Jennifer L. Dotson

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.

Histoplasmosis Complicating Tumor Necrosis Factor–α Blocker Therapy: A Retrospective Analysis of 98 Cases

BACKGROUND Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Racial disparities in readmission, complications, and procedures in children with Crohn's disease.

Background:Racial disparities in care and outcomes contribute to mortality and morbidity in children; however, the role in pediatric Crohns disease is unclear. In this study, we compared cohorts of black and white children with Crohns disease to determine the extent race is associated with differences in readmissions, complications, and procedures among hospitalizations in the United States. Methods:Data were extracted from the Pediatric Health Information System (January 1, 2004–June 30, 2012) for patients with 21 years or younger hospitalized with a diagnosis of Crohns disease. White and black cohorts were randomly selected in a 2:1 ratio by hospital. The primary outcome was time from index hospital discharge to readmission. The most frequent complications and procedures were evaluated by race. Results:There were 4377 patients. Black children had a shorter time to first readmission and higher probability of readmission (P = 0.009) and a 16% increase in risk of readmission compared with white children (P = 0.01). Black children had longer length of stay and higher frequency of overall and late (30-d to 12-mo postdischarge) readmissions (P < 0.001). During index hospitalization, more black children had perianal disease and anemia (P < 0.001). During any hospitalization, black children had higher incidence of perianal disease, anemia, and vitamin D deficiency, and greater number of perianal procedures, endoscopies, and blood product transfusion (P < 0.001). Conclusions:There are differences in hospital readmissions, complications, and procedures among hospitalized children related to race. It is unclear whether these differences are due to genetic differences, worse intrinsic disease, adherence, access to treatment, or treatment disparities.

Feasibility and validity of the pediatric ulcerative colitis activity index in routine clinical practice.

Objectives: The Pediatric Ulcerative Colitis Activity Index (PUCAI) is a noninvasive disease activity index developed as a clinical trial endpoint. More recently, practice guidelines have recommended the use of PUCAI in routine clinical care. We therefore sought to evaluate the feasibility, validity, and responsiveness of PUCAI in a large, diverse collection of pediatric gastroenterology practices. Methods: We extracted data from the 2 most recent encounters for patients with ulcerative colitis in the ImproveCareNow registry. Feasibility was determined by the percentage of patients for whom all PUCAI components were recorded, validity by correlation of PUCAI scores across physician global assessment (PGA) categories, and responsiveness to change by the correlation between the change in PUCAI and PGA scores between visits. Results: A total of 2503 patients were included (49.5% boys, age 15.2 ± 4.1 years, disease duration 3.7 ± 3.2 years). All items in the PUCAI were completed for 96% of visits. PUCAI demonstrated excellent discriminatory ability between remission, mild, and moderate disease; discrimination between moderate and severe disease was less robust. There was good correlation with PGA (r = 0.76 [P < 0.001] and weighted kappa &kgr; = 0.73 [P < 0.001]). The PUCAI change scores correlated well with PGA change scores (P < 0.001). Test–retest reliability of the PUCAI was good (intraclass correlation coefficient 0.72 [95% confidence interval 0.70–0.75], P < 0.001). Guyatt responsiveness statistic was 1.18, and the correlation of &Dgr;PUCAI with &Dgr;PGA was 0.69 (P < 0.001). Conclusions: The PUCAI is feasible to use in routine clinical settings. Evidence of its validity and responsiveness supports its use as a clinical tool for monitoring disease activity for patients with ulcerative colitis.

Exploring the Differential Diagnosis of Joint Complaints in Pediatric Patients with Inflammatory Bowel Disease

About one quarter of children with inflammatory bowel disease (IBD) experience an extraintestinal manifestation, with the most common being arthritis or arthralgia. Because of the frequency of these joint complaints and their effect on quality of life, it is important to consider all possible etiologies in order to promptly evaluate, diagnose, and possibly refer to other specialists. Pediatric gastroenterologist and IBD specialists are cognizant of the extraintestinal joint manifestations, but may be less familiar with rheumatic disease and the musculoskeletal examination. We explore the differential diagnosis of joint complaints in children, with a focus on IBD-related disease and rheumatic disease.

