Anticipation in familial Crohn’s disease

Background—Offspring with a family history of Crohn’s disease have an earlier age of onset than their parents. This might be due to genetic anticipation, characterised by earlier and/or more severe disease in subsequent generations.Aims—To investigate the possibility of genetic anticipation in affected parent-child pairs with Crohn’s disease from France and Belgium.Patients and methods—In a cohort of 160 multiply affected families with Crohn’s disease, 57 parent-first affected child pairs were detected. Clinical characteristics (age at diagnosis, disease extent, and type) of both parents and children were registered and compared.Results—Children were younger than their parents at diagnosis in 48/57 (84%) pairs. The median age at diagnosis was 16 years younger in children than in parents (p<0.0001). However, the difference was related to the age at diagnosis in the parents and was not present in 12 parent-child pairs with an early age at diagnosis for the parents. In most cases, disease extent and type were not considered more severe in children than in parents. Parental sex affected neither age at diagnosis nor extent and type of disease in children.Conclusion—Patients in the second affected generation acquire their disease at an earlier time in life in some but not all familial cases of Crohn’s disease. Several explanations including genetic anticipation and environmental factors might explain this phenomenon.

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Relationship between the IL23R SNPs and Crohn’s Disease Susceptibility and Phenotype in the Polish and Bosnian Populations: A Case-Control Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16091551 ◽

2019 ◽

Vol 16 (9) ◽

pp. 1551

Author(s):

Krzysztof Borecki ◽

Iwona Zawada ◽

Nermin Nusret Salkić ◽

Beata Karakiewicz ◽

Grażyna Adler

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Case Control Study ◽

Age Of Onset ◽

Severe Disease ◽

Polish Population ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Increased Risk ◽

Control Study

It is suggested that IL-23/IL-17 axis and single nucleotide polymorphisms (SNPs) of IL23R may have crucial role in pathogenesis of Crohn’s disease (CD). Thus, we sought to assess the IL23R SNPs contribution to susceptibility and phenotype of CD. We recruited 117 CD subjects and 117 controls from Poland and 30 CD subjects and 30 controls from Bosnia and Herzegovina (B&H). Two common IL23R SNPs: rs1004819, rs7517847 were genotyped using TaqMan SNP assays. In the Polish population it was found that allele rs1004819: A increases the risk of CD, while allele rs7517847: A is protective against disease development. In Poles the co-carriage of two IL23R risk genotypes was associated with increased risk of CD. A significantly increased risk of CD early onset was observed in Poles carrying at least one rs7517847: G allele. It was also found that IL23R SNPs may be associated with structuring/penetrating CD behavior, as alleles rs1004819: A and rs7517847: G were significantly less frequent in patients without complications, from Poland and B&H, respectively. Allele rs1004819: A was also significantly more frequent in Poles with penetrating CD. These results confirm IL23R SNPs contribution to CD susceptibility in the Polish population and suggest their impact on early age of onset and more severe disease course.

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Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn’s Disease Surgical Patients

Mediators of Inflammation ◽

10.1155/2021/8854916 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Francesco Giudici ◽

Tiziana Cavalli ◽

Cristina Luceri ◽

Edda Russo ◽

Daniela Zambonin ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Perioperative Complications ◽

Severe Disease ◽

Diagnostic Delay ◽

Age At Diagnosis ◽

Clinical Biomarkers ◽

Long Term Follow Up

Background. CARD15/NOD2 is the most significant genetic susceptibility in Crohn’s disease (CD) even though a relationship between the different polymorphisms and clinical phenotype has not been described yet. The study is aimed at analyzing, in a group of CD patients undergoing surgery, the relationship between CARD15/NOD2 polymorphisms and the clinical CD behavior after a long-term follow-up, in order to identify potential clinical biomarkers of prognosis. Methods. 191 surgical CD patients were prospectively characterized both for the main single nucleotide polymorphisms of CARD15/NOD2 and for many other environmental risk factors connected with the severe disease form. After a mean follow-up of 7.3 years, the correlations between clinical features and CD natural history were analyzed. Results. CARD15/NOD2 polymorphisms were significantly associated with younger age at diagnosis compared to wild type cases ( p < 0.05 ). Moreover, patients carrying a 3020insC polymorphism presented a larger Δ between diagnosis and surgery ( p = 0.0344 ). Patients carrying an hz881 and a 3020insC exhibited, respectively, a lower rate of responsiveness to azathioprine ( p = 0.012 ), but no difference was found in biologic therapy. Finally, the risk of surgical recurrence was significantly associated, respectively, to age at diagnosis, to familial CD history, to diagnostic delay, to arthritis, and to the presence of perioperative complications. Conclusions. 3020insC CARD15 polymorphism is associated with an earlier CD onset, and age at CD diagnosis < 27 years was confirmed to have a detrimental effect on its clinical course. In addition, the familiarity seems to be connected with a more aggressive postoperative course. Finally, for the first time, we have observed a lower rate of responsiveness to azathioprine in patients carrying an hz881 and a 3020insC.

