Pediatric-onset Crohn Research Articles

S1489 Polygenic Risk Scores Only Partially Explain the Risk of Pediatric Onset Crohn's Disease

S1489 Polygenic Risk Scores Only Partially Explain the Risk of Pediatric Onset Crohn's Disease

Early predictors of intestinal complications in pediatric-onset Crohn's disease: A long-term cohort study in Taiwan

PurposeIdentifying reliable prognostic factors for pediatric-onset Crohn's disease (CD) is important for guiding early treatment. This study aimed to evaluate the validity of various clinical parameters for predicting long-term intestinal complications in pediatric-onset CD patients with CD in Taiwan. MethodsThis was a single-center, retrospective study. Patients diagnosed with CD under 18 years of age at our hospital between January 1999 and December 2021 were enrolled. The baseline clinical variables and the Pediatric Crohn's Disease Activity Index (PCDAI) were obtained. Patients were categorized into low-, medium-, or high-risk groups based on the 2020 European Crohn's and Colitis Organization and European Society for Pediatric Gastroenterology Hepatology and Nutrition (ECCO-ESPGHAN) guidelines. The primary endpoint was the occurrence of new intestinal complications. ResultsAmong 53 enrolled patients (33 males and 20 females), 8 patients (33.96%) developed intestinal complications during the follow-up period (median 6.42 years, 3.17–9.75 years). Patients in the initial ECCO-ESPGHAN medium- or high-risk group had a 4.71-fold higher risk of intestinal complications than those in the low-risk group [hazard ratio = 4.71, p = 0.023] after adjusting for PCDAI in the multivariate Cox proportional hazard analysis. The other clinical variables did not reach statistical significance in predicting intestinal complications. The positive and negative predictive values of the ECCO-ESPGHAN stratification method for intestinal complications were 48.15% and 80.77%, respectively. ConclusionsECCO-ESPGHAN risk stratification is an effective early predictor of long-term intestinal complications in the Taiwanese population and may be used in clinical practice to guide early advanced therapy.

Surgical management of pediatric Crohn's disease

Management of pediatric-onset Crohn's disease uniquely necessitates consideration of growth, pubertal development, psychosocial function and an increased risk for multiple future surgical interventions. Both medical and surgical management are rapidly advancing; therefore, it is increasingly important to define the role of surgery and the breadth of surgical options available for this complex patient population. Particularly, the introduction of biologics has altered the disease course; however, the ultimate need for surgical intervention has remained unchanged. This review defines and evaluates the surgical techniques available for management of the most common phenotypes of pediatric-onset Crohn's disease as well as identifies critical perioperative considerations for optimizing post-surgical outcomes.

Association between body mass index and age of disease onset with clinical outcomes in paediatric-onset Crohn’s Disease (CD): a UK nation-wide analyses using the NIHR-IBD BioResource

BackgroundThe evidence on the relationship between adiposity and disease outcomes in paediatric Crohn’s disease (CD) is limited and lacks consensus.AimTo investigate the relationship between (a) body mass index (BMI) and clinical CD outcomes (hospitalisation, surgery, disease behaviour, biologic use, extra-intestinal manifestations (EIMs)) and (b) the age of CD onset with clinical outcomes.DesignClinical outcomes were examined in CD patients diagnosed at age <17 years and enroled in the National Institute for Health Research IBD-UK BioResource at a median age of 24 years. All outcomes and BMI were recorded at the time of enrolment. Participants were categorised into normal (<25 kg/m2) and high (≥25 kg/m2) BMI. Age at disease diagnosis was categorised into pre-puberty/early puberty (<11 years), puberty (11–14 years) and post-puberty (15–17 years). Spearman rank correlation was used to test the associations between continuous variables and chi-square test to compare categorical variables.Results848 participants with CD were included (51.8% males) and median age at diagnosis was 14 years. Participants with high BMI experienced a greater frequency of EIMs (P = 0.05) than those with low BMI (1 type of EIM: 18.5% vs. 13.2%, respectively; ≥2 types of EIMs: 7.8% vs. 5.6%, respectively). Age at diagnosis and BMI showed weak correlations with corticosteroid use (ρ = 0.08, P = 0.03 and ρ = −0.09, P = 0.01; respectively). An early diagnosis (<11 years) was associated with higher occurrence of stenosing and penetrating disease behaviour (P = 0.01) and hospitalisations (P < 0.001).ConclusionsA higher BMI and an earlier age of disease onset are associated with worse CD clinical presentation.

