Characteristics of Pediatric Inflammatory Bowel Disease in Korea: Comparison with EUROKIDS Data

Background/Aims

Pediatric inflammatory bowel disease (IBD) has been increasing worldwide. The characteristics of pediatric-onset IBD have mainly been reported in Western countries. We investigated the clinical characteristics of pediatric IBD in Korea and compared these with the data from the 5-year European multicenter study of children with new-onset IBD (EUROKIDS registry).

Methods

Children who were diagnosed with IBD between July 1987 and January 2012 were investigated at five Korean university hospitals. Their clinical characteristics were retrospectively evaluated by medical record review. The results were compared with the EUROKIDS data.

Results

A total of 30 children with Crohn’s disease (CD) and 33 children with ulcerative colitis (UC) were enrolled. In comparison with the EUROKIDS group, Korean pediatric IBD patients showed a male predominance (86.7% vs 59.2%, p=0.002 in CD; 75.8% vs 50%, p=0.003 in UC). Korean pediatric CD patients had a higher prevalence of terminal ileal disease (36.7% vs 16.3%, p=0.004) and perianal disease (33.3% vs 8.2%, p<0.001) than patients in the EUROKIDS group. Korean pediatric UC patients had a higher prevalence of proctitis than patients in the EUROKIDS group.

Conclusions

Our results suggest that the characteristics of Korean pediatric IBD patients and European pediatric IBD patients may be different.     

Seasonal Variation in Months of Birth and Symptom Flares in Korean Patients with Inflammatory Bowel Disease

Background/Aims

Seasonal variation may influence the development and exacerbation of inflammatory bowel disease (IBD). However, most epidemiologic studies on this topic have been conducted in Western countries. The purpose of this study was to determine whether birth dates and symptom flares follow a seasonal pattern in Korean patients with IBD.

Methods

Patients with a diagnosis of IBD established between January 2003 and December 2010 were investigated at six university hospitals in Korea. The expected births and flares, with a uniform distribution during the year and considering differences in the number of days in the months of 1 year, were calculated.

Results

A total of 411 patients with ulcerative colitis (UC) and 316 patients with Crohn disease (CD) were included in the study. Birth during the winter period, and especially in January and February, was associated with an increased risk of IBD, especially in UC patients. The symptom flares of CD patients occurred most frequently in the spring, with a nadir in the autumn. However, no disease flare seasonality was noted for UC patients.

Conclusions

Our data suggest that seasonally varying environmental factors during pregnancy and the postpartum period are associated with a susceptibility to IBD later in life and that exacerbations of CD are influenced by seasonal factors.     

Fatigue Severity and Factors Associated with High Fatigue Levels in Korean Patients with Inflammatory Bowel Disease

Background/Aims

Many patients with inflammatory bowel disease (IBD) often complain of fatigue. To date, only a few studies in Western countries have focused on fatigue related to IBD, and fatigue has never been specifically studied in Asian IBD patients. The aim of the present study was to investigate the fatigue level and fatigue-related factors among Korean IBD patients.

Methods

Patients in remission or with mild to moderate IBD were included. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue and the Brief Fatigue Inventory. Corresponding healthy controls (HCs) also completed both fatigue questionnaires.

Results

Sixty patients with Crohn disease and 68 patients with ulcerative colitis (UC) were eligible for analysis. The comparison group consisted of 92 HCs. Compared with the HCs, both IBD groups were associated with greater levels of fatigue (p<0.001). Factors influencing the fatigue score in UC patients included anemia and a high erythrocyte sedimentation rate (ESR).

Conclusions

Greater levels of fatigue were detected in Korean IBD patients compared with HCs. Anemia and ESR were determinants of fatigue in UC patients. Physicians need to be aware of fatigue as one of the important symptoms of IBD to better understand the impact of fatigue on health-related quality of life.     

Ethnic variation in the annual rates of adult inflammatory bowel disease in hospitalized patients in Vancouver, British Columbia

BACKGROUND:

There is currently little available information regarding the impact of ethnicity on the clinical features of inflammatory bowel disease (IBD). Migrating populations and changing demographics in Vancouver, British Columbia (BC) provide a unique opportunity to examine the role of ethnicity in the prevalence, expression and complications of IBD.

