Genetic Counselling and Family in IBD: 30 years' Experience at the Cleveland Clinic

The Cleveland Clinic has followed 1288 patients with inflammatory bowel disease (IBD) (437 with mucosa! ulcerative colitis and 851 with Crohn's disease) from 1955 through 1984. Of the 437 patients with mucosal ulcerative colitis, the index patient had one or more family members develop IBD. These data indicate the need for the treating physician to institute case-finding questions within the family so that early diagnoses can be established. From 1975 through 1984, 94 patients had a positive family history and 63 had additional family members with disease. The highest risk group was the sibling-sibling group (6.4% in mucosa! ulcerative colitis and 8.3% in Crohn's disease). Both groups had similar percentages for all immediate family members; namely, 16.5% and 17.3%. In the group of patients reported from 1975 to 1984, the location of disease in the index patient and the immediate family member was the same in 67.5% and different in 30.0%. In this same group of patients, the disease similarity in the index patient and the immediate family member was the same in 86.8% and different in 12.0%. These data suggest that while genetic factors undoubtedly increase the susceptibility for IBD, there is no specific genetic pattern identified. Also, environmental and other factors may be present. The data also suggest that the age of onset is a factor, perhaps showing increased association with a positive family history.

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The Social Toll of Inflammatory Bowel Disease

Canadian Journal of Gastroenterology ◽

10.1155/1994/207267 ◽

1994 ◽

Vol 8 (7) ◽

pp. 433-437 ◽

Cited By ~ 5

Author(s):

Richard G Farmer

Keyword(s):

Quality Of Life ◽

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bowel Disease ◽

Cleveland Clinic ◽

The Social ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) – ulcerative colitis and Crohn’s disease – has become one the most important chronic digestive disorders found in the younger population. As a result of the nature of the illness, with remission and exacerbation of the inflammatory process, there has been increasing concern regarding the costs, both financial and social, of IBD. There have been attempts to quantify disease activity and to assess the results of treatment and the ability of the patient to function in society. As a result, there has been an increased interest in the ‘social toll’ of IBD. Begi1ming in 1988, and using a direct interview technique, ambulatory patients with IBD were evaluated for quality of life at the Cleveland Clinic Foundation. Included were patients whose disease had been present for about 10 years, and both surgical and nonsurgical patients. The interview questionnaire consisted of 47 items in four categories: functional/economic, social/recreational, affect/life in general and medical/symptoms. Patients with ulcerative colitis had better quality of life than those with Crohn’s disease and patients without surgery had better quality of life than those who had undergone surgery. Over the ensuing five-year period, it was shown that quality of life measures are of value in assessing the results of medical and surgical therapy, and the measures frequently give information not usually obtained by physicians and have implications for quality assurance and outcome measurement.

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Familial Association between Coeliac Disease and Ulcerative Colitis: Preliminary Communication

Journal of the Royal Society of Medicine ◽

10.1177/014107688607900405 ◽

1986 ◽

Vol 79 (4) ◽

pp. 204-205 ◽

Cited By ~ 10

Author(s):

J F Mayberry ◽

H L Smart ◽

P J Toghill

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Coeliac Disease ◽

Family Members ◽

First Degree Relatives ◽

Increased Risk ◽

Familial Association ◽

Preliminary Communication

One hundred and twenty patients who were members of the Nottinghamshire Coeliac Group completed a questionnaire about the occurrence of coeliac disease, ulcerative colitis and Crohn's disease amongst first-degree relatives. Siblings were at a 20-fold risk of developing coeliac disease and a 15-fold risk of developing ulcerative colitis, and significantly increased risks for these two conditions were also seen in other family members. The relatives of patients with coeliac disease are at increased risk not only of developing coeliac disease but also ulcerative colitis. This provides further support for a possible role of a dietary allergen in the development of ulcerative colitis.

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Inflammatory bowel disease: introduction

10.1093/med/9780198569862.003.0041 ◽

2011 ◽

Cited By ~ 1

Author(s):

R. Mark Beattie ◽

Anil Dhawan ◽

John W.L. Puntis

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Family History ◽

Crohn's Disease ◽

Bowel Disease ◽

History Of ◽

Inflammatory Bowel ◽

The Uk

Inflammatory bowel disease 288• 25 % of inflammatory bowel disease (IBD) presents in childhood, usually as Crohn's disease or ulcerative colitis. The UK incidence is 5.2/100 000 children <16 years of age. Crohn's disease is the more common. Family history of Crohn's disease or ulcerative colitis is common. Both diseases can occur in the same family....