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Why children with inflammatory bowel disease are diagnosed at a younger age than their affected parent

Gut ◽

10.1136/gut.44.6.808 ◽

1999 ◽

Vol 44 (6) ◽

pp. 808-811 ◽

Cited By ~ 37

Author(s):

J C W Lee ◽

S Bridger ◽

C McGregor ◽

A J S Macpherson ◽

J E Lennard Jones

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Age Differences ◽

Bowel Disease ◽

Age At Diagnosis ◽

Affected Parent ◽

Inflammatory Bowel ◽

Parent Child

BACKGROUNDGenetic anticipation has been proposed to explain observed age differences at diagnosis of Crohn’s disease in affected parents and offspring.AIMSTo compare affected parent-child pairs with Crohn’s disease and ulcerative colitis with a control group of non-familial patients with inflammatory bowel disease (IBD) in order to quantify whether ascertainment bias could account for this effect.METHODS137 affected parent-child pairs from 96 families and 214 patients with sporadic IBD were studied. Age at onset of symptoms and diagnosis were ascertained by interview and disease confirmed from clinical records.RESULTSOf the 137 affected parent-child pairs, 50 had Crohn’s disease only, 51 had ulcerative colitis only, and in 36, one had Crohn’s disease and the other ulcerative colitis. The median age of parents at diagnosis was 17.5 years older, 16 years older, and 18 years older in the Crohn’s disease, ulcerative colitis, and mixed disease families respectively (p<0.001 in each case). These observed age differences were compatible with those predicted from the regression lines of years of birth against age at diagnosis for the non-familial IBD patients. No evidence was found for an effect of parental sex on age at diagnosis or disease extent in offspring.CONCLUSIONSThere was no evidence of genetic anticipation or genomic imprinting of age at diagnosis in this sample of IBD families. Ascertainment bias is responsible for the age differences at diagnosis between affected parents and children.

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Impact of Intestinal Ultrasound on Classification and Management of Crohn’s Disease Patients with Inconclusive Colonoscopy

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2016/8745972 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Rune Wilkens ◽

Kerri L. Novak ◽

Eleonore Lebeuf-Taylor ◽

Stephanie R. Wilson

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Significant Contribution ◽

Severe Disease ◽

Potential Contribution ◽

Disease Extent ◽

Cross Sectional ◽

Diseased Segment ◽

Cross Sectional Imaging

Background and Aims. We aim to evaluate the benefit of ultrasound in the assessment of Crohn’s disease and to demonstrate its potential contribution to disease management.Methods. We conduct a retrospective review of adult patients with Crohn’s disease examined with sonography and colonoscopy within 30 days. Study patients were identified in whom colonoscopy did not access a pathological segment, detected and evaluated by ultrasonography. Changes in management were predominantly attributed to ultrasound in those cases where the diseased segment was not assessed on endoscopy.Results. From 115 patients with temporally related ileocolonoscopy and ultrasound, 41 had disease fully assessed on ultrasound only, with complications in 26/41. Twenty-nine of 41 had mild or no endoscopic inflammation with moderate or severe disease on ultrasound at the same segment or at a segment proximal to the reach of the endoscope. Changes in management were significantly attributed to ultrasound in 22 of these 29 patients.Conclusion. The benefit of cross-sectional imaging is invaluable for the comprehensive assessment of bowel not shown on ileocolonoscopy. Ultrasound may make a significant contribution to correct classification of disease extent and severity of Crohn’s disease. Prospective studies are needed to further understand the contribution of US in patient management.

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Localization and Activity of Inflammatory Bowel Disease Using 111ln Leukocyte Imaging

Nuklearmedizin ◽

10.1055/s-0038-1629438 ◽

1988 ◽

Vol 27 (03) ◽

pp. 83-86 ◽

Cited By ~ 3

Author(s):

B. Briele ◽

F. Wolf ◽

H. J. Biersack ◽

F. F. Knapp ◽

A. Hotze

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Cell Uptake ◽

Disease Extent ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Leukocyte Imaging

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.