OBJECTIVES:

To determine the demographics of IBD and its subtypes leading to hospitalization in the adult population of BC.

METHODS:

A one-year retrospective study was performed for all patients who presented acutely with IBD to Vancouver General Hospital from January 1, 2006 to December 31, 2006. Data regarding sex, age, ethnicity, IBD type and extent of disease, complications and management strategies were collected. Clinical data were confirmed by pathology and radiology reports.

RESULTS:

There were 186 cases of IBD comprising Crohn’s disease (CD) 56%, ulcerative colitis (UC) 43% and indeterminate colitis (1%) 1%. The annual rate of IBD cases warranting hospitalization in Caucasians was 12.9 per 100,000 persons (7.9 per 100,000 persons for CD and 5.0 per 100,000 persons for UC). This was in contrast to the annual rate of IBD in South Asians at 7.7 per 100,000 persons (1.0 per 100,000 persons for CD and 6.8 per 100,000 persons for UC) and in Pacific Asians at 2.1 per 100,000 persons (1.3 per 100,000 persons for CD, 0.8 per 100,000 persons for UC). The male to female ratio was higher in South Asians and Pacific Asians than in Caucasians. The extent of disease was significantly different across racial groups, as was the rate of complications.

CONCLUSIONS:

These early results suggest that there are ethnic disparities in the annual rates of IBD warranting hospitalization in the adult population of BC. There was a significantly higher rate of CD in the Caucasian population than in South Asian and Pacific Asian populations. The South Asian population had a higher rate of UC, with an increased rate of complications and male predominance. Interestingly, the rate of CD and UC was lowest in the Pacific Asian population. These racial differences – which were statistically significant – suggest a role for ethnodiversity and environmental changes in the prevalence of IBD in Vancouver.     

Evaluation of Antibody Response to Polysaccharide Vaccine and Switched Memory B Cells in Pediatric Patients with Inflammatory Bowel Disease

Background/Aims

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients.

Methods

Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated.

Results

Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9±32.5 µg/mL vs 219.8±59.0 µg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed.

Conclusions

A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.     

Inflammatory bowel disease: A Canadian burden of illness review

BACKGROUND:

Inflammatory bowel diseases (IBD) – Crohn’s disease (CD) and ulcerative colitis (UC) – significantly impact quality of life and account for substantial costs to the health care system and society.

OBJECTIVE:

To conduct a comprehensive review and summary of the burden of IBD that encompasses the epidemiology, direct medical costs, indirect costs and humanistic impact of these diseases in Canada.

METHODS:

A literature search focused on Canadian data sources. Analyses were applied to the current 2012 Canadian population.

RESULTS:

There are approximately 233,000 Canadians living with IBD in 2012 (129,000 individuals with CD and 104,000 with UC), corresponding to a prevalence of 0.67%. Approximately 10,200 incident cases occur annually. IBD can be diagnosed at any age, with typical onset occurring in the second or third decade of life. There are approximately 5900 Canadian children <18 years of age with IBD. The economic costs of IBD are estimated to be $2.8 billion in 2012 (almost $12,000 per IBD patient). Direct medical costs exceed $1.2 billion per annum and are driven by cost of medications ($521 million), hospitalizations ($395 million) and physician visits ($132 million). Indirect costs (society and patient costs) total $1.6 billion and are dominated by long-term work losses of $979 million. Compared with the general population, the quality of life patients experience is low across all dimensions of health.

CONCLUSIONS:

The present review documents a high burden of illness from IBD due to its high prevalence in Canada combined with high per-patient costs. Canada has among the highest prevalence and incidence rates of IBD in the world. Individuals with IBD face challenges in the current environment including lack of awareness of IBD as a chronic disease, late or inappropriate diagnosis, inequitable access to health care services and expensive medications, diminished employment prospects and limited community-based support.     

