Comparison of Short-Term Outcomes for Standard Versus Nonstandard Induction Dosing of Infliximab for Pediatric Inflammatory Bowel Disease.

OBJECTIVE: Recent studies have emphasized the early use of infliximab (IFX) in pediatric patients with inflammatory bowel disease. Standard dosing of 5 mg/kg/dose may not be sufficient to achieve optimal clinical outcomes. The aim of our study was to compare short-term outcomes with standard dosing of IFX to higher, nonstandard dosing of IFX for induction therapy. METHODS: Retrospective study of 162 pediatric patients receiving either standard (5-6 mg/kg, n = 90) or nonstandard (>6 mg/kg, n = 72) dosing of IFX during induction was performed. Patient demographics, clinical outcomes, and laboratory data were collected. Need for dose escalation during the first 6 months, combination therapy with immunomodulators, and steroid-free progression were investigated. RESULTS: Clinical remission rates between the 2 groups were significantly different, with patients receiving nonstandard dosing demonstrating higher rates (58% vs 78%; p = 0.012). Use of combination therapy with immunomodulators was significantly different between standard and nonstandard groups (80% vs 48%; p < 0.001). Numeric trend in need for IFX dose escalation in the first 6 months was seen between standard and nonstandard groups (54% vs 39%, respectively; p = 0.087). Post-induction IFX trough concentrations, rates of antibody development, drug discontinuation, and infusion reaction were similar. CONCLUSIONS: Nonstandard induction dosing of IFX was associated with higher rates of clinical remission, despite similar rates of serum IFX trough concentrations. There was a numeric trend towards the standard group requiring dose escalation within the first 6 months of therapy. Patients given nonstandard dosing may achieve superior clinical outcomes compared with those on standard dosing.

Differences in Clinical Presentation of Eosinophilic Esophagitis in Pediatric Patients With Ulcerative Colitis and Crohn Disease.

SIGNIFICANCE: Eosinophilic esophagitis (EoE) is an inflammatory condition characterized by T helper-2 (T H 2) cytokines. Ulcerative colitis (UC) and Crohn disease (CD) are inflammatory conditions with different clinical presentations and immune profiles. UC is associated with T H 2 cytokines and CD with T H 1 cytokines. We investigated potential differences in the association of EoE with UC and CD because of these different immune profiles. METHODS: We utilized ICD-9 and ICD-10 codes to find patients with inflammatory bowel disease (IBD) and EoE. We defined EoE as any esophageal biopsy with >15 eosinophils. We collected demographic, clinical, laboratory, endoscopic, and histological data. RESULTS: Thirty patients had both EoE and IBD. 14.9% of UC patients had EoE and 5.7% of CD patients had EoE. 64.7% of UC patients presented with UC and EoE at the same time, whereas 76.9% of CD patients presented with EoE at follow up. Ten of 13 CD patients were on anti-tumor necrosis factor (TNF) at EoE diagnosis. No UC patients were on anti-TNF at EoE diagnosis. Eighty-three percent of CD patients had mild disease or were in remission, whereas 50% of UC patients had moderate to severe disease at the time of EoE diagnosis. CONCLUSION: A higher percentage of UC than CD patients had EoE. EoE was more likely to be present at the initial diagnosis of UC than CD. EoE was more likely after diagnosis and treatment of CD with anti-TNF, when CD activity was mild or in remission. The difference in presentation suggests that anti-TNF or it's impact on inflammation may differentially impact the association of EoE with CD and UC.

Association of Fecal Calprotectin With Endoscopic and Histologic Activity in Pediatric Inflammatory Bowel Disease.

Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation used for screening and ongoing monitoring of inflammatory bowel disease (IBD); it is unclear the association of specific FC values with disease activity. The aim of our study was to examine the association of FC values with endoscopic and histologic severity. Methods: We performed a retrospective chart review of patients who had FC done between 30 days and 1 day before colonoscopy at our institution. IBD patients were graded using the simple endoscopic score for Crohn's disease or Mayo endoscopic score for ulcerative colitis. Histologic slides were graded using the Geboes method. Results: Three-hundred thirty-one patients were included in the study and 107 had IBD. For endoscopy, median FC was lowest for all IBD patients with no disease (181 µg/g) and highest in severe disease (921 µg/g), with significant difference between no disease and moderate and severe disease (P = 0.019, 0.003), and between mild and severe disease (P = 0.012). For histology, median FC was lowest with no disease (328 µg/g) and highest in severe disease (895 µg/g), with significant difference between no disease and moderate and severe disease (P = 0.021, 0.018). The control population had a significantly lower median FC than the IBD population in endoscopic remission (35.5 versus 181 µg/g; P = 0.018). Conclusions: There was a linear increase in FC values associated with increasing disease severity in the undifferentiated IBD cohort. Values for IBD patients in endoscopic remission were significantly different from our control population. FC may be a useful noninvasive marker to assess disease severity.

Superior Mesenteric Artery Syndrome Complicated by Gastric Mucosal Necrosis Following Congenital Scoliosis Surgery: A Case Report.

