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Cytomegalovirus colitis complicating ulcerative colitis in the steroid-naive patient.

We report a case of cytomegalovirus (CMV) presenting as acute refractory colitis in a patient with a pre-existing 14-month history of ulcerative colitis (UC) who had never previously been treated with corticosteroids or immunosuppressants. A review of existing literature and previous cases of patients with coincident CMV and UC are examined, stratifying these cases based upon absence or presence of corticosteroid use. To date, only five previous case reports of CMV colitis in patients naive to corticosteroids have been described, and only one previous case has had UC diagnosed over 4 wk before the development of CMV colitis. We further discuss the relationship between these two diseases as well as the diagnosis, treatment, patient characteristics, and outcome of CMV infection of the colon in patients with underlying UC. We discuss the need to consider the diagnosis of CMV colitis in patients with refractory UC who are not receiving corticosteroid treatment as well as those who are refractory and are being treated with immunosuppressants and/or corticosteroids.

Acute Disease↗

[Immunopathology of ulcerative colitis and granulomatous colitis (author's transl)].

There is no convincing evidence as yet for a key role of immunological processes in the pathogenesis of unspecific colitis. However clinical findings as well as immunological data do support the hypothesis that immune reactions are involved primarily or secondarily in the pathogenesis and the clinical course of ulcerative colitis and granulomatous colitis. In such patients a specific adaptation of humoral and cell-bound immune reactions against antigenic material from the colon and other tissues has been found in peripheral blood, lymphatic tissue and bowel wall. In this context it seems to be especially noteworthy, that lymphocytes taken from patients with colitis lead to disintegration of colon epithelial cells in vitro. This cytotoxic effect of the lymphocytes is lost after colectomy or remission of the disease. Ulcerative and granulomatous colitis do have many clinical and immunological peculiarities in common. This makes one think, that possibly the same noxious factors induce differential local reactions because of different hereditary disposition.

Antigen-Antibody Complex↗

Comparison of fecal granulocyte excretion in ulcerative colitis and Crohn's colitis.

Impaired granulocyte migration has been suggested to be present in Crohn's disease on the basis of in vitro granulocyte function tests and in vivo skin window studies. This idea is supported by the impression histologically that the acute inflammatory infiltrate in diseased bowel is less in Crohn's disease than ulcerative colitis. We have developed a method of quantitating the acute inflammatory infiltrate in inflamed bowel by measuring fecal indium-111 granulocyte excretion and have compared this assessment in patients with ulcerative colitis and Crohn's colitis matched for disease activity. For equivalent disease groups in ulcerative colitis and Crohn's colitis, there was no significant difference between fecal granulocyte excretion. These findings provide no support for the contention that there is a reduced granulocyte infiltration in Crohn's disease.

Colitis, Ulcerative↗

Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human: a study of histopathology, B-catenin and p53 expression and the role of inflammation.

Animal models of colitis, which develop dysplasia and cancer similar to human ulcerative colitis are needed to further investigate the dysplasia cancer sequence. This study describes the expression of B-catenin and p53 along with the histopathology and inflammation scores as they relate to dysplasia and cancer in the dextran sulfate sodium (DSS) colitis model. Swiss Webster mice were fed with 5% DSS as follows: group A, four cycles of DSS, 84 days total (1 cycle = 7 days DSS + 14 days H(2)O); group B, four cycles DSS followed by 120 days H(2)O, 204 days total; group C, 7 days DSS followed by 180 days H(2)O, 187 days total; group D, 7 days DSS followed by 90 days H(2)O, 97 days total. The incidences of dysplasia and/or cancer were 15.8, 37.5, 18.1 and 0% in groups A-D, respectively. Dysplasia and/or cancer occurred as flat lesions or as dysplasia-associated lesion or mass (DALM) as observed in the human. Thirty-three percent of cancers had associated dysplasia. Within group A, inflammation scores were significantly higher in animals with dysplasia and/or cancer compared with those without dysplasia and/or cancer (P < 0. 05-P < 0.0001). Inflammation scores were significantly higher in animals with cancers versus those with dysplasia (P < 0.015) and in flat dysplasia and/or cancer versus DALM (P < 0.0042). B-catenin showed translocation from the cell membrane to the cytoplasm and/or nucleus in 100% of DALM and 5.8% of flat dysplasia and/or cancer. A total of 94.2% of flat dysplasia and/or cancer had exclusive cell membrane expression compared with 0% DALM (P < 0.0001). Only 7.4% of dysplasia and/or cancer showed nuclear expression of p53. In colitis-associated dysplasia and/or cancer in the DSS model: (i) histology resembles that in the human; (ii) inflammation plays a significant role in the dysplasia cancer sequence and whether dysplasia and/or cancer grows as a flat lesion or a DALM; (iii) the early molecular pathways are different for flat dysplasia and/or cancer versus DALM, with nuclear/cytoplasmic translocation of B-catenin as an early event in DALM but not flat dysplasia and/or cancer; and (iv) p53 has little or no role in dysplasia and/or cancer. This well characterized model provides an excellent vehicle for studying the roles of inflammation, the molecular events and the role of chemopreventive agents in colitis-associated neoplasia.