Red cell distribution width: a novel marker of activity in inflammatory bowel disease

Background/Aims

Studies concerning red cell distribution width (RDW) for use in the assessment of inflammatory bowel disease (IBD) activity are limited. We investigated whether RDW is a marker of active disease in patients with IBD.

Methods

In total, 61 patients with ulcerative colitis (UC) and 56 patients with Crohn''s disease (CD) were enrolled in the study group, and 44 age- and-sex-matched healthy volunteers were included as the control group. A CD activity index >150 in patients with CD indicated active disease. Patients with moderate and severe disease based on the Truelove-Witts criteria were considered to have active UC. In addition to RDW, serum C-reactive protein levels, erythrocyte sedimentation rates, and platelet counts were measured.

Results

Twenty-nine (51.7%) patients with CD and 35 (57.4%) patients with UC had active disease. The RDW was significantly higher in patients with CD and UC than in controls (p<0.001 and p<0.001, respectively). A subgroup analysis indicated that for a RDW cut-off of 14%, the sensitivity for detecting active CD was 79%, and the specicity was 93% (area under curve [AUC], 0.935; p<0.001). RDW was the most sensitive and specific marker for active CD. However, it was not valid for UC, as the ESR at a cutoff of 15.5 mm/hr showed a sensitivity of 83% and a specicity of 76% (AUC, 0.817; p<0.001), whereas the RDW at a cutoff of 14% showed 17% sensitivity and 84% specicity for detecting active UC.

Conclusions

RDW was elevated in IBD in comparison with healthy controls and increased markedly in active disease. RDW may be a sensitive and specific marker for determining active CD, whereas ESR is an important marker of active UC.     

Emerging Inflammatory Bowel Disease in Saudi Outpatients: A Report of 693 Cases

Background/Aim:

Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology and considered traditionally as a disease of the western world. Recently, rising trends have been observed in countries previously known to have a low prevalence and incidence. The aim of this study is to collect epidemiological data on IBD outpatients and to add data from the Kingdom of Saudi Arabia (KSA) to the available IBD literature.

Patients and Methods:

The medical records of 693 Saudi patients with IBD over a period of 17 years, between 1993 and 2009, were reviewed. The demographic and clinical data and methods of diagnosis were retrieved.

Results:

The total number of patients in this cohort was 693. It constituted 238 (34.3%) ulcerative colitis (UC) and 455 (65.7%) Crohn''s disease (CD) patients. UC was steady throughout the years, whereas only 1.2 CD patients were diagnosed per year in the first 11 years, and 73.7 per year in the last six years. The median age of UC patients was 34 years, ranging from 10 to 80 years with a peak between 21 and 40 years and in CD it was 27 years, ranging from 11 to 73 years with a peak between 11 and 30 years. There was a male preponderance of 1.5:1 and 2:1, respectively. The rest of the data is discussed in this study.

Conclusion:

IBD is no longer a rare disease in KSA. UC is in a steady state, whereas CD is increasing significantly and far outnumbering UC.     

Impact of Pediatric Inflammatory Bowel Disease on Linear Growth: Data from a National Cohort Study in Saudi Arabia

Background/Aim:

Linear growth impairment (LGI) is one of the most important features peculiar to children with inflammatory bowel disease (IBD). The aim of this report is to define the impact of IBD on the linear growth of children in the Kingdom of Saudi Arabia (KSA).

Setting and Design:

Multicenter retrospective study.

Patients and Methods:

Data from a cohort of newly- diagnosed children with IBD from 2003 to 2012 were analyzed retrospectively. The diagnosis of IBD was confirmed in accordance with the published criteria. Length/height for age was measured at diagnosis. The World Health Organization (WHO) reference was used and LGI was defined by length/height for age <-2 standard deviation.

Results:

There were 374 children from 0.33 to 16 years of age, including 119 ulcerative colitis (UC) (32%), and 255 Crohn''s disease (CD) (68%) patients. The prevalence of LGI was 26%, 28%, and 21% in IBD, CD, and UC, respectively. In children below 10 years, LGI was significantly more common in CD (P = 0.010), while in UC children, it was more common in older children (P = 0.011).

