Marsha Kay

Long-term outcome of maintenance infliximab therapy in children with Crohn's disease

Background: Infliximab therapy has short‐term benefits in children with moderate‐to‐severe Crohns disease (CD). We assessed the long‐term outcome of infliximab maintenance therapy in children with CD. Methods: We performed a multicenter cohort study of 729 pediatric patients with CD enrolled in the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry. Children younger than 16 years and newly diagnosed with CD were eligible for this study. Disease and medication information were collected prospectively from the treating physician at diagnosis, 30 days, and quarterly thereafter. No interventions were specified, per protocol. Results: In all, 202 of 729 patients received infliximab: 62%, 23%, and 15% within 1, 1–2, and >2 years of diagnosis, respectively. The mean age at infliximab initiation was 12.7 years. A total of 158 infliximab‐treated patients received maintenance therapy, 29 episodic (8 converted to maintenance), and 15 had incomplete follow‐up. Among 128 patients administered maintenance infliximab and followed for ≥1 year, concomitant medications at infliximab initiation included corticosteroids (52%) and immunomodulators (90%). By 1, 2, and 3 years, <10% of patients continuing on maintenance infliximab were receiving corticosteroids (P < 0.001). Following maintenance therapy initiation, 26%, 44%, and 33% of patients continuing on maintenance infliximab over 0–1, 1–2, and 2–3 years, respectively, had clinically inactive disease not requiring corticosteroids or surgery. The likelihood of continuing maintenance infliximab at 1, 2, and 3 years was 93%, 78%, and 67%, respectively. Conclusions: Infliximab maintenance therapy was a durable and effective treatment that was associated with prolonged corticosteroid withdrawal over a 3‐year period in children with CD.

Appraisal of the pediatric ulcerative colitis activity index (PUCAI)

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 Crohns Disease Activity Index (odds ratio = 45.8, 95% confidence interval [CI] 28.6–73.5) obtained for children with Crohns 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 physicians 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. (Inflamm Bowel Dis 2009)

Caustic ingestions in children

Purpose of review The purpose of this review is to outline the current epidemiology, mechanism of injury, clinical manifestations, management and long-term complications of caustic ingestions in pediatric patients. Recent findings Recent data suggest that more than 200 000 exposures to household or industrial cleaning products occur annually in the United States. It is difficult to determine what fraction of these exposures represents caustic ingestions. Caustic ingestions occur most commonly in children less than age 6 years. Because of the accidental nature of the ingestions, the case fatality rate for pediatric patients is significantly less than that of adolescents and adults. Despite laws to limit the concentration of household cleaning products, farm and industrial products and products stored in nonoriginal containers represent a significant source of caustic agents. Endoscopy remains the preferred method of staging injury. In children the absence of symptoms does not predict lack of relevant injury. However, the presence of three or more symptoms is associated with a high likelihood of significant injury. Long-term complications in pediatric patients may be severe and include esophageal cancer. Summary Caustic ingestions remain a significant cause of pediatric morbidity in the United States and abroad. Endoscopy is the primary method of staging injury following a caustic ingestion. Extent of injury at initial evaluation remains the best predictor of morbidity and mortality in pediatric patients following an accidental caustic ingestion.

Outcome following infliximab therapy in children with ulcerative colitis

OBJECTIVES:Infliximab is effective in treating moderate/severe ulcerative colitis (UC) in adults. The aim of this study was to determine the outcome after treatment with infliximab in pediatric UC.METHODS:We performed a multicenter cohort study of 332 pediatric patients with UC enrolled in the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry. Children ≤16 years of age and newly diagnosed with UC are enrolled in the registry. Disease and medication information are collected prospectively from the treating physician at diagnosis, 30 days, and quarterly thereafter. No interventions were specified, per protocol.RESULTS:Of 332 patients, 52 (16%) received infliximab (23% <3 months from diagnosis, 38% 3–12 months, 38% >12 months). Mean age at infliximab initiation was 13.3±2.6 (range 6–17) years; 87% of patients had pancolitis. Median follow-up was 30 months. Continuous maintenance (CM) therapy was given in 65%, episodic in 21%, episodic converted to CM in 6%, and insufficient data in 8% of patients. Sixty-three percent of patients were corticosteroid refractory, and 35% were corticosteroid dependent. Concomitant medications at first infliximab infusion included corticosteroids (87%), thiopurines (63%), and 5-aminosalicylates (51%). Corticosteroid-free inactive disease by physician global assessment was noted in 12/44 (27%), 15/39 (38%), and 6/28 (21%) patients at 6, 12, and 24 months, respectively. Kaplan–Meier analysis showed that the likelihood of remaining colectomy free after treatment with infliximab was 75% at 6 months, 72% at 12 months, and 61% at 2 years.CONCLUSIONS:In this cohort of children with UC receiving infliximab, corticosteroid-free inactive disease was observed in 38 and 21% of patients at 12 and 24 months, respectively. By 24 months, 61% of patients had avoided colectomy.