Animals↗

Can ischemic colitis be differentiated from C difficile colitis in biopsy specimens?

Pseudomembranous colitis is often caused by Clostridium difficile; however, it may also be due to ischemia. To determine if any histologic features could be used to differentiate C difficile from ischemia, 49 biopsies of pseudomembranous colitis (25 from patients with C difficile colitis and 24 from patients with ischemic colitis) were coded, randomized, and evaluated for the presence of numerous variables, including the amount and distribution of mucosal necrosis, lamina propria hyalinization, and atrophic "micro-crypts." Hyalinization of the lamina propria was seen in 19 cases of ischemia but not in C difficile colitis (p < 0.0001). Atrophic-appearing micro-crypts were seen in 18 ischemic cases and 6 C difficile cases (p < 0.0006). Lamina propria hemorrhage, full-thickness mucosal necrosis, and a diffuse microscopic distribution of pseudomembranes were significantly more common in ischemia than C difficile. Endoscopic examination identified pseudomembranes significantly more often with C difficile than ischemia, while the endoscopic appearance of masses or polyps was seen exclusively in cases of ischemia. The presence of a hyalinized lamina propria appeared to be a specific and sensitive marker for ischemia in colon biopsies with pseudomembranes. The presence of atrophic micro-crypts, lamina propria hemorrhage, full-thickness mucosal necrosis, diffuse involvement of all the surface of all biopsies by pseudomembranes, and the endoscopic impression of a localized process, polyp, or mass were also markers of ischemia, while the endoscopic identification of diffuse pseudomembranes favored the diagnosis of C difficile.

Adult↗

Collagenous colitis and lymphocytic colitis.

The most recently recognized and least understood forms of inflammatory bowel disease are two types of idiopathic microscopic colitis-collagenous colitis and lymphocytic colitis. These disorders share many clinical and histologic features, but they have a few notable differences. Whether these are two distinct entities or different presentations of the same disease remains controversial. Bismuth subsalicylate is effective in some patients and treatment is symptomatic and empirical in others. Unlike ulcerative colitis and Crohn's disease, these forms of inflammatory bowel disease rarely require surgery. Ileostomy with or without colectomy is curative for the rare patient with severe symptoms that are refractory to medical measures. Collagenous and lymphocytic colitis are not associated with an increased risk of malignancy.

Biopsy, Needle↗

Outcome of restorative proctocolectomy with ileal reservoir for ulcerative colitis: comparison of distal colitis with more proximal disease.

BACKGROUND: An increasing number of patients with severe or refractory ulcerative colitis involving only the rectum and sigmoid colon are being offered restorative proctocolectomy with ileal reservoir but very few data are available concerning the outcome for these patients. AIM: This study was designed to compare the outcome of ileal pouch procedures for distal ulcerative colitis with procedures performed for more extensive disease. PATIENTS: A consecutive series of 177 patients undergoing restorative proctocolectomy for ulcerative colitis between January 1984 and December 1994. METHODS: Data were collected prospectively in a dedicated ileal pouch database and included demographic details, indication for surgery, surgical procedures performed, early (< 30 days) and late morbidity, functional outcome, and histopathology. RESULTS: There was no mortality in the series. The incidence and range of early morbidity (< 30 days) and the functional outcome (daytime stool frequency, nocturnal frequency, and the incidence of incontinence) were similar for all groups. Log rank analysis of Kaplan-Meier estimates showed no significant difference between groups in the likelihood of developing pouchitis (p > 0.2). CONCLUSIONS: Patients undergoing restorative proctocolectomy for distal colitis experience a similar outcome to patients with more extensive disease. These data refute the hypothesis that pouchitis is more common in patients with total colitis.

Adolescent↗

[Microscopic colitis and collagenous colitis. An entity not yet reported in Chile].

