Adult-onset Inflammatory Bowel Disease Research Articles

Colorectal Cancer associated with pediatric inflammatory bowel disease: a case series

BackgroundInflammatory bowel disease (IBD) is associated with an increased risk of Colorectal cancer (CRC), and its most important risk factors are the duration and extent of the disease. Pediatric-onset inflammatory bowel disease has a tendency for a more extensive, more severe, and longer predicted disease duration than adult-onset inflammatory bowel disease. This study aimed to identify the clinical characteristics of patients with CRC related to pediatric-onset IBD and consider the appropriateness of current surveillance endoscopy recommendations for the detection of premalignant lesions and early-stage CRC.MethodsWe searched a research platform based on the SUPREME electronic medical record data-mining system to identify cases of colorectal malignancy in patients with pediatric IBD that presented between 2000 and 2020.ResultsDuring the follow-up, 4 (1.29 per 1000 person years) out of 443 patients with PIBD was diagnosed with CRC. The median age at diagnosis of CRC was 18.5 (range: 15–24) years, and the median period from diagnosis of IBD to CRC was 9.42 (range: 0.44–11.96) years. The sigmoid colon was the most frequent location of CRC (in 3 of the 4 cases). Adenocarcinoma was the most common histological type (in 2 of the 4 cases).ConclusionsPatients with pediatric-onset IBD exhibited a much shorter disease duration than that of adult-onset IBD at the time of diagnosis of CRC, suggesting that surveillance endoscopy for the detection of precancerous lesions and early-stage cancer should be initiated earlier in pediatric patients than in adult patients.

Adult-onset inflammatory bowel disease and rate of serious infections compared to the general population: a nationwide register-based cohort study 2002–2017

Objectives To investigate absolute and relative risk of serious infections in adult/elderly inflammatory bowel disease (IBD) diagnosed 2002–2017. Methods Nationwide, register-based cohort study of Swedish patients with IBD compared with general population matched reference individuals with regard to time to first serious infection, equal to hospital admission. Multivariable Cox regression estimated hazard ratios (HRs) for any serious infection. Secondary outcomes included site-specific infections, opportunistic infections and sepsis. Results We identified 47 798 individuals with IBD. During a follow-up of 329 000 person-years, they had 8752 first serious infections (26.6 per 1000 person-years). This compared with an incidence rate of 10.7 per 1000 person-years in matched reference individuals, corresponding to a 2.53-fold increased hazard of serious infections (95%CI = 2.47–2.59). The HR for serious infection in elderly-onset IBD was 2.01 (95%CI = 1.95–2.08). The relative hazard of serious infection was somewhat higher in Crohn’s disease (2.94; 95%CI = 2.81–3.06) than in ulcerative colitis (2.24; 95%CI = 2.17–2.31). The HR for serious infections was high in the first year of follow-up (5.17; 95%CI = 4.93–5.42). Individuals with IBD were at a particularly high relative hazard of gastrointestinal and opportunistic infections. The HR for sepsis was 2.47 (95%CI = 2.32–2.63). The relative rates for serious infections in IBD increased in recent years. Conclusions Patients with adult-onset IBD are at increased risk of serious infections, particularly gastrointestinal and opportunistic infections. Relative rates were highest just after IBD diagnosis, and seem to have increased in recent years.

Disease- and Treatment-related Complications in Older Patients With Inflammatory Bowel Diseases: Comparison of Adult-onset vs Elderly-onset Disease.