Conclusion:

This study demonstrates a prevalence of LGI consistent with that reported in the literature, but higher in CD children with early onset (<10 years) and in older children with UC, underscoring the importance of monitoring growth in children with IBD in the Saudi population. Prospective studies are needed to define the impact of IBD on growth velocity, puberty, and final adult stature.     

Insufficient Knowledge of Korean Gastroenterologists Regarding the Vaccination of Patients with Inflammatory Bowel Disease

Background/Aims

There is an increased risk for inflammatory bowel disease (IBD) patients to develop infections due to the use of immunomodulators and biologics. Several infections are preventable by immunizations. This study investigated the knowledge and awareness of Korean gastroenterologists regarding the vaccination of patients with IBD.

Methods

A self-reported questionnaire was sent by e-mail to the faculty members of tertiary hospitals. Gastroenterologists were asked ten questions regarding the immunization of patients with IBD. A total of 56 gastroenterologists completed the questionnaire.

Results

A majority of gastroenterologists (>60%) had rarely or never recorded an immunization history from their patients with IBD. Moreover, 50% to 70% of the gastroenterologists did not know that live vaccines should be avoided in immunosuppressed patients. The most commonly mentioned resistance to vaccinations was "the lack of concern and knowledge regarding vaccination." Gastroenterologists more frequently asked about the immunization history of influenza, pneumococcal, hepatitis A, and hepatitis B vaccines and recommended these vaccines more often than others.

Conclusions

Korean gastroenterologists'' awareness and knowledge regarding the vaccination of patients with IBD were very poor. Intensive educational programs on immunization guidelines directed toward gastroenterologists who care for patients with IBD are required to ensure that these patients receive the necessary vaccinations.     

Is Whole Exome Sequencing Clinically Practical in the Management of Pediatric Crohn’s Disease?

Background/Aims

The aim of this study was to identify the profile of rare variants associated with Crohn’s disease (CD) using whole exome sequencing (WES) analysis of Korean children with CD and to evaluate whether genetic profiles could provide information during medical decision making.

Methods

DNA samples from 18 control individuals and 22 patients with infantile, very-early and early onset CD of severe phenotype were used for WES. Genes were filtered using panels of inflammatory bowel disease (IBD)-associated genes and genes of primary immunodeficiency (PID) and monogenic IBD.

Results

Eighty-one IBD-associated variants and 35 variants in PID genes were revealed by WES. The most frequently occurring variants were carried by nine (41%) and four (18.2%) CD probands and were ATG16L2 (rs11235604) and IL17REL (rs142430606), respectively. Twenty-four IBD-associated variants and 10 PID variants were predicted to be deleterious and were identified in the heterozygous state. However, their functions were unknown with the exception of a novel p.Q111X variant in XIAP (X chromosome) of a male proband.

Conclusions

The presence of many rare variants of unknown significance limits the clinical applicability of WES for individual CD patients. However, WES in children may be beneficial for distinguishing CD secondary to PID.     

Prevalence and incidence of antimicrobial-resistant organisms among hospitalized inflammatory bowel disease patients

BACKGROUND:

Patients with inflammatory bowel disease (IBD) experience frequent hospitalizations and use of immunosuppressive medications, which may predispose them to colonization with antimicrobial-resistant organisms (ARO).

OBJECTIVE:

To determine the prevalence of ARO colonization on admission to hospital and the incidence of infection during hospitalization among hospitalized IBD patients.

METHODS:

A chart review comparing the prevalence of colonization and incidence of infection with methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL) in hospitalized IBD patients with those of non-IBD controls was performed.

RESULTS:

On admission, there were no significant differences between IBD inpatients and controls in the prevalence of colonization of methicillin-resistant S aureus (1.0% versus 1.2%; P=0.74), vancomycin-resistant enterococci (0.2% versus 0%; P=1.0) or ESBL (4.1% versus 5.5%; P=0.33). Pooling data from historical clinic-based cohorts, IBD patients were more likely than controls to have ESBL colonization (19% versus 6.6%; P<0.05). Antibiotic use on admission was associated with ESBL colonization among IBD inpatients (OR 4.2 [95% CI 1.4 to 12.6]). The incidence of ARO infections during hospitalization was not significantly different between IBD patients and controls. Among IBD patients who acquired ARO infections during hospitalizations, the mean time interval from admission to infection was shorter for those who were already colonized with ARO on admission.

