Acute cytomegalovirus infection associated with the onset of inflammatory bowel disease

A 29-year-old man was admitted with high-grade fever, crampy abdominal pain, and watery diarrhea that had persisted for 2 weeks before his admission. Symptomatic treatment (acetaminophen only) was of no benefit. On physical examination, there was diffuse abdominal tenderness. Laboratory tests showed a leukomoid reaction with atypical lymphocytosis, and serology tests revealed acute cytomegalovirus infection. Abdominal computed tomography and colonoscopy revealed an inflammatory process involving the large intestine. On histologic examinations of intestinal biopsy samples, there was an active inflammation with no inclusion bodies.The patient was treated with ganciclovir with only mild improvement. Adding 5-aminosalicylic acid caused little further improvement. Repeated colonoscopy performed 2 months later showed severe chronic ulcerative colitis. Only the addition of systemic steroids caused complete resolution of the symptoms.On review of the literature (Medline search for cytomegalovirus colitis in immunocompetent patients), 18 cases were found. On follow-up, 10 of these patients were found to have inflammatory bowel disease.     

Fulminant colitis in inflammatory bowel disease

PURPOSE: The morphologic features of fulminant colitis may be nonspecific, making differentiation between ulcerative colitis and Crohn's disease difficult, even after colectomy. The aims of this study were 1) to identify histologic features that accurately differentiated ulcerative colitis, Crohn's disease, and indeterminate colitis in fulminant colectomy specimens; 2) to determine how frequently subsequent clinical course altered the pathologic diagnosis; and 3) to evaluate the natural history of histologically diagnosed indeterminate colitis. METHODS: Ninety-five fulminant colectomy specimens were evaluated, of which 85 had an original diagnosis of fulminant inflammatory bowel disease. Complete pathologic material and comprehensive clinical follow-up information was available on 67 cases of inflammatory bowel disease. These were re-evaluated in a blinded fashion, and histopathologic features were compared with the original diagnosis and reviewed in the light of subsequent clinical behavior to reach a final diagnosis. RESULTS: Evaluation of macroscopic features was not helpful in differentiating ulcerative colitis from Crohn's disease. Microscopic examination correctly diagnosed ulcerative colitis or Crohn's disease in only 58 of 67 (87 percent) cases. A further three cases (4 percent) were definitively classified after correlation with clinical data, leaving a residual six cases that were diagnosed as indeterminate colitis. Granulomas and lymphoid aggregates were the two most specific indicators of Crohn's disease. CONCLUSIONS: Histopathologic evaluation alone has limitations in the accurate classification of fulminant inflammatory bowel disease. Histologically diagnosed indeterminate colitis is a heterogeneous group that may include some patients who subsequently prove to have ulcerative colitis or Crohn's disease.Presented at the meeting of the United States and Canadian Academy of Pathology, Orlando, Florida, March 1 to 7, 1997.     

Cytomegalovirus colitis complicating inflammatory bowel disease

When patients with inflammatory bowel disease (IBD) are admitted to the hospital with a flare of acute severe colitis, the possibility of a concurrent cytomegalovirus (CMV) infection causing or worsening the colitis is often considered. IBD patients are usually immunosuppressed, and therefore presumably at increased risk for active CMV infection and disease. Multiple techniques are used to diagnose CMV infection, including endoscopy, histology, serology, viral culture, CMV antigen testing, and CMV DNA testing. Immunohistochemistry (IHC) performed on colon biopsy specimens with monoclonal antibodies directed against CMV immediate early antigen is considered by most to be the current gold standard for diagnosis. The prevalence of CMV infection in acute severe colitis appears to be 21-34%, and the prevalence of CMV infection in the steroid refractory subgroup of these patients is 33-36%. After antiviral therapy, colitis remission rates in IBD patients with CMV infection range from 67% to 100%, though CMV histological infection or the presence of circulating virus alone is not always associated with steroid resistance, and may not require antiviral therapy.     

