Detection of Cytomegalovirus in Colonic Mucosa of Children With Inflammatory Bowel Disease: Inflammatory Bowel Disease.

OBJECTIVES: Although it has been recommended to perform sigmoidoscopy to screen for cytomegalovirus (CMV) reactivation in acute severe colitis, the frequency of CMV reactivation in children with inflammatory bowel disease (IBD) is unknown. The aim of this study was to determine the frequency and management of CMV detection in colonic mucosa of children with IBD. METHODS: In a retrospective study, consecutive IBD patients, <17 years old, with moderate to severe colitis who had sigmoid biopsy specimens evaluated for CMV by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and polymerase chain reaction (PCR) were included. RESULTS: A total of 90 sigmoid biopsies were collected from 67 patient encounters from 58 patients with colitis: 61 patient encounters (91%) with UC/IBD-U including biopsy samples from colectomy specimens of eight patients who had colectomy during the study period. Medication exposure included corticosteroids for 40 (69%) patients, and immunosuppressive agents for 31 (53.4%) patients. Four of 61 patient encounters (6.6%) with UC/IBD-U, two with corticosteroid refractory disease, had positive biopsies for CMV by PCR but negative H&E and IHC. They responded to escalated medical therapy, without needing anti-viral therapy, and none required colectomy over a median duration of follow up of 1.1 year (IQR 1-1.6). CONCLUSIONS: CMV presence is uncommon in colonic mucosa of children with IBD. Studies examining the underlying sero-prevalence of CMV and its role of reactivation of colitis are required to determine if the current recommendation for routine sigmoidoscopy to exclude CMV infection in corticosteroid-refractory acute severe colitis is justified.

Serum Vitamins and Minerals at Diagnosis and Follow-up in Children With Celiac Disease.

OBJECTIVES: Children with celiac disease (CD) may experience deficiencies of several micronutrients. The objectives of the present study were to determine the prevalence of micronutrient deficiencies in children with CD at diagnosis, 6 months, and 18 months after the start of a gluten-free diet (GFD), and examine any correlation between micronutrient deficiencies, serum tissue transglutaminase (TtG) immunoglobulin A (IgA) antibody titers, and the degree of mucosal damage at diagnosis. METHODS: Children (<17 years) with CD had their serum vitamins, minerals, and anti-TtG IgA antibodies measured at diagnosis, 6 and 18 months after starting a GFD. Histopathological changes of duodenal biopsies at diagnosis were documented using modified MARSH classification. RESULTS: The medical records of 140 children (mean age at diagnosis 7.8 ±â€Š4.01 years, 87 girls [621%]) with CD were examined. At diagnosis, serum vitamin D was the most commonly deficient vitamin in 70% of children. Serum ferritin was subnormal in 34.5% with zinc in 18.6% children but only 12 (10.9%) children had iron deficiency anemia. There was no correlation between micronutrient deficiencies at diagnosis and serum TtG IgA antibody titers or the degree of villous atrophy. The majority of serum levels of measured micronutrients had normalized after 6 months of starting GFD except for vitamin D, which improved but remained subnormal. CONCLUSIONS: At diagnosis, most children with CD have vitamin D deficiency. The degree of micronutrient deficiencies does not correlate with the degree of villous atrophy or serum titers of anti-TtG IgA antibodies.

Therapeutic drug monitoring was helpful in guiding the decision-making process for children receiving infliximab for inflammatory bowel disease.

AIM: This study examined the impact of therapeutic drug monitoring (TDM) on clinical decision-making for children receiving infliximab for inflammatory bowel disease (IBD). METHODS: The medical records of children with IBD who had infliximab trough levels (ITLs) measured between January 2013 and December 2015 at two Canadian tertiary-care centres were examined. The indications for TDM, clinical and laboratory disease activity indices and TDM-driven treatment changes to infliximab therapy were documented. RESULTS: We included 107 consecutive serum measurements of ITLs in 73 children (40 boys), with a median age of 16.1 years, including 52 with Crohn's disease. TDM was performed due to concerns about clinical disease activity in 24/107 (22.4%) measurements and 83 (77.6%) were ordered as routine tests. Of these, 38 (35.5%) ITLs were suboptimal (<3.5 µg/mL) and 36 (34.0%) resulted in more frequent doses of infliximab, with subsequent improvements in disease biomarkers. Interval changes were implemented as a result of 34 (32.0%) ITLs, with shorter intervals in 19 (17.0%) cases, and seven (6.5%) ITLs resulted in adding or increasing doses of immunomodulators. In addition, four children were switched to adalimumab. CONCLUSION: Therapeutic drug monitoring was helpful in guiding the decision-making process for children with IBD on infliximab.

Barriers to clinical research in children with inflammatory bowel disease: The patients' perspective.

BACKGROUND: The aim of this study was to determine the proportion of patients' caregivers willing to participate in clinical research and examine the possible barriers against recruitment to clinical research in children with inflammatory bowel disease. METHODS: In a cross-sectional study, caregivers and children with inflammatory bowel disease were surveyed via a questionnaire that addressed parents' willingness to participate in clinical studies and factors influencing their willingness to participate. RESULTS: A total of 118 caregivers to children with inflammatory bowel disease [median age 14.5, IQR: 12.0-15.8 years, 60 boys, 61 (52%) with Crohn's disease] who were followed for a median duration of 1.73 years (IQR 0.4-3.6 years) completed the survey. One hundred and four (88.2%) caregivers answered "Definitely" or "Probably" to participate in clinical research while 14 (11.8%) were "Neutral" or "Probably" unwilling to participate (P<0.001). Patients were less likely to participate in clinical research if they had longer disease duration (P = 0.019), or were in clinical relapse (P = 0.03). Parents' education, income, age of children at diagnosis, money incentive, disease relapse and medications at the time of the survey did not have any significant effect on willingness to participate. CONCLUSIONS: The majority of children with inflammatory bowel disease and their caregivers are willing to participate in clinical research.

Impact of Fecal Calprotectin Measurement on Decision-making in Children with Inflammatory Bowel Disease.

BACKGROUND: The use of fecal calprotectin (FCal) as a marker of intestinal inflammation, in the management of inflammatory bowel disease (IBD) is increasing. The aim of this study was to examine the impact of FCal measurements on decision-making and clinical care of children with IBD. MATERIALS AND METHODS: In a retrospective cohort study, FCal, clinical activity indices, and blood markers were measured in children with established diagnoses of IBD. Pearson correlation coefficient analysis was performed to examine association between FCal and other markers. Decisions based on FCal measurements were prospectively documented and participants were evaluated 3-6 months later. RESULTS: A total of 115 fecal samples were collected from 77 children with IBD [median age 14, interquartile range (IQR) 11-15.6 years, 42 females, 37 with Crohn's disease]. FCal positively correlated with clinical activity indices (r = 0.481, P < 0.05) and erythrocyte sedimentation rate (r = 0.40, P < 0.05) and negatively correlated with hemoglobin (r = -0.40, P < 0.05). Sixty four out of 74 (86%) positive FCal measurements (≥250 µg/g of stools) resulted in treatment escalation with subsequent significant clinical improvement while in the FCal negative group, 34 out of 41 (83%) measurements resulted in no change in treatment and were associated with remission on follow-up. CONCLUSION: Based on high FCal, the majority of children had treatment escalation that resulted in clinical improvement. FCal measurements were useful and reliable in decision-making and clinical care of children with IBD.