CONCLUSIONS:

This particular population of hospitalized IBD patients was not shown to have a higher prevalence or incidence of ARO colonization or infection compared with non-IBD inpatients.     

Bone Density and Bone Metabolism in Patients with Inflammatory Bowel Disease

Background/Aims:

Patients with inflammatory bowel disease (IBD) are at high risk for low bone mineral density (BMD). This study aimed to evaluate BMD in IBD patients and its relationship with bone metabolism in a group of Iranian patients.

Patients and Methods:

A cross-sectional study was conducted on patients with IBD to assess BMD status and serum biochemical factors. After getting the demographic data from 200 patients, they were screened using dual-energy X-ray absorptiometry of the lumbar spine (L2–L4) and femoral neck for BMD status. Serum levels of calcium, phosphate, alkaline phosphatase (ALP), and 25-hydroxyvitamin D (25-OH vitamin D) were measured to assess the bone metabolism status.

Results:

Two hundred patients with IBD were enrolled in the study. One hundred and eighty three (91.5%) patients were identified as having ulcerative colitis (UC) and 17 (8.5%) as having Crohn''s disease (CD). Based on the lumbar and femoral neck bone mass densitometry, 148 (74.4%) patients had low BMD at either lumbar spine or femoral neck. Of these, 100 patients (50.3%) were osteopenic and 48 patients (24.1%) were osteoporotic. A 58.6% and 61% of patients with UC had low BMD in the lumbar and femoral neck, respectively. These results for those with CD were 76.5% and 70.6%, respectively. The mean of femoral neck and lumbar T-scores in patients with UC were -1.14 and -1.38, and in patients with CD were -1.24 and -1.47, respectively (P > 0.05). The mean (±SD) levels for calcium (Ca) in UC and CD were in the normal range. The mean (±SD) levels of ALP and 25-OH vitamin D in both the groups were in the normal range, and in comparison between groups (UC and CD), no significant differences were observed (P = 0.20 for ALP and P = 0.44 for 25-OH vitamin D). In the assessment of correlation between biochemical markers and BMD, an inverse correlation between lumbar T-score and ALP or 25-OH vitamin D only in patients with UC was observed.

Conclusions:

The high prevalence of low BMD in the Iranian population with IBD needs attention. The subclinical vitamin D deficiency may contribute to bone loss in IBD patients, which is more pronounced in patients with UC in this study because of the small population of patients with CD.     

Prevalence of self-reported spondyloarthritis features in a cohort of patients with inflammatory bowel disease

BACKGROUND:

Musculoskeletal symptoms belonging to the spectrum of ‘seronegative spondyloarthritis’ (SpA) are the most common extraintestinal manifestations in patients with inflammatory bowel disease (IBD) and may lead to important disease burden. Patients with suspected SpA should be referred to a rheumatologist for further evaluation.

OBJECTIVE:

To investigate the self-reported prevalence of musculoskeletal SpA features in a cohort of patients with IBD and to compare this with actual referrals to a rheumatologist.

METHODS:

Consecutive patients with IBD visiting the outpatient clinic were interviewed by a trained research nurse about possible SpA features using a standardized questionnaire regarding the presence or history of inflammatory back pain, peripheral arthritis, enthesitis, dactylitis, psoriasis, uveitis and response to nonsteroidal anti-inflammatory drugs. All patient files were verified for previous visits to a rheumatologist and any rheumatic diagnosis.

RESULTS:

At least one musculoskeletal SpA feature was reported by 129 of 350 (36.9%) patients. No significant differences between patients with Crohn disease and ulcerative colitis were found. Review of medical records showed that 66 (51.2%) patients had ever visited a rheumatologist. Axial SpA was diagnosed in 18 (27.3%) patients, peripheral SpA in 20 (30.3%) patients and another rheumatic disorder in 14 (21.2%) patients.

