Hyperexpression of inducible costimulator and its contribution on lamina propria T cells in inflammatory bowel disease

BACKGROUND & AIMS: To investigate the role of inducible costimulator (ICOS), a new member of the CD28 family involved in regulation of T-cell activation and chronic intestinal inflammation, we assessed its expression and functional role in patients with inflammatory bowel disease (IBD). METHODS: Expression of ICOS, CD28, and cytotoxic T-lymphocyte antigen (CTLA) 4 on intestinal lamina propria mononuclear cells (LPMC) from patients with ulcerative colitis (UC), Crohn's disease (CD), and normal controls was determined using flow cytometry and immunohistochemistry. Expressions of the ICOS ligand, B7h, on lamina propria B cells, macrophages, and epithelial cells (EC) in the intestinal mucosa were also determined using flow cytometry. The functional costimulatory effect of ICOS on LPMC was assessed by the proliferative response and cytokine production. RESULTS: CD4(+) LPMC expressing ICOS was significantly increased in the inflamed mucosa of IBD patients but not in inflammatory or normal controls. B7h was also significantly up-regulated on B cells, macrophages, and EC in inflamed mucosa of IBD patients. Proliferative responses of anti-CD3/ICOS costimulation were significantly higher compared with those of anti-CD3 monoclonal antibody (mAb) alone. Anti-CD3/ICOS-stimulated-LPMC from UC secreted significantly increased amounts of interleukin (IL)-5 among the 3 groups. In contrast, anti-CD3/ICOS-stimulated-LPMC from CD secreted significantly increased amounts of interferon (IFN)-gamma in the presence of IL-12. CONCLUSIONS: Highly expressed ICOS in activated CD4(+) LPMC of IBD patients contributes to the dysregulated immune responses in IBD. Because ICOS hyperexpression was limited to inflammatory sites in IBD patients, ICOS would be a feasible therapeutic target for the treatment of IBD.     

Two-color immunofluorescence and flow cytometric analysis of lamina propria lymphocyte subsets in ulcerative colitis and Crohn's Disease

By using two-color immunofluorescence with fluorescein isothiocyanate (FITC) and phycoerythrin (PE)-labelled monoclonal antibodies and multiparameter flow cytometry, we investigated lamina propria lymphocyte subsets of patients with ulcerative colitis (UC) and Crohn's disease (CD). Leu-3/Leu-2 (CD4/CD8) ratio of lamina propria lymphocytes (LPL) of CD (mean±sd: 1.9±0.8,P<0.01) was significantly decreased compared with controls (3.3±1.1), because of an increased number of CD8+lymphocytes. The majority of lamina propria CD4+cells were CD4+, Leu-8-and CD4+, CD45R-both in controls and IBD tissue. Many lamina propria T lymphocytes were activated, expressing HLA-DR antigen not only in IBD but also in controls. NK cells defined by CD16 and CD 56 (3.0±1.4%,P<0.01) were significantly decreased in patients with UC compared with controls (6.5±3.0%). A low proportion of B cells in the intestinal mucosa expressed Leu-8 antigen and CD23 antigen. The proportion of activated B cells of LPL was high in IBD mucosa as well as normal mucosa. These findings suggest that local activation of B cells leads to the loss of the expression of Leu-8 antigen and CD23.     

Increased proliferation and apoptosis of colonic epithelial cells in dextran sulfate sodium-induced colitis in rats