The incidence and prevalence of inflammatory bowel diseases (IBD) in older adults are rising. There is a limited comparative assessment of risk of disease- and treatment-related complications in older patients (older than 60 years) with adult-onset (age at disease onset, 18-59 years; AO-IBD) vs elderly-onset IBD (age at disease onset, older than 60 years; EO-IBD). We compared clinical outcomes in older patients with IBD with AO-IBD vs EO-IBD. We conducted a retrospective cohort study comparing risk of disease-related complications (IBD-related surgery, hospitalization, treatment escalation, clinical flare, or disease complication) and treatment-related complications (serious infection, malignancy, or death) in older patients with AO-IBD vs EO-IBD through Cox proportional hazard analysis, adjusting for age at cohort entry, disease phenotype, disease duration, prior surgery and/or hospitalization, medication use, disease activity at cohort entry, and comorbidities. We included 356 older patients with IBD (AO-IBD, 191 patients, 67 ± 5 y at cohort entry; EO-IBD, 165 patients, 72 ± 8 y at cohort entry). No significant differences were observed in the risk of disease-related complications in older patients with prevalent vs incident IBD (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.58-1.25), although risk of IBD-related surgery was lower in older patients with prevalent IBD (aHR, 0.47; 95% CI, 0.25-0.89). Older patients with prevalent IBD were significantly less likely to experience treatment-related complications (aHR, 0.58; 95% CI, 0.39-0.87). Patients with AO-IBD have lower risk of treatment-related complications as they age compared with patients with EO-IBD, without a significant difference in risk of disease-related complications.

Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn\u2019s disease

X-linked inhibitor of apoptosis (XIAP) is the most potent human inhibitor of apoptosis, and is also involved in NOD2-dependent NFκB and MAPK signalling cascade activation. The absence or defective function of XIAP leads to the development of a rare and severe primary immunodeficiency known as X-linked lymphoproliferative syndrome type 2 (XLP-2), which is characterized by a triad of clinical manifestations, including a high incidence of haemophagocytic lymphohistiocytosis (HLH), lymphoproliferation and inflammatory bowel disease (IBD), usually with very early onset. Here, we present a novel XIAP mutation identified in a patient with atypical adult-onset IBD complicated by relapsing HLH, splenomegaly and sarcoid-like disease. The c.266delA mutation in the XIAP gene creates a premature stop codon, and causes a severe reduction in XIAP protein expression. The mutation is also associated with impaired spontaneous and staurosporine- and PMA-induced apoptosis accompanied by significantly increased expression of pro-apoptotic genes. We also confirmed the negative impact of this particular XIAP mutation on NOD2-dependent NFκB and MAPK activation, while NOD2-independent activation was found to be unaffected. Moreover, we assume that the mutation has an impact on the overproduction of IL-12 and IFNγ, the shift towards the Th1 immune response and increased numbers of central memory and effector memory CD4+ and CD8+ T cells. All these changes contribute to immune dysregulation and the clinical manifestation of XLP-2.

Progression of Elderly Onset Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Population-Based Cohort Studies

The incidence of inflammatory bowel diseases (IBDs) in older adults is increasing. We performed a systematic review and meta-analysis to evaluate progression of elderly onset (EO) IBD in population-based cohorts and compared it with adult onset (AO) IBD. In a systematic review through June 1, 2019, we identified population-based cohort studies of EO IBD reporting the cumulative risk of hospitalization, surgery, mortality, treatment patterns, escalation, and/or malignancy. Data were synthesized using random-effects meta-analysis as cumulative risk of events at 1 year, 5 years, and 10 years, and compared with data from patients with AO IBD in the same cohorts. We identified 9 studies, comprising 14,765 patients with EO IBD. In patients with EO Crohn's disease (CD), the cumulative 5-year risk of surgery was 22.6% (95% CI, 18.7-27.2) and was similar to that of patients with AO CD (relative risk [RR], 1.04; 95% CI, 0.80-1.34). Overall exposure to corticosteroids was comparable between patients with EO CD vs AO CD (5-year risk: 55.4%; 95% CI, 53.4-57.4; RR, 0.88; 95% CI, 0.78-1.00), but exposure to immunomodulators (31.5%; 95% CI, 29.7-33.4; RR, 0.62; 95% CI, 0.51-0.77) or biologic agents (6.5%; 95% CI, 5.6-7.6; RR, 0.36; 95% CI, 0.25-0.52) was significantly lower for patients with EO CD than for patients with AO CD. Similarly, in patients with EO ulcerative colitis (UC), the cumulative 5-year risk of surgery was 7.8% (95% CI, 5.0-12.0), similar to the risk for patients with AO UC (RR, 1.29; 95% CI, 0.79-2.11). Overall exposure to corticosteroids was comparable between patients with EO UC vs AO UC (5-year risk: 57.2%; 95% CI, 55.6-58.7; RR, 0.98; 95% CI, 0.91-1.06), but exposure to immunomodulators (16.1%; 95% CI, 15.0-17.2; RR, 0.58; 95% CI, 0.54-0.62) or biologic agents (2.0%; 95% CI, 1.6-2.5; RR, 0.36; 95% CI, 0.24-0.52) was significantly lower for patients with EO UC than for patients with AO UC. Patients with EO IBD appeared to have increased mortality, but not malignancy, compared with the general population. There were few data on comorbidities or adverse effects of medications. In a systematic review and meta-analysis, we found that patients with EO IBD have a similar risk of surgery as patients with AO IBD. However, patients with EO IBD are less likely to receive treatment with immunomodulators or biologic agents.

