Time Of Crohn's Disease Diagnosis Research Articles

Prevalence and Impact of Obesity in a Population-Based Cohort of Patients With Crohn's Disease.

Obesity is on the rise within the inflammatory bowel disease population. The impact obesity has on the natural history of Crohn's disease (CD) is not well-understood. We aimed to describe the prevalence of obesity in a population-based cohort of newly diagnosed patients with CD, and the impact obesity had on disease phenotype and outcomes of corticosteroid use, hospitalization, intestinal resection, and development of fistulizing or penetrating disease. A chart review was performed on Olmsted County, Minnesota residents diagnosed with CD between 1970 and 2010. Data were collected on demographics, body mass index, CD location and behavior, CD-related hospitalizations, corticosteroid use, and intestinal resection. The proportion of individuals considered obese at the time of CD diagnosis was evaluated over time, and CD-associated complications were assessed with Kaplan-Meier survival analysis. We identified 334 individuals diagnosed with CD between 1970 and 2010, of whom 156 (46.7%) were either overweight (27.8%) or obese (18.9%) at the time of diagnosis. The proportion of patients considered obese at the time of their diagnosis of CD increased 2-3 fold over the course of the study period. However, obesity did not have a significant impact on the future risk of corticosteroid use, hospitalization, intestinal resection, or development of penetrating and stricturing complications. Obesity is on the rise in patients with CD, although in this cohort, there did not appear to be any negative association with future CD-related outcomes. Further prospective studies, ideally including obesity measures such as visceral adipose tissue assessment, are warranted to understand the implications of the rising prevalence of obesity on CD outcomes.

P1189 Clinical features and surgical necessity rate of fistulising perianal disease in newly diagnosed patients with Crohn's disease: Interim analysis of inception cohort registry study of patients with Crohn's disease (iCREST-CD)

Abstract Background Fistulising perianal diseases (FPD) are common in patients with Crohn's disease (CD) in Asia, but the treatment pattern and the proportion of patients who develop new FPD after diagnosis are not clear. An interim analysis of a large registry study was performed to evaluate the difference in prognosis between patients with and without FPD at diagnosis of CD and the incidence and timing of onset of FPD in patients without FPD at diagnosis of CD. Methods iCREST-CD is a prospective, non-interventional, longitudinal, observational registry study conducted at 19 tertiary centres in Japan. Patients newly diagnosed with CD from June 2016 to June 2020 based on the diagnostic criteria of the Japanese Guidelines, aged ≥16 years at the time of informed consent with no prior exposure to biologics were enrolled. Patient demographics, clinical data, disease activity and medical treatment record up to June 2022 were used. FPD were defined as a perianal abscess and/ or perianal fistula. Results Of the 662 patients with newly diagnosed CD for whom with or without FPD were recorded, 236 patients [35.6%] had FPD at diagnosis (Group A). Of the 426 patients who did not have FPD at the time of diagnosis, 32 patients developed FPD during the observation period (Group B), and 394 patients did not develop it (Group C). The mean age [SD] at the time of CD diagnosis in Groups A, B, and C was 25.0 [8.6], 31.6 [15.5], and 31.7 [14.4] years, respectively. The proportion of female was 21.2%, 34.4% and 37.8%, respectively; L2 disease location was 14.6%, 23.3%, and 18.0%, respectively; and B2+B3 disease behaviour was 27.5%, 53.1%, and 40.6%, respectively. The mean CRP (mg/L [SD]) was 28.5 [33.8], 42.4 [43.6], and 27.1 [36.3], respectively. For disease activity based on HBI score, the proportion with moderate (8≦HBI≦16) and severe (16<HBI) activity was 17.6%, 36.8%, and 24.0%, respectively (Table). The rate of patients who developed FPD was 4.5% (19 patients) by 12 months and 6.5% (28 patients) by 24 months, respectively (Figure). In Group A with a mean observation period (month [SD]) of 27.9 [8.8], 12.3% and 17.3% of patients needed perianal surgery at 12 and 24 months, respectively. In Group B with a mean observation period of 29.7 [7.7], 7 FPD patients [21.9%] subsequently underwent perianal surgery, all within 12 months of FPD onset. Conclusion Patients who did not have a perianal abscess or fistula at the time of their CD diagnosis but later developed these problems tended to have numerically higher CD activity at the time of diagnosis and were more likely to require perianal surgery. These results suggest that patients with highly active CD are at risk of developing new FPD and should be carefully monitored.