We have evaluated morphologic alterations and epithelial cell apoptosis and proliferation of colonic mucosa in the acute and chronic phases of DSS-induced colitis. Colitis was induced in Sprague-Dawley rats by 7 days of 4% DSS oral administration followed by 7 days of tap water for one, two, and three cycles. Control rats receved tap water only. Morphological changes in colonic mucosa were evaluated and scored by light and scanning electron microscopy. Apoptosis was studied by TUNEL assay and cell proliferation by Ki-67 immunoreaction. The expression of both proapoptotic (Fas, FasL, Bax, p53) and antiapoptotic (Bcl2) cellular proteins was determined by immunohistochemistry. Morphologic assessment showed the most severe colonic epithelial lesions and inflammation in the distal colon with a trend to increasing severity from the first to the third DSS cycle. In DSS rats, the epithelial apoptotic index increased 20-fold after the first cycle and 120-fold after the second and third cycles compared with the controls; in the same way, the expression index of proapoptotic proteins (Fas, FasL, Bax, p53) dramatically increased. The proliferative index increased about 40 to 60-fold compared to controls, with no difference among the three DSS cycles. In conclusion, DSS-induced colitis in rats, which has many structural and ultrastructural features similar to those seen in human ulcerative colitis, is a suitable model for studying increased epithelial apoptosis and proliferation. Further studies employing this model will permitt two hypotheses to be tested. (1) Increased apoptosis may lead to a breakdown of the epithelial barrier function and facilitate the mucosal invasion of intraluminal microorganisms and/or antigens. (2) Abnormal and persistent epithelial hyperproliferation could be causally related to the development of colorectal cancers in the setting of chronic colonic inflammation.     

Sodium chloride exacerbates dextran sulfate sodiuminduced colitis by tuning proinflammatory and antiinflammatory lamina propria mononuclear cells through p38/MAPK pathway in mice

AIM To investigate the influence of high salt on dextran sulfate sodium(DSS)-induced colitis in mice and explore the underlying mechanisms of this effect.METHODS DSS and NaC l were used to establish the proinflammatory animal model. We evaluated the colitis severity. Flow cytometry was employed for detecting the frequencies of Th1, macrophages and Tregs in spleen, mesenteric lymph node and lamina propria. The important role of macrophages in the promotion of DSS-induced colitis by NaCl was evaluated by depleting macrophages with clodronate liposomes. Activated peritoneal macrophages and lamina propria mononuclear cells(LPMCs) were stimulated with NaCl, and proteins were detected by western blotting. Cytokines and inflammation genes were analyzed by enzyme-linked immunosorbent assay and RT-PCR, respectively.RESULTS The study findings indicate that NaC l up-regulates the frequencies of CD11b~+ macrophages and CD4~+IFN-γ~+IL-17~+ T cells in lamina propria in DSS-treated mice. CD3~+CD4~+CD25~+Foxp~3+ T cells, which can secrete high levels of IL-10 and TGF-β, increase through feedback in NaCl-and DSS-treated mice. Furthermore, clodronate liposomes pretreatment significantly alleviated DSSinduced colitis, indicating that macrophages play a vital role in NaCl proinflammatory activity. NaCl aggravates peritoneal macrophage inflammation by promoting the expressions of interleukin(IL)-1, IL-6 and mouse inducible nitric oxide synthase. Specifically, high NaCl concentrations promote p38 phosphorylation in lipopolysaccharide-and IFN-γ-activated LPMCs mediated by SGK1. CONCLUSION Proinflammatory macrophages may play an essential role in the onset and development of NaCl-promoted inflammation in DSS-induced colitis. The underlining mechanism involves up-regulation of the p38/MAPK axis.     

Infiltration of peroxidase-producing eosinophils into the lamina propria of patients with ulcerative colitis

