Inflammatory bowel disease course in Crohn’s disease: Is the natural history changing?

Crohn’s disease(CD)is a multifactorial potentially debilitating disease.It has a variable disease course,but the majority of patients eventually develop penetrating or stricturing complications leading to repeated surgeries and disability.Studies on the natural history of CD provide invaluable data on its course and clinical predictors,and may help to identify patient subsets based on clinical phenotype.Most data are available from referral centers,however these outcomes may be different from those in population-based cohorts.New data suggest the possibility of a change in the natural history in Crohn’s disease,with an increasing percentage of patients diagnosed with inflammatory disease behavior.Hospitalization rates remain high,while surgery rates seem to have decreased in the last decade.In addition,mortality rates still exceed that of the general population.The impact of changes in treatment strategy,including increased,earlier use of immunosuppressives,biological therapy,and patient monitoring on the natural history of the disease are still conflictive.In this review article,the authors summarize the available evidence on the natural history,current trends,and predictive factors for evaluating the disease course of CD.     

Inflammatory bowel disease and the risk for cardiovascular disease: Does all inflammation lead to heart disease?

Inflammation has a strong role in the development of atherosclerotic cardiovascular disease (ASCVD). Several systemic inflammatory conditions have been linked to an increased risk of ASCVD; however, this has not been well established in Inflammatory Bowel Disease (IBD). IBD is comprised of Ulcerative Colitis and Crohn's disease, both of which involve chronic inflammation of the intestinal tract, often with evidence of systemic involvement. Several ASCVD risk factors such as smoking, diabetes, poor diet and the presence of obesity may increase the risk of ASCVD in patients suffering from IBD, despite a lower prevalence of hypertension and hypercholesterolemia. Medications used to treat IBD and target inflammation, such as steroids, may also accelerate the risk of the risk for ASCVD heart failure while exacerbating ASCVD risk factors. Several studies have demonstrated an elevated risk of acute myocardial infarction and stroke in these patients, most notably in women and in younger patients. Some cohort studies have also suggested a link between IBD and both atrial fibrillation and heart failure, particularly during periods of active flares. All IBD patients, particularly younger individuals, should be screened for ASCVD risk factors with aggressive risk factor modification to reduce the risk of cardiovascular events. Further research is needed to identify how to prevent and treat cardiovascular events that occur in patients with IBD, particularly during active flares.     

Inflammatory bowel disease： Genetic and epidemiologic considerations

Genome-wide association studies have firmly established that many genomic loci contribute to inflammatory bowel disease, especially in Crohn＇s disease. These studies have newly-established the importance of the interleukin 23 and autophagy pathways in disease pathogenesis. Future challenges include： （1） the establishment of precisely causal alleles, （2） definition of altered functional outcomes of associated and causal alleles and （3） integration of genetic findings with environmental factors.     

Inflammatory bowel disease in rats： Bacterial and chemical interaction

AIM：To develop a novel model of colitis in rats, using a combination of iodoacetamide and enteropathogenic E. coli（EPEC）, and to elucidate the pathophysiologic processes implicated in the development of ulcerative colitis （UC）.
METHODS： Hale Sprague-Dawley rats （/7 = 158） were inoculated intrarectally on a weekly basis with 4 different combinations： （a） 1% methylcellulose （HC）, （b） 100 μL of 6% iodoacetamide （IA） in 1% HC, （c） 200 p.L containing 4×10^8 colony factor units （CFU） of EPEC, and （d） combined treatment of （IA） followed by bacteria （13） after 2 d. Thirty days post treatment, each of the four groups was divided into two subgroups; the inoculation was stopped for one subgroup and the other subgroup continued with biweekly inoculation until the end of the experiment. Colitis was evaluated by the clinical course of the disease, the macroscopic and microscopic alterations, activity of myeloperoxidase （HPO）, and by TNF-α gene expression. RESULTS： Findings indicative of UC were seen in the combined treatment （IA ＋ B） as well as the IA continued treatment groups： the animals showed slow rate of increase in body weight, diarrhea, bloody stools, high colonic ulcer score, as well as histological alterations characteristic of UC, with an extensive inflammatory reaction. During the course of the experiment, the MPO activity was consistently elevated and the TNF-α gene expression was upregulated compared to the control animals.
CONCLUSION： The experimental ulcerative colitis model used in the present study resembles, to a great extent, the human disease. It is reproducible with characteristics indicative of chronicity.     

Inflammatory bowel disease and the lung: is there a link between surgery and bronchiectasis?

