Cytomegalovirus infection in ulcerative colitis

OBJECTIVE: Cytomegalovirus (CMV) infection has been reported as an exacerbating factor in inflammatory bowel disease but the relationship between CMV infection and ulcerative colitis (UC) remains unclear. There has been no detailed research to elucidate the clinicopathologic features of CMV infection in UC using surgical specimens. The aim of this study was to investigate the clinicopathologic features of CMV infection in UC patients who had undergone colectomy. MATERIAL AND METHODS: Surgical specimens taken from UC patients were examined for CMV infection. The patients were divided into three groups: severe, refractory, and UC-associated dysplasia or cancer according to the operative indications. CMV infection rates were evaluated and a comparison of clinical parameters was made between CMV-positive and CMV-negative patients, and the risk factors for CMV infection were analyzed using multivariate analyses. RESULTS: It was found that 25% of 32 patients were positive for CMV in the severe UC group; 8.3% of 72 patients were positive for CMV in the refractory UC group. None of the 22 patients was positive for CMV in the UC-associated dysplasia or cancer group. The CMV-positive rate in the severe UC group was significantly higher than that in the other groups (p<0.05). Patients' age at the time of operation was higher in the CMV-positive group than in the CMV-negative group among the patients with severe UC (p<0.01), and age at operation was an independent risk factor for CMV infection. CONCLUSIONS: CMV is found more frequently in severe UC than refractory UC and UC-associated cancer or dysplasia. Higher age can be a risk factor for CMV infection in patients with severe UC. However, a high steroid dose may not always be a risk factor for CMV infection.     

Cytomegalovirus infection in ulcerative colitis

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

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

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

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

Incidence of ulcerative colitis in Central Greece： A prospective study

AIM: To study the incidence of ulcerative colitis UC in the prefecture of Trikala, Central Greece. METHODS: A prospective and population based epidemiological study of UC from 1990 to the end of 1994 was conducted. Trikala is a semirural prefecture of Central Greece with a population of 138 946 (census 1991). Three gastroenterologists (one hospital based, two private doctors) of the prefecture participated in this study. RESULTS: During the study period, 66 new historically verified cases of UC were recorded. The mean annual incidence of the disease in 1990-1994 was 11.2 per 105 inhabitants (95%CI: 8.7-14.3). There was no difference between men and women (annual incidence: 10.5 and 12.0 per 105 inhabitants respectively), either among urban, semirural or rural populations (annual incidence: 11.7, 17.1 and 9,9 per 105 inhabitants respectively). The majority (56%) of the patients never smoked and a quarter were ex-smokers. About a half of all cases had proctitis. CONCLUSION: UC is common in Central Greece and its incidence is similar to that in North-Western European countries.     

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.     

Cytomegalovirus in colorectal cancer and idiopathic ulcerative colitis

Cytomegalovirus (CMV) is a genus in the family Herpesviridae that has been associated with gastrointestinal syndromes. In this work we looked for a possible association of CMV infection with colorectal cancer and ulcerative colitis (UC). Blood and enteric tissue samples of 14 patients with colorectal cancer and of 21 with UC were subjected to a nested-PCR that amplifies part of the gB gene of CMV and also to immunohistochemistry using a specific monoclonal antibody to IE 76 kDa protein of CMV. CMV was detected by nested-PCR in the blood and/or the enteric tissue of nine (64.3%) colorectal cancer and 16 (76.2%) ulcerative colitis patients. In the immunohistochemistry it was observed that 12 (12/21, 57.1%) positive enteric tissue samples of patients with UC and none from patients with colorectal cancer (0/14) were positive to CMV. The positivity of CMV infections in the UC patient group (12/21, 57.1%) showed by both techniques, was significantly higher (p = 0.015) than that observed for colorectal cancer patients (2/14, 14.3%). These results suggest an association of ulcerative colitis with CMV infection of the enteric tissue.     

Cytomegalovirus and ulcerative colitis: Place of antiviral therapy

The link between cytomegalovirus(CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis(UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools(numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flareups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease.     

Chronic ulcerative colitis: incidence and prevalence in a community.