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P007 CROHN’S DISEASE: PREDICTORS OF HOSPITAL DISPOSITION AND COSTS USING DEMOGRAPHIC, CLINICAL, AND TREATMENT DATA

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.122 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S48-S48

Author(s):

Hartman Brunt ◽

Mason Adams ◽

Michael Barker ◽

Diana Hamer ◽

J C Chapman

Keyword(s):

Logistic Regression ◽

Crohn’S Disease ◽

Abdominal Pain ◽

Crohn's Disease ◽

Hospital Admission ◽

Categorical Variables ◽

History Of ◽

The Difference ◽

The Impact ◽

Total Charges

Abstract Purpose Crohn’s disease (CD) is an inflammatory bowel disease (IBD) caused by an abnormal immune response to intestinal microbes in a genetically susceptible host. The objective of this cohort analysis is to compare demographic characteristics, cost difference, and treatment modalities between patients who were discharged from the Emergency Department (ED) and those who were admitted to the hospital. Methods This study is a retrospective chart review of adult patients diagnosed with CD who were discharged from the ED and those who were admitted to the hospital between January 1, 2014 and January 1, 2017. We compared demographic and clinical characteristics as well as total charges incurred by these patients. A chi square test of independence and a Mann Whitney U-Test were used to compare categorical variables. Linear and logistic regression analyses were utilized to identify predictors of hospitalization and total charges. Results Of a total 195 patients, 97 were discharged from the ED and 98 were admitted to the hospital (Table 1). Patients who presented with fever, nausea/vomiting, or abdominal pain or who had a history of a fistula or stenosis were more likely to be hospitalized, as were patients who presented on steroids, 5-ASA compounds, or narcotics (Table 2). A logistic regression adjusted for these factors showed patients presenting with abdominal pain (OR=0.239, 95% CI 0.07 – 0.77) are less likely, while patients presenting with fever (OR=7.0, 95% CI 1.9 – 24.5) and history of stenosis (OR=17.8, 95% CI 5.7 – 55.9) are more likely to have a hospital admission. An increase in age and white blood cell count was associated with an increase in likelihood of admission (OR=1.04, 95% CI 1.01 – 1.07 and OR=1.2, 95% CI 1.1 – 1.4), while an increase in HGB was associated with a decrease in likelihood of admission (OR=0.682, 95% CI 0.55 – 0.83). Patients on 5-ASA compounds had the strongest association with hospital admission (OR=4.5, 95% CI 1.03 – 20.4). A linear regression analysis predicting total charges of hospitalization identified an increase of $37,500 (95% CI 6,600 – 68,489) for obese patients and of $29,000 (95% CI 20 – 57,000) for patients on narcotics prior to hospitalization. Notably, blacks were on average 6 years younger than whites (μ=36.2, st.d.=13.2 v μ=42.7, st.d.=18.2, p=0.031, respectively). No other differences in presentation or outcomes of CD were identified between these races. Conclusion This study describes the difference between CD patients who were admitted to the hospital compared to those who were discharged from the ED. The impact that 5-ASA compound, steroid, and narcotic use prior to presentation has on hospital admission and charges highlights the need for consistent outpatient care to manage the symptoms and disease progression in patients with CD in Baton Rouge. The difference in age at presentation between blacks and whites should also be considered in future research.

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Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

Mediators of Inflammation ◽

10.1155/2015/493012 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 69

Author(s):

Bruno Rafael Ramos de Mattos ◽

Maellin Pereira Gracindo Garcia ◽

Julia Bier Nogueira ◽

Lisiery Negrini Paiatto ◽

Cassia Galdino Albuquerque ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Severe Disease ◽

Biological Therapies ◽

Promising Alternative ◽

Biological Treatments ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

And Behavior

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.

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Genotype–phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients

BMC Gastroenterology ◽

10.1186/s12876-021-01880-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Priyatharsan Yoganathan ◽

Jean-Benoit Rossel ◽

Sebastian Bruno Ulrich Jordi ◽

Yannick Franc ◽

Luc Biedermann ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Severe Disease ◽

Regulatory Region ◽

Disease Course ◽

Pyrin Domain ◽

Homozygous Genotype ◽

Increased Risk ◽

Major Allele ◽

The Impact

Abstract Background Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.

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