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[Microscopic colitis--more common cause of diarrhea than believed. Biopsies are the only way to diagnosis, drug treatment is effective].

Microscopic colitis, encompassing collagenous and lymphocytic colitis, is a fairly common cause of chronic watery diarrhoea, especially in elderly women. In recent epidemiological studies the annual incidence of each disorder was 4-6/100.000 inhabitants. The aetiology is unknown. The main clinical symptoms are watery diarrhoea, weight loss and abdominal pain. Laboratory analyses are nondiagnostic, and the diagnoses rely on histopathological examination of colonic mucosal biopsies. There is an association to autoimmune diseases such as thyroid disorders, diabetes mellitus, celiac disease and arthritis. Budesonide is the best-documented treatment of collagenous colitis. It is superior to placebo in short-term therapy, but the long-term efficacy is not well studied. The evidence for other therapeutic alternatives such as loperamide, cholestyramine, bismuth subsalicylate, or 5-aminosalicylates is weak. In unresponsive severe disease azathioprine or methotrexate may be tried. There are at present no controlled data on the treatment of lymphocytic colitis. The long-term prognosis of microscopic colitis is good, serious complications are rare and there is no increased mortality.

Age Factors↗

Clinical evolution in an outpatient series with indeterminate colitis.

PURPOSE: Diagnosis of indeterminate colitis, which is mainly based on histologic criteria, could represent either an interlocutory or a definite classification within inflammatory bowel diseases. A later evaluation could allow elimination of cases with transient attacks of colitis and the eventual change of diagnosis to that of ulcerative colitis (UC) or Crohn's disease of the colon in some other patients. METHODS: A clinical follow-up study for a mean of 64 months was performed in 37 patients with inflammatory bowel disease with an initial diagnosis of indeterminate colitis. RESULTS: At the end of the follow-up period, 21 patients complained of persistent symptoms, and in 13 of these patients, endoscopic and histologic evolution of colitis was controlled. In four patients with initially a normal endoscopy, the pattern of normality was confirmed also on a histologic basis at the end of the follow-up. In seven of the remaining nine patients with an initial UC-like endoscopic picture, the UC diagnosis was made eventually also on a histologic basis. CONCLUSIONS: A closer monitoring, as with UC patients, could be recommended only in moderate patients with indeterminate colitis, with an initial UC-like endoscopic picture.

Adolescent↗

Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis.

BACKGROUND: We explored the potential of early decompressive colonoscopy with intracolonic vancomycin administration as an adjunctive therapy for severe pseudomembranous Clostridium difficile colitis with ileus and toxic megacolon. METHODS: We reviewed the symptoms, signs, laboratory tests, radiographic findings, and outcomes from the medical records of seven patients who experienced eight episodes of severe pseudomembranous colitis with ileus and toxic megacolon. All seven patients underwent decompressive colonoscopy with intracolonic perfusion of vancomycin. RESULTS: Fever, abdominal pain, diarrhea, abdominal distention, and tenderness were present in all patients. Five of seven patients were comatose, obtunded, or confused, and six of the seven required ventilatory support. The white blood cell count was greater than 16,000 in seven cases (six patients). Colonoscopy showed left-side pseudomembranous colitis in one patient, right-side colitis in one patient, and diffuse pseudomembranous pancolitis in five patients. Two patients were discharged with improvement. Five patients had numerous medical problems leading to their death. Complete resolution of pseudomembranous colitis occurred in four patients. One patient had a partial response, and two patients failed therapy. CONCLUSION: Colonoscopic decompression and intracolonic vancomycin administration in the management of severe, acute, pseudomembranous colitis associated with ileus and toxic megacolon is feasible, safe, and effective in approximately 57% to 71% of cases.

Aged↗

Pseudomembranous colitis: a lethal complication of Hirschsprung's disease unrelated to antibiotic usage.