Development of Physiologically Responsive Human iPSC-Derived Intestinal Epithelium to Study Barrier Dysfunction in IBD.

In inflammatory bowel disease (IBD), the intestinal epithelium is characterized by increased permeability both in active disease and remission states. The genetic underpinnings of this increased intestinal permeability are largely unstudied, in part due to a lack of appropriate modelling systems. Our aim is to develop an in vitro model of intestinal permeability using induced pluripotent stem cell (iPSC)-derived human intestinal organoids (HIOs) and human colonic organoids (HCOs) to study barrier dysfunction. iPSCs were generated from healthy controls, adult onset IBD, and very early onset IBD (VEO-IBD) patients and differentiated into HIOs and HCOs. EpCAM+ selected cells were seeded onto Transwell inserts and barrier integrity studies were carried out in the presence or absence of pro-inflammatory cytokines TNFα and IFNγ. Quantitative real-time PCR (qRT-PCR), transmission electron microscopy (TEM), and immunofluorescence were used to determine altered tight and adherens junction protein expression or localization. Differentiation to HCO indicated an increased gene expression of CDX2, CD147, and CA2, and increased basal transepithelial electrical resistance compared to HIO. Permeability studies were carried out in HIO- and HCO-derived epithelium, and permeability of FD4 was significantly increased when exposed to TNFα and IFNγ. TEM and immunofluorescence imaging indicated a mislocalization of E-cadherin and ZO-1 in TNFα and IFNγ challenged organoids with a corresponding decrease in mRNA expression. Comparisons between HIO- and HCO-epithelium show a difference in gene expression, electrophysiology, and morphology: both are responsive to TNFα and IFNγ stimulation resulting in enhanced permeability, and changes in tight and adherens junction architecture. This data indicate that iPSC-derived HIOs and HCOs constitute an appropriate physiologically responsive model to study barrier dysfunction and the role of the epithelium in IBD and VEO-IBD.

Peripheral Blood Eosinophilia and Long-term Severity in Pediatric-Onset Inflammatory Bowel Disease

Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.

DOP47 The changing pattern of inflammatory bowel disease incidence in Northern France: A continuing increase in the young women (1988–2014)