Utilising the population based data resources of the Rochester Epidemiology Project, we determined the incidence and prevalence of chronic ulcerative colitis among Rochester, Minnesota, residents over the 20 year period, 1960-79. One hundred and thirty eight cases met diagnostic and residency criteria, for an overall age, and sex adjusted chronic ulcerative colitis incidence rate of 15.0 per 100,000 person years. The male:female ratio of age adjusted rates was 1.5:1. Age specific incidence was roughly bimodal in appearance but was not consistent in different patient subgroups. On 1-1-80, there were 120 Rochester residents with a history of chronic ulcerative colitis, corresponding to a prevalence rate of 225.2 per 100,000 population. Fifty three per cent of chronic ulcerative colitis incidence cases were 'definite' and 47% were 'probable', the former requiring consistent observations for at least six months. The definite group had proportionately more men and disease of greater extent and severity. Pancolitis comprised about one-third of all cases (4.6 per 100,000 person years). Proctitis and distal disease (7.1 and 2.0 per 100,000 person years) made up most of the rest. One-fourth of all patients had 'severe' or 'moderate' disease (3.8 per 100,000 person years), while the remainder had either 'mild' or 'transient' chronic ulcerative colitis (11.2 per 100,000 person years). In residents of Rochester, Minnesota, chronic ulcerative colitis is most often a mild disease. The over-representation of severe or complicated examples that results from selected referral to major centres probably distorts the natural clinical spectrum of the disease.     

Severe ulcerative colitis: prospective study of parameters determining outcome

BACKGROUND: One-third of patients with exacerbations of ulcerative colitis (UC) require colectomy and 1% die. Although several studies have reported parameters associated with failure of medical treatment, studies using multivariate analysis of various predictors are scanty. METHODS: Demographic, clinical and laboratory parameters within 48 h of admission of 50 consecutive patients (55 episodes) were prospectively recorded. Each episode was treated with intravenous hydrocortisone, antibiotics and fluid administration. The data of patients who failed to respond, deteriorated, developed complications requiring emergency surgery or died within 7 days of hospitalization, were compared with the data of those who responded during this period using Mann-Whitney U-test or chi-squared tests. Variables found to be significant on univariate analysis were entered into a multivariate model. RESULTS: Medical treatment failed in 10 of 55 episodes; eight had surgery (one died), another died with bowel perforation and peritonitis and one left hospital in a moribund state. Younger age, pedal edema, transverse colonic diameter >5 cm on abdominal radiograph, low hemoglobin, low serum albumin, high C-reactive protein, presence of fibrin degradation product (FDP) in serum, low serum fibrinogen, prolonged prothrombin time, Truelove-Witt's fulminant disease, and high clinical activity index were associated with failure of medical treatment on univariate analysis. All the above variables were significant by multivariate analysis except age, serum albumin level and presence of FDP. CONCLUSION: It may be possible to predict the failure of medical treatment in exacerbations of UC using a scoring system based on clinical parameters and simple laboratory tests.     

Stress and exacerbation in ulcerative colitis: a prospective study of patients enrolled in remission

OBJECTIVE: We sought to determine whether psychosocial factors influence the course of ulcerative colitis, hypothesizing that high perceived stress among patients with inactive disease will increase the risk of subsequent exacerbation. METHODS: Sixty-two patients with known ulcerative colitis were enrolled into a prospective cohort study while in clinical remission. Their perceived stress, depressive symptoms, and stressful life events were followed, along with potential confounders, for up to 45 months; exacerbation status was monitored for up to 68 months. RESULTS: The 27 patients who experienced an exacerbation were compared with those who remained in remission. Having a score in the upper tertile on the long-term (past 2 yr) baseline Perceived Stress Questionnaire significantly increased the actuarial risk of exacerbation (hazards ratio = 2.8, 95% confidence interval 1.1-7.2). At any given study visit, high long-term stress tripled the risk of exacerbation during the next 8 months (risk for the three tertiles, 8.3%, 16.7%, and 26.2%, p = 0.02). Shorter sleep time, briefer remission, histological activity, and use of nonsteroidal antiinflammatory drugs, antibiotics, or oral contraceptives also increased the medium- and/or long-term risk of exacerbation, but adjustment for these variables did not eliminate the associations with stress. Exacerbation was not associated with stressful life events, depressive symptoms, short-term (past month) perceived stress, smoking, disease extent or duration, or severity of recent course. CONCLUSIONS: Short-term stress does not trigger exacerbation in ulcerative colitis, but long-term perceived stress increases the risk of exacerbation over a period of months to years.     

Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan

AIM： TO investigate active cytomegalovirus （CMV） infection following the cydosporine A （CyA） treatment of steroid-refractory ulcerative colitis （UC）. METHODS： Twenty-three patients with severe UC not responding to steroid therapy （male 14, and female 9） enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA （average 4 mg/kg per day） for 1 mo. Serum and colonic biopsy samples were collected before CyA treatment and 4 d, 10 d, 20 d, and 30 d after treatment. Patients were evaluated for CMV by using serology （IgM antibody by ELISA）, quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin （HE）-stained colonic biopsies. CMV infection was indicated by positive results in any test. RESULTS： No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV （IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients, 78.2%; and inclusion bodies in 4/23 patients, 17.3%）. There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment, leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection （83.3%） required surgical treatment because of severe deteriorating colitis. Treatment with ganciclovir rendered surgery avoidable in three patients. CONCLUSION： Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immunosuppressive therapy.     

