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.     

Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease

Cytomegalovirus(CMV) infection is common in humans.The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression.The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn’s disease(CD) and ulcerative colitis(UC).CMV does not interfere in the clinical course of CD.However,CMV reactivation is frequent in severe or steroid-resistant UC.It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease.Different methods are used to diagnose CMV colitis.Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry,other tests on blood or tissue samples are currently being investigated.Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease;further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa.Specific endoscopic features have not been described in active UC and CMV infection.CMV colitis is usually treated with ganciclovir for several weeks,there are different opinions about whether or not to stop immunosuppressive therapy.Other antiviral drugs may be used.Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.     

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。     

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.     

Vaccinations in patients with inflammatory bowel disease

Treatment of inflammatory bowel disease (IBD) frequently requires administration of immunosuppressive therapies, which increases susceptibility to a number of infectious pathogens. However, many infections can be prevented by correct and appropriate utilization of vaccinations. While several guidelines have been published on vaccination schedules in patients with IBD, vaccination rates remain suboptimal and even lower than those in the general population. This is due to many factors including poor awareness of the importance of vaccines by gastroenterologists and general practitioners as well as potential prejudices of patients regarding the safety and benefits of vaccines. With the aim of increasing awareness about the key role of immunization in the management of patients with IBD, the present review examines the existing literature relating to the main vaccinations and their application in these patients. We also summarize current evidence in order to provide clinicians with an easy source of reference for the principal recommendations for prevention of infectious diseases in patients with IBD. In addition, the recommendations about traveling for IBD patients are briefly explored. Lastly, since it is important for gastroenterologists to be aware of recommendations on vaccination, we recommend implementing educational programs to ensure compliance with current guidelines.     

Communicating with patients with inflammatory bowel disease

Ulcerative colitis and Crohn's disease, the two main forms of inflammatory bowel disease (IBD), are chronic illnesses that affect hundreds of thousands of Americans. Patients with IBD suffer chronically from diarrhea, abdominal pain, gastrointestinal bleeding, malabsorption, and weight loss requiring continuous medical and surgical attention. Despite recent advances in therapy, IBD follows a course of exacerbations and remissions with approximately 25-50% of patients relapsing annually. Hence, these diseases are readily encountered in primary care and gastroenterology clinics. Though medical and surgical treatment options have improved significantly, little has been written about the psychosocial aspects of IBD. Currently, there is a paucity of data concerning effective communication methods enabling physicians to develop stronger rapport with patients suffering from IBD, the care of whom requires a multidisciplinary approach involving primary care physicians, gastroenterologists, and colorectal surgeons. Because IBD has a high morbidity, it is worthwhile to further investigate those social factors that will improve patients' quality of life. In this paper, we summarize some of the common problems that emerge when taking care of patients with IBD and provide initial guidelines based on the world literature regarding the management and education of patients with IBD. Both primary care physicians and specialists (gastroenterologists, colorectal surgeons) need to be aware of the questions and concerns of IBD patients and to be capable of dispensing the information in a clear and concise manner. Using the case scenario format, we review the most common aspects of communication for health care professionals taking care of IBD patients and suggest ways to establish and maintain long-term doctor-patient relationships. The two most significant interventions that dramatically improve quality of life and patient-physician relationships are proper patient education and appropriate treatment of concurrent depression and anxiety. We hope that our review will form a framework by which different members of the medical team learn their roles in the complex management decisions affecting IBD patients.     

Mast cell mediated ion transport in intestine from patients with and without inflammatory bowel disease

Background—Mast cells have been shown to regulateintestinal ion transport in animal models and normal human colon buttheir physiological role in human intestinal inflammatory disorders is unknown.
Aims—To examine mast cell regulation of iontransport in inflammatory bowel disease (IBD).
Subjects and methods—Small and large intestinewas obtained from patients with and without IBD undergoing surgicalresection. Short circuit current (Isc) responses to rabbitantihuman IgE, histamine, and electrical stimulation were measured inUssing chambers. Specimens were also examined for mast cell numbers and degree of inflammation.
Results—Isc responses to anti-IgEand histamine were smaller in magnitude in IBD compared with non-IBDtissues. In all tissues, anti-IgE Isc responses werereduced by about 80% in chloride free buffer. The histamineH₁ receptor antagonist, pyrilamine, decreased anti-IgEresponses in non-IBD tissues. Greater inhibition with pyrilamine wasseen in IBD small intestine but its effect was less in IBD colon.Histamine pretreatment of non-IBD control tissues reduced anti-IgEresponses to levels seen in IBD colon but had no effect in smallintestine. Mast cell numbers were greater in IBD compared with non-IBDsmall intestine while no differences were observed between the colonicgroups. Isc responses to anti-IgE were not correlated withthe degree of mucosal inflammation.
Conclusions—This study provides further evidencethat mast cells are capable of mediating alterations of ion transportin human gut but that this regulatory role may be altered in IBD. Thedata suggest that prior activation of mast cells with release ofhistamine may account for the reduced secretory response to anti-IgEobserved in IBD colonic tissues.