P1125 Incidence and Neoplastic Risk Associated with Colonic Stricture in Pediatric-Onset Crohn's Disease: A Population-based Study

Abstract Background The identification of colonic stricture in patients with Crohn's disease (CD) often leads to surgery due to concerns about associated neoplasia. Nevertheless, information regarding the neoplastic risk associated to colonic stricture is still limited. The objective of this study was to assess both the incidence of colonic stricture in pediatric-onset CD and the associated neoplastic risk at the population-based level. Methods All patients diagnosed with CD before age 17 between 1988 and 2011, and included in a population-based registry, were followed until 2013. Colonic stricture was defined as a narrowing of the digestive lumen observed on endoscopic or radiological examination. Excluded were stricture in the ileocaecal valve, anal canal, or low rectum. Univariate risk factors for colonic stricture were explored using Cox proportional hazards models with time-dependent variables, and a multivariable Cox model analysis was performed. Results A total of 1,007 patients diagnosed with CD between 1988 and 2011 were included. Median age at diagnosis was 14.5 years [IQR: 12.0-16.1]. Throughout the follow-up period (median follow-up, 8.8 years [4.6-14.2]), patients were predominantly exposed to 5-aminosalicylates (88.1%), immunosuppressants (70.6%), and biologics (47.9%). Colonic stricture was diagnosed in 52 patients, including 11 at CD diagnosis. The cumulative incidence of colonic stricture in CD was 2.9% [1.8%-4.0%] at 5 years. The overall incidence rate of colonic stricture in CD was 5.4 cases/1000 person-years, 95% CI [4.1-7.1]. In multivariable analysis, an increased risk of colonic stricture was observed during periods of active disease (HR = 2.62, [1.40-4.89], p&amp;lt;0.01). Conversely, the absence of colonic involvement at diagnosis (HR = 0.18, [0.04, 0.80], p&amp;lt;0.05) or treatment with aminosalicylates (HR = 0.39, [0.19-0.79], p&amp;lt;0.05) was associated with a lower risk of colonic stricture. After a median follow-up of 6.4 [2.4-12.7] years, colonic stricture surgical resection was performed in 29 patients (55.8%). Colon adenocarcinoma was detected in one patient (1.9%) within 6 months after the diagnosis of colonic stricture. Conclusion In this population-based study of pediatric-onset Crohn's disease, 52 patients (5%) experienced colonic stricture, with a 2.9% incidence rate observed after 5 years of follow-up. Additionally, one patient (2%) presented with an associated adenocarcinoma.

S19 Delivery and Disease Outcomes of Pregnant Adults With Pediatric-Onset Crohn’s Disease

S19 Delivery and Disease Outcomes of Pregnant Adults With Pediatric-Onset Crohn’s Disease

S102 Pediatric-Onset Crohn’s Disease in Hispanics: A Comparison With an Adult-Onset Cohort

S102 Pediatric-Onset Crohn’s Disease in Hispanics: A Comparison With an Adult-Onset Cohort

Transcutaneous auricular vagus nerve stimulation attenuates inflammatory bowel disease in children: a proof-of-concept clinical trial

