scholarly journals Genetic and Functional Profiling of Crohn's Disease: Autophagy Mechanism and Susceptibility to Infectious Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Annalisa Marcuzzi ◽  
Anna Monica Bianco ◽  
Martina Girardelli ◽  
Alberto Tommasini ◽  
Stefano Martelossi ◽  
...  

Crohn's disease is a complex disease in which genome, microbiome, and environment interact to produce the immunological background of the disease. Disease in childhood is more extensive and characterized by a rapid progression, leading to severe repercussions in the course of the disorder. Several genetic variations have been associated with an increased risk of developing the disease and most of these are also implicated in other autoimmune disorders. The gut has many tiers of defense against incursion by luminal microbes, including the epithelial barrier and the innate and adaptive immune responses. Moreover, recent evidence shows that bacterial and viral infections, as well as inflammasome genes and genes involved in the autophagy process, are implicated in Crohn's disease pathogenesis. The aim of this review is to establish how much the diagnostic system can improve, thus increasing the success of Crohn's disease diagnosis. The major expectation for the near future is to be able to anticipate the possible consequences of the disease already in childhood, thus preventing associated complications, and to choose the best treatment for each patient.

2005 ◽  
Vol 19 (10) ◽  
pp. 603-606 ◽  
Author(s):  
Hugh J Freeman

Erythema nodosum and pyoderma gangrenosum may occur in Crohn's disease. In the present evaluation of consecutive patients with Crohn's disease spanning more than two decades, erythema nodosum was seen in 45 patients and pyoderma gangrenosum was seen in seven patients. Forty-one of 566 women (7.2%) and nine of 449 men (2.0%) were affected. Of these, 45 (4.4%) had erythema nodosum and seven (0.7%) had pyoderma gangrenosum, including two (0.2%) with both dermatological disorders at different times during their clinical courses. Recurrent erythema nodosum was also detected in nine patients (20%) including eight women, while recurrent pyoderma gangrenosum was seen in two patients (28.6%). There was an age-dependent effect on the appearance of erythema nodosum in women, with the highest percentages seen in those younger than 20 years of age. Detection rates for erythema nodosum in women only approached the low mens' rates in Crohn's disease at older than 40 years of age. Most patients with these dermatological disorders had colonic disease with or without ileal involvement as well as complex disease, usually with penetrating complications. The present study documents a sex-based and age-dependent effect on the clinical expression of erythema nodosum in Crohn's disease. This suggests that some components of the inflammatory process in Crohn's disease may be modulated by estrogen-mediated events, particularly in adolescents and young adults.


2003 ◽  
Vol 17 (1) ◽  
pp. 43-46 ◽  
Author(s):  
Hugh J Freeman

Earlier investigations demonstrate an increased risk for colon cancer in Crohn's disease. For other intestinal neoplasms, such as carcinoids, studies are limited. In Crohn's disease, repeated endoscopic and imaging studies along with intestinal resections may facilitate clinical recognition of neoplastic diseases, including appendiceal neoplasms. To date, however, only sporadic cases of appendiceal carcinoids have been described in Crohn's disease. In the present study, in a single clinician database of 1000 Crohn's disease patients, three of the 441 patients who had undergone intestinal resection had appendiceal carcinoids, all of which were pathologically confirmed. All were observed in female patients and were not suspected before surgical treatment. In one case, even though management was not altered, the tumour had already invaded serosal fat indicating a potential for more advanced disease. In this series, a carcinoid tumour was found in a resection specimen during a later clinical case review and another was a microcarcinoid, implying that these tumours may be overlooked in Crohn's disease. The percentage detected in the entire database (0.3%) exceeds the reported rates of detection of appendiceal carcinoids after removal of the appendix for appendicitis, as well as the rate of detection of appendiceal carcinoids in autopsy studies. This percentage would be higher if only those having an intestinal resection were considered (0.68%). Additional studies are needed to further define this risk of appendiceal carcinoids in Crohn's disease.


2021 ◽  
Vol 160 (6) ◽  
pp. S-80
Author(s):  
Simon Chan ◽  
Ye Chen ◽  
Kevin Casey ◽  
Ola Olen ◽  
Jonas F. Ludvigsson ◽  
...  

2021 ◽  
Vol 14 (4) ◽  
pp. e241256
Author(s):  
Timothy Zef Hawthorne ◽  
Rachel Shellien ◽  
Lucy Chambers ◽  
Graham Devereux

This case report discusses the rare presentation of cytomegalovirus (CMV) pneumonitis in a young patient with moderately severe Crohn’s disease managed with low dose azathioprine. CMV pneumonitis was initially suspected on CT chest images and confirmed by PCR for CMV. She was treated with intravenous ganciclovir and later stepped down to oral valganciclovir. Although this patient had a prolonged and complicated hospital admission, a good clinical outcome was achieved. CMV infection was raised as an early differential and antiviral treatment was started without delay. This case study, therefore, makes the case for increased awareness of the possibility of, and recognition of CMV pneumonitis among healthcare professionals as a way of preventing significant morbidity and mortality. It also raises awareness of checking for slow metabolisers of azathioprine before initiation to look for individuals who may be at increased risk of azathioprine’s adverse effects.


