DIGEST: Developing innovative gastroenterology specialty training.

Individuals with cystic fibrosis (CF) now have an increased life expectancy, due to advances in care provided by a multidisciplinary team. The care model has expanded over time to include multiple subspecialties. The Cystic Fibrosis Foundation conducted a survey of Care Center Directors and identified a need for pediatric and adult gastroenterologists with expertise in the diagnosis and treatment of intestinal, pancreatic and hepatic complications of CF. To address this need, the Developing Innovative GastroEnterology Specialty Training (DIGEST) program was created. The development, implementation, and early results of this training program are reported herein.

Concordance between gene expression in peripheral whole blood and colonic tissue in children with inflammatory bowel disease.

BACKGROUND: Presenting features of inflammatory bowel disease (IBD) are non-specific. We hypothesized that mRNA profiles could (1) identify genes and pathways involved in disease pathogenesis; (2) identify a molecular signature that differentiates IBD from other conditions; (3) provide insight into systemic and colon-specific dysregulation through study of the concordance of the gene expression. METHODS: Children (8-18 years) were prospectively recruited at the time of diagnostic colonoscopy for possible IBD. We used transcriptome-wide mRNA profiling to study gene expression in colon biopsies and paired whole blood samples. Using blood mRNA measurements, we fit a regression model for disease state prediction that was validated in an independent test set of adult subjects (GSE3365). RESULTS: Ninety-eight children were recruited [39 Crohn's disease, 18 ulcerative colitis, 2 IBDU, 39 non-IBD]. There were 1,118 significantly differentially (IBD vs non-IBD) expressed genes in colon tissue, and 880 in blood. The direction of relative change in expression was concordant for 106/112 genes differentially expressed in both tissue types. The regression model from the blood mRNA measurements distinguished IBD vs non-IBD disease status in the independent test set with 80% accuracy using only 6 genes. The overlap of 5 immune and metabolic pathways in the two tissue types was significant (p<0.001). CONCLUSIONS: Blood and colon tissue from patients with IBD share a common transcriptional profile dominated by immune and metabolic pathways. Our results suggest that peripheral blood expression levels of as few as 6 genes (IL7R, UBB, TXNIP, S100A8, ALAS2, and SLC2A3) may distinguish patients with IBD from non-IBD.

Differences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals.

In humans the expression of lactase changes during post-natal development, leading to phenotypes known as lactase persistence and non-persistence. Polymorphisms within the lactase gene (LCT) enhancer, in particular the -13910C > T, but also others, are linked to these phenotypes. We were interested in identifying dynamic mediators of LCT regulation, beyond the genotype at -13910C > T. To this end, we investigated two levels of lactase regulation in human intestinal samples obtained from New England children and adolescents of mixed European ancestry: differential expression of transcriptional regulators of LCT, and variations in DNA methylation, and their relation to phenotype. Variations in expression of CDX2, POU2F1, GATA4, GATA6, and HNF1α did not correlate with phenotype. However, an epigenome-wide approach using the Illumina Infinium HM450 bead chip identified a differentially methylated position in the LCT promoter where methylation levels are associated with the genotype at -13910C > T, the persistence/non-persistence phenotype and lactase enzymatic activity. DNA methylation levels at this promoter site and CpGs in the LCT enhancer are associated with genotype. Indeed, taken together they have a higher power to predict lactase phenotypes than the genotype alone.

Risk factors for low bone mineral density in pediatric inflammatory bowel disease: the positive role of physical activity.

OBJECTIVE: In pediatric inflammatory bowel disease (IBD), the prevalence of low bone mineral density (BMD) and bone fractures and the relationship between these are still debated. Our aim was to report data from a cohort of pediatric patients with IBD. PATIENTS AND METHODS: Cross-sectional assessment of growth and BMD [(dual-energy x-ray absorptiometry (DXA)] and retrospective chart review were performed to report the lifetime prevalence of bone fractures and clinical associations with patients' data. RESULTS: We examined 216 patients with IBD, 8-25 years old (median: 14 years). Low BMD was found in 12.5% (spine) and 27% (total body). Multiple regression analysis showed that BMD was predicted by Z-scores for height and weight at DXA. History of menstrual irregularities and nasogastric tube feedings was associated with lower BMD, whereas physical activity and higher Z-score for height at DXA were associated with higher BMD.The prevalence of lifetime fractures was 11.8%. Patients with a history of fractures had lower Z-scores for spine BMD (-1.20 vs. -0.69, P=0.020) and total-body BMD (-1.30 vs. -0.75, P=0.014) compared with those without a history of fractures. Patients with spine BMD Z-score of up to -2 SD score had significantly increased prevalence of fractures compared with those with Z-score more than -2 SD score (28 vs. 10%, P=0.015). CONCLUSION: This study provides further insight into risk factors for low BMD in pediatric IBD. Novel findings were the association between low BMD and fractures, and the positive relationship between BMD and physical activity.

