Clinical features and pattern of indeterminate colitis: Crohn's disease with ulcerative colitis-like clinical presentation

Background.Although an accurate diagnosis of inflammatory bowel disease (IBD) and differentiation between ulcerative colitis (UC) and Crohn's disease (CD) can be made in most patients, it is sometimes impossible to distinguish UC from CD even after thorough pathological study. Recently, clinicians have used the term indeterminate colitis (IC) for patients with features of both diseases that overlap temporarily or persistently. The frequency, reasons, and outcome of patients with a clinical diagnosis of IC based on radiological, endoscopic, and histopathological findings were investigated retrospectively. Methods. Based on records of 735 patients with IBD, IC was defined as having features of both UC and CD, with differentiation from each other impossible at least once during the observation period (average 6.8 years) based on diagnostic criteria using endoscopic, radiological, and histological findings. Results. Twenty-three patients were identified as having IC. They were classified into three patterns according to the clinical cource and the final diagnosis: (1) UC changing to CD (n = 8); (2) CD changing to UC (n = 5); and (3) UC or CD (n = 10). The frequency of IC was 24.5%–43.4% of colitis-type CD (n = 53), 2.3%–6.5% of all CD (n = 352), and 3.1% of IBD (n = 735). The reasons for the indetermination were temporary (56.5%) or persistent (43.5%) overlapping of UC-like and CD-like presentations. Treatment of IC was inappropriate in only two patients, and the prognoses of all patients except one were fairly good. Conclusions. Overlapping of UC-like presentations (persistent bloody stool and diffuse colitis) was frequently observed with Crohn's colitis but less so in CD patients during their clinical course. The basis of differentiation and treatment of IC needs more attention.     

Cholangiocarcinoma and Crohn's disease

Summary Cholangiocarcinoma is an infrequent complication of inflammatory bowel disease. Although increasing numbers of cholangiocarcinomas are being reported in association with ulcerative colitis, the occurrence of this disease in patients with Crohn's disease is rare. To understand this complication better, we have reported the case of a patient with Crohn's disease in whom cholangiocarcinoma subsequently developed and reviewed the literature.     

Coexisting Crohn's disease and ulcerative colitis

This case report describes a patient initially presenting with Crohn's disease of the ileum who subsequently developed ulcerative proctocolitis. Reports of patients with both inflammatory bowel disease confirmed by histopathologic examination are rare.     

Effects of current cigarette smoking on clinical course of Crohn's disease and ulcerative colitis

Cigarette smoking worsens Crohn's disease (CD) but ameliorates ulcerative colitis (UC). In Israel, where there is no epidemiological association of smoking with CD, we examined the effects of current smoking on the course of CD and UC. Patients at nine public hospitals completed a questionnaire detailing their smoking history, disease course and treatments; subjects altering their smoking habit after the onset of disease were excluded. Sixty-four smokers and 144 nonsmokers had CD, and 34 smokers and 158 nonsmokers had UC. No differences were found between CD smokers and nonsmokers for hospitalizations, operations, and requirement for corticosteroid and immunosuppressive treatment. By contrast, UC smokers had less extensive disease than nonsmokers (P < 0.02) and fewer hospitalizations (P = 0.01) and operations (P = 0.025). Our results agree with a minority of studies showing no adverse effect of smoking on the course of CD, and confirm the protective effect of smoking in UC.     

High normal serum levels of C3 and C1 inhibitor,two acute-phase proteins belonging to the complement system,occur more frequently in patients with Crohn's disease than ulcerative colitis

Few data are available on measurements of serum concentrations of complement proteins in inflammatory bowel disease (IBD). Therefore we measured serum levels of C3, C4, and C1-esterase inhibitor (C1-INH) as well as C-reactive protein (CRP) in 167 patients with Crohn's disease (CD) and 111 patients with ulcerative colitis (UC). Median serum concentrations of C3 and C1-INH were significantly higher in CD than in UC. According to multiple logistic regression analysis adjusted to age, sex, activity of disease, and presence of extraintestinal manifestations, IBD patients with high-normal (128%, 75th percentile ) C1-INH concentrations had significantly (0.0275) higher odds ratio to have a diagnosis of CD than UC. Patients with high-normal C3 (1.40 g/liter) and high (20 mg/liter) CRP concentrations had an even higher odds ratio of a CD diagnosis (P = 0.0132). Our findings indicate that measurement of C3, C1-INH, and CRP can be used as an additional marker to pANCA/ASCA for distinguishing patients with CD and UC.     

