workup of suspected IBD (n = 8). Outcome measures were classified as diagnostic when multiple ulcerations were present, suspicious when </=3 ulcerations were seen, and nonspecific or normal. RESULTS: WCE findings were diagnostic for CD in 20 patients and suspicious for small-bowel CD in 10 patients. Seventeen of 20 patients with diagnostic WCE findings improved with increased IBD-directed medical therapy, as did 7 of 10 patients with suspicious study results. WCE was normal or showed nonspecific findings in the remaining 20 patients. Notably, identification of small-bowel lesions in 5 patients with a previous history of isolated colitis resulted in a change in diagnosis to CD after confirmatory ileoscopy with biopsy. CONCLUSIONS: Results of this preliminary study suggest that WCE is a novel and potentially clinically useful method of directly visualizing and diagnosing small-bowel lesions in patients with IBD that can be missed by traditional endoscopic and radiological procedures.

Dubinsky MC, Ofman JJ, Urman M, Targan SR, Seidman EG. · Department of Pediatrics, University of Montreal, Quebec, Canada. · Am J Gastroenterol. · Pubmed #11280547 No free full text.

Abstract: OBJECTIVES: Confronted with nonspecific symptoms, accurate screening tests would be useful to clinicians to distinguish between functional childhood disorders and inflammatory bowel disease (IBD), thus avoiding invasive diagnostic testing. Traditional ulcerative colitis-specific perinuclear antineutrophil cytoplasmic antibody (pANCA) and Crohn's disease-specific anti-Saccharomyces cerevisiae antibody (ASCA) serodiagnostic assays have recently been modified, with ELISA cut-off values recalculated to maximize sensitivity. The aim of this study was to determine whether the combination of these serodiagnostic tests could maximize diagnostic accuracy and minimize invasive investigations in pediatric patients presenting with nonspecific symptoms suggestive of IBD. METHODS: With investigators blinded to clinical diagnoses, ASCA, ANCA, and pANCA profiles were obtained prospectively from 128 patients undergoing complete diagnostic evaluation for IBD. In phase I, diagnostic accuracy and predictive values of the modified and traditional assays were compared for the IBD (n = 54) and non-IBD groups (n = 74). In phase II, the overall accuracy of a novel sequential diagnostic testing strategy was determined. Additionally, the potential number of invasive investigations avoided with the hypothetical application of this strategy to the cohort was determined. RESULTS: For phase I, the modified serodiagnostic assay was more sensitive (81 vs 69%), whereas the traditional assay had a higher specificity (96 vs 72%) for IBD (p < 0.05) For phase II, false-positive diagnoses would have been reduced by 81%, yielding an overall sequential testing strategy accuracy of 84%. CONCLUSIONS: The incorporation of sequential noninvasive testing into a diagnostic strategy may avoid unnecessary and costly evaluations and facilitate clinical decision making when the diagnosis of IBD in children is initially uncertain.