Seventy-two new cases of Hirschsprung's disease were seen between 1980 and 1985. Twenty-six patients (36%) developed the clinical features of enterocolitis and, of nine patients who died, colitis was the immediate cause of death in six. Histologic material was available from 20 patients with colitis; this showed nonspecific inflammation typical of Hirschsprung's colitis in 13 cases but seven had pseudomembranous colitis (PMC). Five of the patients with PMC had not recently been exposed to antibiotics. PMC was responsible for three of the six deaths from colitis. All patients with Hirschsprung's disease who develop signs of colitis should have stool testing for Clostridium difficile toxin and should be treated with an antibiotic active against Clostridium difficile.

Bacterial Proteins↗

Changes in mucosal fatty acid profile in inflammatorybowel disease and in experimental colitis: a common response to bowel inflammation.

BACKGROUND AND AIMS: Plasma polyunsaturated fatty acid profile in patients with inflammatory bowel disease is abnormal. We aimed to assess the mucosal fatty acid pattern in patients with ulcerative colitis and Crohn's disease, and in rats with trinitrobenzene-sulfonic acid (TNB) induced colitis. METHODS: Fatty acids were measured in colonic mucosa of patients with ulcerative colitis (n = 30), Crohn's disease (n = 21), and healthy controls (n = 13). Likewise, they were assessed in the colonic mucosa of rats with TNB- and sham-colitis. RESULTS: There was an increase of the end-products (C22:5n3, C22:6n3, C20:4n6, C22:5n6) and a decrease of the precursors (C18:3n3, C18:2n6) of both n3 and n6 polyunsaturated fatty acids in the mucosa of active ulcerative colitis and TNB-colitis. Also, high values of saturated (C16:0, C18:0) and low values of monounsaturated fatty acids (C18:1n9) were observed. Furthermore, the mucosa of active Crohn's disease showed substantial changes in saturated, monounsaturated and essential fatty acids, but not in polyunsaturated fatty acids. Mucosa of patients with inactive disease showed intermediate fatty acid values between the mucosa of active patients and healthy controls. CONCLUSIONS: Colonic inflammation causes a characteristic modification of the mucosal fatty acid profile which appears to be common to different aetiologies and seems to be related to the degree of inflammation.

Journal Article↗

Timing of surgery for fulminating pseudomembranous colitis.

BACKGROUND: With increasing antibiotic usage Clostridium difficile colitis is becoming more common. Surgery for fulminating C. difficile colitis, however, is rare because of the effectiveness of specific anticlostridial chemotherapy. Surgical outcome in five patients with fulminating C. difficile colitis involved in a recent outbreak of this disease is reported. METHODS: Five of 138 patients developed fulminating C. difficile colitis unresponsive to medical therapy. All patients had antibiotics in the preceding period. Indications for operation in those who underwent surgery were systemic toxicity with a pyrexia, marked leukocytosis and abdominal signs leading to progressive organ failure, despite appropriate anticlostridial antibiotic therapy. RESULTS: At operation all patients had a markedly oedematous colon with normal serosa but with acute mucosal colitis. All underwent subtotal abdominal colectomy and ileostomy. Progressive organ failure persisted in four, leading to death, giving a mortality rate of four in five in the operated group in comparison with 3.8 per cent (five of 133 patients) in those treated medically. CONCLUSIONS: These results indicate that this increasingly common disease frequently leads to a fatal outcome in patients requiring surgery and implies that earlier surgical consultation may be necessary to improve survival in patients with fulminating C. difficile colitis unresponsive to antibiotic therapy.

Abdomen, Acute↗

Involvement of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the pathogenesis of granulomatous colitis in rats.

Although increased expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) has been demonstrated in inflammatory sites of various diseases, its role in colitis remains unknown. In this study, we examined whether MAdCAM-1 is involved in the pathogenesis of granulomatous colitis induced by peptidoglycan-polysaccharide (PG-PS). Experimental colitis was induced by intramural injection of PG-PS to rat colon. After 3 weeks the colon was removed and the mucosal inflammation was assessed. The area of MAdCAM-1-positive venules and the subsets of infiltrating cells were determined in colonic mucosa by immunohistochemistry. In another experiment, monoclonal antibody against MAdCAM-1 was administered intraperitoneally to examine its attenuating effect on colitis. The intramural injection of PG-PS induced significant colonic inflammation with granuloma formation. The submucosa was drastically thickened with the infiltration of CD4 positive lymphocytes and ED-1 positive macrophages. Intense MAdCAM-1 expression was observed on endothelium of the submucosal venules in inflamed mucosa. Administration of anti-MAdCAM-1 antibody significantly attenuated the PG-PS-induced colonic damage and cell infiltration. Enhanced expression of MAdCAM-1 was demonstrated in venular endothelium of the inflamed colon in PG-PS-induced colitis. The attenuating effect of anti-MAdCAM-1 suggests the importance of the MAdCAM-1-dependent process in the formation of chronic granulomatous colitis.