Purpose One-third of patients with inflammatory bowel disease (IBD) has extracolonic manifestations. Inflammatory bowel-associated pulmonary disease is one of the less commonly recognized and more recently described manifestations. Here, we report the experience of our patients with inflammatory bowel-associated bronchiectasis.Methods A retrospective analysis of case notes of patients with IBD and respiratory manifestations was undertaken. Relevant demographic, clinical, radiological, and pulmonary physiology laboratory results were reviewed.Results Ten patients with IBD and bronchiectasis were identified. Eight developed respiratory symptoms after surgery for IBD. Five of the ten had ulcerative colitis. Their lung function abnormality is mild to moderate in severity. Small airways disease (forced expiratory flow between 25–75% is <50%) was evident in seven of the ten patients.Conclusions This preliminary study supports an association between surgery for IBD and development of symptomatic lung disease, particularly bronchiectasis, in susceptible patients. The pulmonary manifestations of IBD in some patients may only become clinically significant after surgery and the withdrawal of medical treatment.     

Inflammatory bowel disease and laterality: is left handedness a risk?

BACKGROUND: Left handedness has been associated with inflammatory bowel disease (IBD) and autoimmune diseases. AIMS: To determine whether left handedness is associated with IBD in two prospective national birth cohorts. METHODS: Subjects with Crohn's disease (CD) and ulcerative colitis (UC) were identified from two national longitudinal birth cohorts at age 26 years (1970 British Cohort Study (BCS70), born in 1970) and age 33 years (National Child Development Study (NCDS), born in 1958). Laterality was determined at age 10 (BCS70) or seven (NCDS) years, based on hand preference for writing and foot preference for kicking a ball (BCS70 only). Multiple logistic regression was used to assess the relationship of handedness with CD, UC, and IBD in the cohorts combined and adjusted for sex. RESULTS: Both cohorts combined showed increased adjusted relative odds of 2.13 (95% confidence interval (CI) 0.97--4.65; p=0.059), 2.13 (95% CI 0.92--4.91; p=0. 077), and 2.13 (95% CI 1.20--3.78; p=0.010) for CD, UC, and IBD, respectively in left handers. CONCLUSIONS: The study suggests a link between IBD and left handedness which may be genetic and/or environmental in origin.     

Inflammatory bowel disease and lower limb lymphedema: a fortuitous association?

Introduction

Extra-intestinal manifestations of chronic inflammatory bowel disease (CIBD) are various. Cases of genital lymphedema has previously been reported in Crohn's disease.

Case reports

We report two women aged 57 and 68 years who presented with a lower limb lymphedema 8 and 20 years after a diagnosis of CIBD (Crohn's disease and ulcerative colitis), respectively. At the time of diagnosis of lymphedema, CIBD was asymptomatic.

Conclusion

Pathophysiological mechanisms of this rare manifestation are unclear and lymphedema outcome is unrelated to CIBD activity.     

New genes in inflammatory bowel disease: lessons for complex diseases?

The chronic inflammatory bowel diseases Crohn's disease and ulcerative colitis are common causes of gastrointestinal disease in northern Europe, affecting as many as one in 250 people. Although mortality is low, morbidity associated with these diseases is substantial. We review the recent advances in the genetics of inflammatory bowel disease, with particular emphasis on the data that have been generated since the discovery of the CARD15 (NOD2) gene in 2001.     

Inflammatory bowel diseases: From the mystical to the cellular and now the molecular

It is of interest in an era of increasing biomedical sophistication to recall that a relatively short time ago, early in the 20th century, 'simple' ulcerative colitis was an obscure 'medical curiosity' emerging slowly from an unknown past. Crohn's     

Inflammatory bowel diseases： From the mystical to the cellular and now the molecular

It is of interest in an era of increasing biomedical sophistication to recall that a relatively short time ago, early in the 20th century, ‘simple‘ ulcerative colitis was an obscure ‘medicalcuriosity‘ emerging slowly from an unknown past. Crohn‘s disease was yet unidentified as a separate entity although careful review of the IBD literature documented its early presence, masquerading as‘intestinal tuberculosis‘. Into the 1930s, the etiology and pathogenesis of ulcerative colitis and Crohn‘s disease were unknown, and investigative hypotheses were scarce. Therapeutic resources were limited and treatment was primitive. At a time of limited biomedical knowledge and minimal clinical awareness, unsubstantiated views prevailed, including‘vague reactions to foods‘ (sugar,margarine, corn flakes), deficiency of a ‘protective factor‘in pig intestine, and psychiatric disease.     