Altered lectin binding by colonic epithelial glycoconjugates in ulcerative colitis and Crohn's disease

Evidence is accumulating that colonic mucin glycoconjugates are altered in ulcerative colitis. In order to investigate this further, the lectin-binding properties of rectal glycoconjugates have been studied in ulcerative colitis, Crohn's disease, and controls using lectin-peroxidase histochemistry. Ten lectins were used including peanut agglutinin (PNA) which is known to bind to malignant and adenomatous but not normal colonic mucins. Eight of 21 ulcerative colitis rectal biopsies and 10 of 17 Crohn's disease rectal biopsies showed PNA positivity, particularly in the supranuclear region of surface epithelial cells. There was no correlation between PNA positivity and duration of disease or inflammation, and none of the biopsies showed evidence of dysplasia. This abnormality in epithelial cell glycoconjugates seems to be commonly present in nondysplastic mucosa and occurs in both ulcerative colitis and Crohn's disease. It may reflect a fundamental abnormality in mucus glycoprotein synthesis in inflammatory bowel disease.     

Cytomegalovirus infection in ulcerative colitis

Objective. Cytomegalovirus (CMV) infection has been reported as an exacerbating factor in inflammatory bowel disease but the relationship between CMV infection and ulcerative colitis (UC) remains unclear. There has been no detailed research to elucidate the clinicopathologic features of CMV infection in UC using surgical specimens. The aim of this study was to investigate the clinicopathologic features of CMV infection in UC patients who had undergone colectomy.

Material and methods. Surgical specimens taken from UC patients were examined for CMV infection. The patients were divided into three groups: severe, refractory, and UC-associated dysplasia or cancer according to the operative indications. CMV infection rates were evaluated and a comparison of clinical parameters was made between CMV-positive and CMV-negative patients, and the risk factors for CMV infection were analyzed using multivariate analyses.

Results. It was found that 25% of 32 patients were positive for CMV in the severe UC group; 8.3% of 72 patients were positive for CMV in the refractory UC group. None of the 22 patients was positive for CMV in the UC-associated dysplasia or cancer group. The CMV-positive rate in the severe UC group was significantly higher than that in the other groups (p<0.05). Patients’ age at the time of operation was higher in the CMV-positive group than in the CMV-negative group among the patients with severe UC (p<0.01), and age at operation was an independent risk factor for CMV infection.

Conclusions. CMV is found more frequently in severe UC than refractory UC and UC-associated cancer or dysplasia. Higher age can be a risk factor for CMV infection in patients with severe UC. However, a high steroid dose may not always be a risk factor for CMV infection.     

Up-regulation of E-selectin and intercellular adhesion molecule-1 differs between Crohn's disease and ulcerative colitis

In present study, we investigated if inflammatory mediators secreted by the inflamed colonic mucosa from patients with Crohn's disease and ulcerative colitis had the ability to up-regulate the expression of two adhesion molecules, E-selectin and intercellular adhesion molecule-1. Organ culture techniques and enzyme-linked immunoassays were used to quantify these up-regulations in human umbilical vein endothelial cells. Our results show that, in Crohn's disease patients, the expression of E-selectin was up-regulated 5.5-fold over control values and intercellular adhesion molecule-1 expression was increased 2.4-fold. In ulcerative colitis patients, E-selectin expression was up-regulated twofold over controls with only a 1.5-fold increase in intercellular adhesion molecule-1 expression. Histologically, there was no difference in the degree of inflammation between the two disease groups. Sulfasalazine, in a dose-dependent manner, inhibited E-selectin expression up to 58% and intercellular adhesion molecule-1 up to 62% when stimulated by lipopolysaccharide. The up-regulation of E-selectin and intercellular adhesion molecule-1 may play an important role in mediating the inflammatory process in inflammatory bowel disease. The observed difference between Crohn's disease and ulcerative colitis may reflect differences in inflammatory cell infiltrates or the histopathological differences between the two diseases.Support by The Crohn's and Colitis Foundation of America.     