The Utility of the Systemic Inflammatory Respsonse Syndrome Score on Admission in Children With Acute Pancreatitis.

OBJECTIVES: Pediatric patients with acute pancreatitis (AP) may meet criteria at admission for the systemic inflammatory response syndrome (SIRS). Early SIRS in adults with AP is associated with severe disease. Our aim was to evaluate the importance of SIRS in children presenting with AP on various outcomes. METHODS: This is a retrospective cohort study of children hospitalized with AP at Boston Children's Hospital in 2010. Increased length of stay (LOS) and/or admission to the intensive care unit (ICU) served as the primary outcomes. Statistical analyses of measures studied included the presence of SIRS, demographic, and clinical information present on admission. RESULTS: Fifty encounters, in which AP was the primary admitting diagnosis, were documented. Patients had a median LOS of 4.5 (interquartile range, 2-9) days. Systemic inflammatory response syndrome was present in 22 (44%) of 50 patients at admission. Systemic inflammatory response syndrome at admission was an independent predictor of increased LOS (odds ratio, 7.99; P = 0.045) as well as admission to the ICU (odds ratio, 12.06; P = 0.027). CONCLUSIONS: The presence of SIRS criteria on admission serves as a useful and easy-to-calculate predictor of increased LOS and admission to ICU in children with AP.

Trends in Pharmacologic Interventions for Preventing Recurrence of Crohn's Disease After Ileocolonic Surgery.

BACKGROUND: Prophylactic treatment of postoperative Crohn's disease (CD) plays a critical role in maintaining clinical remission. We performed the first study in the last decade to examine secular trends in the use of pharmacologic interventions after ileocolonic resection in the United States, to understand whether clinical practice converges with recent advances in scientific knowledge. METHODS: A retrospective study of a U.S. national claims database was performed. The study cohort included 106 CD patients in the years 1999 to 2001 (prebiologic era) and 294 CD patients in the years 2009 to 2011 (postbiologic era), who underwent ileocolonic resection. Medication use in the 12 months after the surgery was examined. RESULTS: Significant variations in care were evident in both study periods. Across the 2 study periods, there was an increased use of biologics (from 0% to 36.4%) and a substantial reduction in the use of 5-aminosalicylic acid (from 50.9% to 28.2%; P < 0.0001). Therapeutic interventions that have been found ineffective in published studies continued to be widely applied: one-third of patients were prescribed corticosteroids, and several cases of prolonged use of corticosteroids or antibiotics were observed in both cohorts. Disease behavior (penetrating, stricturing, or nonpenetrating and nonstricturing) was not associated with the choice of postoperative therapeutic interventions, with the exception of an increased use of antibiotics among patients with penetrating disease. CONCLUSIONS: There is a substantial gap between advances in postoperative care for ileocolonic CD and clinical practice. Strategies to expedite the integration of new knowledge and evidence into practice are urgently needed.

Functional significance of single nucleotide polymorphisms in the lactase gene in diverse US patients and evidence for a novel lactase persistence allele at -13909 in those of European ancestry.

