Pulmonary embolism and portal vein thrombosis in an immunocompetent adolescent with acute cytomegalovirus hepatitis

Cytomegalovirus infection is usually asymptomatic or resembles infectious mononucleosis with fever, pharyngitis, arthralgias, lymphadenopathy, and atypical lymphocytosis. Even though primary CMV infection is usually self-limited in healthy individuals, significant complications can develop in immunocompromised patients. Venous or arterial thromboembolic phenomena are uncommon, yet very serious complications of CMV infection. Most published reports describe immunosupressed patients after organ transplantation or in the presence of HIV co-infection. However, thrombotic events in CMV infected immunocompetent individuals may occur. We describe the case of an immunocompetent adolescent with acute cytomegalovirus hepatitis that was complicated with pulmonary embolism and portal vein thrombosis. To our knowledge, this is the first reported case in which these two thrombotic phenomena occurred simultaneously in an adolescent with no obvious predisposing factors for thrombosis in the setting of an acute CMV infection.     

Acute portal and mesenteric thrombosis: unusual presentation of cytomegalovirus infection

Cytomegalovirus infection is a benign disease in immunocompetent patients. In-vitro and in-vivo studies show that cytomegalovirus may cause arterial and venous thrombosis through different mechanisms. We describe two cases of acute cytomegalovirus infection complicated by portal and mesenteric vein thrombosis leading to intestinal ischemia. Both patients carried the heterozygous prothrombin G20210A mutation. The presence of this unusual complication should be searched for in patients with acute cytomegalovirus infection and abdominal symptoms in order to start early anticoagulation. The necessity for full thrombophilic screening is also pointed out.     

Cholestasis,ascites and pancytopenia in an immunocompetent adult with severe cytomegalovirus hepatitis

Human cytomegalovirus (CMV) is a herpesvirus, which establishes lifelong latency after primary infection and leads to severe disease in immunocompromised patients. However, CMV infection in immunocompetent patients is usually asymptomatic and severe organ damage is rarely reported. We report a case of severe CMV hepatitis in an immunocompetent patient presenting with cholestasis, portal hypertension-related ascites and pancytopenia. The patient was asymptomatic with normal liver function and negative CMV DNA after two weeks of antiviral therapy. This case is an example of a common infection with an uncommon presentation, and suggests that testing for CMV should be carried out, even in patients with normal immune status, presenting with severe liver damage or cholestasis.     

Acute cytomegalovirus infection and venous thrombosis: role of antiphospholipid antibodies

Cytomegalovirus (CMV)-induced thrombosis has been reported in immunocompromised patients, such as transplant recipients and patients with AIDS. Recent cases also describe thrombotic phenomena in immunocompetent patients with CMV infection. Various mechanisms may explain the role of CMV in thrombosis: this virus can damage endothelial cells, activate coagulation factors, and induce production of antiphospholipid (aPL) antibodies. We present a case report of a previously healthy white woman with a pulmonary embolism associated with CMV infection and the presence of aPL antibodies, and we discuss the role of the aPL antibodies associated with CMV infection in the pathogenesis of thrombosis.     

Liver disease in cytomegalovirus mononucleosis: a light microscopical and immunoperoxidase study of six cases

Six liver biopsies from previously healthy adult patients with cytomegalovirus (CMV) mononucleosis were studied by routine light microscopy and by the immunoperoxidase technique for CMV antigen. Light microscopical findings consisting of a mononuclear portal and sinusoidal infiltrate, increased hepatocellular mitotic activity and minimal hepatocellular necrosis were consistently found. Less common features were granuloma formation and bile duct epithelial damage. Typical CMV nuclear inclusions and CMV antigen were identified in only one case, a patient with marked leukopenia secondary to CMV who had received corticosteroid therapy. The other five cases contained no inclusions and CMV antigen could not be identified by immunoperoxidase staining. This data suggests that, as with hepatitis B, viral antigen is not identifiable in acute CMV hepatitis in the immunocompetent host, perhaps due to active destruction of infected cells. The immunoperoxidase technique for CMV appears to be of little value in the diagnosis of acute CMV hepatitis.     

Complications of infections attributed to cytomegalovirus in a group of 52 kidney transplant patients

Cytomegalovirus (CMV) infection after renal transplantation was studied over a one year period in 52 patients receiving immunosuppressive drugs. During the infectious episodes, viral shedding was systematically detected in the blood and urines by culture on MRC5 cells and CMV antibodies were titrated in the serum by ELISA (IgG: M. A. Bioproducts, IgM: immunocapture Wellcome) and compared to the initial antibody titer determined the day of transplantation. Primary CMV infection was observed in 6 of 22 seronegative patients, attested by CMV shedding from urine and/or blood and by the emergence of CMV IgM antibodies. This primary infection was severe, including at least 4 of the following features: fever greater than 38 degrees C, neutropenia, thrombocytopenia, cytolytic hepatitis, pneumonia, impaired renal function, neurological syndrome, usually occurring about 6 weeks after transplantation. Reactivation was found in 12 of 30 seropositive patients, as shown by excretion of CMV in the urine and significant rise of specific antibodies. This reactivation occurring about 9 weeks after surgery was symptomatic in 5 patients with severe illness and associated with the presence of IgM antibodies in 2 cases. Rise of CMV antibodies was observed in 10 seropositive patients without excretion of virus. It coincided with symptomatic infection in only three patients who displayed severe symptoms, with presence of CMV IgM antibodies in one case. As previously reported, we confirm that CMV infection is a frequent complication of organ transplantation. It may be clinically silent in renal transplant patients or cause problems ranging from fever to pneumonia or retinitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thrombosis associated with acute cytomegalovirus infection: a meta-analysis

Background

Thrombosis associated with acute cytomegalovirus (CMV) infection has been reported in the medical literature almost 100 times thus far. Still, the clinical characteristics of patients with both conditions have never been systematically reviewed and described.