Smoking Status at Diagnosis and Subsequent Smoking Cessation: Associations With Corticosteroid Use and Intestinal Resection in Crohn's Disease.

The impact of smoking at diagnosis and subsequent smoking cessation on clinical outcomes in Crohn's disease (CD) has not been evaluated in a population-based cohort. Using a nationally representative clinical research database, we identified incident cases of CD between 2005 and 2014. We compared the following outcomes: overall corticosteroid (CS) use; flares requiring CS; CS dependency and intestinal surgery between smokers and non-smokers at time of CD diagnosis. Differences in these outcomes were also compared between persistent smokers and smokers who quit within 2 years of diagnosis. We identified 3553 patients with a new CD diagnosis over the study period of whom 1121 (32%) were smokers. Smokers at CD diagnosis had significantly higher CS-use (56 versus 47%, p < 0.0001), proportionally more CS flares (>1 CS flare/year: 9 versus 6%, p < 0.0001), and higher CS dependency (27 versus 21%, p < 0.0001) than non-smokers. Regression analysis identified smoking at diagnosis to be associated with a higher risk of intestinal surgery (HR 1.64, 95% CI 1.16-2.52). There was a significantly higher proportion of 'quitters' who remained steroid-free through follow-up in comparison to 'persistent smokers' (45.4 versus 37.5%, respectively, p = 0.02). 'Quitters' also had lower rates of CS dependency compared to 'persistent smokers' (24 versus 33%, p = 0.008). Smokers at CD diagnosis have higher CS-use, CS dependency and higher risk of intestinal surgery. Quitting smoking appears to have beneficial effects on disease related outcomes, including reducing CS dependency highlighting the importance of offering early smoking cessation support.

Assessment of factors associated with smoking cessation at diagnosis or during follow-up of Crohn's disease.

Smoking cessation is known to improve the course of Crohn's disease (CD). However, the factors associated with smoking cessation after CD diagnosis have not been well established. Clinical characteristics and change in smoking status were evaluated in 445 current smokers at the time of CD diagnosis. Patients were classified into three subgroups based on their final smoking status and time of smoking cessation: non-quitters, quitters at diagnosis, and quitters during follow-up. The overall smoking cessation rate was 55.7% (248 of 445 patients). The diagnosis of CD was the main reason for quitting (41.5%, 103 of 248 patients). Smoking cessation at the time of CD diagnosis was associated with intestinal resection within 3months from CD diagnosis (odds ratio [OR] 2.355, 95% confidence interval [CI] 1.348-4.116, P=0.003), light smoking (OR 2.041, 95% CI 1.157-3.602, P=0.014), and initiation of smoking before 18years of age (OR 0.570, 95% CI 0.327-0.994, P=0.047). Light smoking (OR 1.762, 95% CI 1.019-3.144, P=0.043) and initiation of smoking before 18years (OR 0.588, 95% CI 0.381-0.908, P=0.017) were also associated with overall smoking cessation. Quitters after CD diagnosis, including quitters at diagnosis and quitters during follow-up, had features distinct from those of non-quitters. Given the motivation at CD diagnosis, a detailed history of smoking habits should be taken and all current smokers should be encouraged to quit smoking at the time of CD diagnosis.