Mortality from Crohn's disease and ulcerative colitis in England-Wales and the U.S. from 1950 to 1983

As the etiology of inflammatory bowel disease remains unknown, studies of its time trends may provide clues to understanding the underlying mechanisms. This study examines mortality from Crohn's disease and ulcerative colitis in England and Wales and the U.S. during the period 1950 to 1983. Mortality from Crohn's disease and ulcerative colitis changed in both countries similarly. The death rates from Crohn's disease increased until 1970 to 1974 and decreased thereafter. The death rates from ulcerative colitis decreased throughout the observation period. Similar time trends occurred in men and women, and in the U.S. in whites and nonwhites. In the U.S., the death rates from both diseases were twofold higher in whites than nonwhites. The temporal changes suggest that mortality from inflammatory bowel disease is affected by exogenous factors and that these factors are different for Crohn's disease than for ulcerative colitis. These factors seem to have changed similarly in England and in the U.S. Supported by grant So 172/1-1 from the Deutsche Forschungsgemeinschaft.     

Monozygotic twins with Crohn's disease and ulcerative colitis: a unique case report

Background—A large number of monozygotic anddizygotic twin pairs with inflammatory bowel disease have beenreported. To date no twin pair has developed phenotypically discordantinflammatory bowel disease. This case report is the first documentedoccurrence of discordant inflammatory bowel disease occurring inmonozygotic twins.
Case report—Twenty two year old identical maletwins presented within three months of each other with inflammatorybowel disease that proved to be discordant in overall disease type,disease distribution, clinical course, and histopathological findings. Twin 1 developed a severe pancolitis necessitating total colectomy while twin 2 developed a predominantly distal patchy colitis with frequent granulomas, controlled by aminosalicylates. Twin 1 was antineutrophil cytoplasmic antibody (ANCA) negative at the time oftesting while twin 2 (Crohn's disease) was ANCA positive.Significantly, the twins possessed the HLA type DR3-DR52-DQ2 previouslyassociated with extensive colitis.
Conclusion—This case report confirms the importantrole played by genetic factors in the development of inflammatory bowel disease. It also highlights the crucial role of undeterminedenvironmental agents in dictating disease expression and phenotype.

Keywords:monozygotic twins; ulcerative colitis; Crohn'sdisease; inflammatory bowel disease

     

Right-sided ulcerative colitis

This report describes a case of right-sided ulcerative colitis in which multiple shallow ulcers and erosion with symmetric luminal stenosis were distributed segmentally from the ascending colon to the cecum, with a skip lesion composed of superficial erosions in the right half of the transverse colon. Both the rectum and the left colon were spared at the time of onset. Biopsies taken from the lesions showed non-specific inflammation, while those from the rectum and sigmoid colon showed no abnormal findings. A 5-year follow-up study was made based on radiography and endoscopy. Other inflammatory bowel diseases, such as Crohn's disease, tuberculosis, Yersinosis, Behçet's disease, and ischemic colitis were all ruled out, based on the macroscopic and microscopic findings as well as the clinical course. To our knowledge, this is the first report of right-sided ulcerative colitis that has been followed for a long period.     

Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn's disease and ulcerative colitis

OBJECTIVES: The aims of this study were to assess bone metabolism in inflammatory bowel disease (IBD) patients and to evaluate potential differences between Crohn's disease (CD) and ulcerative colitis (UC) with respect to the mechanisms underlying bone loss in this group of diseases. DESIGN AND SETTING: This was a cross-sectional study which started in 1992. Patients were randomly selected for invitation to participate and were examined during the years 1992-95 in one research clinic in Milan. SUBJECTS AND METHODS: Fifty-one patients suffering from CD (30 women and 21 men, mean age 38.7 +/- 13.2 years) and 40 with UC (15 women and 25 men, mean age 34.4. +/- 12.5 years) entered the study. Thirty healthy subjects were selected as sex- and age-matched controls (C). Spine and femoral neck bone mineral density (expressed as T score), calciotropic hormones (parathyroid hormone, PTH; 25-hydroxycholecalciferol, 25(OH)D3; 1,25-hydroxycholecalciferol, 1, 25(OH)D3) and biochemical markers of bone turnover (ostecalcin, OC; total alkaline phosphatase, ALP; type I collagen C-terminal telopeptide, ICTP) were evaluated. RESULTS: Spine and femur T scores were similar in the two groups (spine: CD = -1.49 +/- 1.46; UC = -1. 67 +/- 1.13; femur: CD = -1.80 +/- 1.36; UC = -1.60 +/- 1.03). Based upon the WHO guidelines, only 8% of CD patients and 15% of UC patients had a normal bone mineral density (BMD), 55% (CD) and 67% (UC) were osteopenic, and 37% (CD) and 18% (UC) were osteoporotic. The distribution amongst the three different diagnostic groups was not significantly different between CD and UC groups (P = 0.11). PTH and 25(OH)D3 concentrations were not significantly different between CD and UC patients and controls, whilst 1,25(OH)D3 concentrations were significantly lower in both CD and UC patients compared with controls (P < 0.05). Bone turnover was increased in UC but not in CD patients, as shown by significantly increased concentrations in UC patients of both OC (CD = 7.77 +/- 5.06, UC = 10.03 +/- 6.24, C = 6. 58 +/- 2.87, P < 0.05 vs. C) and ICTP (CD = 5.74 +/- 3.94, UC = 10.2 +/- 8.47, C = 3.48 +/- 0.95, P < 0.05 vs. CD and C). In a stepwise regression that included age, sex, disease duration and cumulative prednisolone dose as independent variables, the femur T score was significantly inversely related to disease duration (r2 = 0.125, F = 6.06) in CD patients. In UC patients, the spine T score was inversely related to age (r2 = 0.107, F = 5.49) and significantly related to sex (more negative in males: r2 = 0.3, F = 16.1); the femur T score was significantly related to sex (more negative in males) and inversely related to the cumulative prednisolone dose (r2 = 0.283, F = 7.3). CONCLUSIONS: These data show that IBD patients have a diffuse osteopenia, the degree of which is not different in CD and UC; however, bone turnover is significantly higher in UC. Finally, osteopenia is related to disease duration in CD, whilst it is related to the male sex and glucocorticoid treatment in UC.     

Fracture risk is increased in Crohn's disease, but not in ulcerative colitis

AIMS: To study fracture rates and risk factors for fractures in patients with Crohn's disease and ulcerative colitis. METHODS: 998 self administered questionnaires were issued to members of the Danish Colitis/Crohn Association, and 1000 questionnaires were issued to randomly selected control subjects. 845 patients (84.5%) and 645 controls (65.4%) returned the questionnaire (p<0.01). 817 patients and 635 controls could be analysed. RESULTS: Analysis was performed on 383 patients with Crohn's disease (median age 39, range 8-82 years; median age at diagnosis 26, range 1-75 years), 434 patients with ulcerative colitis (median age 39, range 11-86 years; median age at diagnosis 29, range 10-78 years), and 635 controls (median age 43, range 19-93 years, p<0.01). The fracture risk was increased in female patients with Crohn's disease (relative risk (RR) = 2.5, 95% confidence interval (CI) 1.7-3.6), but not in male patients with Crohn's disease (RR = 0.6, 95% CI 0.3-1.3) or in patients with ulcerative colitis (RR = 1.1, 95% CI 0.8-1.6). An increased proportion of low energy fractures was observed in patients with Crohn's disease (15.7% versus 1.4 % in controls, 2p<0. 01), but not in patients with ulcerative colitis (5.4%, 2p=0.30). The increased fracture frequency in Crohn's disease was present for fractures of the spine, feet, and toes and fractures of the ribs and pelvis. Fracture risk increased with increasing duration of systemic corticosteroid use in Crohn's disease (2p=0.028), but not in ulcerative colitis (2p=0.50). CONCLUSIONS: An increased risk of low energy fractures was observed in female patients with Crohn's disease, but not in male patients with Crohn's disease or in patients with ulcerative colitis.     