Keywords:mast cells; intestine; ion transport; histamine; ulcerative colitis; Crohn's disease

     

Surveillance of patients with inflammatory bowel disease

Patients with inflammatory bowel disease involving the colon are at increased risk for developing colorectal cancer. Colonoscopy surveillance is important to identify and treat IBD associated dysplasia. The SCENIC consensus provides evidence-based recommendations for optimal surveillance and management of dysplasia in IBD. Chromoendoscopy, with the surface application of dyes to enhance mucosal visualization, is the superior endoscopic surveillance strategy to detect dysplasia. Most dysplasia is visible, and can be endoscopically resected. Future studies should determine the effect of new surveillance strategies on the incidence of CRC and mortality in patients with IBD.     

Characteristics of cytomegalovirus enterocolitis in patients with or without inflammatory bowel diseases

Objectives: Cytomegalovirus (CMV) disease is more common in immunocompromised patients but may occur in people with normal immune function. In addition, CMV enterocolitis can aggravate inflammatory bowel diseases (IBD), but there was little knowledge of differences in clinical and endoscopic features of CMV enterocolitis between patients with IBD and without IBD. The aim of this study was to determine the difference in clinical implication in CMV enterocolitis between the IBD patients and non-IBD patients.

Methods: This was a retrospective study of 82 patients with CMV enterocolitis based on the pathologic findings at two tertiary referral hospitals from 2003 to 2013. Clinical and endoscopic characteristics and clinical course were analyzed according to the presence of IBD.

Results: Of the 82 patients, 25 (30.5%) had IBD and 57 (69.5%) did not have IBD. Hematochezia was more common in IBD patients (84.0% vs. 35.1%; p = .001), but fever and positive CMV antigenemia were more common in non-IBD patients (50.9% vs. 12.0%; p = .001; 54.4% vs. 28.0; p = .027). Endoscopic findings showed more ulcer with inflammation in IBD patients (68.0% vs. 35.2%; p = .005). Sixty-four patients were treated with antiviral agents and 12 patients who did not receive antiviral agents recovered spontaneously. All naturally healed patients were in normal immune status.

Conclusions: Hematochezia is more common in IBD patients and fever/CMV antigenemia is more common in patients without IBD. In patients without IBD, the natural resolution of CMV enterocolitis is expected at least in normal immune function.     

Prevalence of inflammatory bowel disease in patients with airways disease

BACKGROUND: Case reports and case series have suggested an association between inflammatory bowel disease (IBD) and airways disease, but there are no data demonstrating a higher prevalence of IBD among patients with airways disease. Furthermore, no consistent radiological, pulmonary or pathological abnormalities have been demonstrated in patients with both conditions. AIMS: To determine the prevalence of IBD among patients with airways disease and to evaluate clinical and pathophysiological features. METHODS: A retrospective analysis of outpatients with airways disease over a 10-year period. RESULTS: IBD was four times more prevalent among patients with airways disease compared with published local IBD prevalence [Odds Ratio 4.26, 95% CI 1.48, 11.71, p=0.006; Crohn's disease OR 5.96, 95% CI 1.94, 18.31, p=0.002 and ulcerative colitis OR 4.21, 95% CI 1.71, 10.41, p=0.001]. IBD was more frequent in all types of airways disease except asthma; the association was particularly strong for conditions associated with productive cough. All except 1 patient had established IBD before the onset of respiratory symptoms. There were no obvious radiological differences between ulcerative colitis and Crohn's disease cases. There was a trend for a higher lymphocyte count (despite a tendency to lower blood lymphocyte count) but lower sputum neutrophil count in patients with Crohn's disease compared with ulcerative colitis. There were no significant differences in physiological measurements of pulmonary function between the two types of IBD. CONCLUSION: Our findings support an association between airways disease and inflammatory bowel disease, particularly non-asthmatic airways disease with productive cough.     

Psychiatric comorbidities in patients with inflammatory bowel disease

Background

Psychiatric comorbidities are associated with inflammatory bowel disease (IBD). We conducted an observational study to evaluate the prevalence of depression and anxiety in patients with IBD.

Methods

Seventy consecutive consenting patients with IBD (62 ulcerative colitis [UC], 8 Crohn’s disease [CD]; 40 males, mean age [SD] 36.2 [11.3] years) and 100 healthy volunteers (44 males, age 31.22 [SD] [10.5] years) as controls were enrolled. All participants were directed to take self-assessment tests, Patient Health Questionnaire -9 (PHQ-9) and Symptom Checklist Anxiety Scale (SCL-A20). Participants having a score ≥ 10 on PHQ-9, or ≥ 29 on SCL-A20 were administered the Hamilton Depression Rating Scale (HAM-D) or Hamilton Anxiety (HAM-A) scales, respectively. The severity of depression and anxiety was graded with HAM-D and HAM-A scales, respectively. The protocol was approved by the Institutional Ethics Committee.

Results

The prevalence of depression (34.3% vs. 5%, p?<?0.0001, OR 9.7) and anxiety (18.6% vs. 2%, p?=?0.0002, OR 11.17) was higher in patients with IBD as compared to controls. The severity of depression was higher in patients compared to controls (mean rank 17 vs. 7, p?=?0.04). The prevalence of depression was not different between UC and CD; all IBD patients with anxiety had UC. The mean duration of disease and history of corticosteroid treatment or surgery for IBD were not associated with the presence of depression or anxiety. Patients with severe CD (Crohn’s disease activity index, CDAI?>?450) had more severe depression. The severity of UC did not correlate with severity of anxiety or depression in UC.

Conclusions

Anxiety and depression are more prevalent in IBD patients as compared to healthy individuals.

     

Smoking habits in patients with inflammatory bowel disease

The proportion of smokers in this study was significantly lower among patients with ulcerative colitis (13%) than among patients with Crohn's disease (47%), the difference being significant for both sexes and for the age groups both below and above 40 years. The proportion of male ex-smokers among patients with ulcerative colitis (28%) was higher than among patients with Crohn's disease (8%), whereas the proportions of non-smokers differed less. Many of the patients with ulcerative colitis who had a late onset were male ex-smokers. The smoking patients with ulcerative colitis were mainly women. They smoked less than the smoking patients with Crohn's disease and less than the ex-smokers in each group. No smoking patient with ulcerative colitis smoked greater than 20 cigarettes/day. In the group of male ex-smokers with ulcerative colitis, there was an accumulation of onsets during the 4 years after the definitive smoking stop. The number of colectomies performed on patients with ulcerative colitis did not vary with smoking habits. In the group of ex-smokers the colectomy was performed after the smoking stop in 19 out of 20 patients.     

Spleen size in patients with inflammatory bowel disease

The finding that splenic atrophy is associated with a high complication rate in colitis has led to a long-term, prospective study of spleen size in inflammatory bowel disease. The spleen has been measured in 116 patients undergoing laparotomy for inflammatory bowel disease —2-80 Crohn's disease and 36 ulcerative colitis—from 1975 to 1985. Small spleen size, of lesser degree than that of classic splenic atrophy, is associated with presurgery disease complications as well as infective problems after surgery. Spleen size was not related to site or extent of disease, or to recurrence, but the wide range of spleen size seen in inflammatory bowel disease, comparable to that seen in malignancy suggests that more sophisticated tests of splenic function might show a closer correlation with disease patterns Dr. Jorge Pereira was supported by a fellowship from Rotary International.     

Cytomegalovirus infection in patients with inflammatory bowel disease

OBJECTIVE: It has been suggested that, in inflammatory bowel disease, cytomegalovirus behaves in the intestine as a nonpathogenic bystander, and even its finding in intestinal mucosa has unclear clinical relevance. We report our experience with a small series of patients with refractory inflammatory bowel disease and cytomegalovirus infection and their clinical outcome. METHODS AND RESULTS: Nine patients with moderate-severe attacks of inflammatory bowel disease did not respond to i.v. prednisone (1 mg/kg/day) for a mean of 24 days. Four of these patients were further treated with i.v. cyclosporine A (4 mg/kg/day). Cytomegalovirus infection was diagnosed in two patients after resection for treatment failure. In the remaining patients, cytomegalovirus infection was diagnosed in endoscopic mucosal biopsies and i.v. ganciclovir was then administered at a dose of 10 mg/kg/day for 2-3 wk. Five of these patients went into clinical remission, allowing corticosteroid and cyclosporine A discontinuation. Follow-up biopsies were performed and in all cases cytomegalovirus could not be detected in the colonic tissue. Two patients needed to be treated with intravenous cyclosporine A after antiviral therapy because of persistence of clinical symptoms despite the elimination of cytomegalovirus infection. CONCLUSIONS: Cytomegalovirus infection may play a role in the natural history of refractory inflammatory bowel disease and in some of its complications. The clearance of cytomegalovirus in colonic mucosa may lead some of these patients to remission.     

Fracture-associated hospitalizations in patients with inflammatory bowel disease

Background  

Maintenance of bone health is an important concern in patients with inflammatory bowel disease (IBD). They may frequently have impaired bone density resulting in greater incidence of fractures.