Little information is available to explain the pathogenesis of ulcerative colitis (UC). In this study, we focused on eosinophils in the lamina propria of the mucosa of patients with UC in the active phase. Biopsy specimens were taken from 17 patients with UC in the active phase, 17 in the inactive phase, and 20 control patients, and submitted for histochemical staining for peroxidase and chloroacetate esterase for microscopic examination. Both peroxidase-producing and chloroacetate esterase-producing cells in the lamina propria increased markedly in the active phase (8.3 ± 3.1/0.01 mm² and 6.6 ± 2.7/0.01 mm², respectively), compared with values in the inactive phase (0.8 ± 0.6/0.01 mm² and 1.3 ± 0.6/0.01 mm²) or in the controls (1.3 ± 0.8/0.01 mm² and 1.3 ± 0.4/0.01 mm²). Triple staining for peroxidase, chloroacetate esterase, and nonspecific esterase in the specimens revealed that the peroxidase-producing cells constituted a different population from that of neutrophils, macrophages/monocytes, or basophils. A monoclonal antibody specific for eosinophil peroxidase stained almost all infiltrated peroxidase-producing cells. These results indicated that eosinophils with strong peroxidase activity had infiltrated the lamina propria in UC, suggesting an allergic background and the involvement of released peroxidase in the mucosal damage characteristic of UC. (Received Mar. 28, 1997; accepted July 25, 1997)     

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.     

Aberrant activation of nuclear factor of activated T cell 2 in lamina propria mononuclear cells in ulcerative colitis

AIM： To investigate the role of nuclear factor of activated T cell 2 （NFAT2）, the major NFAT protein in peripheral T cells, in sustained T cell activation and intractable inflammation in human ulcerative colitis （UC）. METHODS： We used two-dimensional gel-electrophoresis, immunohistochemistry, double immunohistochemical staining, and confocal microscopy to inspect the expression of NFAT2 in 107, 15, 48 and 5 cases of UC, Crohn＇s disease （CD）, non-specific colitis, and 5 healthy individuals, respectively. RESULTS： Up-regulation with profound nucleotranslocation/activation of NFAT2 of lamina propria mononuclear cells （LPMC） of colonic mucosa was found specifically in the affected colonic mucosa from patients with UC, as compared to CD or NC （P〈0.001, Kruskal- Wallis test）. Nucleo-translocation/activation of NFAT2 primarily occurred in CD8＋T, but was less prominent in CD4＋ T cells or CD20＋B cells. It was strongly associated with the disease activity, including endoscopic stage （τ= 0.2145, P=0.0281） and histologic grade （τ= 0.4167, P 〈 0,001）, CONCLUSION： We disclose for the first time the nucleo-translocation/activatin of NFAT2 in lamina propria mononuclear cells in ulcerative colitis. Activation of NFAT2 was specific for ulcerative colitis and highly associated with disease activity. Since activation of NFAT2 is implicated in an auto-regulatory positive feedback loop of sustained T-cell activation and NFAT proteins play key roles in the calcium/calcineurin signaling pathways, our results not only provide new insights into the mechanism for sustained intractable inflammation, but also suggest the calcium-calcineurin/NFAT pathway as a new therapeutic target for ulcerative colitis.     

氧化型低密度脂蛋白对可诱导共刺激分子在人外周血T细胞表达的影响

目的:探讨可诱导共刺激分子(ICOS)在人外周血T细胞的表达及氧化低密度脂蛋白(ox-LDL)的干预作用。方法:以人外周血T细胞为实验模型,通过间接免疫荧光法、RT-PCR和Western blot等方法,观察ox-LDL对人外周血T细胞表达ICOS的影响。结果:①ICOS表达于人外周血T细胞膜,荧光信号呈点状散在分布于细胞表面。RT-PCR检测显示,ICOS mRNA的扩增片段位于相当于Marker 368 bp的位置。Western blot检测显示,ICOS的分子量约为55 kD。②ox-LDL刺激组ICOS的吸光度(A)值高于空白对照组,提示ox-LDL能够明显增加人外周血T细胞中的ICOS mRNA和其蛋白的表达(P0.05)。结论:ICOS表达于人外周血T细胞表面,ox-LDL能够上调ICOSmRNA和其蛋白的表达,这可能是动脉粥样硬化的免疫学发病机制之一。     

Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis

Background Neutrophil elastase (NE) is a major secretory product from activated neutrophils and a major contributor to tissue destruction. However, little is known about the pathogenic contribution of NE to ulcerative colitis (UC). This study was designed to investigate the contribution of NE by measuring NE activity in plasma and colonic mucosal tissue from UC patients and a murine acute colitis model, and to elucidate the therapeutic effect of the NE-specific inhibitor ONO-5046. Methods The NE enzyme activities in plasma and colonic mucosal tissue from UC patients were directly measured using an enzyme–substrate reaction. Acute colitis was induced in mice by administration of 1.5% dextran sulfate sodium (DSS) for 5 days. DSS-induced colitis mice were then treated with ONO-5046 (50 mg/kg body weight) intraperitoneally twice a day. Results In UC patients, the NE enzyme activity was significantly elevated in both the plasma and colonic mucosal tissue compared with healthy controls. In DSS-induced colitis mice, the NE enzyme activity increased in parallel with the disease development. ONO-5046 showed therapeutic effects in DSS-treated mice by significantly reducing weight loss and histological score. ONO-5046 suppressed the NE enzyme activities in both plasma and culture supernatant of colonic mucosa from DSS-induced colitis mice. Conclusions ONO-5046, a specific NE inhibitor, prevented the development of DSS-induced colitis in mice. NE therefore represents a promising target for the treatment of UC patients.     

Effects of germinated barley foodstuff on dextran sulfate sodium-induced colitis in rats

Germinated barley foodstuff (GBF), derived from the aleurone and scutellum fractions of germinated barley, is rich in glutamine and low-lignified hemicellulose, and increases mucosal protein, RNA, and DNA content in the intestine when fed to normal rats. The aim of this study was to evaluate the effects of feeding GBF or germinated gramineous seeds on experimental ulcerative colitis. Sprague-Dawley rats that received 3% dextran sulfate sodium in their diets were used as an experimental colitis model. The effects of sulfasalazine, a drug used to treat inflammatory bowel disease, were compared with those of GBF. After rats had consumed diets containing GBF or various aleurone and scutellum fractions, mucosal damage; the content of mucosal protein, RNA, and DNA in the colo-rectum; and serum interleukin-8 and α₁-acid glycoprotein levels were assessed. GBF and germinated seeds more effectively prevented bloody diarrhea and mucosal damage in colitis compared with controls and rats receiving sulfasalazine, but non-germinated samples did not have a protective effect. GBF increased mucosal protein and RNA content in the colitis model. The consumption of GBF appears to prevent inflammation in a colitis model, and its effect seems to be related to the germination process. GBF and germinated seeds have the potential to serve as nutritional therapy for ulcerative colitis. (Received Mar. 17, 1997; accepted July 25, 1997)     

Racial differences in the prevalence of ulcerative colitis and Crohn's disease in Singapore

BACKGROUND: The aim of this study was to determine the prevalence rates of inflammatory bowel disease in the different races in Singapore. METHODS: The patients studied consisted of 58 people with an established diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) as determined by a combination of clinical, radiological, endoscopic and histological criteria. The patients were residents of a well-defined geographical area in the northern part of Singapore and had been referred to the single regional hospital. Epidemiological data including sex, age, ethnicity, family history and disease type and extent were collected from case records and patient interviews. RESULTS:There were 37 UC and 21 CD patients. Of the patients with UC, 67.5% were Chinese, 13.5% were Malay and 19% were Indian. The CD group consisted of 81% Chinese, 9.5% Malay and 9.5% Indian patients. The study population from which the patients were drawn was approximately 0.5 million in size. CONCLUSIONS: The overall prevalence of UC was 6 per 100,000 and of CD was 3.6 per 100,000 in Singapore. There were disproportionately more Indians suffering from UC, with a prevalence of 16.2 per 100,000 in comparison with six per 100,000 for Chinese and seven per 100 000 for Malays. The relative risk of UC in Indians is 2.9-fold greater than for the Chinese (CI= 1.25-6.7) which was statistically significant. This trend was not seen for CD.     

Compensatory response of colon tissue to dextran sulfate sodium-induced colitis

Depletion of goblet cells (the main mucin-producing cells in the colon) is one of the most reliable histological characteristics of ulcerative colitis, whereas a major symptom of this disease is bloody diarrhea containing a large amount of mucus. The discrepancy between these phenomena was investigated in a time-course study in rats with experimental colitis induced by treatment with oral dextran sulfate sodium (DSS) for 1, 3, or 5 days. Biochemical analysis showed a reduction in mucin content in the distal side of the colon that was proportional to the duration of DSS administration. In the proximal side of the colon, however, there was a significant increase in mucin content already on the first day of treatment with DSS. This increase in colonic mucin content continued for the 5 days of treatment. In the distal side, both sulfomucin and sialomucin decreased proportionally to the duration of DSS administration. In the proximal side, there was an increase in high iron diamine-Alcian blue-positive mucins, and confirming the proliferation of goblet cells. The proliferated glands were predominantly sialylated. Goblet cell depletion and an increase in mucin production occurred in different parts of the colon. This phenomenon may be a type of compensatory function of colon tissue in response to the localized decrease of mucin production in certain portions of the colon. (Received Sept. 7, 1998; accepted Nov. 27, 1998)     

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.     

Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin

The use of oral and intravenous cyclosporin represents a significant advance in the therapy of refractory inflammatory bowel diseases (IBD). However, oral administration of cyclosporin is fraught with improper delivery of cyclosporin to the colon for its topical action. Because of unpredictable metabolism by cytochrome P-450 IIIA, the targeted blood level for systemic effect is not reached at low doses. Furthermore, the doses that have been used for therapy of IBD have been shown to induce several adverse side effects. Thus, an alternate method of delivering cyclosporin to the colon is desirable. In this study, the effect of intracolonically administered cyclosporin was tested for its efficacy to heal mucosal erosions in dextran sulfate sodium (DSS)-induced colitis in mice. Both acute and chronic colitis was induced by feeding female Swiss-Webster mice with 5% DSS (30,000–40,000 mol wt) for five or seven days, respectively. Therapy was advocated prophylactically, prophylaxis plus therapy and therapeutically during the acute and chronic phase of the disease and therapeutically during the chronic phase of the disease. Intracolonic cyclosporin given prophylactically showed adverse effects by increasing the damage to the colonic mucosa. However, intracolonic cyclosporin given therapeutically in 2.5, 5, and 10 mg/kg after the induction of colitis resulted in dramatic responses in terms of reducing the disease activity and histologic scores, corroborated by complete histological resolution compared to oral cyclosporin given at identical doses. Intracolonic cyclosporin (5 mg/kg) was also very effective in reducing the chronic inflammation. The results of this study highlight the application of this animal model for therapeutic research. Furthermore, cyclosporin administered as an enema provides a new stratagem for the therapy of IBD because of its rapid onset of action at very low doses without the risk inherent in oral or systemic administration.     

Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model

BACKGROUND: As an important mechanism underlying the increased risk of colorectal carcinoma development in patients with long-standing ulcerative colitis, promotion as a result of the regenerative process has been proposed. In the present study, a dysplasia-carcinoma sequence in a novel repeated colitis model in mice is documented. METHODS: Repeated colitis was induced by nine administration cycles of 3% dextran sulfate sodium (DSS; molecular weight, 54 000): each administration cycle comprised 3% DSS for 7 days followed by distilled water for the subsequent 14 days, to give conditions similar to the clinically observed active and remission phases in humans. RESULTS: Multiple colorectal tumors (nine low- and four high-grade dysplasias and two carcinomas) developed in 25 mice. These neoplastic lesions consisted of tubular structures, presenting as various types of elevated, flat and depressed tumor, similar to those in ulcerative colitis patients. A time-course study with assessment of the severity of colitis and in vivo bromodeoxyuridine uptake during a single 3% DSS administration cycle revealed a high level of regenerative activity in the colitis-affected mucosal epithelia. CONCLUSION: Thus, with the present repeated colitis model, regeneration and neoplastic lesions were apparent, the biological features of which provide evidence of a colorectal dysplasia-invasive carcinoma sequence in ulcerative colitis.     

CC-10004 but not thalidomide or lenalidomide inhibits lamina propria mononuclear cell TNF-α and MMP-3 production in patients with inflammatory bowel disease

BackgroundThalidomide, one of whose activities is to inhibit Tumour Necrosis Factor (TNF)-α production, has been reported to be an effective treatment for refractory inflammatory bowel disease (IBD). TNF-α driven production of matrix metalloproteinase (MMP)-3 by gut lamina propria mononuclear cells (LPMCs) is a major pathway of tissue injury in IBD; however the effect of thalidomide and newer more potent immunomodulatory derivatives on this pathway has not been studied.AimTo investigate the effect of thalidomide, CC-4047 (pomalidomide), CC-5013 (lenalidomide), and CC-10004 (apremilast) on gut LPMC TNFα and MMP-3 production in patients with IBD.MethodsGut LPMCs and myofibroblasts were isolated from patients with IBD, and cultured with thalidomide, CC-4047, CC-5013, and CC-10004. MMP-3 and TIMP-1 levels were determined by western blotting and real-time PCR, and TNF-α levels by ELISA.ResultsCC-10004 significantly reduced both TNF-α production and MMP-3 production by cultured LPMCs. Thalidomide and CC-4047 and CC-5013 had no significant effect on the production of TNF-α or MMP-3 by LPMCs.ConclusionThese results provides a mechanistic rationale for both the failure of lenalidomide (CC-5013) in a recent randomised controlled trial in Crohn's disease, and for the evaluation of CC-10004 as a novel oral therapy in the treatment of CD and UC.     

葡聚糖硫酸钠诱导小鼠实验性结肠炎的临床和组织病理学特征研究

目的研究葡聚糖硫酸钠(DSS)诱导小鼠实验性结肠炎的临床和病理特征,以便于指导选择合适的溃疡性结肠炎(ulcerative colitis,UC)小鼠模型。方法予3%DSS溶液喂饲野生型C57BL/6成年小鼠诱导急性结肠炎模型,分别于第0天、第3天、第5天、第7天和第10天麻醉处死小鼠,取结肠观察不同时期结肠病理学特征,造模过程中连续观察并记录小鼠体质量、大便和死亡情况。结果小鼠造模第3天开始出现粪便潜血,第5天开始出现血便,第10天开始出现死亡小鼠,死亡率为30%。DSS诱导小鼠急性结肠炎模型疾病活动指数第3天后与饮用纯净水的小鼠比较明显增高(P0.05)。小鼠结肠炎造模第3天黏膜上皮细胞开始逐渐丧失,第7~10天最为严重;隐窝结构的紊乱从第3天开始发生,第7天出现固有层塌陷;炎性细胞浸润从第3天开始数量逐渐增加,第10天最为严重。DSS诱导小鼠急性结肠炎模型结肠组织病理评分第5天后与饮用纯净水的小鼠比较明显增高(P0.05)。结论 3%DSS诱导野生型C57BL/6成年小鼠急性结肠炎模型可用于UC的实验研究,第3天出现明显的炎症表现,第7天模型较理想,小鼠死亡少。     

Effects of appendectomy and oral tolerance on dextran sulfate sodium colitis

To evaluate the concomitant effects of appendectomy and oral tolerance on colitis.METHODS:Delayed-type hypersensitivity (DTH) was investigated at a 7-d interval after ovalbumin (OVA) administration and immunization under normal and colitis conditions in appendectomized or sham-operated mice.Pathological scores for the colon were graded after ingestion of colon-extracted protein (CEP) and induction of dextran sulfate sodium (DSS) colitis in appendectomized or sham-operated mice.Thereafter,Th1 and Th2 in Peye...     

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.