CONCLUSION:

Musculoskeletal SpA features are frequently present in patients with IBD. However, a substantial group of patients is not evaluated by a rheumatologist. Gastroenterologists play a key role in early referral of this often debilitating disease.     

Metabolic Syndrome Frequency in Inflammatory Bowel Diseases

Background/Aim:

Metabolic syndrome (MetS) is a clinical condition characterized by central obesity, elevated triglycerides, low–high density lipoproteins, impaired fasting glucose, and hypertension. There is insufficient data on the prevalence of MetS in patients with inflammatory bowel disease (IBD). This study sought to determine the prevalence of MetS in a Turkish cohort of patients with IBD and the association between insulin resistance (IR) and the MetS parameters, in this population.

Patients and Methods:

A total of 177 patients over 18 years of age (62 with Crohn''s disease (CD) and 115 with ulcerative colitis (UC)) were enrolled in the study. The presence of at least three criteria of the International Diabetes Federation (IDF) was accepted for the diagnosis of MetS. The Homeostasis Model Assessment (HOMA) was used to determine IR. HOMA values < 1 were considered normal and values > 2.5 indicated a high probability of IR.

Results:

MetS frequency was higher in patients n=34 (29.5%) with UC than in patients n=11 (17.7%) with CD (P < 0.01). MetS was detected in 12 of the 117 patients (10.3%) with IBD, under 45 years of age, and in 33 of 60 patients (55%) over 45 years of age. HOMA value in n=31 patients (27%) with UC was > 2.5. Body mass index, insulin (P < 0.001), waist circumference, fasting plasma glucose, leukocyte count (P < 0.01), triglycerides, C-reactive protein, and uric acid values (P < 0.05) were significantly higher in UC patients with IR than those without IR.

Conclusion:

Frequent occurrence of MS with increasing age in IBD, particularly in UC, showed the importance of early diagnosis and treatment of cardiovascular disease risk factors in the long-term follow-up of these diseases.     

Psychiatric comorbidities in patients with inflammatory bowel disease

Background

Psychiatric comorbidities are associated with inflammatory bowel disease (IBD). We conducted an observational study to evaluate the prevalence of depression and anxiety in patients with IBD.

Methods

Seventy consecutive consenting patients with IBD (62 ulcerative colitis [UC], 8 Crohn’s disease [CD]; 40 males, mean age [SD] 36.2 [11.3] years) and 100 healthy volunteers (44 males, age 31.22 [SD] [10.5] years) as controls were enrolled. All participants were directed to take self-assessment tests, Patient Health Questionnaire -9 (PHQ-9) and Symptom Checklist Anxiety Scale (SCL-A20). Participants having a score ≥ 10 on PHQ-9, or ≥ 29 on SCL-A20 were administered the Hamilton Depression Rating Scale (HAM-D) or Hamilton Anxiety (HAM-A) scales, respectively. The severity of depression and anxiety was graded with HAM-D and HAM-A scales, respectively. The protocol was approved by the Institutional Ethics Committee.

Results

The prevalence of depression (34.3% vs. 5%, p?<?0.0001, OR 9.7) and anxiety (18.6% vs. 2%, p?=?0.0002, OR 11.17) was higher in patients with IBD as compared to controls. The severity of depression was higher in patients compared to controls (mean rank 17 vs. 7, p?=?0.04). The prevalence of depression was not different between UC and CD; all IBD patients with anxiety had UC. The mean duration of disease and history of corticosteroid treatment or surgery for IBD were not associated with the presence of depression or anxiety. Patients with severe CD (Crohn’s disease activity index, CDAI?>?450) had more severe depression. The severity of UC did not correlate with severity of anxiety or depression in UC.

Conclusions

Anxiety and depression are more prevalent in IBD patients as compared to healthy individuals.