CASE: This is a report of severe superior mesenteric artery (SMA) syndrome in an 11-year-old girl with congenital scoliosis following posterior spinal fusion and segmental spinal instrumentation. This was complicated by gastric mucosal necrosis but resolved satisfactory with prolonged nasogastric suction, intravenous fluids, and total parental nutrition. CONCLUSIONS: All pediatric spine surgeons should be aware of SMA syndrome following spine surgery. This case demonstrates that although rare, significant complications such as gastric mucosal necrosis can occur. When present, it can be treated successfully with prolonged conservative management. Comanagement with pediatric gastroenterology and pediatric general surgery is recommended.

Time to antibody detection and associated factors for presence of anti-drug antibodies in pediatric inflammatory bowel disease patients treated with anti-TNF therapy.

BACKGROUND: Loss of response in pediatric inflammatory bowel disease patients treated with biologic medications can be due to development of anti-drug antibodies. Natural history of anti-drug antibodies development has not been well described in pediatric inflammatory bowel disease. The primary aim of this study was to describe a single-center experience for the temporal onset of anti-drug antibodies detection. METHODS: We performed a retrospective, single-center chart review of pediatric inflammatory bowel disease patients at the Division of Pediatric Gastroenterology, Hepatology, and Nutrition at Rainbow Babies and Children's Hospital from 2010 to 2015. Patients were treated with infliximab or adalimumab and had at least two evaluations for anti-drug antibodies with the homogenous mobility shift assay. Demographics, laboratory and medication data, and clinical disease activity were collected. RESULTS: A total of 75 subjects are included in the analysis. Eighty-one percent of subjects were treated with infliximab. Eleven subjects developed anti-drug antibodies; average time to anti-drug antibodies detection was 13.2 ± 7.3 months. Longer duration of inflammatory bowel disease, L1 location in Crohn's disease, and not having immunomodulatory therapy before biologic was associated with higher risk of antibody detection. Antibody detection occurred more frequently with infliximab vs. adalimumab. Time-to-antibody detection for infliximab and adalimumab was 14.83 and 23.48 months, respectively. CONCLUSION: Chances of anti-drug antibodies detection in the infliximab group were higher than the adalimumab group. Time-to-antibody detection was 8.65 months longer in patients who received adalimumab when compared to infliximab. These results may have implications for long-term therapy and help guide use of concomitant immunomodulators.

Reversal of Immunogenicity in Pediatric Inflammatory Bowel Disease Patients Receiving Anti-Tumor Necrosis Factor Medications.

Loss of response to anti-tumor necrosis factor (anti-TNF) agents in the treatment of inflammatory bowel disease (IBD) is a major consideration to maintain sustained response. Reversal of immunogenicity can re-establish response and increase the durability of these agents. Strategies to reverse immunogenicity include dose-intensification and/or the addition of an immunomodulator. However, there is a relative paucity of data on the efficacy of such interventions in pediatric IBD patients. Available reports have not strictly utilized homogenous mobility shift assay, which reports on anti-drug antibodies even in the presence of detectable drug, whereas prior studies have been confounded by the use of drug sensitive assays. We report four pediatric inflammatory bowel disease patients with successful reversal of immunogenicity on an anti-TNF agent using dose intensification and/or addition of an immunomodulator.

NASPGHAN Clinical Report on Postoperative Recurrence in Pediatric Crohn Disease.

Pediatric Crohn disease is characterized by clinical and endoscopic relapses. The inflammatory process is considered to be progressive and may lead to strictures, fistulas, and penetrating disease that may require surgery. In addition, medically refractory disease may be treated by surgical resection of inflamed bowel in an effort to reverse growth failure. The need for surgery in childhood suggests severe disease and these patients have an increased risk for recurrent disease and potentially more surgery. Data show that up to 55% of patients had clinical recurrence in the first 2 years after initial surgery. The current clinical report on postoperative recurrence in pediatric Crohn disease reviews the risk factors for early surgery and postoperative recurrence, operative risk factors for recurrence, and prevention and monitoring strategies for postoperative recurrence. We also propose an algorithm for postoperative management in pediatric Crohn disease.

Challenges in pediatric inflammatory bowel disease.

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.

Food protein sensitivity with partial villous atrophy after pediatric liver transplantation with tacrolimus immunosuppression.

We report three pediatric liver transplant recipients receiving tacrolimus immunosuppression presented with vomiting, heme-positive stools and failure to thrive, who had subtotal villous atrophy in their histology because of food protein sensitivity. Case findings and current literature of the casual relationship between tacrolimus and food allergies briefly reviewed.

Differential Effect of PGE(2) on Adult and Neonatal T-Cell Dependent Immunoglobulin Secretion.

Prostaglandin E(2) (PGE(2)) and other cAMP elevating agents inhibited neonatal but not adult T cell dependent Ig production. PGE(2) did not inhibit IL-2-dependent anti-CD3 stimulated neonatal T cell proliferation or T cell-dependent neonatal B cell proliferation. The results could not be explained by differences in the effect of PGE(2) on cAMP production by neonatal and adult B and T cells or by a unique sensitivity of CD5+ B cells to inhibition by PGE(2). The enhanced sensitivity of neonatal T cell dependent Ig production to inhibition by PGE(2) may play a role in the increased susceptibility of neonatal B and T cells to tolerance induction.