Sexuality in patients with ulcerative colitis before and after restorative proctocolectomy: a prospective study

BACKGROUND: The purpose of this study was to assess sexuality in patients with ulcerative colitis (UC), before and one year after an ileal-pouch anal anastomosis (IPAA). METHODS: Group I comprised 14 medically treated patients (7 M) and Group II comprised 29 patients (18 M), operated with colectomy and ileostomy, with preservation of the rectum. Patients were interviewed about desire, excitement and general sexual satisfaction before and one year after the IPAA operation. RESULTS: Most of the patients had restarted sexual activity < or = 3 months after surgery. Sexual desire and desire for intercourse had not changed from before the IPAA operation. In Group I, one woman suffered from dyspareunia both before and after the IPAA. In Group II, three women had dyspareunia before the IPAA and four after surgery. Erection and ejaculation were normal in all men before the IPAA operation. After IPAA, one man in Group I and two men in Group II had loss of ejaculation. In Group 1, 10 out of 14 patients were satisfied with their sexual life both before and after the IPAA. In Group II the corresponding figures were 15 out of 28 before and 22 after IPAA surgery. CONCLUSIONS: A third of the patients stated that they were dissatisfied with their sexual life before IPAA. Although a few patients experienced sexual imperfections such as loss of ejaculation and dyspareunia, the majority of patients in both groups considered that the overall general satisfaction with their sexual life had normalized considerably after surgery.     

Sexuality in patients with ulcerative colitis before and after restorative proctocolectomy: a prospective study

Background: The purpose of this study was to assess sexuality in patients with ulcerative colitis (UC), before and one year after an ileal‐pouch anal anastomosis (IPAA). Methods: Group I comprised 14 medically treated patients (7 M) and Group II comprised 29 patients (18 M), operated with colectomy and ileostomy, with preservation of the rectum. Patients were interviewed about desire, excitement and general sexual satisfaction before and one year after the IPAA operation. Results: Most of the patients had restarted sexual activity ≤3 months after surgery. Sexual desire and desire for intercourse had not changed from before the IPAA operation. In Group I, one woman suffered from dyspareunia both before and after the IPAA. In Group II, three women had dyspareunia before the IPAA and four after surgery. Erection and ejaculation were normal in all men before the IPAA operation. After IPAA, one man in Group I and two men in Group II had loss of ejaculation. In Group I, 10 out of 14 patients were satisfied with their sexual life both before and after the IPAA. In Group II the corresponding figures were 15 out of 28 before and 22 after IPAA surgery. Conclusions: A third of the patients stated that they were dissatisfied with their sexual life before IPAA. Although a few patients experienced sexual imperfections such as loss of ejaculation and dyspareunia, the majority of patients in both groups considered that the overall general satisfaction with their sexual life had normalized considerably after surgery.     

Increased circulating platelet-neutrophil, platelet-monocyte complexes, and platelet activation in patients with ulcerative colitis: a comparative study

It is reported that the incidence of thromboembolism is increased in ulcerative colitis (UC), and hypercoagulability persists even when patients are in remission. We evaluated the association of inflammatory response parameters with UC activity, and activation parameters of the platelets, endothelium, and the coagulation system in UC. Eighteen UC patients and 19 healthy subjects were included in the study. The patients' clinical features were recorded down; whole blood counts and acute phase parameters were evaluated. UC patients were divided into two as active (9 patients) and inactive (9 patients) according to combined clinical activity index (CAI) and endoscopic activity index (EAI) scores. In all subjects, platelet CD62P expression, platelet-monocyte complexes (PMC), platelet-neutrophil complexes (PNC), and platelet microparticles (PMP) were determined by flow cytometry. E-selectin, thrombin-antithrombin complex (TAT) levels in plasma, and sCD40L levels in serum were determined by ELISA. In both active and inactive UC patients, platelet CD62P expression, the percentages of PMC, and PNC were significantly higher than those in the control group (P< 0.01). PMP level was higher in the control group than in inactive UC patients (P = 0.001). sCD40L level was significantly higher in active UC group than in the control group (P < 0.01). EAI score correlated significantly with PMP (r = 0.5, P = 0.04) and sCD40L (r = 0.48, P = 0.044); CAI score had a negative correlation (r = -0.68, P = 0.002) with sE-selectin level. In addition to increased CD62P expression and sCD40L, increased formation of PMC and PNC suggests a role for platelet-leukocyte complex formation together with platelet activation in thromboembolic events observed in UC.