     

Oxidative Stress Markers in Intestinal Mucosa of Tunisian Inflammatory Bowel Disease Patients

Background/Aims:

Inflammatory bowel diseases (IBDs), Crohn''s disease (CrD) and ulcerative colitis (UC), are chronic gastrointestinal inflammatory disorders. The precise etiology of IBD remains unclear, and it is thought that interactions among various factors, including, genetic factors, the host immune system and environmental factors, cause disruption of intestinal homeostasis, leading to dysregulated inflammatory responses of the gut. As inflammation is intimately related to formation of reactive intermediates, including, reactive oxygen species, oxidative stress has been proposed as a mechanism underlying the pathophysiology of IBD. The purpose of this study is to examine the lipid peroxidation, protein oxidation and anti-oxidative profile in Tunisian IBD.

Materials and Methods:

Malondialdehyde (MDA), conjugated dienes (CD), protein thiol levels, as well as the catalase (CAT) activity were evaluated in intestinal biopsies of 17 patients affected by IBD (12 CrD and 5 UC) and 12 healthy control individuals.

Results:

Oxidative stress was confirmed in these two types of disease biopsies as compared to controls. MDA and CD levels were significantly increased in both UC and CrD patients’ biopsies as compared to controls’ biopsies (P < 0.001). CAT activity was similar in UC and CrD biopsies’ and was not significantly increased in IBD patients’ biopsies compared with controls’ biopsies (P > 0.05). Anon-significant decrease in thiol (SH) level was observed in both UC and CrD patients’ biopsies compared with controls’ biopsies (P > 0.05).

Conclusion:

Increased levels of MDA and CD in IBD patients’ biopsies underline the implication of oxidative stress in the physiopathology of IBD.     

Assessing inflammatory bowel disease-associated antibodies in Caucasian and First Nations cohorts

BACKGROUND:

First Nation populations in Canada have a very low incidence of inflammatory bowel disease (IBD). Based on typical infections in this population, it is plausible that the First Nations react differently to microbial antigens with a different antibody response pattern, which may shed some light as to why they experience a low rate of IBD.

OBJECTIVE:

To compare the positivity rates of antibodies known to be associated with IBD in Canadian First Nations compared with a Canadian Caucasian population.

METHODS:

Subjects with Crohn’s disease, ulcerative colitis (UC), rheumatoid arthritis (RA) (as an immune disease control) and healthy controls without a personal or family history of chronic immune diseases, were enrolled in a cohort study aimed to determine differences between First Nations and Caucasians with IBD or RA. Serum from a random sample of these subjects (n=50 for each of First Nations with RA, First Nations controls, Caucasians with RA, Caucasians with Crohn’s disease, Caucasians with UC and Caucasians controls, and as many First Nations with either Crohn’s disease or UC as could be enrolled) was analyzed in the laboratory for the following antibodies: perinuclear antineutrophil cytoplasmic antibody (pANCA), and four Crohn’s disease-associated antibodies including anti-Saccharomyces cerevisiae, the outer membrane porin C of Escherichia coli, I2 – a fragment of bacterial DNA associated with Pseudomonas fluorescens, and the bacterial flagellin CBir-1. The rates of positive antibody responses and mean titres among positive results were compared.

RESULTS:

For pANCA, First Nations had a positivity rate of 55% in those with UC, 32% in healthy controls and 48% in those with RA. The pANCA positivity rate was 32% among Caucasians with RA. The rates of the Crohn’s disease-associated antibodies for the First Nations and Caucasians were comparable. Among First Nations, up to one in four healthy controls were positive for any one of the Crohn’s disease-associated antibodies. First Nations had significantly higher pANCA titres in both the UC and RA groups than Caucasians

DISCUSSION:

Although First Nation populations experience a low rate of IBD, they are relatively responsive to this particular antibody panel.

CONCLUSIONS:

The positivity rates of these antibodies in First Nations, despite the low incidence of IBD in this population, suggest that these antibodies are unlikely to be of pathogenetic significance.     

Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases

Purpose

Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls.

Results

IL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (>?5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance.

Conclusions

Only a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.

     

Long-Term Outcomes of Cytomegalovirus Reactivation in Patients with Moderate to Severe Ulcerative Colitis: A Multicenter Study

Background/Aims

Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the long-term outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment.

Methods

This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated.

Results

The mean duration of follow-up for the 72 patients was 43.16±19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state.

Conclusions

The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation.