Ulcerative Colitis: Bousvaros A

Kappelman MD, Bousvaros A. · Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, MA, USA. · Mol Nutr Food Res. · Pubmed #18324705 No free full text.

Abstract: In approximately one-fourth of patients with Crohn's disease (CD) and ulcerative colitis (UC), disease onset occurs during childhood and adolescence. In addition to gastrointestinal and extraintestinal symptoms of inflammatory bowel disease (IBD), children with these conditions often experience one or more nutritional complications of their disease including growth failure, delayed puberty, osteoporosis, anemia, and micronutrient deficiencies. This article provides an overview of the epidemiology, pathophysiology, evaluation, and management of selected nutritional complications in pediatric IBD.

Rufo PA, Bousvaros A. · Children's Hospital Boston, Inflammatory Bowel Disease Center, Boston, Massachusetts 02115, USA. · Curr Opin Gastroenterol. · Pubmed #17545777 No free full text.

Abstract: PURPOSE OF REVIEW: The induction and maintenance of disease remission and prevention of complications are primary goals in the management of inflammatory bowel disease. Recent research has added new insights into the pathogenesis, epidemiology, and treatment options for children with inflammatory bowel disease, and the findings will enable clinicians to develop a more rational approach to the diagnosis and treatment of pediatric patients with ulcerative colitis and Crohn's disease. RECENT FINDINGS: Population-based studies have confirmed the increased incidence of inflammatory bowel disease in children. Previous medical history and serologies can be predictive of complications in Crohn's disease. Newer radiological and capsule endoscopic modalities have a potential future role in the diagnosis and interval assessment of patients with inflammatory bowel disease. Biological therapies play an increasingly prominent role in the management of children with ulcerative colitis and Crohn's disease. Studies of children with inflammatory bowel disease suggest that behavioral interventions may have a positive impact on morbidity and overall quality of life. SUMMARY: New information concerning the natural history of Crohn's disease and ulcerative colitis and a better understanding of different treatment modalities will enable the development of increasingly effective and individualized pharmacological treatment plans for children with inflammatory bowel disease.

Rufo PA, Bousvaros A. · Center for Inflammatory Bowel Diseases, Combined Program in Gastroenterology and Nutrition, Children's Hospital, Boston, Massachusetts 02115, USA. · Paediatr Drugs. · Pubmed #17037946 No free full text.

Abstract: Ulcerative colitis (UC) and Crohn disease (CD) are chronic intestinal inflammatory diseases that can present as bloody diarrhea, abdominal pain, and malnutrition. Collectively, these disorders are referred to as inflammatory bowel disease (IBD). All patients with IBD share a common pathophysiology. However, there are a number of developmental, psychosocial, and physiologic issues that are unique to the approximate, equals 20% of patients that present during childhood or adolescence. These include the possibility of disease-induced delays in linear growth or physical development, differences in drug dosing, and the changes in social and cognitive development that occur as children move from school-age years into adolescence and early adulthood. Gastroenterologists caring for these children must therefore develop an optimal regimen of pharmacologic therapies, nutritional management, psychologic support, and properly timed surgery (when necessary) that will maintain disease remission, minimize disease and drug-induced adverse effects, and optimize growth and development. This article reviews current approaches to the management of patients with UC and CD and highlights issues specific to the treatment of children with IBD. The principal medical therapies used to induce disease remission in patients with UC are aminosalicylates (for mild disease), corticosteroids (for moderate disease), and cyclosporine (ciclosporin) (for severe disease). If a patient responds to the induction regimen, maintenance therapies that are used to prevent disease relapse include aminosalicylates, mercaptopurine, and azathioprine. Colectomy with creation of an ileal pouch anal anastomosis (J pouch) has become the standard of care for patients with severe or refractory colitis and results in an improved quality of life in most patients. Therefore, the risks associated with using increasingly potent immunosuppressant agents must be balanced in each case against a patient's desire to retain their colon and avoid a temporary or potentially permanent ileostomy. Decisions about drug therapy in the management of patients with CD are more complex and depend on both the location (e.g. gastroduodenal vs small intestinal vs colonic), as well as the behavior of the disease (inflammatory/mucosal vs stricturing vs perforating) in a given patient. Induction therapies for CD typically include aminosalicylates and antibiotics (for mild mucosal disease), nutritional therapy (including elemental or polymeric formulas), corticosteroids (for moderate disease), and infliximab (for corticosteroid-resistant or fistulizing disease). Aminosalicylates, mercaptopurine, azathioprine, methotrexate, and infliximab can be used as maintenance therapies. Because surgical treatment of CD is not curative, it is typically reserved for those patients either with persistent symptoms and disease limited to a small section of the intestine (e.g. the terminal ileum and cecum) or for the management of complications of the disease including stricture or abdominal abscess. When surgery is necessary, maintenance medications administered postoperatively will postpone recurrence. Patients with UC and CD are at risk for the development of micronutrient deficiencies (including folate, iron, and vitamin D deficiencies) and require close nutritional monitoring. In addition, patients with UC and CD involving the colon are at increased risk of developing colon cancer, and should be enrolled into a colonoscopy surveillance program after 8-10 years of disease duration.