Age at Diagnosis of Crohnʼs Disease May Explain NOD2-Smoking Interactions

Introduction: A recent meta-analysis demonstrated that patients with Crohn's disease (CD) who carry a 1007fs variant in the NOD2 gene were significantly less likely to be a current or former smoker at the time of CD diagnosis. We hypothesize that the NOD2-smoking interaction is explained by the differential prevalence of NOD2 variants and smoking status based on age at diagnosis. Methods: A case-only study was used to assess the interaction between smoking status at diagnosis and the 1007fs allele of the NOD2 gene among patients with CD (N=733). Smoking status was defined as current, former (quit smoking more than 1 year prior to diagnosis), and lifelong non-smoker prior to diagnosis. The 1007fs variant of the NOD2 gene was identified using a golden gate custom chip. Chi-squared tests were used to assess the association between the 1007fs variant, smoking status, and age at diagnosis as defined by the Montreal Classification: A1 (≤16 years of age); A2 (17 to 40 years); and A3 (> 40 years). Logistic regression was used to estimate the odds ratio (OR) of being a carrier of the 1007fs variant and an ever smoker (current or former) at diagnosis for patients more than 40 years old at diagnosis (A3) compared to those less than 40 at diagnosis (A1+A2). Results: Among the733 patients with CD 76 (10.4%) were carriers for the 1007fs variant; 227 (31.0%) were current smokers at diagnosis and 89 (12.1%) were former smokers. Overall, 107 (14.9%) patients were A1; 487 (67.9%) were A2; and 123 (17.2%) were A3. The prevalence of the 1007fs variant varied significantly with age of diagnosis (Figure 1; p < 0.01). In contrast, the proportion of patients that were ever smokers at diagnosis was significantly higher among A3 patients (Figure 1; p < 0.001). Diagnosis after the age of 40 years significantly decreased the odds of being a 1007fs carrier (OR 0.24, 95% CI 0.09 to 0.68) and increased the odds of having ever smoked (OR 3.36, 95% CI 2.22 to 5.08).Figure 1Conclusion: Although meta-analysis data has demonstrated a significant negative interaction between the 1007fs variant and cigarette smoking, the mechanism for the protective effect of these two risk factors remains unknown. Our data suggests that this interaction may result from differences in the prevalence of the 1007fs mutation in NOD2 and smoking status at age of diagnosis. Consequently, gene-environment interaction studies should be powered to examine age-specific interactions.

Impact of the early use of immunomodulators or TNF antagonists on bowel damage and surgery in Crohn's disease.

The impact of early treatment with immunomodulators (IM) and/or TNF antagonists on bowel damage in Crohn's disease (CD) patients is unknown. To assess whether 'early treatment' with IM and/or TNF antagonists, defined as treatment within a 2-year period from the date of CD diagnosis, was associated with development of lesser number of disease complications when compared to 'late treatment', which was defined as treatment initiation after >2years from the time of CD diagnosis. Data from the Swiss IBD Cohort Study were analysed. The following outcomes were assessed using Cox proportional hazard modelling: bowel strictures, perianal fistulas, internal fistulas, intestinal surgery, perianal surgery and any of the aforementioned complications. The 'early treatment' group of 292 CD patients was compared to the 'late treatment' group of 248 CD patients. We found that 'early treatment' withIM or TNF antagonists alone was associated with reduced risk of bowel strictures [hazard ratio (HR) 0.496, P = 0.004 for IM; HR 0.276, P = 0.018 for TNF antagonists]. Furthermore, 'early treatment' with IM was associated with reduced risk of undergoing intestinal surgery (HR 0.322, P = 0.005), and perianal surgery (HR 0.361, P = 0.042), as well as developing any complication (HR 0.567, P = 0.006). Treatment with immunomodulators or TNF antagonists within the first 2years of CD diagnosis was associated with reduced risk of developing bowel strictures, when compared to initiating these drugs >2years after diagnosis. Furthermore, early immunomodulators treatment was associated with reduced risk of intestinal surgery, perianal surgery and any complication.

Crohn's disease with pulmonary manifestations in children: 2 case reports and review of the literature

Crohn's disease (CD) is a chronic granulomatous disease of unknown etiology that affects primarily the gastrointestinal system but can be associated with extraintestinal manifestations. Latent pulmonary involvement in children with CD has been described, but symptomatic pulmonary disease has rarely been reported in children. In this review, we report two pediatric cases, one with pleural effusion at the time of CD diagnosis and the other with bilateral cavitary lesions in a previously diagnosed CD patient. We review the current literature and summarize the diagnosis and management of pulmonary involvement in CD. Awareness of these pulmonary complications of CD in children may lead to more prompt diagnosis, guide appropriate therapy, and decrease morbidity.