Collagenous and microscopic colitis have been described as causes for abundant watery diarrhea with a normal radiologic and endoscopic aspect of the colonic mucosa. Microscopic colitis is characterized by diffuse intraepithelial lymphocytic infiltration and collagenous colitis by thickening of subepithelial collagen layer greater than 15 microns with or without inflammatory changes of the mucosa. Here are reported 5 patients with microscopic colitis and 4 with collagenous colitis. The mean age was 52 years (range 40 to 68) with an equal sex distribution. Diarrhea was of longstanding duration without weight loss, anemia or hypoalbuminemia. Occasionally the volume of diarrhea was over 1 L a day. One patient had steatorrhea that proved resistant to a gluten free diet. Endoscopic and radiologic findings were normal in every patient and the diagnosis was based on typical histology. Azulfidine therapy was successful in 7 patients and prednisone in another. Colonic biopsy should be performed in every patient with chronic diarrhea.

Adult↗

Colitis carcinoma in ulcerative colitis.

During the period from 1963 till 1981 altogether 342 patients suffering from ulcerative colitis were treated. In their material authors found 6 patients (1.7%) who achieved cancer of the colon beginning 7, 9, 14, 18, 18 und 21 years after the onset of ulcerative colitis symptoms. According to the clinical data their ulcerative colitis could be considered to belong to the severe or the moderate type. From the anatomical point of view the extension of the process exceeded the sigmoid colon in all but one. Respecting the clinical course of the disease, malignant transformation took place in 3 patients of the relapsing-remitting type, in 2 instances the clinical course could not be classified, the sixth case proved to the chronic continuous type. Colonic tissue was gained and diagnosis stated with traditional methods within 4 instances, while in 2 it was gained from tissue specimens passing through the stool. In 3 cases the tumour was multiple. From the morphological point of view the features had a plaque form in 2 cases, a polypous nature in other 2 cases, while among each one patient a fibrous stricture and ordinary colorectal cancer occurred. The tumour was identified as well differentiated and poorly differentiated adenocarcinoma in identically 3 instances. All the patients underwent an operation, only one of them is still alive. In sake of detecting colitis carcinoma earlier, they suggest yearly endoscopic and biopsy survey of ulcerative colitis patients.

Adult↗

The association of the amoebic colitis and chronic ulcerative colitis.

Three patients with idiopathic ulcerative colitis and infection of Entamoeba histolytica were reviewed. They represented three different relationships between the two conditions, vis asymptomatic carrier, coexisting infection and superinfection causing exacerbation of colitis. A two-way relationship between amoebic colitis and ulcerative colitis has been discussed and the possible mechanisms in the literature have been reviewed. In patients with a short history of diarrhoea and in tropical countries where amoebic infection is endemic, it is important to role out amoebic colitis before commencing steroid therapy for inflammatory disease.

Adrenal Cortex Hormones↗

[Collagen colitis and lymphocytic (microscopic) colitis: different or common origin?].

Collagenous and lymphocytic colitis are two chronic inflammatory colonic diseases characterized by chronic watery diarrhea. They can only be diagnosed by histological examination of colonic biopsies. The pathogenesis is unknown, but may be of an inflammatory possibly autoimmune nature. Others hypothesize that a bacterial toxin or another noxious luminal factor is responsible for the development of the microscopic colitis syndrome. Some studies suggest that NSAIDs may be an etiologic factor in collagenous colitis in a subgroup of patients with this disease. These disorders may be different entities, although some data support the possibility that they are only different manifestations of the same disease. Therapy with 5-aminosalicylate and in severe cases corticosteroids, is successful in most patients. The course of these chronic diseases is commonly benign and is characterized by periods of spontaneous remissions and relapses, but clinical and histopathological resolutions are occasionally seen. On the basis of our own two cases and the literature, these two diseases will be discussed. These patients were admitted to our hospital within a month of each other due to therapy-refractive chronic watery diarrhea. A 70-year-old woman had been suffering from diarrhea for more than ten years. The histological examination produced a diagnosis of collagenous colitis. Lymphocytic colitis was diagnosed from a histological examination in a 30-year-old man who had been suffering from diarrhea for six months. Both received a therapy of mesalazine and the symptoms disappeared within three weeks.

Adult↗

Histopathology differentiates acute self-limited colitis from ulcerative colitis.