Bousvaros A, Mueller B. · Division of Gastroenterology, Boston Children's Hospital/Harvard Medical School, Massachusetts 02115, USA. · Drugs. · Pubmed #11398909 No free full text.

Abstract: Thalidomide was originally marketed as a sedative, but was removed from the market in 1961 after it was associated with an epidemic of severe birth defects. Subsequently, it has been shown to have therapeutic efficacy in a number of the gastrointestinal tract conditions characterised by immune dysregulation. The exact mechanism of the immunosuppressive effects of thalidomide is unknown; proposed mechanisms include inhibition of tumour necrosis factor alpha release and inhibition of angiogenesis. In chronic graft versus host disease, use of high dose thalidomide (1200 mg/day) may bring about a response in 20% of patients with refractory disease. Thalidomide 200 mg/day helps eradicate ulcers in 50% of patients with HIV-associated oral aphthous ulceration. In Behçet's disease, thalidomide 100 to 300 mg/day can decrease the number of mucocutaneous ulcers, although full remission occurs in less than 20% of patients. In Crohn's disease, thalidomide 50 to 300 mg/day may decrease the severity of mucosal disease and prompt closure of fistulae. Patients to be placed on thalidomide therapy must practice either abstinence or strict birth control; women must undergo regular pregnancy testing and utilise 2 forms of contraception. Other adverse effects include sedation (present in nearly all patients), symptomatic neuropathy (present in approximately 20%), and skin rashes. Given the potential toxicity, thalidomide use should generally be limited to clinical protocols with institutional review board oversight.

Lu Y, Jacobson DL, Ashworth LA, Grand RJ, Meyer AL, McNeal MM, Gregas MC, Burchett SK, Bousvaros A. · Division of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, Children's Hospital Boston, Boston, Massachusetts 02115, USA. · Am J Gastroenterol. · Pubmed #19174786 No free full text.

Abstract: OBJECTIVES: Patients with inflammatory bowel disease (IBD) frequently receive immunosuppressive therapy. The immune response in these patients to vaccines has not been well studied. We conducted a prospective, open label study to evaluate the serologic response to influenza vaccine in children with IBD. METHODS: Serum was obtained from 146 children and young adults with IBD (96 Crohn's disease, 47 ulcerative colitis, and 3 indeterminate colitis) for baseline influenza titer, immediately followed by immunization with trivalent (A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 (B)) inactivated influenza vaccine. Patients returned for repeat titers 3-9 weeks later. Seroprotection against each influenza strain was defined as hemagglutination inhibition titer > or = 40. Patients were categorized as nonimmunosuppressed (NIS; aminosalicylates only, antibiotics only, or no therapy) or immunosuppressed (IS; any immunosuppressive agent). IS patients were further subcategorized as: (i) tacrolimus, (ii) tumor necrosis factor-alpha (TNF-alpha) inhibitor, (3) immunomodulator, and (4) corticosteroids only. RESULTS: More patients were seroprotected against strains A/H1N1 and A/H3N2 than B strain (P<0.02), regardless of immunosuppression status. The proportion of seroprotected patients and geometric mean titers at post-vaccination were similar between NIS and IS groups for all three strains. Subanalysis of patients not seroprotected at baseline showed that those receiving anti-TNF therapy were less likely to be seroprotected against strain B (14%) compared to patients in the NIS group (39%, P=0.025). There were no serious vaccine-associated adverse events. CONCLUSIONS: Influenza vaccination produces a high prevalence of seroprotection in IBD patients, particularly against A strains. The vaccine is well tolerated. Routine influenza vaccination in IBD patients is recommended, irrespective of whether patients receive immunosuppressive medications.

Bitton A, Peppercorn MA, Antonioli DA, Niles JL, Shah S, Bousvaros A, Ransil B, Wild G, Cohen A, Edwardes MD, Stevens AC. · Gastroenterology Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. · Gastroenterology. · Pubmed #11208709 No free full text.

Abstract: BACKGROUND & AIMS: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. We aimed to assess whether clinical, biological, and histologic parameters in quiescent UC predict time to clinical relapse. METHODS: Seventy-four patients with clinically and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse. Serum erythrocyte sedimentation rate; C-reactive protein, interleukin (IL)-1beta, IL-6, and IL-15 values; anti-neutrophil cytoplasmic antibody titers; and rectal biopsy specimens were obtained at baseline, at 6 and 12 months, and/or at relapse. Multivariate survival analysis was performed to determine independent predictors of clinical relapse. RESULTS: Twenty-seven patients relapsed (19/42 women; 8/32 men). Multivariate Cox regression analysis retained younger age (P = 0.003; hazard ratio, 0.4 per decade), greater number of prior relapses in women (P < 0.001; hazard ratio, 1.6 per prior relapse), and basal plasmacytosis (P = 0.003; hazard ratio, 4.5) on rectal biopsy specimens as predictors of shorter time to clinical relapse. Kaplan-Meier survival curves showed the 20-30-year-old age group and women with more than 5 prior relapses to be groups with shorter times to relapse. CONCLUSIONS: Younger age, multiple previous relapses (for women), and basal plasmacytosis on rectal biopsy specimens were independent predictors of earlier relapse. These findings may help identify patients with inactive UC who will require optimal maintenance medical therapy.