Animals↗

Therapy of ulcerative colitis.

PURPOSE OF REVIEW: The past year has brought forth several controversies regarding the treatment of ulcerative colitis along with several potentially important clinical advances. The aim of this review is to provide the practicing gastroenterologist with a summation of these recent developments, with particular emphasis on advances that have already moved toward acceptance into clinical practice. RECENT FINDINGS: Controversies remain regarding the optimal formulations and doses of aminosalicylates. At the same time, the potential for chemoprotective effects in patients using maintenance therapy with mesalamine derivatives has been expanded. In addition, advances in biologic therapy for Crohn disease are beginning to be formally evaluated in ulcerative colitis, although the benefits of anti-tumor necrosis factor therapy in this condition remain to be established. Biologic therapies are beginning to be explored as adjunctive therapy for steroid-refractory ulcerative colitis, where trials of calcineurin inhibitors are also advancing clinical practice for this poor prognostic subgroup of patients. Finally, after surgery for ulcerative colitis, the treatment and prevention of pouchitis has become the one established indication for probiotic therapy. SUMMARY: Despite some inroads into the medical therapy of ulcerative colitis, controversies remain regarding the optimal dosing and delivery systems of the most fundamental therapies, and how to optimize therapy for severe ulcerative colitis. Clinical research will continue to investigate new biologic agents that inhibit tumor necrosis factor and other pro-inflammatory cytokines, and ongoing trials with leukocyte apheresis are currently under way.

Journal Article↗

Amebic colitis masquerading as acute inflammatory bowel disease: the role of serology in its diagnosis.

Amebic colitis needs to be considered in the differential diagnosis of infectious colitis or inflammatory bowel disease (IBD). Misdiagnosing amebic colitis as idiopathic inflammatory disease may be fatal. Although stool studies remain the initial approach to diagnosis, the incidence of false-negatives associated with this method is high. We report two cases of amebic colitis presenting as inflammatory bowel disease in which the diagnosis of amebic colitis was made by serology. Neither patient had any risk factors for acquiring amebiasis. Paired serology for amebic infections (2-4 weeks apart) should be performed in patients being evaluated for infectious colitis and inflammatory bowel disease.

Animals↗

Computed tomographic findings in pseudomembranous colitis: an important clue to the diagnosis.

Computed tomography (CT) is increasingly used to evaluate abdominal diseases, including those of the colon. Recent CT studies have documented colonic abnormalities in patients with pseudomembranous colitis; however, these findings are not widely appreciated by primary care physicians. Over a 25-month period, we prospectively identified 13 patients who had proven pseudomembranous colitis evaluated by abdominal CT. The primary indications for CT were abdominal pain with or without fever in 9 patients, fever of unknown origin in 1, evaluation of other abdominal processes in 1, and as part of this study after documentation of pseudomembranous colitis in 2. Importantly, the diagnosis of pseudomembranous colitis was first considered on the basis of the CT findings in 9 patients with abdominal pain or fever. Diffuse thickening of the colonic wall, ranging from 4 to 40 mm, was the most common radiologic finding, seen in 8 patients (62%). In 3 cases, wall thickening was seen in the descending colon and rectosigmoid, with one of these also having a thickened transverse colon. Colonic wall thickening, which may be dramatic, appears to be an almost uniform accompaniment of pseudomembranous colitis and may be present without clinically severe disease. These CT findings in the appropriate clinical setting should suggest colitis due to Clostridium difficile and prompt the appropriate evaluation for this disease.

Abdominal Pain↗

The outcome of surgery in fulminant Clostridium difficile colitis.