OBJECTIVES: Recent data from mainly homogeneous European and African populations implicate a 140-bp region 5' to the transcriptional start site of LCT (the lactase gene) as a regulatory site for lactase persistence and nonpersistence. Because there are no studies of US nonhomogeneous populations, we performed genotype/phenotype analysis of the -13910 and -22018 LCT single nucleotide polymorphisms (SNPs) in New England children, mostly of European ancestry. METHODS: Duodenal biopsies were processed for disaccharidase activities, RNA quantification by reverse transcription polymerase chain reaction (RT-PCR), allelic expression ratios by PCR, and genotyping and SNP analysis. Results were compared with clinical information. RESULTS: Lactase activity and mRNA levels, and sucrase-to-lactase ratios of enzyme activity and mRNA, showed robust correlations with genotype. None of the other LCT SNPs showed as strong a correlation with enzyme or mRNA levels as did -13910. Data were consistent, with the -13910 being the causal sequence variant instead of -22018. Four individuals heterozygous for -13910T/C had allelic expression patterns similar to individuals with -13910C/C genotypes; of these, 2 showed equal LCT expression from the 2 alleles and a novel variant (-13909C>A) associated with lactase persistence. CONCLUSIONS: The identification of -13910C/C genotype is likely to predict lactase nonpersistence, consistent with prior published studies. A -13910T/T genotype will frequently, but not perfectly, predict lactase persistence in this mixed European-ancestry population; a -13910T/C genotype will not predict the phenotype. A long, rare haplotype in 2 individuals with -13910T/C genotype but equal allele-specific expression contains a novel lactase persistence allele present at -13909.

Potential role of IGF-1 z score to predict permanent linear growth impairment in children with IBD.

In this pilot study, we analyzed serum insulin-like growth factor 1 (IGF-1)- and IGF-binding protein-3-for-age z scores from 54 inflammatory bowel disease children with no, temporary, or permanent growth impairment. Although our findings did not reach statistical significance, patients with permanent linear growth impairment had lower IGF-1-for-age z scores (-1.76 [-2.25 to -0.43]) compared with those with no or temporary growth impairment (-0.84 [-1.49 to -0.3]) and -1.16 [-1.59 to -1.51], respectively). IGF-binding protein-3 levels were similar across the 3 groups. In the absence of significant inflammation and malnutrition, lower IGF-1-for-age z scores may help distinguish patients likely to have permanent growth impairment from those whose growth impairment is likely to be temporary.

Acute cognitive and behavioral effects of systemic corticosteroids in children treated for inflammatory bowel disease.

Systemic corticosteroids are a mainstay of treatment for many pediatric medical conditions. Although their impact on the central nervous system has been well-studied in animal models and adults, less is known about such effects in pediatric populations. The current study investigated acute effects of corticosteroids on memory, executive functions, emotion, and behavior in children and adolescents with inflammatory bowel disease (IBD). Patients 8-17 years with IBD (Crohn's disease, CD; ulcerative colitis, UC) on high-dose prednisone (n = 33) and IBD patients in remission off steroids (n = 33) completed standardized neuropsychological tests and behavior rating scales. In the IBD sample as a whole, few steroid effects were found for laboratory cognitive measures, but steroid-treated patients were rated as exhibiting more problems with emotional, and to a lesser extent with cognitive function in daily life. Steroid effects, assessed by laboratory measures and questionnaires, were more prevalent in CD than UC patients; UC patients on steroids sometimes performed better than controls. Sleep disruption also predicted some outcomes, diminishing somewhat the magnitude of the steroid effects. Corticosteroid therapy can have acute effects on cognition, emotion, and behavior in chronically ill children; the clinical and long-term significance of these effects require further investigation.

Prevalence and risk factors for hypovitaminosis D in young patients with inflammatory bowel disease.

Vitamin D plays an important role in bone homeostasis. We aimed to report the prevalence of hypovitaminosis D in children with inflammatory bowel disease (IBD) and risk factors associated with low serum 25-hydroxyvitamin D (25OHD) concentration in children with IBD. Risk factors for deficiency of this vitamin are similar to those in healthy children, with the addition of higher erythrocyte sedimentation rate. Both patients with ulcerative colitis and Crohn disease are at risk for hypovitaminosis D.

Efficacy and harms of nasal calcitonin in improving bone density in young patients with inflammatory bowel disease: a randomized, placebo-controlled, double-blind trial.