2014 ◽  
Vol 51 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Siu-tong LAW ◽  
Kin Kong LI

ContextData from Asian populations about gender-related differences in Crohn’s disease are few.ObjectivesThis study was to analyze the clinical characteristics between women and men affected by Crohn’s disease.MethodsThis was a retrospective cohort study to analyze consecutive Crohn’s disease patients from Jan 2000 to Dec 2012. Clinical and phenotypic characteristics and treatment outcomes were evaluated.Results79 patients (55 male and two of them with positive family history) were diagnosed with Crohn’s disease. Ileocolonic disease and inflammatory lesion was the most dominant site of involvement and disease behavior respectively in both men and women. Apart from higher frequency of nausea (45.83 vs 23.64%, P 0.024) and lower body mass index (19.44 vs 22.03 kg/m2, P 0.003) reported in women, no significant gender-related differences in clinical characteristics were observed. Women were more associated with delay use of immunosuppressive therapy (12 vs 36 months, P = 0.028), particularly for those aged less than 40 years old (85 vs 62.6%,P = 0.023). Cox proportional hazard regression analysis revealed that active smoking (HR, 4.679; 95% CI, 1.03-21.18) and delayed use of immunosuppressive therapy (HR, 4.13; 95% CI, 1.01-16.88) were only independent risk factors associated with increased risk of complications.ConclusionsThere were no significant gender-specific differences in clinical and phenotypic characteristics between male and female Crohn’s disease patients. Smoking history and delay use of immunosuppressive therapy were associated with higher risk of complications.


2001 ◽  
Vol 85 (03) ◽  
pp. 430-434 ◽  
Author(s):  
James Blanchard ◽  
Donald Houston ◽  
Andre Wajda ◽  
Charles Bernstein

Summary Background: There is an impression mostly from specialty clinics that patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolic disorders. Our aim was to determine the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) from a population-based database of IBD patients and, to compare the incidence rates to that of an age, gender and geographically matched population control group. Methods: IBD patients identified from the administrative claims data of the universal provincial insurance plan of Manitoba were matched 1:10 to randomly selected members of the general population without IBD by year, age, gender, and postal area of residence using Manitoba Health’s population registry. The incidence of hospitalization for DVT and PE was calculated from hospital discharge abstracts using ICD-9-CM codes 451.1, 453.x for DVT and 415.1x for PE. Rates were calculated based on person-years of follow-up for 1984-1997. Comparisons to the population cohort yielded age-adjusted incidence rate ratios (IRR). Rates were calculated based on person-years of follow-up (Crohn’s disease = 21,340, ulcerative colitis = 19,665) for 1984-1997. Results: In Crohn’s disease the incidence rate of DVT was 31.4/10,000 person-years and of PE was 10.3/10,000 person-years. In ulcerative colitis the incidence rates were 30.0/10,000 person-years for DVT and 19.8/10,000 person-years for PE. The IRR was 4.7 (95% CI, 3.5-6.3) for DVT and 2.9 (1.8-4.7) for PE in Crohn’s disease and 2.8 (2.1-3.7) for DVT and 3.6 (2.5-5.2) for PE, in ulcerative colitis. There were no gender differences for IRR. The highest rates of DVT and PE were seen among patients over 60 years old; however the highest IRR for these events were among patients less than 40 years. Conclusion: IBD patients have a threefold increased risk of developing DVT or PE.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Priyatharsan Yoganathan ◽  
Jean-Benoit Rossel ◽  
Sebastian Bruno Ulrich Jordi ◽  
Yannick Franc ◽  
Luc Biedermann ◽  
...  

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.


Author(s):  
Audrey Bennett ◽  
Alexander Mamunes ◽  
Mindy Kim ◽  
Caroline Duley ◽  
Ailish Garrett ◽  
...  

Abstract Background Prior research demonstrates Crohn’s disease patients often do well in pregnancy; however, less is known about the risk of flare in the postpartum period. Methods A retrospective chart review was conducted at a tertiary care inflammatory bowel disease center. All pregnant women with Crohn’s disease who were followed in the postpartum period, defined as 6 months after delivery, were included. Statistical analysis included χ 2 analysis, Wilcoxon rank sum test, and logistic regression analysis. The primary outcome of interest was rate of flare in the postpartum period. Results There were 105 patients included in the study, with a majority (68%) on biologic medication during pregnancy. Thirty-one patients (30%) had a postpartum flare at a median of 9 weeks (range 2–24 weeks). Twenty-five patients (81%) had their postpartum flare managed in the outpatient setting with medications (only 4 of these patients required prednisone). 6 of 31 patients (19%) were hospitalized at a median of 4 weeks (range 2–26 weeks) after delivery, requiring intravenous corticosteroids or surgery. In multivariable regression, there was no significant increase in risk of postpartum flare with increasing maternal age, flare during pregnancy, or steroid or biologic use during pregnancy. Smoking during pregnancy increased risk of postpartum flare (odds ratio, 16.2 [1.72–152.94], P < 0.05). Conclusion In a cohort of Crohn’s disease patients, 30% experienced a postpartum flare despite being on medical therapy, but most were able to be managed in the outpatient setting.


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