BackgroundVagus nerve stimulation is an investigational anti-inflammatory therapy targeting the nervous system to modulate immune activity. This study evaluated the efficacy and safety of transcutaneous auricular VNS (ta-VNS) in patients with pediatric-onset Crohn’s disease (CD) or ulcerative colitis (UC).MethodsParticipants were 10–21 years of age with mild/moderate CD or UC and fecal calprotectin (FC) > 200 ug/g within 4 weeks of study entry. Subjects were randomized to receive either ta-VNS targeting the cymba conchae of the external left ear, or sham stimulation, of 5 min duration once daily for a 2-week period, followed by a cross over to the alternative stimulation for an additional 2 weeks. At week 4, all subjects received ta-VNS of 5 min duration twice daily until week 16. Primary study endpoints were clinical remission, and a ≥ 50% reduction in FC level from baseline to week 16. Heart rate variability measurements and patient-reported outcome questionnaires were completed during interval and week 16 assessments.ResultsTwenty-two subjects were enrolled and analyzed (10 CD, 12 UC). Six of 10 with CD had a wPCDAI > 12.5 and 6/12 with UC had a PUCAI > 10 at baseline, correlating to mild to moderate symptom activity. Among the 12 subjects with active symptomatic disease indices at baseline, clinical remission was achieved in 3/6 (50%) with CD and 2/6 (33%) with UC at week 16. Despite all subjects having FC levels ≥ 200 within 4 weeks of enrollment, five subjects (4 UC, 1 CD) had FC levels < 200 at the baseline visit and were excluded from the FC analysis. Of the remaining 17, median baseline FC was 907 µg/g (IQR 411–2,120). At week 16, 11/17 (64.7%) of those with baseline FC ≥ 200 had a ≥ 50% reduction in FC (95% CI 38.3—85.8). In the UC subjects, there was an 81% median reduction in FC vs baseline (833 µg/g; p = 0.03) while in the CD subjects, median reduction in FC at 16 weeks was 51% (357 µg/g; p = 0.09). There were no safety concerns.ConclusionNoninvasive ta-VNS attenuated signs and symptoms in a pediatric cohort with mild to moderate inflammatory bowel disease.Trial RegistrationNCT03863704—Date of registration 3/4/2019.

A Novel 8-Predictors Signature to Predict Complicated Disease Course in Pediatric-onset Crohn's Disease: A Population-based Study.

The identification of patients at high risk of a disabling disease course would be invaluable in guiding initial therapy in Crohn's disease (CD). Our objective was to evaluate a combination of clinical, serological, and genetic factors to predict complicated disease course in pediatric-onset CD. Data for pediatric-onset CD patients, diagnosed before 17 years of age between 1988 and 2004 and followed more than 5 years, were extracted from the population-based EPIMAD registry. The main outcome was defined by the occurrence of complicated behavior (stricturing or penetrating) and/or intestinal resection within the 5 years following diagnosis. Lasso logistic regression models were used to build a predictive model based on clinical data at diagnosis, serological data (ASCA, pANCA, anti-OmpC, anti-Cbir1, anti-Fla2, anti-Flax), and 369 candidate single nucleotide polymorphisms. In total, 156 children with an inflammatory (B1) disease at diagnosis were included. Among them, 35% (n = 54) progressed to a complicated behavior or an intestinal resection within the 5 years following diagnosis. The best predictive model (PREDICT-EPIMAD) included the location at diagnosis, pANCA, and 6 single nucleotide polymorphisms. This model showed good discrimination and good calibration, with an area under the curve of 0.80 after correction for optimism bias (sensitivity, 79%, specificity, 74%, positive predictive value, 61%, negative predictive value, 87%). Decision curve analysis confirmed the clinical utility of the model. A combination of clinical, serotypic, and genotypic variables can predict disease progression in this population-based pediatric-onset CD cohort. Independent validation is needed before it can be used in clinical practice.

Natural History of Anal Ulcerations in Pediatric-Onset Crohn's Disease: Long-Term Follow-Up of a Population-Based Study.

Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD. All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Cox model was used to evaluate the risk of evolution of anal ulcerations toward suppurative lesions. Among the 1,005 included patients (females, 450 [44.8%]; median age at diagnosis 14.4 years [interquartile range 12.0-16.1]), 257 (25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (95% confidence interval [CI] 35.2-41.4) and 44.0% (95% CI 40.5-47.2), respectively. In multivariable analysis, the presence of extraintestinal manifestations (hazard ratio [HR] 1.46, 95% CI 1.19-1.80, P = 0.0003) and upper digestive location (HR 1.51, 95% CI 1.23-1.86, P < 0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location (L1) was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, 95% CI 1.11-2.06, P = 0.0087; L3 vs L1 HR 1.42, 95% CI 1.08-1.85, P = 0.0116). The risk of fistulizing perianal CD (pCD) was doubled in patients with a history of anal ulceration (HR 2.00, 95% CI 1.45-2.74, P < 0.0001). Among the 352 patients with at least 1 episode of anal ulceration without history of fistulizing pCD, 82 (23.3%) developed fistulizing pCD after a median follow-up of 5.7 years (interquartile range 2.8-10.6). In these patients with anal ulceration, the diagnostic period (pre vs biologic era), exposure to immunosuppressants, and/or anti-tumor necrosis factor did not influence the risk of secondary anoperineal suppuration. Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least 1 episode after 10 years of evolution. Fistulizing pCD is twice as frequent in patients with present or past anal ulceration.

P155 Natural history of anal stricture in pediatric-onset Crohn’s disease: a two-decades population-based study

Abstract Background The natural history of anal stricture complicating pediatric-onset Crohn’s disease (CD) is poorly known. The aims of this study were: to determine in a population-based study the risk of anal stricture in pediatric-onset CD; to identify risk factors for anal stricture; and to evaluate the natural history of anal stricture at the population level. Methods All patients with a diagnosis of CD made before the age of 17 years between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. A specific collection of additional data was performed in patients with anal stricture at diagnosis or during follow-up. Variables collected included: proctological examination, diagnostic management and treatment. Multivariate Cox models were used to identify factors associated with anal stricture. Results Among the 1,007 included CD patients (females, 451 (44.8%); median age at diagnosis 14.4 years (IQR, 12.0-16.1), median follow-up 8.8 years (IQR, 4.6-14.2)), only one (0.1%) had anal stricture at diagnosis while 26 (2.6%) presented anal stricture during follow-up. Cumulative incidence of anal stricture at 5 and 10 years after diagnosis was 0.6% (CI95%, 0.1-1.1) and 1.4% (CI95%, 0.5-2.3), respectively. Among the 27 patients with anal stricture, 25 (92.6%) had already at least one episode of anal ulceration or fistulizing perianal CD (pCD). In multivariable analysis, the presence of extra-intestinal manifestations (Hazard Ratio (HR) 2.2, CI95% 1.0-4.8, p=0.027), colonic location (L1 vs L3 HR 0.0 (-); L2 vs L3 HR 1.2, CI95% 0.6-2.7, p=0.006) and history of fistulizing pCD (HR 9.9, CI95% 4.3-22.8, p&amp;lt;0.0001) were significantly associated with anal stricture. Eleven (41%) patients needed at least one dilation. After a median follow-up of 16.9 years (IQR, 11.5-20.2), healing of anal stricture was observed only once. One patient (3.7%) presented an anal cancer 7 years after the diagnosis of anal stricture. Nine (33.3%) patients needed a stoma. Among them, 8 already had a fistulizing pCD and 4 needed an abdominoperineal amputation. Anal stricture was significantly associated with an increased risk of stoma (HR 5.8, CI95% 2.3-14.3), p=0.0002). Conclusion Anal stricture is a rare event in pediatric onset CD, occurring in 1.5% of patients over a 10 year-period after diagnosis. However, anal stricture had a negative impact on disease prognosis with a five-fold increase of the risk of stoma.

P207 Colonic location at diagnosis of pediatric-onset Crohn’s disease is associated with a pejorative disease course: a two decades population-based study

Abstract Background Crohn's disease (CD) location would influence the risk of complications and therapeutic strategies. The objective of this study was to compare the clinical presentation at diagnosis and the natural history of colonic CD in comparison to ileal CD and ulcerative colitis (UC) in pediatric-onset inflammatory bowel disease. Methods All children (&amp;lt; 17 years) with a diagnosis of CD or UC made between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. Presentation at diagnosis, risks of complicated disease, surgery, hospitalization and exposure to treatments in ileal CD (L1), colonic CD (L2) and UC were compared. Disease location was defined at diagnosis. In case of extension of the disease (L1 or L2 to L3), follow-up was censored. Results A total of 215 L1 patients, 234 L2 patients and 337 UC patients were included. At diagnosis, the proportion of males (L1 53.5%; L2 53.4%; UC 42.7%; p=0.012), age at diagnosis (15.0; 13.7; 14.0 years; p=0.003), family history of IBD (12.6%; 12.7%; 5.0%; p=0.005), diagnostic delay (3.0; 3.0; 2.0 months; p=0.001) and smoking prevalence (11.6%; 8.1%; 5.6%; p=0.041) were different between the three groups. Bloody stool and diarrhea at diagnosis was observed in respectively 14.9%, 44.4%, and 91.1% (p &amp;lt; 0.001) and 47.0%, 71.8%, and 65.0% (p &amp;lt; 0.001) of L1, L2 and UC. At diagnosis, granuloma was identified in 12.6% of L1 patients and 31.2% of L2 patients (p&amp;lt;0.001). The risk of extension to L3 was significantly higher in the L2 group than in the L1 group (at 5 years - 37% vs. 14%, p&amp;lt;0.001). Compared to L1 location, L2 was associated with a lower risk of luminal fistula (HR 0.41 [0.21-0.79], p=0.008) but a higher risk of anoperineal lesion (HR 2.11 [1.29-3.45], p=0.003). The prevalence of extra-intestinal manifestations, articular (p&amp;lt;0.001) and cutaneous (p&amp;lt;0.001) was higher in L2. While the risk of surgery was significantly higher in case of L1 (at 5 years – L1 37%, L2 13% and UC 13%; p&amp;lt;0.001), the risk of hospitalization (at 5 years - 22%, 39% and 33%; p=0.01), exposure to corticosteroids (at 5 years - 55%, 69% and 67%; p&amp;lt;0.001), immunosuppressants (at 5 years - 47%, 61% and 42% - p&amp;lt;0.001) and anti-TNF (at 5 years - 16%, 35% and 22%; p&amp;lt;0.001) were higher in case of L2. Conclusion The clinical presentation at diagnosis and natural history of ileal and colonic CD differ significantly. Colonic location is associated with a high risk of perianal CD, extra-intestinal manifestations, hospitalization as well as exposure to steroids, immunosuppressants and anti-TNF. These differences may justify different therapeutic strategies in the future.

Age determines the risk of familial inflammatory bowel disease-A nationwide study.

To estimate familial aggregation of inflammatory bowel disease (IBD), we performed a nationwide, case-control study and examined the odds for patients with IBD (vs controls) to have a first-degree relative (FDR) with IBD, by age of diagnosis, type of family history and IBD subtype. To assess the incidence of future IBD in relatives of incident IBD patients, we performed a cohort study. Individuals diagnosed with IBD (N=50,667) between 2003 and 2017 with at least one FDR were identified from Swedish national registers and compared to general population controls (N=506,720) with at least one FDR. We used logistic regression to calculate adjusted odds ratios (ORs) and Cox regression to estimate hazard ratios (HRs). Compared to controls, IBD cases more often had a mother (3.0% vs 0.9%, OR=3.5; 95% CI: 3.3-3.7), father (2.9% vs 0.8%, OR=3.5; 95% CI: 3.3-3.7), full sibling (5.3% vs 1.5%, OR=3.6; 95% CI: 3.4-3.8) and child (2.4% vs 0.9%, OR=2.6; 95% CI: 2.4-2.8) with IBD. The strength of association increased with the number of affected FDRs and was modified by subtype of IBD and age of diagnosis. Highest ORs were observed for paediatric IBD among paediatric-onset Crohn's disease (OR=10.6; 95% CI: 8.2-13.5) and paediatric-onset ulcerative colitis (OR=8.4; 95% CI: 6.4-10.9) cases. The 10-year cumulative incidence of IBD was 1.7% in full-siblings of incident IBD patients vs 0.4% among full-siblings of reference individuals. The variations in the strength of familial IBD and future risk of IBD in FDRs support differences in genetic predisposition and call for targeted approaches in potential screening programmes.

Implementation of exclusive enteral nutrition in pediatric patients with Crohn\u2019s disease\u2014results of a survey of CEDATA-GPGE reporting centers

BackgroundExclusive enteral nutrition (EEN) is the first-line therapy for pediatric-onset Crohn’s disease (CD) patients. CEDATA-GPGE® is the largest patient registry for children and adolescents with inflammatory bowel disease (IBD) in Europe, collecting data from over 5000 patients since 2004 in Germany and Austria. Since the application of EEN over 8 weeks is difficult and a high dropout rate is often described, the mode of application including a supporting structure is crucial for success. The aim of this study was to ascertain the variation in the application of EEN across the participating centers and to associate these with the outcome.ResultsThirty-one centers responded to the survey (81.6%). 88.5% of CD patients were recommended EEN for induction therapy, 71.8% actually started with EEN, and 22.1% terminated the EEN prematurely. The duration of EEN typically lasted 6 to 8 weeks, and the polymeric formula was mainly used. 80.6% of the clinics added flavorings to the formulas. After EEN, the most preferred diet for maintenance therapy was a healthy, well-balanced diet considering individual intolerances.ConclusionsEEN is widely recommended as an induction therapy by the German and Austrian pediatric gastroenterologists for children and adolescents with CD. However, this questionnaire-based study has shown a wide variation in EEN protocols used by the different pediatric clinics of CEDATA-GPGE®.

Perianal Crohn Disease Is More Common in Children and Is Associated With Complicated Disease Course Despite Higher Utilization of Biologics: A Population-based Study From The epidemiology group of the Israeli IBD Research Nucleus (epiIIRN).

Both perianal and pediatric-onset Crohn disease (CD) disease are associated with complicated disease course and higher drug utilization. we aimed to explore the differences between pediatric and adult-onset perianal CD and their disease course. We included all patients with newly diagnosed CD from 2005 to 2019 at two Israeli Health Maintenance Organizations, covering 78% of the population. A combination of ICD-9 codes, radiology and procedures was used to define fistulizing perianal CD (PCD) and its severity according to the association with simple and complex perianal disease. A total of 12,905 patients were included (2186 [17%] pediatric-onset, 10,719 [83%] adults), with a median follow-up of 7.8 years. PCD was diagnosed in 1530 (12%) patients, with higher incidence in children (308 [14%] children vs 1222 adults [11%]; P < 0.001). Children had higher incidence of severe PCD (141/308 [47%] vs 433/1222 [35%]; P < 0.001). At 5 years, children with PCD were more likely than adults to be treated with biologics (212 [69%] vs 515 [42%]; odds ratio [OR] 2.6 [95% confidence interval (CI) 1.6-4.0]; P < 0.001) and immunomodulators (238 [74%] vs 643 [53%]; OR 2.8 [95% CI 2.1-3.6]; P < 0.001). PCD in children was still associated with poorer disease outcomes as shown for surgeries (36 [12%] vs 93 [8%]; P = 0.02) and steroid-dependency (52 [17%] vs 156 [13%]; P < 0.001). Multivariable modeling indicated that the severity of PCD is a stronger predictor of disease course than age. PCD is more common in pediatric-onset CD and is associated with higher drug utilization and worse disease outcomes, in large due to higher rate of severe PCD in children.

OP35 Natural history of anal ulcerations in pediatric-onset Crohn’s Disease: A population-based study

Abstract Background Anal ulcerations are frequently observed in Crohn’s disease (CD). Their natural history remains poorly known, especially in pediatric-onset CD. The aims of this study were: to determine in a population-based study the risk of anal ulcerations in pediatric onset CD; to identify risk factors for anal ulcerations; to evaluate the risk of progression towards suppurative lesions; to evaluate the risk factors of progression towards suppurative lesions. Methods All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. A specific collection of additional data was performed in patients with anal ulcerations at diagnosis or during follow-up. The variables collected included: proctological examination, diagnostic management (perineal MRI, endoscopic ultrasound, examination under general anaesthesia) and treatment (medical or surgical). Multivariate Cox models were used to identify factors associated with anal ulcerations and factors of progression towards suppurative lesions. An adjusted time-dependent Cox model was used to evaluate the risk of progression of anal ulcerations towards suppurative lesions. Results 1005 patients were included (females, 450 (44.8%); median age at diagnosis 14.4 years (IQR, 12.0–16.1)). 257 (25.6%) had anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (CI95%, 35.2–41.4) and 44.0% (CI95%, 40.5–47.2). The presence of extra-intestinal manifestations (HR 1.46, CI95% 1.19–1.80, p=0.0003) and upper digestive location (HR 1.51, CI95% 1.23–1.86, p&amp;lt;0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location at diagnosis was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, CI95% 1.11–2.06, p=0.0087; L3 vs L1 HR 1.42, CI95% 1.08–1.85, p=0.0116). Among the 352 patients with at least one episode of anal ulceration, 82 (23.3%) developed perianal suppuration after a median follow-up of 5.7 years (IQR, 2.8–10.6). The risk of perianal suppuration was doubled in patients with anal ulceration compared to those who did not have any ulceration (HR 2.0, CI95% 1.45–2.74, p&amp;lt;0.0001). In patients with anal ulceration, the diagnostic period (before or since the “biologic era”), exposure to immunosuppressants and/or anti-TNF did not influence the risk of perianal suppuration. Conclusion Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least one episode after 10 years of evolution. Perianal suppurations are twice as frequent in patients with present or past anal ulceration. These results plead for a proactive therapeutic approach in case of anal ulcerations.

Oral and Otorhinolaryngological Findings in Adults Who Were Diagnosed With Pediatric Onset Crohn's Disease: A Controlled Study.

Up to 50% of pediatric patients with Crohn's disease (CD) report oral manifestations, but less is known about their oral health when they become adults. Our aim was to provide detailed descriptions of the presence of oral and otorhinolaryngological manifestations in patients with pediatric onset CD once they reached adulthood, to look for predisposing factors and to compare the findings to matched controls. Adult patients diagnosed with CD in childhood at the Children's Hospital, University of Helsinki, Finland, after 2000 were invited for a follow-up appointment in 2016 and 24 were examined by a dentist and otorhinolaryngologist. They were compared with 22 matched controls from the Population Register Centre. The participants completed questionnaires about their general health, any special diets, and their health-related quality of life. Their nutrition was evaluated from food records. Patients with CD had minor oral manifestations at a median of 9 years after their childhood diagnosis and the most common was angular cheilitis, which affected 6 patients and 1 control, but was not statistically significant (P=0.0984). CD with perianal abscessing disease correlated to orofacial findings (P=0.0312). Most of the patients had normal otorhinolaryngological findings. Subjects with oral lesions had lower mean health-related quality of life scores than subjects without oral findings and the differences were clinically but not statistically significant. Oral manifestations were not associated with differences in energy intake. Oral manifestations in adult patients with pediatric onset CD were mild and were not associated with otorhinolaryngological pathology.

Quality of life and colorectal function in Crohn\u2019s disease patients that underwent ileocecal resection during childhood

Psychosocial and functional outcomes after intestinal resection in pediatric Crohn’s disease (CD) are lacking. Therefore, we (I) assessed health-related quality of life (HRQOL), colorectal function, and satisfaction with surgery and (II) investigated their relationship with surgical outcomes, after ileocecal resection for CD. Crohn’s patients that underwent ileocecal resection during childhood were included. HRQOL and colorectal function were assessed using SF-36 and COREFO, respectively, and compared with reference values. Satisfaction was scored on a 5-point Likert scale. In total, 80 patients (50% male, median age 23.0 years) were included. Physical HRQOL was impaired (SF-36 [mean]: CD, 47 vs. general, 54; p < 0.001), while mental HRQOL was similar to that in the general population. Overall colorectal function was impaired (COREFO [mean]: CD, 12.6 vs. normal, 7.2; p < 0.001). Worse colorectal function was associated with increasing clinical disease activity and longer interval since resection. Majority of patients was satisfied with surgery (81% satisfied/very satisfied, 11% neither satisfied nor dissatisfied, 8% dissatisfied/very dissatisfied). Decreased satisfaction with surgery was associated with increased clinical disease activity but not related to colorectal function.Conclusions: Physical HRQOL and colorectal function in CD patients who underwent ileocecal resection during childhood seem impaired and related to adverse surgical outcomes. This emphasizes the need for post-operative monitoring and prophylactic therapies.What is Known:• Up to 25% of pediatric-onset Crohn’s disease (CD) patients undergo an intestinal resection within 5 years from diagnosis.• Many children and adults with CD experience disruption of their daily activities and health-related quality of life (HRQOL).What is New:• Physical HRQOL and colorectal function are impaired in patient with CD that underwent ileocecal resection during childhood.• Increasing clinical disease activity, a longer interval since surgery, severe complications related to surgery, and recurrent surgeries are all associated with worse colorectal function.

Growth failure in pediatric onset inflammatory bowel disease: mechanisms, epidemiology, and management.

Impairment of growth is recognized as one of the most significant complications of inflammatory bowel disease (IBD) in pediatric patients. The reported incidence of growth failure at diagnosis is 15-40% in pediatric onset Crohn's disease (CD) and 3-10% in ulcerative colitis (UC). Growth failure is associated with decreased appetite, abdominal symptoms, malabsorption due to mucosal inflammation, growth hormone (GH) resistance due to inflammation, and even genetic factors. Several population-based studies and cohort studies suggest that patients with pre-pubertal onset CD have a higher risk of growth failure at disease onset. Final adult height is still lower than that of healthy controls; however, its prevalence is generally lower than that at the disease onset. Several IBD treatments were reported to improve patients' growth. In addition to enteral nutrition therapy, treatment with anti-tumor necrosis factor (TNF) agents was reported to have favorable effects on growth of patients with pre-pubertal onset CD. Avoiding corticosteroids (CS) and achieving deep remission seems to be important to maintain optimal growth in patients with pediatric onset IBD.

Long-term outcome of pediatric-onset Crohn’s disease: A population-based cohort study

BackgroundPediatric-onset Crohn’s disease (CD) may represent a more severe form of disease. The aim of this study was to describe long-term outcome and identify associated risk factors of complicated behavior in a large population-based pediatric-onset CD cohort. Patients and methodsCases included all patients recorded in the EPIMAD registry diagnosed with definite or probable CD between January 1988 and December 2004, under the age of 17 years at the time of diagnosis, with at least two years of follow-up. ResultsFive hundred and thirty-five patients were included. Median follow-up was 11.1 years [IQR, 7.3–15.0]. At the end of follow-up, 8% (n = 44) of patients had pure ileal disease (L1), 8% (n = 44) had pure colonic disease (L2), and 83% (n = 439) had ileocolonic disease (L3). L4 disease and perianal disease were observed in 42% (n = 227) and 16% (n = 85) of patients, respectively. At the end of follow-up, 58% (n = 308) of patients presented complicated disease behavior (B2, 39% and B3, 19%), and 42% (n = 163) of patients with inflammatory behavior at diagnosis had evolved to complicated behavior. During follow-up, 86% of patients (n = 466) received at least one course of corticosteroids, 67% (n = 357) of patients had been exposed to immunosuppressants and 35% (n = 187) of patients received at least one anti-TNF agent. Forty-three percent (n = 230) of patients underwent at least one intestinal resection. The overall mortality rate was 0.93% and the SMR was 1.6 [0.5–3.8] (p = 0.20). Five cancers were reported with a crude cancer incidence rate of 1.1% and an SIR of 3.3 [1.2–7.0] (p = 0.01). In a multivariate Cox model, ileal (HR, 1.87 [1.09–3.21], p = 0.022) or ileocolonic (HR, 1.54 [1.01–2.34], p = 0.042) and perianal lesions at diagnosis (HR, 1.81 [1.13- 2.89], p = 0.013) were significantly associated with complicated behavior. ConclusionAbout 80% of patients with pediatric-onset CD presented extensive ileocolonic disease during follow-up. The majority of patients evolved to complicated behavior. Surgery, cancer and mortality were observed in 43%, 0.9% and 0.9% of patients, respectively.