OBJECTIVES: There are very few published studies of agents having the potential to improve bone health in children with inflammatory bowel disease (IBD). The objective of this study was to establish the efficacy and safety of intranasal calcitonin in improving bone mineral density (BMD) in young patients with IBD and to define additional factors that impact bone mineral accrual. METHODS: We conducted a randomized, placebo-controlled, double-blind clinical trial in 63 participants, ages 8-21 years, with a spinal BMD Z-score ≤ -1.0 s.d. measured by dual energy X-ray absorptiometry. Subjects were randomized to 200 IU intranasal calcitonin (n=31) or placebo (n=32) daily. All received age-appropriate calcium and vitamin D supplementation. Subsequent BMD measurements were obtained at 9 and 18 months. RESULTS: Intranasal calcitonin was well tolerated. Adverse event frequency was similar in both treatment groups, and such events were primarily minor, reversible, and limited to the upper respiratory tract. The BMD Z-score change documented at screening and 9 months and screening and 18 months did not differ between the two therapeutic arms. In participants with Crohn's disease, the spinal BMD Z-score improved between screening and 9 months (change in spine BMD Z-score (ΔZSBMD)(9-0)) in the calcitonin group (ΔZSBMD(9-0)(calcitonin)=0.21 (0.37), ΔZSBMD(9-0)(placebo)=-0.15 (0.5), P=0.02); however, this was only a secondary subgroup analysis. Bone mineral accrual rate during the trial did not lead to normalization of BMD Z-score in this cohort. Factors favoring higher bone mineral accrual rate were lower baseline BMD and higher baseline body mass index Z-score, improvement in height Z-score, higher serum albumin, hematocrit and iron concentration, and more hours of weekly weight-bearing activity. Factors associated with lower bone mineral accrual rate were more severe disease-as indicated by elevated inflammatory markers, need for surgery, hospitalization, and the use of immunomodulators-and higher daily caffeine intake. CONCLUSIONS: Intranasal calcitonin is well tolerated but does not offer a long-term advantage in youth with IBD and decreased BMD. Bone mineral accrual rate remains compromised in youth with IBD and low BMD raising concerns for long-term bone health outcomes. Improvement in nutritional status, catch-up linear growth, control of inflammation, increase in weight-bearing activity, and lower daily caffeine intake may be helpful in restoring bone density in children with IBD and low BMD.

Characterization of expression in mice of a transgene containing 3.3 kb of the human lactase-phlorizin hydrolase (LPH) 5' flanking sequence.

BACKGROUND AND AIM: The regulation of human intestinal lactase-phlorizin hydrolase remains incompletely understood. One kb of pig and 2 kb of rat 5'-flanking sequence controls correct tissue, cell, topographic, and villus LCT expression. To gain insight into human LCT expression, transgenic mouse lines were generated from 3.3 kb of human LPH 5' flanking sequence from a lactase persistent individual fused to a human growth hormone (hGH) reporter bounded by an insulator. METHODS: Four lines were identified in which reporter expression was specifically detectable in the intestine and no other organ, two of which demonstrated hGH expression specific to small and large intestine. Quantitative RT-PCR was carried out on proximal to distal segments of small intestine at fetal days 16.5 and 18.5 and at birth, postnatal days 7 and 28 in line 22. RESULTS: In fetal intestine, hGH expression demonstrated a proximal to distal gradient similar to that in native intestine. There was no significant difference between hGH expression levels at 7 and 28 days in segment 3, the midpoint of the small intestine, where expression of endogenous lactase is maximal at 7 days and declines significantly by 28 days. Distal small intestine displayed high levels of hGH expression in enteroendocrine cells, which were shown to be a subset of the PYY cells. CONCLUSIONS: Thus, a 3.3-kb LPH 5' flanking sequence construct from a lactase persistent individual is able to maintain postnatal expression in transgenic mice post weaning.

Intestinal ferroportin expression in pediatric Crohn's disease.