Acute self-limited colitis (ASLC) must be distinguished from chronic ulcerative colitis (CUC) for the proper early management of patients with the acute onset of bloody diarrhea. This study was undertaken to determine if any clinical, endoscopic, microbiologic, or histologic parameters can be used to make this distinction reliably and quickly. Forty-eight patients with ASLC, 36 patients with chronic ulcerative colitis during their first attack [CUC(F)], and 84 patients with recurrent flares of chronic ulcerative colitis [CUC(R)] were studied prospectively. The presence of fever (temperature greater than 100 degrees F), abdominal pain, or the time from onset of bloody diarrhea to presentation were not discriminatory. Overall clinical and endoscopic severity were identical among the three groups. Microbiologic studies identified an infectious agent in only 42% of patients with ASLC. Histopathologic features always distinguished patients with CUC from those with ASLC. No case of ASLC was misdiagnosed histologically as CUC or vice versa. Plasmacytosis in the lamina propria extending to the mucosal base and mucosal distortion were present in all cases of CUC(F) and CUC(R), but were absent in all cases of ASLC. The finding of focal cryptitis during the resolving phase of ASLC could be confused with similar lesions in biopsy specimens from patients with Crohn's disease and mandates clinical follow-up. Histopathology is thus the only reliable diagnostic tool for the rapid differentiation of ASLC from CUC. However, biopsy specimens are only diagnostic when obtained during the acute phase of illness; that is, usually within the first 4 days from the onset of symptoms.

Acute Disease↗

Incidence of ulcerative colitis and indeterminate colitis in four counties of southeastern Norway, 1990-93. A prospective population-based study. The Inflammatory Bowel South-Eastern Norway (IBSEN) Study Group of Gastroenterologists.

BACKGROUND: The incidence of ulcerative colitis (UC) has been difficult to interpret because prospective studies have only been performed during the past 3 decades. Geographic variations may therefore be due to differences in study design. METHOD: From 1 January 1990 to 31 December 1993 all new cases of UC in four counties in southeastern Norway were prospectively registered. Cases diagnosed as indeterminate colitis (IND) when endoscopy and histopathology were inconclusive or diverged with regard to diagnosis of UC or Crohn's disease (CD) were also included in the study. RESULTS: A total of 525 cases of UC and 93 cases of IND yielded an mean annual incidence of 13.6/10(5) and 2.4/10(5), respectively. There were differences in incidence between counties, and a peak of 21.5/10(5) in the annual incidence was found for the age group 25 to 34 years in UC. The distribution was about equal for each of the groups proctitis and left-sided and extensive colitis. The time interval from onset of symptoms to diagnosis was 4 months. CONCLUSION: In this study one of the highest incidences of UC in the world has been found. The classification 'indeterminate colitis' seems reasonable to use in some of the cases to prevent misclassification at the initial stage of diagnosis.

Adolescent↗

Evaluation of antigenicity of germinated barley foodstuff for the treatment of ulcerative colitis in a chronic murine colitis model.

Germinated barley foodstuff (GBF) contains insoluble protein and dietary fiber, and has the potential to attenuate diarrhea and colonic mucosal damage in colitis. Since GBF contains a poorly digested protein fraction, this protein may be transferred to and absorbed in the colon. It may therefore be possible to detect the GBF antigen in colitis patients with dysfunctional colonic mucosal barrier defense. In this study, the antigenic potency of GBF was examined in vivo and in vitro. Using the AOAC method, the indigestible fraction of GBF (dietary fiber) was obtained, and the poorly digested protein fraction in GBF was determined. Using Sprague Dawley rats with chronic colitis induced by dextran sulfate sodium (DSS, 2.5% in diet), a GBF and control diet were administered, and total and specific serum immunoglobulin E (IgE) against intestinal contents and the soluble GBF protein were determined. In addition, reactivity between serum and intestinal content were examined by gel electrophoresis mobility shift assay (EMSA). GBF showed relatively low protein digestibility (47%) because of its low solubility in neutral pH. Total serum IgE in both dietary groups was not significantly different, and specific IgE antibodies against intestinal contents and the soluble GBF protein were not significantly different. In addition, supershifts were not observed in either dietary group by EMSA. The possible antigenicity of oral GBF was considered to be low in this colitis model.

Animals↗

[Ulcerative colitis and Crohn's colitis. Medical or surgical treatment].

Colectomy with ileorectal anastomosis was performed in 47 patients affected by ulcerative colitis and Crohn's colitis. These two forms of "aggressive idiopathic colitis" present the same problems of therapy from both the pharmacological and the surgical point of view. The topical employment of antiphlogistic steroids and sulphasalazine by daily retention enemas caused a regression of proctitis and allowed a safe ileorectal anastomosis. After the surgical procedure a protective treatment of the rectal mucosa was prosecuted with minimal dosages of the same antiphlogistic drug by daily minienemas. Betametasone in aqueous solution have proved, among the antiphlogistic steroids, to be very suitable for a topical action without side-effects in the long time. The association of topical treatment and surgery is particularly indicated for those patients who cannot recover with medical therapy alone, as it enables them to recover and return to a normal life. The opportunity for colectomy is so much greater as it is possible, as a rule, to spare the rectum and protect the ileorectal anastomosis by means of a topical therapy without limitations of time. Therefore the surgical indication should not be delayed whenever the medical treatment by systemic administration of steroids, sulphasalazine and immunosuppressors is unable to prevent the evolution of aggressive idiopathic colitis to a chronic and seriously invalidating disease.