Use of conscious sedation for lower and upper gastrointestinal endoscopic examinations in children, adolescents, and young adults: a twelve-year review

BACKGROUND Over the past decade, many pediatric endoscopists have replaced general anesthesia with conscious sedation. Sedation is commonly used to minimize discomfort. METHODS To evaluate the safety and efficacy of conscious sedation we reviewed 2711 reports of lower and upper gastrointestinal endoscopic examinations performed in 2026 patients between July 1981 and December 1992. RESULTS Intravenous sedation was accomplished using meperidine and diazepam (914 examinations, 35%) or meperidine and midazolam (1427 examinations, 55%). Single agents were used for 83 examinations (3%), and 96 examinations (3.5%) were performed with the patient under general anesthesia. In the lower endoscopy group sedated intravenously (n = 713), the cecum was reached in 82% of examinations. The procedure could not be completed in 17 cases in which patients were uncooperative despite sedation. In the upper endoscopy group sedated intravenously (N = 1653), all but 91 endoscopies were completed to the descending duodenum. Esophagoscopy had been planned in 76% of these procedures. Minor complications occurred in 7 patients (0.3%). This included two episodes of significant oxygen desaturation that responded to oxygen administration and narcotic reversal. A major complication occurred in 1 patient (0.04%) who had a gastric perforation during esophageal dilation over a defective guide wire. There were no deaths, episodes of cardiorespiratory arrest, or pulmonary aspirations in our series. The combined major and minor complication rate was 0.3%. CONCLUSIONS Intravenous conscious sedation is safe and effective in children undergoing endoscopic examination of the gastrointestinal tract. Selected patients will require general anesthesia.

Extraintestinal manifestations of pediatric inflammatory bowel disease and their relation to disease type and severity.

Objectives: Although it is known that extraintestinal manifestations (EIMs) commonly occur in pediatric inflammatory bowel disease (IBD), little research has examined rates of EIMs and their relation to other disease-related factors in this population. The purpose of this study was to determine the rates of EIMs in pediatric IBD and examine correlations with age, sex, diagnosis, disease severity, and distribution. Patients and Methods: Data were prospectively collected as part of the Pediatric IBD Collaborative Research Group Registry, an observational database enrolling newly diagnosed IBD patients <16 years old since 2002. Rates of EIM (occurring anytime during the period of enrollment) and the aforementioned variables (at baseline) were examined. Patients with indeterminate colitis were excluded from the analysis given the relatively small number of patients. Results: One thousand nine patients were enrolled (mean age 11.6 ± 3.1 years, 57.5% boys, mean follow-up 26.2 ± 18.2 months). Two hundred eighty-five (28.2%) patients experienced 1 or more EIMs. Eighty-seven percent of EIM occurred within the first year. Increased disease severity at baseline (mild vs moderate/severe) was associated with the occurrence of any EIM (P < 0.001), arthralgia (P = 0.024), aphthous stomatitis (P = 0.001), and erythema nodosum (P = 0.009) for both Crohn disease (CD) and ulcerative colitis (UC) during the period of follow-up. Statistically significant differences in the rates of EIMs between CD and UC were seen for aphthous stomatitis, erythema nodosum, and sclerosing cholangitis. Conclusions: EIMs as defined in this study occur in approximately one quarter of pediatric patients with IBD. Disease type and disease severity were commonly associated with the occurrence of EIMs.

Course and treatment of perianal disease in children newly diagnosed with Crohn's disease.

Background: We sought to characterize perianal disease and its treatment in pediatric patients newly diagnosed with Crohns disease. Methods: Data were obtained from the Pediatric Inflammatory Bowel Disease (IBD) Collaborative Group Registry, a prospective, multicenter observational registry recording clinical and laboratory outcomes in children under 16 years of age newly diagnosed with IBD. Patients with Crohns disease were selected who had data on perianal disease and at least 24 months of follow‐up. The records of patients with a Pediatric Crohns Disease Activity Index perianal subscore greater than 0 were reviewed, and patients with abscesses or fistulas were selected. The therapies used and the course of their perianal disease were then assessed. Results: Of the 276 patients identified, 41 had perianal lesions within 30 days of diagnosis. Thirteen of these had skin tags and fissures only, whereas 28 had fistulas and/or abscesses. The latter lesions resolved by 1 year in 20 patients, and 8 had chronic/recurrent perianal disease persisting for more than 1 year following diagnosis. Patients with fistulizing disease were much more likely to be treated and were treated earlier with antibiotics, infliximab, and immunomodulators than were nonfistulizing patients. Patients who developed chronic perianal disease were more likely to have low body mass indices and required more perianal surgery than did patients whose perianal disease resolved. Conclusions: Approximately 10% of newly diagnosed pediatric patients with Crohns disease will have perianal fistulas and/or abscesses at the time of diagnosis. Most of these will resolve within a year with medical therapy alone.