A case-only study of gene-environment interaction between genetic susceptibility variants in NOD2 and cigarette smoking in Crohn's disease aetiology

BackgroundGenetic variation in NOD2 and cigarette smoking are well-established risk factors for the development of Crohn's disease (CD). However, little is known about a potential interaction between these risk factors. We investigated gene-environment interactions between CD-associated NOD2 alleles and cigarette smoking in a large sample of patients with CD.MethodsThree previously reported CD-associated variants in NOD2 (R702W, G908R, 1007fs) were genotyped in 1636 patients with CD continuously recruited between 1995 and 2010 based on physician referral. Data on history of smoking behaviour was obtained for all participants through a written questionnaire. Using a case-only design, we performed logistic regression analyses to investigate statistical interactions between NOD2 risk alleles and smoking status.ResultsWe detected a significant negative interaction between carriership of at least one of the NOD2 risk alleles and history of ever having smoked (OR = 0.71; p = 0.005) as well as smoking at the time of CD diagnosis (OR = 0.68; p = 0.005). Subsequent separate analyses of the three variants revealed a significant negative interaction between the 1007fs variant and history of ever having smoked (OR = 0.64; p = 9 × 10-4) and smoking at the time of CD diagnosis (OR = 0.53; p = 7 × 10-5).ConclusionsThe observed significant negative gene-environment interaction suggests that the risk increase for CD conferred simultaneously by cigarette smoking and the 1007fs NOD2 polymorphism is smaller than expected and may point to a biological interaction. Our findings warrant further investigation in epidemiological and functional studies to elucidate pathophysiology as well as to aid in the development of recommendations for disease prevention.

Prediction of disease complication occurrence in Crohn's disease using phenotype and genotype parameters at diagnosis

Background and aims Complications associated with Crohn's disease (CD) are common and influence treatment decisions and outcomes. Appropriate early treatment may offer a therapeutic advantage to patients. The aim of our study was to indentify predictive factors for occurrence of complications at the time of CD diagnosis. Methods The study population consisted of 269 CD patients treated during a ten year period. Risk factors compared between complicated and non-complicated disease included phenotypical characteristics, disease classification and the presence of NOD2/CARD15 mutations and single nucleotide polymorphisms in selected autophagy and phagosome genes. Results Complete data was obtained for 146 patients with an average follow up of 12 years. Sixty five patients (44%) developed a complication during follow up. The only independent risk factors associated with developing a complication were smoking and male gender. There was no association between developing complications and the presence of selected SNPs (P = 0.07 for Tyrosine residue on both alleles in NCF4 SNP rs4821544 and P = 0.06 for a Guanine residue on both alleles in ATG16L SNP rs2241880). Multivariate analysis using a backwards logistic regression model left only male gender as an independent statistically significant association with complicated disease (OR 2.6017, 95% CI: 1.17 to 5.75). The median time to developing a complication was 4 years, and the most common complication was the need for surgical intervention (54%). Conclusions In the present study, a risk factor for developing CD complication was male gender. Further studies are warranted to assess additional risk factors and how such findings should affect therapy.

Manifestations of small bowel disease in pediatric Crohnʼs disease on magnetic resonance enterography

We report the manifestations of Crohn's disease (CD) observed on magnetic resonance enterography (MRE) in a pediatric population at the time of CD diagnosis. MRE of 95 consecutive pediatric patients with inflammatory bowel disease (IBD) examined in 2006-2009 were retrospectively analyzed, with documentation of findings based on type and location of the small bowel (SB) disease. In all, 51 were boys and 44 girls. 54 had CD, 31 non-CD IBD, and 10 no IBD. The most common site of SB involvement in CD was the terminal ileum seen in 29 (53.7%) patients, followed by ileum in 10 (18.5%) and jejunum in 9 (16.7%) patients. Solitary jejunal inflammation (3.7%), SB stenoses (1.9%), fistula formation (0.95%), and abscess (0.95%) were much less common. Perienteric lymphadenopathy was seen in 30 (55.6%) patients and fatty proliferation in 9 (16.7%). The most common manifestation of SB inflammation was increased contrast enhancement of bowel wall (93.5%), thickening of the bowel wall (90.3%), and derangement of bowel shape with saccular formations (25.8%). MRE in the pediatric population often demonstrates increased contrast uptake, bowel wall thickening, and perienteral lymphadenopathy in CD. More chronic small bowel changes seen commonly in adults and solitary jejunal involvements are less commonly seen.