Anti-Inflammatory Agents↗

Lack of effectiveness of the platelet-activating factor antagonist SR27417A in patients with active ulcerative colitis: a randomized controlled trial. The Platelet Activating Factor Antagonist Study Group in Ulcerative Colitis.

BACKGROUND & AIMS: Platelet-activating factor (PAF) is increased during relapse of ulcerative colitis. In animal models of experimental colitis, specific inhibition of PAF has reduced inflammation. The aim of this study was to evaluate the efficacy and safety of the PAF antagonist SR27417A in moderately active UC. METHODS: A double-blind multicenter trial was conducted during a 28-day period in hospital outpatients with an exacerbation of ulcerative colitis. Patients were randomized to receive 10 mg/day SR27417A or placebo, and both groups were also given 2.4 g mesalazine. Patient classification at the end of the treatment period was based on sigmoidoscopy and clinical scores. RESULTS: One hundred fifty-one subjects entered the study (75 placebo and 76 SR27417A). The remission rate between placebo- and SR27417A-treated patients at 28 days was not significantly different (29.0% and 35.6% respectively; P = 0.44). Similarly, 49.2% treated with SR27417A had a definite or possible improvement of their symptom score compared with 48.3% of those treated with placebo (P = 0.43). Four subjects in the placebo group and 5 subjects in the SR27417A group discontinued the drug treatment because of adverse events. No significant adverse events were thought to be caused by SR27417A. CONCLUSIONS: Although the specific PAF antagonist SR27417A is safe in humans, there is no evidence of efficacy in the treatment of acute ulcerative colitis.

Adult↗

Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU).

OBJECTIVE: Butyrate enemas may be effective in the treatment of active distal ulcerative colitis. Because colonic fermentation of Plantago ovata seeds (dietary fiber) yields butyrate, the aim of this study was to assess the efficacy and safety of Plantago ovata seeds as compared with mesalamine in maintaining remission in ulcerative colitis. METHODS: An open label, parallel-group, multicenter, randomized clinical trial was conducted. A total of 105 patients with ulcerative colitis who were in remission were randomized into groups to receive oral treatment with Plantago ovata seeds (10 g b.i.d.), mesalamine (500 mg t.i.d.), and Plantago ovata seeds plus mesalamine at the same doses. The primary efficacy outcome was maintenance of remission for 12 months. RESULTS: Of the 105 patients, 102 were included in the final analysis. After 12 months, treatment failure rate was 40% (14 of 35 patients) in the Plantago ovata seed group, 35% (13 of 37) in the mesalamine group, and 30% (nine of 30) in the Plantago ovata plus mesalamine group. Probability of continued remission was similar (Mantel-Cox test, p = 0.67; intent-to-treat analysis). Therapy effects remained unchanged after adjusting for potential confounding variables with a Cox's proportional hazards survival analysis. Three patients were withdrawn because of the development of adverse events consisting of constipation and/or flatulence (Plantago ovata seed group = 1 and Plantago ovata seed plus mesalamine group = 2). A significant increase in fecal butyrate levels (p = 0.018) was observed after Plantago ovata seed administration. CONCLUSIONS: Plantago ovata seeds (dietary fiber) might be as effective as mesalamine to maintain remission in ulcerative colitis.

Adult↗

A method for reproducing fatal idiopathic colitis (colitis X) in ponies and isolation of a clostridium as a possible agent.

Severe colitis was induced in two ponies after oral pretreatment with clindamycin and lincomycin, followed by intestinal content from two horses which had died from naturally-occurring idiopathic colitis. Two ponies treated with antibiotic alone, and two ponies treated with intestinal content alone, were unaffected. In a further study, three ponies treated on separate occasions with lincomycin, administered orally, died or were destroyed 67 to 72 h after initial treatment. No established salmonella, yersinia or campylobacter pathogens were isolated from these ponies, but a clostridium closely resembling Clostridium cadaveris was isolated as the predominant clostridium from them all and from the colonic content of one of six horses which died from naturally-occurring idiopathic colitis. It was not isolated from six horses with non-fatal diarrhoea. This clostridium is a candidate as an agent of some cases of fatal colitis in horses.

Animals↗