Bousvaros A, Kirschner BS, Werlin SL, Parker-Hartigan L, Daum F, Freeman KB, Balint JP, Day AS, Griffiths AM, Zurakowski D, Ferry GD, Leichtner AM. · Combined Program in Pediatric Gastroenterology and Nutrition, Boston Children's Hospital, Boston, Massachusetts 02115, USA. · J Pediatr. · Pubmed #11113835 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy of oral tacrolimus as an induction agent in steroid-refractory severe colitis. STUDY DESIGN: Open-label, multicenter trial of oral tacrolimus in patients with severe colitis. Patients not responding to conventional therapy received tacrolimus, 0.1 mg/kg/dose given twice a day, and the dosage was adjusted to achieve blood levels between 10 and 15 ng/mL. Response was defined as improvement in a number of clinical parameters (including abdominal pain, diarrhea, rectal bleeding, and cessation of transfusions). Patients who responded by 14 days continued to receive tacrolimus, and 6-mercaptopurine or azathioprine was added as a steroid-sparing agent 4 to 6 weeks after the tacrolimus was instituted. RESULTS: Fourteen patients were enrolled in the study. One patient elected to withdraw after 48 hours. Of the 13 remaining, 9 (69%) responded and were discharged. Tacrolimus was continued for 2 to 3 months in the responders, except for 1 patient who was given tacrolimus for 11 months. After 1 year of follow-up, only 5 (38%) patients were receiving maintenance therapy; the other 4 responders had undergone colectomy. CONCLUSION: Although tacrolimus is effective induction therapy for severe ulcerative or Crohn's colitis, fewer than 50% of patients treated will successfully achieve a long-term remission.

Turner D, Hyams J, Markowitz J, Lerer T, Mack DR, Evans J, Pfefferkorn M, Rosh J, Kay M, Crandall W, Keljo D, Otley AR, Kugathasan S, Carvalho R, Oliva-Hemker M, Langton C, Mamula P, Bousvaros A, LeLeiko N, Griffiths AM, Anonymous00063. · Pediatric Gastroenterology Unit, Shaare Zedek Medical Center, Jerusalem, Israel. · Inflamm Bowel Dis. · Pubmed #19161178 No free full text.

Abstract: BACKGROUND: We evaluated the psychometric performance of the Pediatric Ulcerative Colitis Activity Index (PUCAI) in a real-life cohort from the Pediatric IBD Collaborative Research Group. METHODS: Two consecutive visits of 215 children with ulcerative colitis (UC) were included (mean age 11.2 +/- 3.6 years; 112 (52%) males; 63 (29%) newly diagnosed and the others after disease duration of 24 +/- 15.6 months). Validity was assessed using several constructs of disease activity. Distributional and anchor-based strategies were used to assess the responsiveness of the PUCAI to change over time following treatment. RESULTS: Reflecting feasibility, 97.6% of 770 eligible registry visits had a completed PUCAI score versus only 47.6% for a contemporaneously collected Pediatric Crohn's Disease Activity Index (odds ratio = 45.8, 95% confidence interval [CI] 28.6-73.5) obtained for children with Crohn's disease accessioned into the same database. The PUCAI score was significantly higher in patients requiring escalation of medical therapy (45 points [interquartile range, IQR, 30-60]) versus those who did not, (0 points [IQR 0-10]; P < 0.001), and was highly correlated with physician's global assessment of disease activity (r = 0.9, P < 0.001). The best cutoff to differentiate remission from active disease was 10 points (area under receiver operating characteristic curve [AUC] 0.94; 95% CI 0.90-0.97). Test-retest reliability was excellent (intraclass correlation coefficient = 0.89; 95% CI 0.84-0.92, P < 0.001) as well as responsiveness to change (AUC 0.96 [0.92-0.99]; standardized response mean 2.66). CONCLUSION: This study on real-life, prospectively obtained data confirms that the PUCAI is highly feasible by virtue of the noninvasiveness, valid, and responsive index. The PUCAI can be used as a primary outcome measure to reflect disease activity in pediatric UC.

Kugathasan S, Nebel J, Skelton JA, Markowitz J, Keljo D, Rosh J, LeLeiko N, Mack D, Griffiths A, Bousvaros A, Evans J, Mezoff A, Moyer S, Oliva-Hemker M, Otley A, Pfefferkorn M, Crandall W, Wyllie R, Hyams J, Anonymous00137, Anonymous00138. · Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · J Pediatr. · Pubmed #17961699 No free full text.

Abstract: OBJECTIVE: To conduct a systematic review of children with newly diagnosed inflammatory bowel disease (IBD) from 2 prospective inception cohorts to examine body mass index (BMI) status at presentation. STUDY DESIGN: Clinical, demographic, and BMI data were obtained from 783 patients with newly diagnosed IBD. National Health and Nutrition Examination Survey data for 2748 healthy children were used as a control. RESULTS: Most children with Crohn's disease and ulcerative colitis had a BMI in the normative range (5%-84%). Low BMI (<5%) was seen in 22% to 24% of children with Crohn's disease and 7% to 9% of children with ulcerative colitis. Ten percent of children with Crohn's disease and 20% to 30% of children with ulcerative colitis had a BMI at diagnosis consistent with overweight or risk for overweight. CONCLUSION: Children with IBD are affected by current population trends toward overweight. A significant subgroup of children with newly diagnosed IBD has a BMI categorized as overweight or at risk for overweight. Clinicians should be aware of possible IBD diagnosis in the presence increased BMI.