CLINICAL AND ENDOSCOPIC FEATURES OF AMYLOIDOSIS SECONDARY TO CROHN'S DISEASE: DIAGNOSTIC VALUE OF DUODENAL OBSERVATION AND BIOPSY

Recent reports have focused on the development of secondary amyloidosis (AMY) as a complication of Crohn's disease (CD). The present study was carried out to investigate the frequency of AMY secondary to CD, its clinical and endoscopic features, and the importance of duodenal biopsy in detecting this disease. This study involved 408 patients diagnosed with CD who were endoscopically and histologically examined at our hospital. At follow up, we analyzed the incidence of AMY complications, the clinical features of AMY and the methods to diagnose AMY. The incidence of AMY was 2.5% (10/408). The disease type at the time of CD diagnosis was small and large bowel type (SL) in eight patients, small bowel type in one and large bowel type in one. The incidence of AMY was significantly higher in patients with SL than in patients with other disease types. The length of time from onset of CD to diagnosis of AMY was 14.1 ± 8.0 years. The cumulative incidence of AMY was 1.0% at 10 years and 5.7% at 20 years after onset. In terms of the method used to diagnose AMY, the positive rate of AMY diagnosis was 100% with endoscopic duodenal biopsy. The incidence of AMY as a complication of CD was low (2.5%). However, because this complication adversely affects patients' prognoses, it is important to check for the presence of AMY, particularly in the duodenum, in patients for whom more than 10 years have elapsed since the development of CD.

Longitudinal study of bone mineral density in children after a diagnosis of Crohn's disease

The purpose of this study was to measure the bone mineral density (BMD) of children with Crohn's disease (CD) and to prospectively assess its evolution. A total of 27 children (20 boys, seven girls), aged 12.1±2.5 years, were recruited at the time of CD diagnosis. Dual-energy X-ray absorptiometry (DEXA) was used to measure BMD, expressed as Z scores for chronological age (BMD/CA) and bone age (BMD/BA). One year later, BMD was measured again to identify any correlations with disease activity [group A (active disease) vs group R (remission)]. BMD/CA and BMD/BA were negatively correlated with delay in diagnosis (P<0.0001 and P<0.05, respectively). BMD/CA was less than -2 standard deviation (SD) in nine patients and BMD/BA was less -2 SD in four patients. At the follow-up, the increase in BMD was smaller in group A (n=14), whether expressed as absolute values (-0.002 vs 0.040 g/cm(2) per year; P<0.024) or as percentages (-0.2 vs 6.6%; P<0.041); changes in BMD/CA (-0.5 vs -0.1 SD/year) and BMD/BA (-0.3 vs 0 SD/year) did not differ. Diagnostic delay greatly affects BMD in children with CD even prior to corticosteroid therapy. The risk of low BMD increases with persistent CD activity, although the risk is reduced in association with bone maturation delay.

Crohn's disease and Sweet's syndrome: an uncommon association

Sweet's syndrome or acute febrile neutrophilic dermatosis (SS) is characterized by the sudden onset of painful erythematous lesions (papules, nodules, and plaques) together with fever and neutrophilia. The lesions are typically located on hands, arms, upper trunk, neck and face, showing an asymmetric distribution. Acute phase reactants are usually elevated and dermal infiltration of neutrophils without vasculitis is seen on skin biopsies. It is considered as a marker of systemic disease in over half of the cases, and is associated with infections, inflammatory bowel disease, autoimmune connective tissue disorders and various neoplasias. Its association with Crohn's disease (CD) is unusual and it appears mainly in association with colonic involvement. Fewer than 50 cases have been published in the medical literature since its first description in 1964, some concurrent with the first episode of CD. We present two patients with Crohn's disease and Sweet's syndrome diagnosed in our department at the time of CD diagnosis, as well as their response to treatment, subsequent course of the disease, and a review of the scientific literature.