BACKGROUND: The clinical presentation of Clostridium difficile infection ranges from asymptomatic carriage, colitis with or without pseudomembranes, to fulminant colitis. Although not common, fulminant C. difficile colitis can result in bowel perforation and peritonitis with a high mortality rate. Colectomy is often indicated in these cases. METHODS: We retrospectively analysed the outcome of 14 patients who underwent surgery for fulminant C. difficile colitis in the period 1996-2003 in our Unit. RESULTS: The indications for surgery were systemic toxicity and peritonitis (n = 10), radiological and clinical evidence of progressive toxic colonic dilatation (n = 3) and progressive colonic dilatation with bowel perforation (n = 1). C. difficile infection as the cause of colitis was diagnosed pre-operatively in seven (50%) patients, six of whom underwent a total colectomy and one a right hemicolectomy. Overall mortality in our series was 35.7%. Total colectomy was associated with a lower mortality rate of 11.1% (1/9) when compared with left hemicolectomy was 100% (4/4) (P = 0.01). One patient who underwent a right hemicolectomy (on the basis of deceptively normal external appearance of the rest of the colon intra-operatively) survived after a prolonged hospital stay. CONCLUSIONS: Early or pre-operative microbiological diagnosis of C. difficile infection can be difficult in patients with a fulminant presentation. Those patients with C. difficile colitis, who develop signs of toxicity, peritonitis or perforation, should undergo a total colectomy as the operation of choice.

Adult↗

Fatal amoebic colitis in a patient with SLE: a case report and review of the literature.

Colitis in systemic lupus erythematosus (SLE) poses a diagnostic challenge as clinical, radiological and laboratory findings are often non-specific. Fulminant amoebic colitis is a rare cause of death in SLE. Early diagnosis coupled with timely surgery can reduce the mortality. The demonstration of haematophagous trophozoites in the stool is diagnostic but insensitive. Early endoscopy with adequate specimen collection is an important part of the diagnosis. Serology is both sensitive and specific but can take up to 2-4 weeks for seroconversion making it less useful in a disease that takes a rapid downhill course if treated inappropriately. We report a fatal case of colitis in a patient with SLE due to invasive amoebiasis which was complicated by Salmonella bacteraemia, disseminated intravascular coagulation, acute oliguric renal failure and adult respiratory syndrome. We also reviewed the literature on the clinical features and diagnosis of fulminant amoebic colitis. Amoebic colitis, although rare, should be considered in the differential diagnosis of lupus patients with colitis.

Adult↗

[Fatal toxic megacolon due to cytomegalovirosis in a patient with ulcerative colitis: case report and review].

BACKGROUND: The toxic megacolon is a rare and severe complication of ulcerative colitis. In general it complicates patients with active colitis that are resistant to clinical treatment and, in some cases, the developing factor is unknown. Cytomegalovirus infection in humans in general is a subclinical condition. However, in patients with immunodeficiency the primary infection or the reactivation of latent infection could have enormous clinical effects. One of these effects is the toxic megacolon. AIM: To report a case of fatal toxic megac lon due to cytomegalovirosis in a patient with ulcerative colitis. PATIENT: A male patient, 38 years old, with complaints of diarrhea and weight loss. The diagnosis of ulcerative colitis was made and a vigorous immunossupressive therapy was performed. RESULTS: Due to the evolution to a toxic megacolon the patient was submitted to colectomy. In the post-operatory period there were severe clinical complications and the patient died. The pathological study of the colon revealed active ulcerative colitis, associated with confluent ulcerations and numerous cells with cytomegalic nuclear inclusions. CONCLUSION: The cytomegalovirosis must be considered as one of the causal agent of toxic megacolon in ulcerative colitis.

Adult↗

The clinical significance of antibiotic-associated pseudomembranous colitis in the 1990s.