Kappelman MD, Rifas-Shiman SL, Kleinman K, Ollendorf D, Bousvaros A, Grand RJ, Finkelstein JA. · Center for Inflammatory Bowel Disease, Division of Gastroenterology and Nutrition, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA. · Clin Gastroenterol Hepatol. · Pubmed #17904915 No free full text.

Abstract: BACKGROUND & AIMS: Previous US studies of inflammatory bowel disease (IBD) prevalence have sampled small, geographically restricted populations and may not be generalizable to the entire nation. This study sought to determine the prevalence of Crohn's disease (CD) and ulcerative colitis (UC) in a large national sample and to compare the prevalence across geographic regions and other sociodemographic characteristics. METHODS: We analyzed the health insurance claims for 9 million Americans, pooled from 87 health plans in 33 states, and identified cases of CD and UC using diagnosis codes. Prevalence was determined by dividing the number of cases by the number of persons enrolled for 2 years. Logistic regression was used to compare prevalence estimates by geographic region, age, sex, and insurance type (Medicaid vs commercial). RESULTS: The prevalence of CD and UC in children younger than 20 years was 43 (95% confidence interval [CI], 40-45) and 28 (95% CI, 26-30) per 100,000, respectively. In adults, the prevalence of CD and UC was 201 (95% CI, 197-204) and 238 (95% CI, 234-241), respectively. The prevalence of both conditions was lower in the South, compared with the Northeast, Midwest, and West. IBD appears to be more common in commercially insured individuals, compared with those insured by Medicaid. CONCLUSIONS: This estimation of the prevalence of IBD in the US should help quantify the overall burden of disease and inform the planning of appropriate clinical services.

Mack DR, Langton C, Markowitz J, LeLeiko N, Griffiths A, Bousvaros A, Evans J, Kugathasan S, Otley A, Pfefferkorn M, Rosh J, Mezoff A, Moyer S, Oliva-Hemker M, Rothbaum R, Wyllie R, delRosario JF, Keljo D, Lerer T, Hyams J, Anonymous00371. · Department of Pediatrics, Children's Hospital of Eastern Ontario, 401 Smyth Rd, Ottawa, Ontario, Canada K1H 8L1. · Pediatrics. · Pubmed #17545378 links to  free full text

Abstract: OBJECTIVE: The goal was to determine how often common laboratory tests yield normal results at the time of diagnosis for children with inflammatory bowel disease. METHODS: Data were obtained from a registry of children with newly diagnosed inflammatory bowel disease who were enrolled prospectively in 18 US/Canadian centers. Laboratory values investigated included hemoglobin level, platelet count, albumin level, and erythrocyte sedimentation rate. Disease severity was categorized by physician global assessment. RESULTS: A total of 526 children (mean age: 11.6 years; 58% male; 392 with Crohn disease and 134 with ulcerative colitis) were studied. All 4 values were normal for 21% of patients with mild Crohn disease and 54% with mild ulcerative colitis. In contrast, only 3.8% of children with moderate/severe Crohn disease and 4.3% with moderate/severe ulcerative colitis had normal results for all 4 tests. The erythrocyte sedimentation rate was least likely to be normal; overall, 26% of patients with inflammatory bowel disease had a normal erythrocyte sedimentation rate, including 18% with moderate/severe disease. Hemoglobin levels were normal for 32%, platelet counts for 50%, and albumin levels for 60%. There was no clear association between Crohn disease location and either severity or number of normal laboratory values. In contrast, there were direct correlations between ulcerative colitis disease severity and both the extent of bowel inflammation and the number of abnormal laboratory tests. CONCLUSION: The presence of normal screening laboratory studies should not dissuade clinicians from considering a diagnosis of inflammatory bowel disease.

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.

Hait EJ, Bousvaros A, Schuman M, Shamberger RC, Lillehei CW. · The Center for Inflammatory Bowel Disease, Children's Hospital Boston, Harvard University, Boston, MA 02115, USA. · J Pediatr Surg. · Pubmed #17208537 No free full text.

Abstract: PURPOSE: The purpose of this article is to describe the outcomes of the pouches of 14 children with ulcerative colitis (UC) who were pretreated with calcineurin inhibitors before they underwent their ileal pouch anal anastomosis (IPAA) surgery. METHODS: An institutional review board-approved retrospective review of the charts of consecutive patients with UC treated with calcineurin inhibitors before undergoing IPAA surgery at a tertiary pediatric center between 1998 and 2003 was performed. The primary endpoint was pouch outcome after at least 2 years of follow-up (healthy pouch, acute pouchitis, chronic refractory pouchitis, or pouch failure); the secondary endpoints were early postoperative complications, number of stages, and time between stages. RESULTS: Fourteen of 53 consecutive patients who underwent IPAA for UC were treated with calcineurin inhibitors before their surgery (26%; 6 with cyclosporine and 8 with tacrolimus). All 14 patients were concomitantly treated with systemic steroids. Ten patients (71%) were also taking 6-mercaptopurine or azathioprine, and 9 (64%) were also taking mesalamine. Three patients (21%) had healthy pouches with no clinical evidence of pouchitis, 6 (43%) had at least one episode of acute pouchitis (average of 2 episodes per year), 3 (21%) had chronic relapsing pouchitis, and 2 (14%) were later determined to have Crohn's disease. There was no pouch failure. Two patients (14%) had an early postoperative complication (intraabdominal abscess, anastomotic stricture). Five patients (36%) had a 2-staged procedure, and 8 (64%) had a 3-staged procedure. For the 2-staged procedures, the mean time between the first and second stages was 3.14 months (range, 3-4 months). For the 3-staged procedures, the mean time between the first and second stages was 4.25 months (range, 2-6 months) and that between the second and third stages was 4 months (range, 2.5-6 months). CONCLUSIONS: In this series, chronic pouchitis was an infrequent complication among children who were pretreated with calcineurin inhibitors. Calcineurin inhibitor use did not lead to or portend increased early postoperative complications or affect the number or duration of surgical stages. Further studies are required to determine if preoperative calcineurin inhibitors improve pouch outcomes or facilitate the performance of 2-staged procedures.

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.

Otley AR, Griffiths AM, Hale S, Kugathasan S, Pfefferkorn M, Mezoff A, Rosh J, Tolia V, Markowitz J, Mack D, Oliva-Hemker M, Wyllie R, Rothbaum R, Bousvaros A, Del Rosario JF, Evans J, Blanchard W, Hyams J, Anonymous00277. · FRCPC, Division of Gastroenterology & Nutrition, IWK Health Centre, Halifax, Nova Scotia, Canada. · Inflamm Bowel Dis. · Pubmed #16917222 No free full text.

Abstract: BACKGROUND AND AIMS: Assessment of health-related quality of life (HRQOL) is of increasing importance in the evaluation of new therapies for inflammatory bowel disease (IBD). Available data concerning HRQOL in pediatric patients are sparse and uniformly cross-sectional. The aim of this study was to describe HRQOL and influential factors in newly diagnosed pediatric patients with Crohn's disease and ulcerative colitis during the first 12 months after diagnosis. MATERIALS AND METHODS: Participants were drawn from a large, prospectively derived observational IBD registry of pediatric patients studied through 18 U.S. and Canadian centers. Patients who had completed a baseline IMPACT questionnaire and for whom there were 12 months of follow-up data available were included. In addition to description of cohort, factors that were believed to influence HLQOL were assessed during the course of the year from diagnosis. RESULTS: Two hundred eighteen children met inclusion criteria (77% Crohn's disease, 23 % ulcerative colitis, mean age 12.7 +/- 1.9 years). Mean total IMPACT score at baseline was 154, 181 at 6 months, and 191 at 1 year (possible range 0-238, with increasing scores representing better quality of life). Repeated measures analysis showed that age and disease severity significantly negatively affected the IMPACT scores during the course of the year. CONCLUSIONS: In this large prospective pediatric IBD cohort, significant improvement in HRQOL is noted during the year from diagnosis. Mean IMPACT scores varied significantly depending on the disease severity and also decreased with increasing age.

Hyams J, Markowitz J, Lerer T, Griffiths A, Mack D, Bousvaros A, Otley A, Evans J, Pfefferkorn M, Rosh J, Rothbaum R, Kugathasan S, Mezoff A, Wyllie R, Tolia V, delRosario JF, Moyer MS, Oliva-Hemker M, Leleiko N, Anonymous00069. · Connecticut Children's Medical Center, Hartford, Connecticut, USA. · Clin Gastroenterol Hepatol. · Pubmed #16820327 No free full text.

Abstract: BACKGROUND & AIMS: The aim of this study was to determine the clinical outcome after corticosteroid therapy in children who are newly diagnosed with ulcerative colitis (UC). METHODS: Data were gathered prospectively from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry database between January 2002 and March 2005. All children who were newly diagnosed with inflammatory bowel disease younger than the age of 16 years were managed according to the dictates of their respective physicians. Demographic, clinical, and laboratory data were collected at diagnosis, at 30 days, and then quarterly. Patients were classified as corticosteroid responsive, corticosteroid dependent, or refractory, and outcomes were determined at 3 months and at 1 year. RESULTS: Ninety-seven patients had a diagnosis of UC and a minimum of 1 year of follow-up evaluation; 77 (79%) received corticosteroids (62 within 30 days of diagnosis [early] and 15 between 31 days and 6 months [late]). At diagnosis, 81% of corticosteroid-treated patients (age, 11.3 +/- 3.5 y) had moderate/severe disease, and 81% had pancolitis. For those treated early with corticosteroids, disease activity at 3 months was inactive in 60%, mild in 27%, and moderate/severe in 11%. At 1 year, 31 of 62 (50%) of the early corticosteroid-treated patients were considered corticosteroid responsive and 28 (45%) were corticosteroid dependent. A total of 4 patients receiving corticosteroids (5%) required colectomy in the first year. Immunomodulators were used in 61% of all corticosteroid-treated patients. CONCLUSIONS: Although short-term clinical response to corticosteroids in children with newly diagnosed UC is excellent, even with the common use of immunomodulators corticosteroid dependence is seen in 45% of patients.