Predictors for Development of Stricture/Obstruction in Patients with Crohnʼs Disease

Purpose: Crohn's disease (CD) is a chronic, inflammatory disorder of the gastrointestinal tract that is often associated with serious complications, including strictures, abscesses, and fistulas. Using a multinational European survey, this study examined predictors for occurrence of stricture/obstruction in patients with CD. Methods: Data were drawn from the Adelphi CD Disease Specific Programme, a cross-sectional study of consulting patients that enrolled 2,969 patients in the United Kingdom, Spain, France, Italy, and Germany in 2008. Three hundred physicians and 1,657 patients completed questionnaires on CD symptoms and quality of life. Physicians also completed patient-report forms describing CD symptoms, health service use, and progression of disease. The current analysis is conducted in patients not currently receiving biologic therapy. A logistic regression analysis was conducted to identify variables predictive of current occurrence of stricture/obstruction. Potential predictors included age, CD severity at time of diagnosis, presence of anal abscess or fistula at time of diagnosis, disease location, and time from diagnosis to the current survey year. Results: A total of 1,268 patients with complete survey data were included in the analysis. Mean patient age was 39 years, and mean CD duration was 52 months. CD severity at the time of diagnosis, disease location, and time from diagnosis to survey year were significant predictors for occurrence of stricture/obstruction. Compared with patients diagnosed with mild CD, patients diagnosed with moderate or severe CD were more likely to have stricture/obstruction during the survey year (odds ratio [OR]=1.7 and 2.2, respectively; both p<0.01). Patients with disease at jejunum, ileum, or ileum and colon were more likely to have stricture compared with other locations (OR=2.9; p<0.001). Greater length of time from diagnosis to the current survey year was associated with greater likelihood of stricture/obstruction at the time of survey (OR=1.03;p<0.05). Conclusion: Patients with greater disease severity at the time of CD diagnosis and longer disease duration were more likely to develop stricture/obstruction. The likelihood of developing stricture/obstruction also varied by location of CD. Disclosure: Dr Louis - Research grant: AstraZeneca, Schering-Plough; Speaker fee: AstraZeneca, UCB, Abbott, Schering-Plough, Ferring; Advisory board member: Abbott, UCB, Ferring Dr Chao - Employee, stocks: Abbott Dr Mulani - Employee, stocks: Abbott. This research was funded by Abbott Laboratories, Abbott Park, IL.

Jejunoileal Crohn's disease: a case-control study

Jejunoileitis might be a severe form of Crohn's disease (CD). The aim of the study was to evaluate clinical characteristics, therapeutics modalities and long-term outcome in CD patients with jejunoileitis (CDJI). All patients with CDJI followed in the department of Gastroenterology from 1963 to 1999 were included and compared to matched (on Year of CD diagnosis) CD controls without jejunoileitis. Data were obtained from retrospective review of medical charts. Eighteen patients with CDJI were compared to 36 matched CD controls. Median follow-up was 7.65 Years in both groups. At time of CDJI diagnosis the following signs were significantly more frequent in patients with jejunoileal CD than in controls: malnutrition (39% vs 3%), pain suggesting obstruction (33% vs 8%), vomiting (28% vs 5%). Patients with CDJI were more frequently male: M/F ratio=2.0/1.1 (P=0.33). Upper digestive involvement (esophagus, stomach and duodenum) (67% vs 36%, P=0.04) and small intestine strictures (61% vs 19%, P=0.06) were more frequent in CDJI. Initial management was more "aggressive" in CDJI than in controls: steroids in 62% vs 30%, azathioprine in 39% vs 3%, total parenteral nutrition in 28% vs 8% and surgery in 33% vs 17%. During follow-up, the need for azathioprine therapy and surgery were more frequent in CDJI than in controls (extensive small bowel resection in two patients). In 10 of 18 patients, jejunoileitis involvement was diagnosed with a median delay of 3.6 Years (range: 0.5-14.5) after CD diagnosis and at time of CD diagnosis in the 8 others; outcome after CDJI diagnosis was similar in these 2 groups. The main revealing signs of jejunoileitis in CD patients are obstruction and malnutrition. Patients with CDJI require more often azathioprine and surgery than CD patients without jejunoileitis. Jejunoileitis is a severe form of CD more frequently complicated by extensive small bowel resection.