巨细胞病毒与炎症性肠病的关系

巨细胞病毒（cytomegalovirus，CMV）为机会致病性病毒，多数人呈隐性或潜伏感染，显性CMV感染常发生在免疫功能抑制者。炎症性肠病（1BD）是一种慢性、复发性的肠道炎症疾病，患者常使用激素或免疫抑制剂治疗，因而有很高的CMV易感性。近年研究表明CMV感染可能在炎症性肠病病情发展变化中起关键作用，CMV通过直接或间接作用致组织损伤，目前新发展的检测技术或联合多种检测手段可增加CMV检出的敏感性和特异性，而不少研究表明难治性IBD时应用抗CMV病毒治疗可明显改善病情。本文就CMV在IBD疾病进展中的作用和关系，以及对CMV的最新检测技术和治疗策略的研究进展作一综述。     

Pathogenic factors in inflammatory bowel disease. I. Ulcerative colitis.

The identification of the early events occurring in ulcerative colitis may lead to a better understanding of the etiology of this disease. Many observations have now indicated that colonic epithelial abnormalities occur independently of the presence of mucosal inflammation and have suggested that early events are more likely to involve the epithelium than immuno-inflammatory mechanisms. Although a large number of candidate luminal and mucosal mechanisms for injuring the epithelium or modulating its function can be identified, the real reasons why the epithelium is abnormal remain unclear. Mucosal inflammation may well be a secondary phenomenon due to influx into the lamina propria of luminal macromolecules with toxic, antigenic, immunoadjuvant and chemoattractant properties. This pathogenic model offers new areas of focus for research and the potential for novel therapeutic approaches.     

Infectious colitis endoscopically simulating inflammatory bowel disease: a prospective evaluation

This prospective evaluation of patients presenting with mucoid bloody diarrhea and suspected idiopathic inflammatory bowel disease demonstrated a 38% incidence of infectious colitides. The infectious agents detected were Campylobacter, Salmonella, Shigella, Amoeba, and Clostridium difficile. An increased awareness and the utilization of selective culture media should allow the clinician to definitively diagnose patients who present with signs and symptoms suggestive of idiopathic inflammatory bowel disease.     

Surveillance issues in inflammatory bowel disease: ulcerative colitis

This review article on the surveillance of patients with ulcerative colitis provides an overview of the criteria for evaluating screening and surveillance programs and applies the criteria to the available evidence to determine the effectiveness of the surveillance of patients with ulcerative colitis. We examine the clinical outcomes associated with surveillance, the additional clinical time required to confirm the diagnosis of dysplasia and cancer, compliance with surveillance and follow-up, and the effectiveness of the individual components of a surveillance program, including colonoscopy and pathologist's interpretation. The disability associated with colectomy is considered, as are the cost and acceptability of surveillance programs. Patients with long-standing ulcerative colitis are at risk for developing colorectal cancer. Recommended surveillance colonoscopy should be supported. New endoscopic and histopathologic techniques to improve the identification of high-risk patients may enhance the effectiveness and cost-effectiveness of surveillance practices.     

Outcome of cytomegalovirus infections in patients with inflammatory bowel disease

OBJECTIVE: The aim of this study was to determine the outcome of cytomegalovirus (CMV) infections complicating the course of inflammatory bowel disease (IBD). METHODS: The records and clinical courses were reviewed for all IBD patients who were evaluated at the IBD Center of the Cedars-Sinai Medical Center and who developed CMV infection. RESULTS: Ten patients with severe, medically refractory IBD (five ulcerative colitis, three Crohn's colitis, and two indeterminate colitis) developed CMV infection. All but two were hospitalized with exacerbation of their underlying disease and were receiving immunosuppressive treatment with steroids, thiopurines, and/or cyclosporine at the time CMV infection was recognized. Eight patients had documented colonic CMV (one had concurrent upper GI tract involvement), one developed interstitial CMV and Pneumocystis carinii pneumonia, and one developed primary CMV mononucleosis. Prompt treatment with ganciclovir and withdrawal of immunosuppressive treatment resulted in gradual improvement and induction of remission of the underlying IBD in five patients. The patient with concomitant CMV and P. carinii pneumonitis died. In two patients, treatment with ganciclovir did not alter the clinical course of their IBD, and one of them underwent colectomy. In one patient CMV was found on the resected colonic specimen. One patient with primary CMV infection responded also to ganciclovir treatment. CONCLUSIONS: CMV infection may aggravate the course of seemingly refractory IBD in patients who either fail to respond or experience worsening of symptoms despite immunosuppressive therapy. Expedient evaluation, prompt treatment intervention with ganciclovir, and withdrawal of immunosuppressive treatment may avoid complications and mortality. This regimen leads to improvement of the underlying IBD in most patients.     