Hande S, Wilson-Rich N, Bousvaros A, Zholudev A, Maurer R, Banks P, Makrauer F, Reddy S, Burakoff R, Friedman S. · Brigham and Women's Hospital, Boston, Massachusetts, USA. · Inflamm Bowel Dis. · Pubmed #16633046 links to  free full text

Abstract: BACKGROUND: Small uncontrolled trials have suggested that 5-aminosalicylate (5-ASA) medications increase 6-thioguanine nucleotide (6-TGn) levels in adults with Crohn's disease (CD) on azathioprine (AZA) or 6-mercaptopurine (6-MP), presumably through the inhibition of thiopurine methyltransferase (TPMT). We tested the theory that coadministration of 5-ASA agents with AZA/6-MP results in higher 6-TGn levels in a large cohort of children and adults with CD or ulcerative colitis (UC). METHODS: A retrospective cohort study identified all children and adults treated for IBD with AZA/6-MP at 2 tertiary medical centers. Patients were included if their TPMT genotype was known and 6-TGn and 6-methymercaptopurine (6-MMP) levels had been obtained after 3 months of clinical remission at a stable dose of AZA/6-MP. 6-TGn and 6-MMP levels were compared between patients taking and those not taking 5-ASA medications through the use of linear regression models to identify and adjust for potentially confounding variables. RESULTS: Of the 126 patients included, 88 were taking 5-ASA medications. Patients on 5-ASA agents had higher mean 6-TGn levels after adjustment for confounding variables (Delta6-TGn, 47.6 +/- 21.8 pmol/8 x 10 red blood cells; P = 0.03). CD and TPMT heterozygosity was independently associated with higher 6-TGn levels (P = 0.01 and P = 0.03, respectively). 5-ASA exposure was not associated with a change in 6-MMP levels. CONCLUSIONS: We found that 5-ASA therapy is associated with higher 6-TGn levels in children and adults with IBD on 6-MP/AZA. TPMT inhibition may not explain this effect because 5-ASA exposure did not affect 6-MMP levels. The observed association of CD with higher 6-TGn levels is novel and needs to be verified in prospective studies.

Zholudev A, Zurakowski D, Young W, Leichtner A, Bousvaros A. · Inflammatory Bowel Disease Center, Division of Gastroenterology and Nutrition, Children's Hospital Boston, Boston, Massachusetts 02115, USA. · Am J Gastroenterol. · Pubmed #15555007 No free full text.

Abstract: OBJECTIVES: Serologic testing is increasingly being utilized to evaluate children with suspected inflammatory bowel disease (IBD). The aim of this paper was to evaluate the sensitivity and specificity of a currently available panel involving four antibodies: deoxyribonuclease (DNase)-sensitive perinuclear antineutrophil cytoplasmic antibody (DNase-sensitive pANCA), IgA and IgG antibodies to Saccharomyces cerevisiae (IgA and IgG ASCA), and antibody to Escherichia coli outer membrane porin (anti-OmpC). We also wished to determine whether antibody levels correlated with disease activity, and whether a specific antibody pattern correlated with location and outcome of disease in children. METHODS: We studied sera from 81 children with Crohn's disease (CD), 54 with ulcerative colitis (UC), and 63 controls. Clinical data, disease activity, and disease diagnosis were gathered at the time of serum sampling, and charts were re-reviewed at time of the study to determine long-term outcome. Enzyme-linked immunosorbent assay was utilized to determine titers of antibodies to ASCA, DNase-sensitive pANCA, and anti-OmpC; the presence of perinuclear staining for ANCA was confirmed by immunofluorescence. RESULTS: We identified ASCA antibodies in 44% of CD patients, 0% of UC patients, and 1 control patient. DNase-sensitive pANCA antibodies were found in 70% of patients with UC, 18% of CD patients (predominantly Crohn's colitis), and 3% of controls. Anti-OmpC as an isolated assay had low sensitivity for both CD (24%) and UC (11%), and displayed a 5% false-positive rate. However, anti-OmpC did identify a small number of IBD patients not detected by the other assays. If any one or more of the four antibodies was positive, the overall sensitivity of the four antibody panel was 65% for CD and 76% for UC, with a specificity of 94%. Patients who were ASCA-positive were more likely to have disease of the ileum or ileum and right colon than patients who were ASCA-negative (58%vs 18%, p < 0.001). Patients with ASCA-positive were also more likely to require ileocecal resection (36%vs 13%, p < 0.05). CONCLUSIONS: A currently available commercial antibody panel has good sensitivity and excellent specificity for CD and UC. The ASCA antibodies, while highly specific for CD, identify predominantly the subset of children with disease of the ileum and ascending colon who may be at increased risk of surgery.

