In parallel with overall population trends, the incidence of paediatric ulcerative colitis (UC) has remained stable, whereas that of paediatric Crohn's disease (CD) has increased in recent decades. Still rare among preschool children, the incidence of both UC and CD rises steadily from middle childhood through adolescence. There is an unexplained preponderance of males with early-onset CD, and an equal gender distribution in paediatric UC. Observations on the familiality of paediatric inflammatory bowel disease (IBD) suggest that genetic susceptibility is particularly important to disease pathogenesis in young patients. In comparison to adult-onset disease, childhood UC is usually extensive but the anatomic localization of paediatric CD varies, as in adults. UC manifests uniformly as bloody diarrhea whereas the symptomatology of paediatric CD is much more diverse. Linear growth impairment frequently complicates chronic intestinal inflammation in paediatric CD. Key contributing factors have been defined; better immunomodulatory therapy and emerging biologic agents will potentially reduce its prevalence.

Specificities of inflammatory bowel disease in childhood.

Epidemiology and the natural course of inflammatory bowel disease.

Context: Both genetic and environmental factors contribute to susceptibility to Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), as well as disease manifestations. Objective: The objective of the study was to define how endogenous/environmental factors contribute to variation in phenotype. Design/Setting: This was a multicenter cohort study. Patients/Outcome Measures: We prospectively collected clinical/biochemical data as part of the protocol for a United Kingdom DNA collection for GD and HT. We investigated, in 2805 Caucasian subjects, whether age at diagnosis, gender, family history (FH), smoking history, and presence of goiter influenced disease manifestations. Results: For 2405 subjects with GD, the presence of goiter was independently associated with disease severity (serum free T4 at diagnosis) (P < 0.001). Free T4 (P < 0.05) and current smoking (P < 0.001) were both independent predictors of the presence of ophthalmopathy. Approximately half of those with GD (47.4% of females, 40.0% of males...

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Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype.

Studies suggest that persons with HIV infection develop non–AIDS-related cancer at earlier ages than the general population and that this may be due to HIV-induced accelerated aging. These data fro...

/pdf/age-at-cancer-diagnosis-among-persons-with-aids-in-the-1uc8jjqwsw.pdf

Age at Cancer Diagnosis Among Persons With AIDS in the United States

Background and aims: Smoking tobacco has opposite effects on the different forms of inflammatory bowel disease (IBD). It predisposes to the development of Crohn's disease (CD) yet is associated with a reduced incidence of ulcerative colitis (UC). We have studied sib pairs discordant for both smoking and IBD phenotype (UC or CD) to investigate whether smoking determines the type of IBD that develops in individuals with very similar genetic susceptibility.

Patients: Smoking habits and disease characteristics were analysed in 242 IBD pedigrees (658 patients). Within this group there were 339 affected sibling pairs of whom 89 were discordant for smoking when diagnosed.

Results: Smoking at diagnosis was associated with development of CD (odds ratio (OR) 3.55; 95% confidence limits 2.50–5.02; p<0.001) in all of the familial patients, with increases when analysed for ileocaecal disease, fibrostenosis, and intestinal resection. Smokers were also protected from UC (OR 0.28; 0.2–0.4; p<0.001). Of 89 sibling pairs discordant for smoking at diagnosis, 23 were also discordant for disease type—in 21 of these, CD occurred in the smoker and UC in the non-smoker (OR 10.5; 2.6–92; p<0.0001).

Conclusions: Smoking is a strong environmental risk factor for Crohn's disease and increases the likelihood of needing surgery. However, sib pairs who are discordant for both smoking and IBD type almost always show CD in the smoker and UC in the non-smoker, and so in some cases tobacco consumption acts on IBD genetic predisposition to shift the phenotype from UC towards CD. The explanation of part of the apparent “protective” effect of smoking on sporadic UC may be that the form of IBD that develops in a proportion of smokers is not UC but CD.

https://gut.bmj.com/content/gutjnl/51/1/21.full.pdf

In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn's disease and non-smokers develop ulcerative colitis

Background—OVspring 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 aVected parentchild pairs with Crohn’s disease from France and Belgium. Patients and methods—In a cohort of 160 multiply aVected families with Crohn’s disease,57 parent-first aVected 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 diVerence was related to the age at diagnosis in the parents and was not present in 12 parentchild 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 aVected 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. (Gut 1998;42:170‐174)

https://gut.bmj.com/content/gutjnl/42/2/170.full.pdf

J Belaïche

Papers

Anticipation in familial Crohn's disease