Serum procalcitonin differentiates inflammatory bowel disease and self-limited colitis

BACKGROUND: The distinction between idiopathic inflammatory bowel disease (IBD) and infectious, usually self-limited enterocolitis is still a diagnostic dilemma. Procalcitonin (PCT) is the prohormone of calcitonin and is considered a specific marker of bacterial infection. The aim of this prospective study was to determine the value of PCT in differentiating flares of IBD from self-limited colitis. In addition, because standard laboratory inflammatory parameters are poorly correlated with disease activity in IBD, the relation between PCT levels and disease activity was investigated. METHODS: A total of 76 patients (26 Crohn's disease, CD; 25 ulcerative colitis, UC; and 25 patients with self-limited enterocolitis) were enrolled. Serum levels of PCT were measured by a sandwich immunoluminometric assay. C-reactive protein (CRP) levels, white blood cell counts, and stool cultures were obtained from all patients. Disease activity was assessed by the Crohn's disease activity index (CDAI) and the Truelove index for CD and UC, respectively. RESULTS: Patients with self-limited enterocolitis showed significantly higher PCT levels when compared with IBD patients (0.36 ng/mL, range 0.18-1.7 vs 0.10 ng/mL, range 0.08 0.5, p < 0.001). For a PCT value of > or =0.4, the sensitivity for self-limited colitis was 92% and specifity 96%. The positive predictive value (PPV) for self-limited colitis was 96%, whereas the negative predictive value (NPV) was 93%. In IBD patients, PCT levels were in the normal range although significantly higher in active disease when compared with inactive disease (0.13 ng/mL, range 0.08-0.5 vs 0.09 ng/mL, range 0.08-0.15, p < 0.001). This difference was less pronounced for CD (0.11 ng/mL, range 0.08-0.2 vs 0.09 ng/mL, range 0.08-0.15, p < 0.05) than for UC (0.14 ng/mL, range 0.08-0.5 vs 0.09 ng/mL, range 0.08-0.11, p < 0.01). In CD, PCT levels correlated significantly 0.5, p < 0.01). with the CDAI (r =0.05, p <0.01). CONCLUSIONS: The measurement of PCT offers two diagnostic options in IBD. Supranormal levels indicate self-limited enterocolitis. Furthermore, although within the normal range in IBD, PCT levels may serve as a new serological marker of disease activity.     

Giant inflammatory polyps associated with idiopathic inflammatory bowel disease

Five cases of giant inflammatory polyps associated with idiopathic inflammatory bowel disease are reported. Polyps produced intestinal obstruction in three cases; consequently, surgery was performed. In a further two cases, intestinal bleeding was improved by endoscopic polypectomy. Electron microscopy showed fibroblasts, myofibroblasts, mast cells, lymphocytes, collagen fibers, capillaries, and venules. Remnants of the original mucosal epithelial cells, smooth muscle cells, and hypertrophic autonomous nerve plexuses were noted. Nerve fibers were interwoven with the matrix of the polyps. Mast cells were closely linked with vessels, nerves, and collagen fibers. They may have an important role in the excessive granulation, angiogenesis, and fibrotic process in giant inflammatory polyps.     

6-mercaptopurine and inflammatory bowel disease: hidden ground for the cytomegalovirus.