Glickman JN, Bousvaros A, Farraye FA, Zholudev A, Friedman S, Wang HH, Leichtner AM, Odze RD. · Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. · Am J Surg Pathol. · Pubmed #15043308 No free full text.

Abstract: BACKGROUND: Anecdotal observations by the authors of this study, together with the results of a few previous smaller studies, suggest that children with new-onset (previously untreated) ulcerative colitis (UC) may occasionally present with discontinuous disease, relative or absolute rectal sparing, and may lack histologic features ofchronicity. Therefore, the objectives of this study were to determine the clinical and pathologic features of new-onset UC in children and to compare the initial presentation of UC in this group with a control group of adults. DESIGN: Routinely processed rectal and colonic mucosal biopsies from 73 pediatric (male/female ratio 33/40, mean age 11.5 years, range 2.5-18 years) and 38 adult patients (male/female ratio 15/23, mean age 41.5 years, range 27-64 years) who presented with new-onset UC were evaluated for a variety of clinical and pathologic features, including duration of symptoms prior to presentation, crypt architectural (e.g., atrophy, branching) and nonarchitectural (e.g., basal plasmacytosis, Paneth cell metaplasia) features of chronicity, degree of active inflammation, and distribution and extent of disease. RESULTS: A significant proportion of children with new-onset UC had patchiness of microscopic features of chronicity (21% of patients), relative (23%), or absolute (3%), rectal sparing, and had little or no crypt architectural distortion in their rectal biopsies (8%). These features were not observed in adult patients with UC. In addition, a higher proportion of children with UC initially presented with subtotal or with pancolitis compared with the adults (42% vs. 11%; P < 0.002). CONCLUSIONS: A significant proportion of children with new-onset UC may show unusual patterns of disease. Pathologists should be aware of these findings since they have significant implications for the differential diagnosis of pediatric inflammatory bowel disease.

Heuschkel R, Afzal N, Wuerth A, Zurakowski D, Leichtner A, Kemper K, Tolia V, Bousvaros A. · Center for Pediatric Gastroenterology, Royal Free Hospital, London, United Kingdom. · Am J Gastroenterol. · Pubmed #11866277 No free full text.

Abstract: OBJECTIVES: We examined the use of complementary alternative medicine (CAM) in children and young adults with inflammatory bowel disease. METHODS: After validation of a questionnaire and completion of a pilot survey, children and young adults with inflammatory bowel disease were enrolled in three centers of pediatric gastroenterology (Boston, Detroit, and London). RESULTS: Two hundred eight questionnaires were completed in total (Boston, 120; Detroit, 37; London, 51). Ages ranged from 3.8 to 23.0 yr, 58% were male, 57% had Crohn's disease, and 35% had ulcerative colitis. The frequency of CAM use was 41%. The most common CAMs were megavitamin therapy (19%), dietary supplements (17%), and herbal medicine (14%). Parental CAM use and the number of adverse effects from conventional medicines were predictors of CAM use (odds ratio = 1.9, 95% CI = 1.2-3.1, p = 0.02; odds ratio = 1.3, 95% CI = 1.2-1.5, p < 0.001, respectively). The most important reasons respondents gave for using CAM were side effects from prescribed medicines, prescribed medicines not working as well as they had hoped, and hoping for a cure. Fifty-nine percent of respondents not taking CAM were interested in learning more about it. CONCLUSIONS: In our survey over 40% of children with chronic inflammatory bowel disease used complementary medicine in addition to conventional therapies. Parental CAM use and number of adverse effects from conventional therapies were the only independent predictors of CAM use. Some complementary therapies have potential for adverse effects and for drug interactions with conventional treatments. Physicians should take a thorough history of CAM use in children with chronic inflammatory bowel disease.

Higuchi LM, Joffe S, Neufeld EJ, Weisdorf S, Rosh J, Murch S, Devenyi A, Thompson JF, Lewis JD, Bousvaros A. · Combined Program in Pediatric Gastroenterology and Nutrition, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #11740233 No free full text.

Abstract: OBJECTIVE: Previous reports suggest an association between inflammatory bowel disease (IBD) and immune thrombocytopenic purpura (ITP) in adults. To date, only five children with both diseases have been described. The aim of the study was to describe the characteristics of children with IBD and ITP. METHODS: Cases were obtained from the pediatric gastroenterology community by means of the pediatric gastroenterology internet bulletin board in June 1999. Eight cases were submitted from seven medical centers. Medical records were reviewed by two pediatric gastroenterologists and a pediatric hematologist. RESULTS: The age range of the patients was 2.1 to 16.5 years, with a mean age of 9.6 +/- 5.2 years. Four children had ulcerative colitis, three had Crohn disease, and one had indeterminate colitis. All had colonic involvement of IBD. Of eight patients, three had IBD first, three had ITP first, and two had both simultaneously. At ITP diagnosis, platelet count was less than 10,000/mL in five children, 17,000/mL in one child, and 50,000 to 60,000/mL in two children. Of the three children diagnosed with ITP first, two initially had rectal bleeding at the time of ITP diagnosis. Bone marrow evaluations, performed in six of eight children, were consistent with ITP. Six of the eight children had chronic ITP, including three children who were 5 years of age or younger. Therapy for ITP included steroids (n = 6), intravenous immunoglobulin (n = 6), Rh o (D) intravenous immunoglobulin (n = 2), and splenectomy (n = 1). CONCLUSIONS: The authors describe the largest pediatric case series of children with IBD and ITP. More than 50% of the children had the chronic form of ITP. Most patients responded to conventional therapy for ITP and IBD.