Antibiotic-associated pseudomembranous colitis is an uncommon but potentially serious adverse reaction, resulting in acute diarrhoea and characterised by colonic pseudomembranes. A direct relationship between the disease, recent antibiotic therapy and proliferation of Clostridium difficile in the colonic lumen was established in the late 1970s. It is thought that antibiotic therapy may alter the enteric flora, enabling C. difficile to proliferate and produce toxins with cytopathic (toxin B or cytotoxin) and hypersecretory (toxin A or enterotoxin) effects on the mucosa. Apart from clindamycin, the first antibiotic recognised to be clearly associated with pseudomembranous colitis, the antimicrobial agents most commonly responsible are cephalosporins and ampicillin (or amoxicillin). However, virtually all antibiotics except parenterally administered aminoglycosides can cause the disease. Vancomycin and metronidazole, 2 drugs used to treat antibiotic-associated pseudomembranous colitis, have also been reported to be responsible for the complication when used parenterally. Pseudomembranous colitis may develop after perioperative prophylactic antibiotic therapy with cephalosporins. Antibiotic-associated pseudomembranous colitis is most frequent in elderly and debilitated patients and in intensive care units. Nosocomial acquisition of C. difficile has been documented. Therefore it has been recommended that enteric isolation precautions should be taken with patients with this disease. The clinical symptoms include watery diarrhoea, abdominal cramping, and frequently fever, leucocytosis and hypoalbuminaemia. Toxic megacolon and acute peritonitis secondary to perforation of the colon are the most serious complications. The pseudomembranes are usually seen during endoscopic procedures, sigmoidoscopy or, if possible, colonoscopy; the most useful microbiological tests for confirmation of the diagnosis include cycloserine cefoxitin fructose agar (CCFA) stool cultures and stool toxin assays on tissues or by immunological techniques. However, cultures and toxin tests may be positive in patients without pseudomembranous colitis or C. difficile-associated diarrhoea. Mild cases may respond to discontinuation of the drug responsible, but therapy with an anticlostridial antibiotic is often necessary: a 10-day course of oral vancomycin, metronidazole or bacitracin should be given. Relapses are seen in 5 to 50% of patients treated. Antibiotic treatment should avoid sporulation leading to other relapses. 'Biotherapy' (lactobacilli, Saccharomyces) has also been proposed.

Anti-Bacterial Agents↗

[Pseudomembranous colitis during antibiotic therapy].

INTRODUCTION: The use of antibiotics is commonly accompanied by diarrhea: idiopathic diarrhea with a benign process and diarrhea caused by Clostridium difficile and pseudomembranous colitis. Clostridium difficile colonizes the gastrointestinal tract and produces a toxin in cases when normal flora is suppressed by antibiotics. Pseudomembranous colitis most frequently appears after application of clindamycin, lincomycin, ampicillin, cephalosporins and other antibiotics. Diagnosis is established after rectoscopic findings of adherent pseudomembrane and pathohistological verification. The diagnosis is confirmed if there is evidence of Cl. difficile toxin in feces. CASE REPORT: We report about the clinical course of two patients with antibiotic-associated colitis. The diagnosis were made by clinical examinations, rectoscopy and pathohistologic verification of biopsy specimen of the intestinal mucosa. Neutralization test was not done due to technical reasons. Patients were treated with metronidazole. Unwanted side-effects of metronidazole therapy were not observed. DISCUSSION: Both our patients confirmed that they previously used different antibiotics. In the first case, diarrhea appeared during the antibiotic therapy, and in the second case, after finishing it. After antibiotic use, diarrhea appears in 5.30% cases, but fortunately pseudomembranous colitis is rare. However, taking into consideration that pseudomembranous colitis has a severe course and requires urgent treatment, one has to consider the possibility of pseudomembranous colitis when diarrhea appears during and after antibiotic use in order to initiate adequate therapy.

Adult↗

In vitro production of TNF-alpha,IL-6 and sIL-2R in Chinese patients with ulcerative colitis.