Epidemiology,disease burden,and treatment challenges of ulcerative colitis in Africa and the Middle East

Introduction: Ulcerative colitis is an idiopathic, chronic, inflammatory bowel disorder characterized by an unpredictable course of alternating cycles of relapse and remission. Traditionally viewed as a disease of Western countries, the prevalence of ulcerative colitis is reported to be increasing in the developing world. In these regions, there is the potential to further explore the etiology of the disease, mainly through genetic studies. With this in mind, we consider available data relating to the epidemiology, clinical manifestations, and disease course of ulcerative colitis in Africa and the Middle East. Current treatment approaches in these countries are also reviewed and discussed in the context of new, small molecule, orally administered therapies.

Areas covered: Available data on the epidemiology, clinical manifestations, and risk factors of ulcerative colitis in Africa and the Middle East are reviewed using a PubMed database search.

Expert commentary: Epidemiologic studies from African and Middle Eastern countries suggest disease trends similar to the West, and an important health and economic burden. The management of ulcerative colitis within these developing countries is challenging, with the need to improve early diagnosis, access to healthcare, and patient education, along with facilitation of access to treatment options and improvement of medication adherence.     

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

The Asia–Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia–Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all‐encompassing, and future revisions are likely as new data continue to emerge.     

Review: Constipation in ulcerative colitis: pathophysiology and practical management

Clinical experience suggests that there is a cohort of patients with refractory colitis who do have faecal stasis that contributes to symptoms. The underlying physiology is poorly understood, partly because until recently the technology to examine segmental colonic motility has not existed. Patients are given little information on how proximal faecal stasis can complicate colitis. Treatment guidelines are scanty and many patients are offered little apart from laxatives and advice on increasing fibre intake, which often makes symptoms worse. This article aims to review the history, pathology and management, and create impetus for future research on this underappreciated condition.     

Heat shock protein gene 70-2 polymorphism is differentially associated with the clinical phenotypes of ulcerative colitis and Crohn's disease

BACKGROUND AND AIM: A single nucleotide polymorphism in heat shock protein 70-2 (HSP70-2) has been shown to be associated with a severe clinical course in Crohn's disease (CD), but it is not known if such a relationship exists in ulcerative colitis (UC). The aim of the present study was to identify associations between the HSP70-2 polymorphism and the clinical courses of CD and UC in Koreans. METHODS: Restriction fragment length polymorphism analysis was performed for HSP70-2 polymorphisms using the PstI-cleavage site present in the B allele but not in the A allele of the DNA obtained from 101 patients with CD, 144 patients with UC, and 245 age- and sex-matched healthy controls. Study subjects were classified by disease behavior, severity and extent of disease. RESULTS: In CD, multivariate analysis showed that the AA genotype of HSP70-2 polymorphisms was associated with non-perforating disease (OR 10.10, 95% CI 1.66-15.38) and male sex (OR 3.56, 95% CI 1.04-12.23), and that the BB genotype was associated with severe CD (OR 12.03, 95% CI 1.60-101.56). In contrast, multivariate analysis for UC showed that the AA genotype was associated with severe UC (OR 2.02, 95% CI 1.34-3.03). CONCLUSIONS: CD patients with BB genotype of HSP70-2 polymorphism tend to experience a more severe clinical course and allele A is associated with more severe UC. HSP70-2 polymorphism may be used to predict CD and UC phenotypes, which can illuminate immunological differences in CD and UC.     