Race Differences in Initial Presentation, Early Treatment, and 1-year Outcomes of Pediatric Crohn's Disease: Results from the Improvecarenow Network

Background: Racially disparate care has been shown to contribute to suboptimal health care outcomes for minorities. Using the ImproveCareNow network, we investigated differences in management and outcomes of pediatric patients with Crohns disease at diagnosis and 1-year postdiagnosis. Methods: ImproveCareNow is a learning health network for pediatric inflammatory bowel disease. It contains prospective, longitudinal data from outpatient encounters. This retrospective study included all patients with Crohns disease ⩽21 years, September 2006 to October 2014, with the first recorded encounter ⩽90 days from date of diagnosis and an encounter 1 year ±60 days. We examined the effect of race on remission rate and treatment at diagnosis and 1 year from diagnosis using t-tests, Wilcoxon rank-sum tests, &khgr;2 statistic, and Fishers exact tests, where appropriate, followed by univariate regression models. Results: Nine hundred seventy-six patients (Black = 118 (12%), White = 858 (88%), mean age = 13 years, 63% male) from 39 sites were included. Black children had a higher percentage of Medicaid insurance (44% versus 11%, P < 0.001). At diagnosis, Black children had more active disease according to physician global assessment (P = 0.027), but not by short Pediatric Crohns Disease Activity Index (P = 0.67). Race differences in treatment were not identified. Black children had lower hematocrit (34.8 versus 36.7, P < 0.001) and albumin levels (3.6 versus 3.9, P = 0.001). At 1 year, Black children had more active disease according to physician global assessment (P = 0.016), but not by short Pediatric Crohns Disease Activity Index (P = 0.06). Conclusions: Black children with Crohns disease may have more severe disease than White children based on physician global assessment. Neither disease phenotype differences at diagnosis nor treatment differences at 1-year follow-up were identified.

Incidence, pattern, and etiology of elevated liver enzymes in pediatric inflammatory bowel disease.

Objectives: Patients with inflammatory bowel disease (IBD) often develop elevated liver enzymes (ELE), which are frequently a benign, transient finding, but may be related to treatment or IBD-associated liver diseases. Distinguishing benign from pathologic ELE is crucial for focused diagnostic and therapeutic interventions. We sought to characterize the incidence, character, chronicity, degree, and etiology of ELE in children with IBD. Methods: Institutional review board–approved retrospective review of all of the patients with IBD (2–21 years) seen between October 2009 and October 2012 with >9 months of follow-up were included in the study. We examined body mass index, disease activity, extent, phenotype, concurrent medications, and character, chronicity, degree of enzyme elevation, and final diagnosis. Results: A total of 219 of 514 patients with IBD had ≥1 episode of ELE. Five patients were excluded for preexisting liver disease, leaving 214 patients (Crohn disease [CD]: 14.8 ± 3.5 years, 46% girls; ulcerative colitis [UC]: 14.4 ± 4.2 years, 37% girls). One hundred forty-eight patients (69%) had a hepatic, 17 (8%) cholestatic, and 49 (23%) mixed character of ELE. There were no significant differences in character, chronicity, or degree of ELE between CD and UC (P = 0.71, P = 0.58, P > 0.33). Of the 128 patients with sufficient data to determine chronicity, 98 (77%) had transient elevations, (CD: n = 66, 75% and UC: n = 32, 80%). Episodes of ELE were idiopathic in 87% of patients with IBD. A final diagnosis of idiopathic ELE was associated with a lower degree of ELE elevation (P < 0.0001). Conclusions: Pediatric patients with IBD commonly experience transient, idiopathic ELE. Our findings suggest that higher degrees of ELE, specifically alanine aminotransferase, are associated with an etiology that requires more extensive evaluation.

Management of Intra-abdominal Abscesses in Children With Crohn's Disease: A 12-year, Retrospective Single-center Review

Background:Intra-abdominal abscesses (IAA) are complications of Crohns disease, which often result in hospitalization, surgery, and increased cost. Initial management may include medical therapy, percutaneous drainage (PD), or surgery, although the optimal management of IAA in children is unclear. Methods:Retrospective review of all pediatric patients with Crohns disease who developed an IAA from January 1, 2000 to April 30, 2012. Three groups, based on initial IAA treatment modality (medical, PD, and surgery), were compared. Results:Thirty cases of IAA were identified (mean age at IAA diagnosis, 15.4 ± 2.6 yr, 67% female, median Crohns disease duration, 2.6 mo). Computed tomography was the most common initial (93%) and follow-up (47%) imaging. The average time to follow-up imaging was 8.5 days. For initial management, 18 received medical therapy, 10 PD, and 2 had surgery. The medical therapy group received more computed tomography scans for follow-up imaging than the PD group (12 [67%] versus 2 [20%], P = 0.046). There were no significant differences in abscess characteristics or management of posttreatment course between these 2 groups. Surgical resection occurred in 3 patients (17%) in the medical group and 2 (20%) in the PD group during index hospitalization. No significant differences were identified among treatment groups for readmissions, complications, or abscess recurrence. By 1 year, 12 of the 18 medically managed patients (67%) had surgery, and 6 of the 10 patients (60%) treated with initial PD ultimately had surgery. Conclusions:The majority of patients with IAA require definitive surgical treatment, and there were no clear predictors of those who did not.

Variation in Management of Intra-Abdominal Abscesses in Children with Crohn's Disease

Background:Complications of Crohns disease may include intra-abdominal abscesses, which often result in hospitalization, surgery, and increased cost. There is a paucity of primary research and practice guidelines regarding optimal management in children. The study objective was to assess the current standard of care in an effort to define best practices and identify priority areas for additional research. Methods:The web-based survey was approved by the Institutional Review Board and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. We examined preferences in imaging, drainage, anti-tumor necrosis factor-&agr; therapy, and antibiotic use. We assessed for associations between provider level of experience and management strategies. Results:A total of 248 of 1608 North American Society for Pediatric Gastroenterology, Hepatology and Nutrition members responded. Of them, 64% were male, 87% practiced in the United States, and 74% practiced in an academic setting. Approximately 26% cared for >50 patients with Crohns disease and 25% were in practice for >20 years. For initial imaging, computed tomography was chosen by 52%, followed by magnetic resonance imaging (26%) and ultrasound (21%), and upon reassessment computed tomography was chosen by 13%, magnetic resonance imaging by 33%, and ultrasound by 47%. About 77% recommended percutaneous drainage, whereas 21% would only do so if antibiotics were unsuccessful, and 2% proceed to immediate surgery. If a fistula was demonstrated, 70% planned medical therapy followed by surgical resection; only 30% planned surgical resection if no fistula was present. Approximately 55% would consider infliximab before surgery. There were no clinically significant associations between treatment strategies and practitioner experience. Conclusions:There is considerable variation in diagnostic and therapeutic interventions in the management of intra-abdominal abscesses, which was not explained by practitioner experience.

North American Pediatric Gastroenterology Fellowship Needs Assessment in Inflammatory Bowel Disease: Trainee and Program Director Perspectives.

Background:Pediatric inflammatory bowel disease (IBD) care is complex and rapidly evolving. The Crohns and Colitis Foundation of America and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition cosponsored a needs assessment survey of pediatric gastroenterology trainees and program directors (PDs) to inform on educational programming. Methods:A Web-based, self-completed survey was provided to North American trainees and PDs during the 2013–2014 academic year. Standard descriptive statistics summarized demographics and responses. Results:One hundred sixty-six of 326 (51%) trainees (62% female) and 37 of 74 (50%) PDs responded. Median trainees per program = 5 and median total faculty = 10 (3 IBD experts); 15% of programs did not have a self-identified “IBD expert” faculty member. Sixty-nine percent of trainees were confident/somewhat confident in their IBD inpatient training, whereas 54% were confident/somewhat confident in their outpatient training. Trainees identified activities that would most improve their education, including didactics (55%), interaction with national experts (50%), trainee-centered IBD Web resources (42%), and increased patient exposure (42%). Trainees were most confident in managing inpatient active Crohns disease/ulcerative colitis, phenotype classification, managing biological therapies, and using clinical disease activity indices. They were least confident in managing J-pouch complications, performing pouchoscopy, managing extraintestinal manifestations, and ostomy-related complications. Eighty-five percent would like an IBD-focused training elective. Most directors (86%) would allow trainees to do electives at other institutions. Conclusions:This IBD needs assessment survey of pediatric gastroenterology trainees and PDs demonstrated a strong resource commitment to IBD training and clinical care. Areas for educational enrichment emerged, including pouch and ostomy complications.