AIM:To determine the tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and soluble interleukin 2 receptor (sIL-2r) from peripheral blood mononuclear cells (PBMC) in 25 Chinese patients with ulcerative colitis and 20 healthy controls.METHODS:PBMC were isolated by density gradient centrifugation of heparinized blood and cultures for 24 or 48 hours by stimulation with LPS or PHA. TNF-alphaand sIL-2r were measured by ELISA method and IL-6 measured by biossay.RESULTS:TNF-alphaproduction stimulated by LPS and sIL-2r production by PHA in ulcerative colitis were significantly lower than in healthy controls (TNF-alpha509(46-7244)ng/L vs 1995(117-18 950)ng/L, P < 0.05; sIL-2r 320U/mlplus minus 165U/ml vs 451U/mlplus minus 247U/ml, P < 0.05).Spontaneous TNF-alphaand sIL-2r production were not significantly different between ulcerative colitis and controls (TNF-alpha304(46-7044)ng/L vs 215(46-4009)ng/L,P > 0.05; sIL-2r 264U/mlplus minus 115U/ml vs 236U/mlplus minus139U/ml, P>0.05). IL-6 production by spontaneous release from PBMC in ulcerative colitis group was 109U/mlplus minus 94U/ml vs 44U/mlplus minus 39U/ml for those in healthy controls, P < 0.01. IL-6 stimulated by LPS in ulcerative colitis group was (261U/ml plus minus 80U/ml) higher than in healthy controls (102U/mlplus minus 54U/ml, P < 0.01). No correlation of TNF-alpha, IL-6, sIL-2r production was found to disease activity, disease location and medication.CONCLUSION:Cytokine production from PBMC was also disturbed in Chinese patients with ulcerative colitis.

Journal Article↗

Surgical management of fulminant pseudomembranous colitis.

The presentation of pseudomembranous colitis ranges from mild self-limiting diarrhea to fulminant colitis with overwhelming sepsis. The management of the severe forms of this disease, including the role of surgical intervention, is poorly defined. To evaluate the management and outcome in severe cases, the authors reviewed the records of six patients (four women, two men) seen at The Toronto Hospital between 1985 and 1989 with pseudomembranous colitis manifesting as fulminant colitis. The patients ranged in age from 19 to 69 years (mean 52 years). All presented with nonbloody diarrhea, had peritoneal signs and were severely dehydrated, and all had received antibiotics between 4 days and 6 weeks before the onset of symptoms. The mean preoperative leukocyte count was 40.9 x 10(9)/L. Radiologically, the colon appeared to be dilated in three patients. Two patients were operated on immediately. The other four were treated medically, but three of them required surgery within 24 hours of presentation. Four (67%) of the six patients died. All four had been treated surgically. The mean age of the survivors was 28 years compared with 64 years for those who died. Pseudomembranous colitis can present as severe acute colitis and can carry a high mortality, especially in the aged. Surgical treatment may be required in those who fail to respond to medical management or have peritoneal signs.

Adult↗

[Clinical study of pseudomembranous colitis: a neurosurgical viewpoint].

In many instances patients who have undergone neurosurgery are given antibiotics. Some of these patients, however, run the risk of developing pseudomembranous colitis. In our department over the past three years, 239 patients, whose hospitalization period exceeded two weeks, were given antibiotics. Of this total number, 6 patients (2.5%) contacted pseudomembranous colitis and a clinical study of these 6 cases was conducted from a neurosurgical viewpoint. This study concentrated on diarrhea, the primary symptom, and the 6 patients consisted of 1 male and 5 females whose ages ranged from 61 to 75 years. All had undergone surgery, and a breakdown of their diseases is as follows: 2 cases of a subarachnoid hemorrhage, 2 cases of an intracerebral hemorrhage, 1 case involving a glioblastoma multiforme, and a case of normal pressure hydrocephalus. Diarrhea was present in all 6 cases and, additionally, pyrexia, abdominal pains, and leukocytosis were seen. On colonoscopic examination, 5 patients were diagnosed as having developed pseudomembranous colitis, and were treated by oral administrations of Vancomycin. In the remaining cases, in which a colonoscopic examination had not been performed, a diagnosis of pseudomembranous colitis had not been achieved and, subsequently, one patient died of multiple organ failure. On autopsy, however, it was determined that the patient had had pseudomembranous colitis. Thus, if symptoms of diarrhea occur during or after administrations of antibiotics, the possibility of pseudomembranous colitis must be assumed, and a colonoscopic examination should be performed immediately, so as to detect the disease at an early stage. This condition can be transmitted within a hospital and, therefore, great emphasis must be placed on preventing secondary infections.

Aged↗