BACKGROUND: Anemia is a frequent complication of Crohn's disease (CD). The intestinal iron exporter ferroportin (FPN) is involved in both iron deficiency anemia and the anemia of chronic disease. To examine its role in CD, intestinal FPN expression was studied in subjects with and without CD. METHODS: Duodenal mucosal biopsies from 29 pediatric subjects with CD (n=19) and without CD (n=10) were obtained. FPN protein was measured using Western blot analysis and mRNA was assessed using quantitative real-time polymerase chain reaction (PCR). RESULTS: Intestinal FPN protein was higher in anemic CD subjects than in nonanemic CD subjects (P=0.01), while FPN mRNA levels were not different (P=0.66). In nonanemic CD subjects, erythrocyte sedimentation rate (ESR) (P=0.04), C-reactive protein (CRP) (P=0.03), and interleukin-6 (IL-6) (P=0.01) levels were elevated compared to controls. Nonanemic CD subjects had a lower median FPN protein than nonanemic controls, although it did not reach statistical significance (P=0.07). Median FPN mRNA was similar between groups (P=0.71). Although no correlation between FPN protein and IL-6 was noted, there was a strong negative correlation between serum iron and IL-6, both in subjects with CD (r=-0.88, P<0.0001) and those without anemia (r=-0.58, P=0.02). CONCLUSIONS: Intestinal FPN protein is upregulated in anemic CD subjects, suggesting that iron deficiency or anemia is the driving force regulating FPN levels. A transporter distinct from FPN appears to be involved in the hypoferremia associated with the inflammatory process of CD.

Association of linear growth impairment in pediatric Crohn's disease and a known height locus: a pilot study.

The etiology of growth impairment in Crohn's disease (CD) has been inadequately explained by nutritional, hormonal, and/or disease-related factors, suggesting that genetics may be an additional contributor. The aim of this cross-sectional study was to investigate genetic variants associated with linear growth in pediatric-onset CD. We genotyped 951 subjects (317 CD patient-parent trios) for 64 polymorphisms within 14 CD-susceptibility and 23 stature-associated loci. Patient height-for-age Z-score < -1.64 was used to dichotomize probands into growth-impaired and nongrowth-impaired groups. The transmission disequilibrium test (TDT) was used to study association to growth impairment. There was a significant association between growth impairment in CD (height-for-age Z-score < -1.64) and a stature-related polymorphism in the dymeclin gene DYM (rs8099594) (OR = 3.2, CI [1.57-6.51], p = 0.0007). In addition, there was nominal over-transmission of two CD-susceptibility alleles, 10q21.1 intergenic region (rs10761659) and ATG16L1 (rs10210302), in growth-impaired CD children (OR = 2.36, CI [1.26-4.41] p = 0.0056 and OR = 2.45, CI [1.22-4.95] p = 0.0094, respectively). Our data indicate that genetic influences due to stature-associated and possibly CD risk alleles may predispose CD patients to alterations in linear growth. This is the first report of a link between a stature-associated locus and growth impairment in CD.

Final adult height of children with inflammatory bowel disease is predicted by parental height and patient minimum height Z-score.

BACKGROUND: This study was designed to elucidate the contribution of parental height to the stature of children with inflammatory bowel disease (IBD), who often exhibit growth impairment. Accordingly, we compared patients' final adult heights and target heights based on measured parental heights and examined predictors of final adult height in pediatric IBD patients. METHODS: We prospectively analyzed the growth of 295 patients diagnosed between ages 1 and 18 (211 Crohn's disease [CD], 84 ulcerative colitis [UC]) and their family members (283 mothers, 231 fathers, 55 siblings). RESULTS: Twenty-two percent had growth impairment (height for age Z-score <-1.64, equivalent to <5th percentile on growth curve) in more than 1 measurement since diagnosis; most growth-impaired patients had CD (88% CD versus 12% UC). Parents of the growth-impaired group had lower mean height Z-scores compared to parents of nongrowth-impaired patients (-0.67 versus 0.02 for mothers [P < 0.001]; -0.31 versus 0.22 for fathers [P = 0.002]). For 108 patients who reached adult heights and had available parental heights, the growth-impaired group continued to demonstrate lower adult height Z-scores (-1.38 versus 0.07; P < 0.001). Adult heights were within 1 SD of target heights even for the growth-impaired group. Only 11.3% remained persistently growth-impaired in adulthood. Multivariate regression analysis demonstrated lower parental height and minimum patient height Z-score as significant predictors of lower final adult height in IBD. CONCLUSIONS: Parental height is a powerful determinant of linear growth even in the presence of chronic inflammation, and should be an integral part of the evaluation of growth in IBD children.

Developmental expression of Eph and ephrin family genes in mammalian small intestine.

BACKGROUND: Eph receptor tyrosine kinases EphB2 and EphB3, and ephrin-B1 ligand play a critical role in regulating small intestinal epithelial cell migration. Although well studied in developing brain, the expression pattern of Ephs/ephrins has not been delineated in the developing small intestine. AIMS: To examine the gene expression of all known members of Ephs/ephrins during development of mouse small intestine. METHODS: We examined the expression of 21 A- and B-Ephs/ephrins in mouse small intestine or the Caco-2 cell line using reverse-transcription polymerase chain reaction (RT-PCR), quantitative (q)RT-PCR, and immunohistochemical analyses. EphB2-expressing cells from isolated crypts were detected by immunofluorescence and fluorescence-activated cell sorting (FACS) analyses. RESULTS: With the exception of EphA5, all family members were expressed throughout the intestine at all ages examined. Most were uniformly expressed. In contrast, levels of EphA4, EphA8, EphB4, and ephrin-B2 messenger RNA (mRNA) were highest during early fetal development and declined with age. At E15, EphB2 and EphB4 proteins were diffusely expressed in proliferating stratified intestinal epithelial cells. By E18, the proteins had become localized to cell membranes of columnar epithelial cells within intervillus regions, and later were expressed on epithelial cell membranes in adult crypts. EphB2-expressing cells can be specifically isolated from crypt cell fractions. CONCLUSIONS: The current study represents the first analysis of Ephs/ephrins during intestinal development. The elevated expression of EphA4, EphA8, EphB4, and ephrin-B2 during the fetal period of intestinal morphogenesis suggests an important role in development. Continued intestinal expression of other family members implicates a role in differentiation.

Established genetic risk factors do not distinguish early and later onset Crohn's disease.

BACKGROUND: Early-onset disease is frequently examined in genetic studies because it is presumed to contain a more severe subset of patients under a higher influence of genetic effects. In light of the dramatic success of Crohn's disease (CD) gene discovery efforts, we aimed to characterize the contribution of established common risk variants to pediatric CD. METHODS: Using 35 confirmed CD risk alleles, we genotyped 384 parent-child trios (mean age of onset 11.7 years) along with 321 healthy controls. We performed association tests on the independent pediatric cohort and compared results to those previously published.1 We also computed a weighted CD genetic risk score for each affected person. Six variants not previously validated in children (at 5q33, 1q24, 7p12, 12q12, 8q24, and 1q32) were significantly associated with pediatric CD (P < 0.03). RESULTS: We detected no significant association between risk score and age at onset through age 30. This analysis illustrates that the genetic effect of established CD risk variants is similar in early and later onset CD. CONCLUSIONS: These results motivate joint analyses of genome-wide association data in early and late onset cohorts and suggest that, rather than established risk variants, independent variants or environmental exposures should be sought as modulators of age of onset.

Immune response to influenza vaccine in children with inflammatory bowel disease.

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.

Profile of depression in adolescents with inflammatory bowel disease: implications for treatment.

BACKGROUND: The purpose was to determine the utility of including neurovegetative symptoms in assessments of depression in youth with inflammatory bowel disease (IBD). METHODS: Forty-one youth with IBD and concurrent depressive symptomatology were enrolled in an intervention trial and received either 9 modules of cognitive-behavioral therapy (PASCET-PI) or treatment as usual (TAU). Youth and their primary caregivers completed the Children's Depression Inventory (CDI) at pre- (T1) and posttreatment (T2). Disease severity measures and current steroid dosage were obtained at each timepoint. Change in the individual items of the CDI was compared across groups and examined in association with change in physical illness course. RESULTS: Paired sample t-tests revealed significant changes in CDI item scores from T1 to T2 for a majority of the depressive symptoms assessed in the PASCET-PI group, but not for the TAU group. These changes did not appear to be linked to changes in disease severity and/or steroid dosage across these same timepoints. CONCLUSIONS: The inclusion of somatic items in the assessment of depression in physically ill youth is important, as these symptoms seem to respond to psychotherapeutic intervention. The present results would suggest that improvements in depressive symptomatology are not solely related to improvements in the course of IBD and that these items do reflect an important part of the profile of depressive symptoms in youth with IBD. Future research is warranted to replicate present findings and explore the generalizability of these results to other pediatric illness populations.