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Roles of IL-17A and IL-23 in the Pathogenesis of Ulcerative Colitis and Crohn’s Disease

Iraqi Journal of Science ◽

10.24996/ijs.2021.62.8.5 ◽

2021 ◽

pp. 2526-2535

Author(s):

Sarah S. Abdul-Hussein ◽

Ekhlass N. Ali ◽

Nawal M. F. Alkhalidi ◽

Neihaya H. Zaki ◽

Ali H. Ad'hiah

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Family History ◽

Crohn's Disease ◽

Smoking Status ◽

Serum Levels ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

History Of ◽

Disease Extension

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, the etiology and pathogenesis of which have been suggested to be influenced by cytokines. Two main clinical types of IBD are recognized, namely ulcerative colitis (UC) and Crohn's disease (CD). The present study examined serum levels of two cytokines (IL-17A and IL-23) in 60 IBD patients (30 UC and 30 CD) and 30 healthy controls. The levels were correlated with age, gender, cigarette-smoking status, disease duration, family history, disease extension, symptoms, extra-intestinal manifestations, and medication. The results depicted that IL-17A level was significantly higher in UC and CD patients compared to control (45.2 ± 23.3 and 47.5 ± 34.4 vs. 15.6 ± 7.5 pg/ml, respectively; p < 0.001). Serum level of IL-23 was similarly increased in UC and CD patients compared to control (64.1± 23.7 and 62.5 ± 27.3 vs. 25.2 ± 11.1 pg/ml, respectively). However, the level of both cytokines showed no significant variation between UC and CD patients (p = 0.713 and 0.777, respectively). Distributing UC and CD patients into subgroups according to some characteristics revealed that IL-17A level was significantly increased in UC male compared to female patients (57.3 ± 18.2 vs. 34.5 ± 22.5 pg/ml; p = 0.005). It was also significantly increased in smoker UC patients compared with non-smoker patients (51.9 ± 19.4 vs. 31.6 ± 25.5 pg/ml; p = 0.022). Smoker CD patients also showed a significantly increased level of IL-23 compared to non-smoker patients (72.7 ± 28.5 vs. 52.2 ± 22.6 pg/ml; p = 0.038). In the case of family history, IL-23 level was significantly decreased in UC patients with a family history of IBD compared to CD patients with a family history (84.5 ± 24.3 vs. 50.4 ± 17.0 pg/ml.; p = 0.042). In conclusion, the present data suggest a role for IL-17A and IL-23 in the etiology and pathogenesis of UC and CD.

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Differential Effect of Genetic Burden on Disease Phenotypes in Crohn’s Disease and Ulcerative Colitis in a Canadian Cohort

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwaa002 ◽

2020 ◽

Author(s):

Jack X Q Pang ◽

Hengameh Kheirkhahrahimabadi ◽

Sunint Bindra ◽

Gurmeet Bindra ◽

Remo Panaccione ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Family History ◽

Crohn's Disease ◽

Odds Ratio ◽

Genetic Risk Score ◽

Disease Extent ◽

Age Of Diagnosis ◽

History Of ◽

Genetic Burden

Abstract Background and Aims Crohn’s disease (CD) and ulcerative colitis (UC) demonstrate considerable phenotypic heterogeneity and course. Accurate predictors of disease behaviour are lacking. The contribution of genetics and specific polymorphisms is widely appreciated; however, their cumulative effect(s) upon disease behaviour remains poorly understood. Here, we investigate the relationship between genetic burden and disease phenotype in a Canadian inflammatory bowel disease (IBD) Cohort. Methods We retrospectively examined a cohort of CD and UC patients recruited from a single tertiary referral center genotyped using a Goldengate Illumina platform. A genetic risk score (GRS) incorporating strength of association (log odds ratio) and allele dose for 151 IBD-risk loci was calculated and evaluated for phenotypic associations. Results Among CD patients, higher GRS was associated with earlier onset of disease (regression coefficient −2.19, 95% confidence interval [CI] −3.77 to −0.61, P = 0.007), ileal disease (odds ratio [OR] 1.45), stricturing/penetrating disease (OR 1.72), perianal disease (OR 1.57) and bowel resection (OR 1.66). Higher GRS was associated with use of anti-tumor necrosis factor (TNF) (P < 0.05) but not immunomodulators. Interestingly, we could not demonstrate an association between higher GRS and family history of IBD (OR 1.27, P = 0.07). Onset of disease remained statistically significant for never smokers (P = 0.03) but not ever smokers (P = 0.13). For UC, having a higher GRS did not predict the age of diagnosis nor was it predictive of UC disease extent (P = 0.18), the need for surgery (P = 0.74), nor medication use (immunomodulators P = 0.53, anti-TNF P = 0.49). We could not demonstrate an association between increased GRS and having a family history of IBD in the UC group. Conclusions Increasing genetic burden is associated with early age of diagnosis in CD and may be useful in predicting disease behaviour in CD but not UC.

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