6-mercaptopurine (6-MP) and azathioprine are important drugs for the treatment of inflammatory bowel disease (IBD) but their actions suppress host defense against infection. A challenging case of a 19-year-old female patient with quiescent Crohn's disease maintained with 6-MP presenting with dyspnea and a normal chest exam and x-ray is presented. She became ventilator-dependent and only after numerous investigations was diagnosed with cytomegalovirus (CMV) pneumonitis. A systematic literature review of CMV infections in IBD patients was performed. The present case is the first report of a patient with quiescent IBD maintained on 6-MP who developed CMV pneumonitis. Other reports have identified patients with active disease on multiple immunosuppressants who developed CMV pneumonitis and also highlight the risk of CMV colitis in refractory IBD. The authors review the approach to the diagnosis of CMV infections in IBD patients with atypical pneumonia and colitis and highlight the importance of considering CMV infection in these settings.     

Idiopathic myointimal hyperplasia of mesenteric veins: a rare mimic of idiopathic inflammatory bowel disease

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood disease that occurs in the rectosigmoid colon of predominantly young, previously healthy male patients. IMHMV typically requires segmental resection due to complications after a relatively protracted clinical course. This disease presents a challenging diagnostic dilemma for the clinician because it is initially often confused with chronic idiopathic inflammatory bowel disease. We report a case of IMHMV, illustrate endoscopic and histopathologic features, and review key characteristics of this rare entity.     

Non-steroidal anti-inflammatory drugs are associated with emergency admission to hospital for colitis due to inflammatory bowel disease.

BACKGROUND: To evaluate the relation between non-steroidal anti-inflammatory drugs (NSAIDs) and colitis due to inflammatory bowel disease. METHODS: A case-control study was conducted using a prospectively constructed, record linkage database containing hospital event and dispensed drug data (1989-93). The study population consisted of 319,465 people resident in Tayside in January 1989, and still resident (or dead) in October 1994. RESULTS: Of the 785 patients admitted to hospital as emergencies with colitis between July 1989 and June 1993, 200 fulfilled the case criterion of colitis due to inflammatory bowel disease. A further 1198 persons were used as community controls. Odds ratios were calculated for three exposure periods (current, recent, and past exposure). The overall odds ratios (with 95% confidence intervals) for current and recent exposure to NSAIDs were 1.77 (1.01 to 3.10) and 1.93 (1.20 to 3.09) respectively. Current and recent exposure to NSAIDs was also associated for incident cases, with odds ratios of 2.96 (1.32 to 6.64) and 2.51 (1.13 to 5.55). There was a trend for recent exposure among non-incident cases. CONCLUSION: The use of NSAIDs may be associated with an increased risk of emergency admission to hospital for colitis due to inflammatory bowel disease, particularly among patients with no previous history.     

Idiopathic pancreatitis associated with inflammatory bowel disease

The list of extraintestinal manifestations of inflammatory bowel diseases does not classically include pancreatitis and pancreatic insufficiency. We report here six cases of unexplained pancreatitis associated with inflammatory bowel disease (five patients with Crohn's disease, one with indeterminate colitis). None of the classical etiologies for pancreatitis was found in our patients; moreover none of them had duodenal localization of Crohn's disease or sclerosing cholangitis, two conditions in which pancreatitis associated with inflammatory bowel disease has been previously described. Pancreatitis was painless (or was associated with moderate and atypical abdominal pain) in four of our six cases; no pancreatic calcification was found in any case; in three patients a total or subtotal exocrine pancreatic insufficiency was evidenced. Endoscopic retrograde pancreatography performed in four subjects showed normal or minimally altered pancreatic ducts even in those with severe pancreatic insufficiency. These cases emphasize the existence of a probably nonfortuitous association of inflammatory bowel disease with pancreatitis. Its recognition could make a significant contribution in the management of inflammatory bowel disease.     

Vascular complications associated with inflammatory bowel disease

Thromboembolic episode is a well known extraintestinal manifestation of inflammatory bowel disease, but it is a clinical rare complication. Histological and hematological studies suggest that a hypercoagulable state is involved in the pathogenesis of inflammatory bowel disease. However, the exact mechanism of hypercoagulability is still unknown. During the acute recurrences there is an increase of factor VIII, fibrinogen, platelet, factor V and decrease of antithrombin III. Hematologic disorders seem markedly correlated with the activity of the disease. We report on two patients with Inflammatory bowel disease and hypercoagulable state. We review the literature and discuss about the pathogenic mechanisms of such complication.