Srivastava M, Zurakowski D, Cheifetz P, Leichtner A, Bousvaros A. · Combined Program in Gastroenterology and Nutrition, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, U.S.A. · J Pediatr Gastroenterol Nutr. · Pubmed #11740227 No free full text.

Abstract: BACKGROUND: Elevated serum levels of several potent angiogenesis factors, including vascular endothelial growth factor and basic fibroblast growth factor have been described in children with active inflammatory bowel disease. Angiogenesis-promoting cytokines may promote inflammation by increasing vascular permeability but also mediate tissue repair by activating fibroblasts. Hepatocyte growth factor (HGF) is another angiogenesis-promoting cytokine that is increased in colon cancer tissues. We therefore evaluated serum HGF levels in individuals with Crohn disease and ulcerative colitis. METHODS: Serum samples were obtained from 60 patients with Crohn disease, 31 with ulcerative colitis, and 38 controls with functional abdominal pain and other gastrointestinal illnesses. Disease activity for Crohn disease patients was determined using the pediatric Crohn disease activity index, and for ulcerative colitis patients using the Kozarek score. The HGF levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum HGF levels were significantly ( P < 0.001) higher for Crohn disease patients (1439 +/- 84 pg/mL) and ulcerative colitis patients (1384 +/- 107 pg/mL) than for control patients (807 +/- 50 pg/mL). Serum HGF levels also rose with increasing disease activity in individuals with both Crohn disease and ulcerative colitis. CONCLUSION: Serum HGF is elevated in children and young adults who have Crohn disease or ulcerative colitis. Levels of serum HGF correlate directly with disease activity. The raised serum HGF suggests that HGF may mediate angiogenesis and vascular permeability in the mucosa of children with inflammatory bowel disease. Alternatively, the raised serum HGF may be an epiphenomenon of inflammation.

Bousvaros A, Marcon M, Treem W, Waters P, Issenman R, Couper R, Burnell R, Rosenberg A, Rabinovich E, Kirschner BS. · Combined Program in Pediatric Gastroenterology and Nutrition, Children's Hospital, Boston, Massachusetts 02115, USA. · Dig Dis Sci. · Pubmed #10630504 No free full text.

Abstract: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare disease of children characterized by aseptic inflammation of the long bones and clavicles. No infectious etiology has been identified, and CRMO has been associated with a number of autoimmune diseases (including Wegener's granulomatosis and psoriasis). The relationship between CRMO and inflammatory bowel disease is poorly described. Through an internet bulletin board subscribed to by 500 pediatric gastroenterologists, we identified six inflammatory bowel disease patients (two with ulcerative colitis, four with Crohn's colitis) with confirmed CRMO. In all cases, onset of the bony lesions preceded the onset of bowel symptoms by as much as five years. Immunosuppressive therapy for the bowel disease generally resulted in improvement of the bone inflammation. Chronic recurrent multifocal osteomyelitis should be considered in any inflammatory bowel disease patient with unexplained bone pain or areas of uptake on bone scan. CRMO may be a rare extraintestinal manifestation of inflammatory bowel disease; alternatively, certain individuals may be genetically predisposed to the development of both diseases.

Bousvaros A, Leichtner A, Zurakowski D, Kwon J, Law T, Keough K, Fishman S. · Department of Research Computing and Biostatistics, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. · Dig Dis Sci. · Pubmed #10063933 No free full text.

Abstract: Vascular endothelial growth factor (VEGF) is a cytokine released by fibroblasts, epithelial cells, and leukocytes that potentiates vascular permeability and growth of new capillaries. Because of these multiple effects, VEGF has been postulated to play a role in the pathogenesis of autoimmune disease, as well as in wound healing. We hypothesized that VEGF was potentially important in mediating the vascular permeability and angiogenesis seen in Crohn's disease, and therefore that VEGF would be increased in the serum of children with Crohn's disease. Serum was obtained from 73 children and young adults with Crohn's disease, 47 with ulcerative colitis, and 29 controls. VEGF levels were measured by enzyme-linked immunosorbent assay. Mean VEGF levels were significantly higher in patients with Crohn's disease (436.4 +/- 37.2 pg/ml) than in ulcerative colitis (306 +/- 41.1 pg/ml) or control (167.8 +/- 29.6 pg/ml) patients. Serum VEGF also correlated significantly with disease activity, being elevated in patients with moderate/severe Crohn's disease and ulcerative colitis. We conclude that serum VEGF is released by inflamed tissues in children with Crohn's disease. This multifunctional cytokine could promote inflammation by increasing vascular permeability or promote wound healing by mediating capillary growth.

Zholudev A, Rifai N, Zurakowski D, Bousvaros A. · No affiliation provided · Inflamm Bowel Dis. · Pubmed #15905715 No free full text.

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