Factors That Determine Risk for Surgery in Pediatric Patients With Crohn's Disease

BACKGROUND & AIMS We examined the incidence of Crohns disease (CD)-related surgery in a multi-center, inception cohort of pediatric patients with CD. We also examined the effect of starting immunomodulator therapy within 30 days of diagnosis. METHODS Data from 854 children with CD from the Pediatric Inflammatory Bowel Disease Collaborative Research Group who were diagnosed with CD between 2002 and 2008 were analyzed. RESULTS Overall, 76 (9%) underwent a first CD-related surgery, 57 (7%) underwent a first bowel surgery (bowel resection, ostomy, strictureplasty, or appendectomy), and 19 (2%) underwent a first non-bowel surgery (abscess drainage or fistulotomy). The cumulative risks for bowel surgery, non-bowel surgery, and all CD-related surgeries were 3.4%, 1.4%, and 4.8%, respectively, at 1 year after diagnosis and 13.8%, 4.5%, and 17.7%, respectively, at 5 years after diagnosis. Older age at diagnosis, greater disease severity, and stricturing or penetrating disease increased the risk of bowel surgery. Disease between the transverse colon and rectum decreased the risk. Initiation of immunomodulator therapy within 30 days of diagnosis, sex, race, and family history of inflammatory bowel disease did not influence the risk of bowel surgery. CONCLUSIONS In an analysis of pediatric patients with CD, the 5-year cumulative risk of bowel surgery was lower than that reported in recent studies of adult and pediatric patients but similar to that of a recent retrospective pediatric study. Initiation of immunomodulator therapy at diagnosis did not alter the risk of surgery within 5 years of diagnosis.

Incidence of Dysplasia in Pelvic Pouches in Pediatric Patients After Ileal Pouch-anal Anastomosis for Ulcerative Colitis

BACKGROUND The purpose of this study was to evaluate the incidence of dysplasia and the mucosal adaptation patterns of pelvic pouches in children and adolescents who had undergone ileal pouch-anal anastomosis for ulcerative colitis. METHODS Between 1982 and 1996, 176 pediatric patients with ulcerative colitis underwent ilial pouch-anal anastomosis. Seventy-six patients were followed up after surgery at the Cleveland Clinic. Pouch biopsy specimens were reviewed for dysplasia and to determine mucosal adaptation patterns. Fifty-eight of the 76 patients had an average of three mucosal biopsies during a mean follow-up of 5 years. Demographic and surgical data were abstracted from archives of medical records. All previously obtained pouch biopsy specimens were re-evaluated by a single pathologist to ensure standardized interpretation. RESULTS No dysplasia was identified in screening specimens of 76 children and adolescents including 5 patients who showed dysplasia in resected colon specimens. The pattern of mucosal adaptation was categorized using previously reported criteria. Type A was defined as normal mucosa or mild villous atrophy with no or mild inflammation. Type B mucosa showed transient atrophy with temporary moderate inflammation followed by normalization of architecture. Type C mucosa was defined as a pattern of persistent atrophy with severe inflammation. In the study cohort, the patterns of mucosal adaptation, type A (56.9%; n = 33), type B (32.8%; n = 19), and type C (10.3%; n = 6), were comparable with those reported in adults. The rate of pouch failure and diagnosis of Crohns disease were similar in each group and were not related to the specific adaptation pattern. Most of the patients with type C mucosa had clinical symptoms of pouchitis requiring periodic antibiotic therapy. No dysplasia was identified in any biopsy specimen reviewed. CONCLUSIONS Similar morphologic changes can be seen in ileal pouches in pediatric and adult patients. There seemed to be no increased risk of dysplasia in children and young adults who had undergone ilial pouch-anal anastomosis surgery for ulcerative colitis during a 5 year follow-up. Because the long-term risk of development of dysplasia is unknown, an initial screening should be performed 5 years after the creation of a pelvic pouch in children or when the total disease duration exceeds 7 years. Once identified, patients with Type C mucosa should have annual screening for dysplasia until further data become available.

Risk of capsule endoscope retention in pediatric patients: a large single-center experience and review of the literature.

Objectives: Capsule retention is a potential complication of capsule endoscopy (CE). The aims of our study were to determine the incidence of capsule retention in pediatric patients undergoing CE and to identify potential risk factors for capsule retention. Materials and Methods: We performed an institutional review board–approved retrospective chart review of pediatric patients undergoing CE studies at a single center. Data collected included patient age, sex, prior diagnosis of inflammatory bowel disease (IBD), CE indication, prior small bowel series results, study result, and complications. Results: Two hundred seven CE procedures were performed in pediatric patients during the study period. Capsule retention occurred in 3 (1.4%) of the 207 studies. All 3 patients had known Crohn disease (CD). The risk of capsule retention in pediatric patients with known IBD was 5.2% (3/58). The risk of capsule retention for patients with suspected IBD and all other indications was 0%. If small bowel disease was identified on upper gastrointestinal series in patients with known CD, then the risk of capsule retention was 37.5% (3/8). Only 7 patients with known IBD had a body mass index (BMI) below the 5th percentile. Of these 7 patients, 3 (43%) had capsule retention. Conclusions: Red flags for potential CE retention identified in our study include known IBD (5.2% retention risk), previous small bowel follow-through demonstrating small bowel CD (37.5% retention risk), and BMI <5th percentile with known IBD (43% retention risk). Caution is advised in these pediatric patients before capsule ingestion.