Sabin-Feldman dye test in ulcerative colitis and Crohn's disease

The prevalence of Toxoplasma infection among patients with inflammatory bowel disease was studied. The Sabin-Feldman dye test was performed on 35 patients with Crohn's disease, 44 patients with ulcerative colitis, and 140 control patients. A higher incidence of positive reactions was found in Crohn's disease patients over the age of 40 (P<0.05). All other factors showed no significant differences among the three groups of patients. These factors include age younger than 40 years, sex, duration of disease, extent of disease, and type of treatment. It is concluded that there is no correlation between inflammatory bowel diseases and toxoplasmosis. Toxoplasma infection, however, should be considered in patients with Crohn's disease who are over 40 years old, and who present with nonspecific signs of intercurrent infection.     

溃疡性结肠炎及克罗恩病的内镜活检病理特点分析

目的 总结溃疡性结肠炎（UC）及克罗恩病（CD）的病理形态学特点,为其诊断提供借鉴.方法 收集临床首次诊断并经病理科证实的UC患者180例、CD患者106例,资料包括年龄、性别及病变累及肠道的部位,并选用病理组织学标准对病变的黏膜结构改变、黏膜慢性炎症细胞浸润、黏膜急性炎症改变、黏膜上皮改变进行评价,比较两类患者间的差异.结果 和CD病例比较,UC病例出现黏膜结构紊乱的比例较高（P＜0.05）,出现局灶间断性炎症的比例较低（P＜0.05）,隐窝炎、隐窝脓肿及固有膜内中性粒细胞浸润发生率较高（P＜0.05）,表面上皮变扁或糜烂、黏液细胞减少的发生率较高.肉芽肿样小结、假幽门腺化生及裂隙状溃疡改变仅出现在CD病例.180例UC病例中90%（162例）病例病变部位局限于结肠.106例CD病例中28%（30例）病变部位局限于回盲部,56%（59例）病变累及到2个及以上不同部位.结论 肠镜活检病理诊断UC及CD是一个综合分析的过程.若病变局限于回盲部或胃肠道多部位累及,黏膜出现肉芽肿样小结、局灶间断性炎细胞浸润、假幽门腺化生等改变则倾向于CD诊断;若病变局限于结肠,黏膜出现弥漫一致性炎或明显的黏膜结构改变、黏膜上皮改变则倾向于UC诊断.     

Breath alkanes determination in ulcerative colitis and Crohn's disease

PURPOSE: By considering the pathophysiologic basis of inflammatory bowel diseases, a role for excessive lipid peroxidation caused by oxygen free radical compounds has been proposed repeatedly. However, to date only a few studies are available on this topic in human beings. This study was designed to assess breath alkanes in a group of patients with active inflammatory bowel disease by a technique that clearly distinguishes pentane from isoprene, to prevent overestimation of values as in previous studies. PATIENTS: Twenty patients with a diagnosis of active inflammatory bowel disease (10 with Crohn's disease and 10 with ulcerative colitis) were studied. Extension of the disease was similar between patient groups, and all were treated with equivalent doses of steroids and salicylates. METHODS: Breath alkanes determination was performed by a standard procedure involving a gas cromatography column able to separate pentane from isoprene. RESULTS: Overall, significant differences between patients with inflammatory bowel diseases and controls were found for ethane, propane, and pentane, but not for butane and isoprene. Isoprene was clearly distinguished from pentane, demonstrating that the significant elevation of pentane levels in patients with inflammatory bowel diseases is a real phenomenon and not an artifact caused by coelution with isoprene. CONCLUSIONS: An excess of lipid peroxidation is probably an important pathogenetic factor in inflammatory bowel diseases, and this may be assessed through a nonivasive method. Because this method previously also has been shown to be able to evaluate disease activity, it could be a useful tool for studying patients with inflammatory bowel diseases.