Abstract Background In industrialised countries, inflammatory bowel disease (IBD) incidence rates appear to have stabilised in adults but not in children. The objective was to describe changes in the incidence and phenotype of adult-onset IBD in northern France over a 27-year period. Methods We included all patients aged 17 or over at IBD diagnosis, recorded in the EPIMAD population-based registry between 1988 and 2014. Standardised incidence rates for Crohn’s disease (CD) and for ulcerative colitis (UC) were calculated in the population as a whole and by age and sex. Patients were divided into three age groups: 17–39, 40–59, and 60 and over. Disease locations were defined according to the Montreal classification. Results 17,686 incident adult-onset IBD cases were recorded, including 10,206 cases of CD (58%), 6,839 cases of UC (38%) and 641 cases of IBD unclassified (IBDU; 4%). The mean [95% CI] annual incidences of adult-onset IBD, CD, UC, and IBDU were 13.5 per 105 [13.3–13.7], 7.5 per 105 [7.4–7.7], 5.4 per 105 [5.3–5.6] and 0.51 per 105 [0.47–0.55] respectively. The median [IQR] age at diagnosis was lower in CD (28 [22–40]) than in UC (36 [27–49]) (p &amp;lt; 0.0001). The median [IQR] age at diagnosis was lower in women than in men: 28 [21–39] vs. 29 [22–40] in CD (p &amp;lt; 0.0001), and 33 [26–45] vs. 39 [28–51] (p &amp;lt; 0.0001) in UC. The incidence of IBD rose from 11.5 per 105 in 1988–1990 to 12.9 per 105 in 2012–2014 (p = 0.053). The incidence of CD steadily increased from 5.5 to 7.9 per 105 (average percent change per year [APC] +1%; [0.5;1.4]; p &amp;lt; 0.0001), whilst that of UC was stable at 5.0 per 105. The largest increase was seen in young women: APC of +2.0% per year for CD (p &amp;lt; 0.0001) and +1.7% per year for UC (p &amp;lt; 0.0001) in the 17–39 age group, and APC of +1.1% per year for both disease (p = 0.019 for CD and p = 0.024 for UC) in the 40–59 age group. The sex ratio did not vary for CD but changed from 0.70 in 1988–1990 to 1.10 in 2012–2014 for UC (p = 0.001). Among CD patients having undergone a full assessment of the ileum and colon, ileal locations increased from 19% to 26% for L1 (p &amp;lt; 0.0001) and from 50% to 58% for L3 (p &amp;lt; 0.0001), while L2 locations decreased from 31% to 16% (p &amp;lt; 0.0001). In the UC group, the proportion of patients with E1 location decreased from 42% to 34%, whereas the proportion with E3 location increased from 19% to 28% (p &amp;lt; 0.0001). Conclusion In a large, population-based study over a period of 27 years, we found that the incidences of CD and UC in the young women in northern France are still rising quickly. Our present results suggest that one or more environmental factors may significantly predispose women to IBD in our region. Among patients with CD, we observed an increase in ileal involvement and a concomitant decrease in colonic involvement.

Impact of Paediatric Versus Adult Care Setting on Health Care Utilization in Adolescents With Inflammatory Bowel Disease.

Paediatric-onset inflammatory bowel disease (IBD) is different from adult-onset IBD with respect to disease severity and its effect on growth and development. Care of paediatric IBD patients in some countries is dispersed among paediatricians and adult care providers, which may result in different outcomes. This study aims to assess the effect of care setting (paediatric vs adult-oriented) on health care utilization in adolescent IBD patients. This is a Dutch population-based cohort study based on an insurance claims database covering 4.2 million insurees (approximately 25% of the Dutch population). We identified IBD patients ages 16 to 18 years and followed them until the age of 19 years or transfer to adult care, whichever came first. We categorized patients according to care setting: paediatric versus adult-oriented. We defined outcomes as corticosteroid use, IBD-related hospital admission, IBD-related surgery, and biological use. We estimated Cox proportional hazards regression models to control for confounding by indication. Among 626 patients, 380 (61%) were in paediatric and 246 (39%) in adult-oriented care. In paediatric care, patients were less likely to be treated with corticosteroids (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.52-0.99) or biologicals (HR 0.57, 95% CI 0.34-0.97), and had fewer IBD-related hospital admissions (HR 0.58, 95% CI 0.37-0.92). In a large and representative community cohort of adolescents with IBD, treatment in paediatric care setting was associated with significantly lower steroid and biological use, without increase in hospital admissions. These results might be used to optimize clinical care for adolescents with IBD.

P278 Comparison of long-standing paediatric-onset and adult-onset inflammatory bowel disease

P278 Comparison of long-standing paediatric-onset and adult-onset inflammatory bowel disease

Recent Advance in Very Early Onset Inflammatory Bowel Disease.

Recent studies on pediatric inflammatory bowel disease (IBD) have revealed that early-onset IBD has distinct phenotypic differences compared with adult-onset IBD. In particular, very early-onset IBD (VEO-IBD) differs in many aspects, including the disease type, location of the lesions, disease behavior, and genetically attributable risks. Several genetic defects that disturb intestinal epithelial barrier function or affect immune function have been noted in these patients from the young age groups. In incidence of pediatric IBD in Korea has been increasing since the early 2000s. Neonatal or infantile-onset IBD develops in less than 1% of pediatric patients. Children with “neonatal IBD” or “infantile-onset IBD” have higher rates of affected first-degree relatives, severe disease course, and a high rate of resistance to immunosuppressive treatment. The suspicion of a monogenic cause of VEO-IBD was first confirmed by the discovery of mutations in the genes encoding the interleukin 10 (IL-10) receptors that cause impaired IL-10 signaling. Patients with such mutations typically presented with perianal fistulae, shows a poor response to medical management, and require early surgical interventions in the first year of life. To date, 60 monogenic defects have been identified in children with IBD-like phenotypes. The majority of monogenic defects presents before 6 years of age, and many present before 1 year of age. Next generation sequencing could become an important diagnostic tool in children with suspected genetic defects especially in children with VEO-IBD with severe disease phenotypes. VEO-IBD is a phenotypically and genetically distinct disease entity from adult-onset or older pediatric IBD.

Early onset inflammatory bowel disease: manifestations, genetics and diagnosis.

Moazzami B, Moazzami K, Rezaei N. Early onset inflammatory bowel disease: manifestations, genetics and diagnosis. Turk J Pediatr 2019; 61: 637-647. Crohn`s disease and ulcerative colitis are immunologically mediated chronic inflammatory conditions, collectively referred to as inflammatory bowel diseases (IBD). While most studies have described the condition in the adult population, recent evidences suggest that IBD in children may represent an etiologically distinct disease from the adult onset IBD. Since a significant proportion of patients diagnosed with IBD demonstrate their clinical manifestations during childhood, knowledge about the disease progression, severity and diagnosis in this particular patient population is crucial. Therefore, in the present study, the clinical manifestations, recent advancements in the genetics of early onset IBD and the clinical approach to diagnoses of IBD in children are described.

Predicting and preventing complications in children with inflammatory bowel disease.

Paediatric-onset inflammatory bowel disease (IBD) is associated with greater disease burden and morbidity compared to adult-onset IBD. Accurate risk prediction for a complicated disease course in childhood onset IBD is essential for making the best treatment choices. Complicating course in IBD is closely linked with choice of therapies and treatment targets. In this review article, we examine risk factors of complicated disease course in children with IBD in the era of increasing use of biologics and tighter treatment targets. We also discuss emerging paediatric data supporting an early intensive approach targeting deeper healing, aiming for remission beyond symptoms with repeat endoscopic examination to make treatment adjustments.

Recent advance in very early-onset inflammatory bowel disease.

Recent studies on pediatric inflammatory bowel disease (IBD) have revealed that early-onset IBD has distinct phenotypic differences compared with adult-onset IBD. In particular, very early-onset IBD (VEO-IBD) differs in many aspects, including the disease type, location of the lesions, disease behavior, and genetically attributable risks. Neonatal or infantile-onset IBD develops in less than 1% of pediatric patients. Children with infantile-onset IBD have high rates of affected first-degree relatives and severe disease course. The suspicion of a monogenic cause of VEO-IBD was first confirmed by the discovery of mutations in the genes encoding the interleukin 10 (IL-10) receptors that cause impaired IL-10 signaling. Patients with such mutations typically presented with perianal fistulae, shows a poor response to medical management, and require early surgical interventions in the first year of life. To date, 60 monogenic defects have been identified in children with IBD-like phenotypes. The majority of monogenic defects presents before 6 years of age, and many present before 1 year of age. Next generation sequencing could become an important diagnostic tool in children with suspected genetic defects especially in children with VEO-IBD with severe disease phenotypes. VEO-IBD is a phenotypically and genetically distinct disease entity from adult-onset or older pediatric IBD.

Increased Mortality of Patients With Childhood-Onset Inflammatory Bowel Diseases, Compared With the General Population

Childhood-onset inflammatory bowel disease (IBD) is believed to be a more severe disease than adult-onset IBD, but there is little information on all-cause and cause-specific mortality in patients with childhood-onset IBD. We performed a population-based cohort study, with 50 years of follow-up, to estimate absolute and relative risks for overall and cause-specific mortality in patients with childhood-onset IBD, during childhood and adulthood. We identified children with a diagnosis of IBD (younger than 18 years) in the Swedish nationwide health registers (1964-2014; n= 9442) and individuals from the general population matched for sex, age, calendar year, and place of residence (reference group; n=93,180). Hazard ratios (HR) for death were estimated usingCox regression separately in patients with ulcerative colitis (n= 4671), Crohn's disease (n= 3780), and IBD unclassified (n= 991). HRs were compared among calendar periods. During 138,690 person-years of follow-up, 294 deaths (2.1/1000 person-years) occurred among the patients with IBD compared with 940 deaths in the reference group (0.7/1000 person-years; adjusted HR, 3.2; 95% confidence interval [CI] 2.8-3.7). Mean age at end of follow-up was 30 years. HRs were increased for patients with ulcerative colitis 4.0, 95% CI 3.4-4.7; Crohn's disease 2.3, 95% CI 1.8-3.0; and IBD unclassified 2.0, 95% CI 1.2-3.4. Among patients younger than 18 years, there were 27 deaths from IBD 4.9, 95% CI 3.0-7.7. Among young adults with IBD, we found no evidence that HRs for death decreased from 1964 through 2014 (P= .90). Children with IBD have a 3-fold increase in risk of death when followed through adulthood. The relative risk for death has not decreased with development of new drugs for treatment of IBD.

Low Sun Exposure and Vitamin D Deficiency as Risk Factors for Inflammatory Bowel Disease, With a Focus on Childhood Onset.

The incidence and prevalence of inflammatory bowel disease (IBD) are increasing worldwide. Some ecological studies show increasing incidence with increasing latitude. Ambient ultraviolet radiation varies inversely with latitude, and sun exposure of the skin is a major source of vitamin D. Vitamin D deficiency is common in patients with IBD. Sun exposure and vitamin D have immune effects that could plausibly reduce, or be protective for, IBD. One quarter of new IBD cases are diagnosed in childhood or adolescence, but most research is for adult-onset IBD. Here, we review the evidence for low sun exposure and/or vitamin D deficiency as risk factors for IBD, focusing where possible on pediatric IBD, where effects of environmental exposures may be clearer. The literature provides some evidence of a latitude gradient of IBD incidence, and evidence for seasonal patterns of timing of birth or disease onset is inconsistent. High prevalence of vitamin D deficiency occurs in people with IBD, but cannot be interpreted as being a causal risk factor. Evidence of vitamin D supplementation affecting disease activity is limited. Further research on predisease sun exposure and well-designed supplementation studies are required to elucidate whether these potentially modifiable exposures are indeed risk factors for IBD.

Is There a New Classification of Inflammatory Bowel Disease (IBD)—Adult-Onset Mixed IBD

Is There a New Classification of Inflammatory Bowel Disease (IBD)—Adult-Onset Mixed IBD

Inflammatory Bowel Disease Across the Age Continuum: Similarity and Disparity

To identify similarities and differences between the pediatric-onset and adult-onset Inflammatory Bowel Disease (IBD) based cohorts and further characterize the pediatric cohort. A retrospective analysis of pediatric patients attending the tertiary referral care gastroenterology center from 2004 to 2016 was conducted. All the patients were clinically evaluated, investigated and followed up at the centre. Sixty five patients with pediatric IBD were compared with 216 patients with adult-onset IBD. The Ulcerative colitis: Crohn's disease (UC:CD) ratio was higher in adult-onset population (2.29:1 vs. 1.7:1). Predominant symptoms in pediatric UC were diarrhea and passage of blood in stools; whereas those in pediatric CD were abdominal pain and failure to gain weight. Ulcerative proctitis was less common (2.4% vs. 18.8%; p = 0.009) and an extensive disease (pancolitis) was more common in the pediatric population (73.1% vs. 30.2%; p < 0.00001). Adult CD had higher L3 (33.3% vs. 46.1%; p = 0.28) disease; whereas in pediatric CD, L1 disease (37.5% vs. 32.3%; p = 0.65) was predominant. There was no difference with respect to penetrating and stricturing complications of CD in adults vs. children (20.8% vs. 23.1%; p = 0.974). 5-ASA agents were used more commonly in the pediatric IBD population (96.9% vs. 79.9%; p = 0.0034) as compared to adults whereas corticosteroids (87.5% vs. 76.9%; p = 0.28) and infliximab (25% vs. 9.2%; p = 0.054) were used more frequently in the pediatric CD subgroup as compared to adult CD subgroup. IBD has significant disease heterogeneity according to the age of onset. Pediatric IBD has distinctive features that set it apart from adult-onset IBD.

Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea.

In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.

Incidence and Treatment of Patients Diagnosed With Inflammatory Bowel Diseases at 60 Years or Older in Sweden

Diagnosis of inflammatory bowel diseases (IBD) is increasing among elderly persons (60 years or older). We performed a nationwide population-based studyto estimate incidence and treatment of IBD. We identified all incident IBD cases in Sweden from 2006 through 2013 using national registers and up to 10 matched population comparator subjects. We collected data on the patients' health care contacts and estimated incidence rates, health service burden, pharmacologic treatments, extra-intestinal manifestations, and surgeries in relation to age of IBD onset (pediatric, <18 years; adults, 18-59 years; elderly, ≥60 years). Of 27,834 persons diagnosed with incident IBD, 6443 (23%) had a first diagnosis of IBD at 60 years or older, corresponding to an incidence rate of 35/100,000 person-years (10/100,000 person-years for Crohn's disease, 19/100,000 person-years for ulcerative colitis, and 5/100,000 person-years for IBDunclassified). During a median follow-up period of 4.2 years (range, 0-9 years), elderly patients had less IBD-specific outpatient health care but more IBD-related hospitalizations and overall health care use than adult patients withIBD.Compared with patients with pediatric or adult-onset IBD, elderly patients used fewer biologics and immunomodulators but more systemic corticosteroids. Occurrence of extra-intestinal manifestations was similar in elderly and adult patients, but bowel surgery was more common in the elderly (13% after 5 years vs 10% in adults) (P < .001). The absolute risk of bowel surgery was higher in the elderly than in the general population, but in relative terms, the risk increase was larger in younger age groups. In a nationwide cohort study in Sweden, we associated diagnosis of IBD at age 60 years or older with a lower use of biologicsand immunomodulators but higher absolute risk of bowel surgery, compared with diagnosis at a younger age. The large differences in pharmacologic treatment of adultsand elderly patients are not necessarily because of a milder course of disease and warrant further investigation.