Enhanced production of macrophage inhibitory protein-1alpha in patients with Behçet's disease

OBJECTIVE: Macrophage inhibitory protein-1alpha (MIP-1alpha), a C-C chemokine, stimulates the activation and migration of leukocytes. We investigated the expression of MIP-1alpha in patients with Beh?et's disease (BD) and evaluated the association of the MIP-1alpha levels with disease activity of BD. METHODS: Serum samples were obtained from 67 BD patients and 30 healthy controls. Simultaneously, whole blood cells were isolated from BD patients (n = 25) and healthy controls (n = 11) and cultured in the absence or presence of lipopolysaccharide (LPS), phytohaemagglutinin (PHA), and phorbol 12-myristate 13-acetate (PMA) plus ionomycin. The concentrations of MIP-1alpha, interleukin-8 (IL-8), regulated on activation, normally T cell expressed and secreted (RANTES), and monocyte chemoattractant protein-1 (MCP-1) were measured in the sera and culture supernatants by enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum levels of MIP-1alpha were higher in BD patients than in healthy controls. When whole blood cells were stimulated with LPS or PMA plus ionomycin, but not PHA, BD patients had higher levels of MIP-1alpha in the culture supernatants compared to healthy controls. In sera and culture supernatants of whole blood cells, MIP-1alpha levels correlated well with those of RANTES, MCP-1, and IL-8 in BD patients. Moreover, patients with active disease had significantly higher levels of serum MIP-1alpha levels compared with those with inactive disease. CONCLUSION: MIP-1alpha levels were elevated in patients with BD, and correlated well with IL-8, RANTES, and MCP-1 levels. These results suggest that the increased MIP-1alpha levels in serum of BD patients may lead to activation and migration of leukocytes, playing a role, like other chemokines, in the pathogenesis of BD.     

eHealth for inflammatory bowel disease self-management – the patient perspective

Background: Electronic health (eHealth) solutions may help address the growing pressure on IBD outpatient services as they encompass a component of self-management. However, information regarding patients’ attitudes towards the use of eHealth solutions in IBD is lacking.

Objective: The aim of this study was to evaluate eHealth technology use and explore the perspectives of IBD patients on what constitutes the ideal eHealth solution to facilitate self-management.

Methods: A mixed methods qualitative and quantitative analysis of the outcomes of a discussion forum and an online survey conducted at a tertiary hospital in Melbourne, Australia between November 2015 and January 2016 was undertaken.

Results: Eighteen IBD patients and parents participated in the discussion forum. IBD patients expressed interest in eHealth tools that are convenient and improve access to care, communication, disease monitoring and adherence. Eighty six patients with IBD responded to the online survey. A majority of patients owned a mobile phone (98.8%), had access to the internet (97.7%), and felt confident entering data onto a phone or computer (73.3%). Most patients (98.8%) were willing to use at least one form of information and communication technology to help manage their IBD. Smartphone apps and internet websites were the two most preferred technologies to facilitate IBD self-management.

Conclusions: This study demonstrates the willifngness of patients to engage with eHealth as a potential solution to facilitate IBD self-management. Future development and testing of eHealth solutions should be informed by all major stakeholders including patients to maximise their uptake and efficacy to facilitate IBD self-management.     

Inflammatory bowel disease in the Asia–Pacific area: A comparison with developed countries and regional differences

The Asia–Pacific region has been marked as an area with a low incidence of inflammatory bowel disease (IBD), although confusion always existed as to whether this low incidence was a result of low diagnostic awareness, a high incidence of infective diarrhoea and its diagnostic overlap or a true low incidence. As epidemiological studies from this region are being made available it is clear that the incidence and prevalence rates of IBD in Asia–Pacific region are low compared with Europe and North America. They are however, increasing rapidly. There are substantial variations in the incidence and prevalence rates of IBD in various ethnic groups in Asia. The highest incidence rates are recorded from India, Japan and the Middle East and there exists a genetic predisposition of South Asians (Indians, Pakistanis and Bangladeshis) to ulcerative colitis (UC). It appears that certain racial groups are more prone than others to develop IBD. For instance, Indians in South-East Asia have higher rates than Chinese and Malays. While there is a host genetic predisposition, environmental factor(s) may be responsible for this difference. The clinical phenotypes and complication rates of Asian IBD resemble those of the Caucasian population in general, but some heterogeneity is observed in different regions of Asia. There is no evidence of a north-south or an east-west divide in the Asia–Pacific region. The available studies suggest an increasing incidence of UC in the Asia–Pacific region and hence it is an appropriate time to launch well-designed epidemiological studies so that etiopathogenetic factors can be identified. There is a male predominance in Crohn's disease in the Asian population. The NOD2/CARD15 gene is not associated with CD in the Japanese, Korean, Chinese and Indian population.