Methods

A literature search was conducted for all (n = 97) reports concerning thrombosis associated with acute CMV infection. The current knowledge concerning this unique association and previous clinical experience are presented here.

Results

The incidence of thrombosis among acute CMV infection hospitalized patients was 6.4%, and the incidence of acute CMV infection among thrombosis hospitalized patients was 1.9-9.1%. Most (n = 64; 65.9%) reported patients were immunocompetent. Mean age of reported patients was 39.7 ± 14.9 years. Female-male ratio was 1:1. DVT/PE, splanchnic vein thrombosis and splenic infarction were the most prevalent thromboses associated with acute CMV infection. While DVT/PE was more prevalent among immunocompromised patients, splanchnic vein thrombosis was more prevalent among immunocompetent patients. Inherited predispositions for thrombosis were significantly more prevalent among immunocompetent patients. Immunocompromised patients were treated with antiviral agents significantly more often. Duration of anticoagulation therapy varied significantly between reported patients. In-hospital mortality rates were 4.9-22.2%.

Conclusions

We believe physicians should be alert for symptoms and signs of thrombosis in patients with acute CMV infection, and for symptoms and signs of acute CMV infection in patients with thrombosis.     

Cytomegalovirus (CMV)-related cutaneous necrotizing vasculitis: case report and literature review

Cytomegalovirus (CMV) infection is usually asymptomatic in immunocompetent patients. A mononucleosis-like syndrome may develop in some patients. Various organ involvements (eg: encephalitis, meningitis, retinitis, myocarditis, pneumonia, hepatitis, enterocolitis, neuritis), which rarely occur in immunocompetent patients, have also been reported. Cutaneous necrotizing vasculitis caused by CMV infection has been reported very rarely in the literature. Here, a case with a very rare clinical form of CMV infection, presenting with persistent fever and livedo reticularis on the extremities and cutaneous necrotizing vasculitis of the toes, is described, and the relevant literature is reviewed. This case report aims to highlight the possibility of CMV infection to be a cause of cutaneous necrotizing vasculitis.     

CASE REPORT: Cytomegalovirus infection as a cause of acute portal vein thrombosis

We report on the case of a 31-year-old woman who developed acute portal vein thrombosis during the course of an acute cytomegalovirus (CMV) infection. We suggest a relationship between CMV infection, its endothelial cell-damaging effects and portal vein thrombosis.     

Disseminated intravascular coagulation due to cytomegalovirus infection in an immunocompetent adult treated with plasma exchange

We report the case of an immunocompetent woman who developed disseminated intravascular coagulation (DIC) due to acute cytomegalovirus (CMV) infection and was successfully treated with plasma exchange. Extensive investigations revealed no other cause for her DIC, and she did not have any recurrence after more than 1 year of follow up. Clinically evident DIC due to CMV infection is most common in immunosuppressed patients. The one previously reported immunocompetent patient with DIC due to acute CMV infection died from the illness despite traditional supportive measures. Plasma exchange is a novel therapy that should be considered in this situation.     

An unusual etiology of viral hepatitis in three renal transplant recipients with normal graft function

Liver impairment in renal transplant recipients is not a common complication and is associated, in most cases, with viral infections (HBV, HCV, HVD, HGV) or drug hepatotoxicity (Cyclosporin, Azathioprine, statins). Cytomegalovirus (CMV) infection is common, with 50 to 80% of the adult population being seropositive for CMV antibodies. In immunocompetent individuals, primary infection is usually asymptomatic or associated with minor illness. CMV remains latent after primary infection. In immunocompromised patients, as in renal transplant recipients or transplant recipients of other solid organ or bone marrow, the virus can cause serious disease. This could be the result of newly acquired infection or reactivation of the latent virus. One of the organs involved in CMV disease is the liver. The subjects of this report are renal transplant recipients with liver impairment due to CMV induced acute hepatitis.     

Acute cytomegalovirus pneumonia and hepatitis presenting during acute HIV retroviral syndrome

Cytomegalovirus (CMV) disease is a frequent opportunistic infection that usually occurs in the late stages of HIV infection as a result of reactivation of a latent infection. We report a case of a 23-year-old man with acute retroviral syndrome complicated by coexisting CMV pneumonia and CMV hepatitis, which were documented by histopathological examination. His CMV pneumonia and hepatitis were assumed to be primary CMV diseases owing to the absence of CMV IgG antibody. To the best of our knowledge, this is the first case of simultaneous CMV pneumonia and hepatitis occurring as primary CMV diseases during primary HIV infection. This case indicates that invasive CMV diseases such as pneumonia and hepatitis should be considered even in patients with primary HIV infection.     

Association between cytomegalovirus infection and venous thromboembolism

It has been suggested that cytomegalovirus (CMV) infection may be associated with thrombosis in immunocompromised patients. In addition, an association between CMV infection and thrombotic events in immunocompetent hosts has been sporadically reported. We report on 1 immunocompromised and 8 immunocompetent adults who were admitted to a tertiary medical center and experienced a venous thromboembolic event during CMV infection. None reported previous thromboembolic events. All patients were diagnosed as suffering from acute CMV infection. Seven of the patients had vein thromboses. Significant additional thrombophilia was identified in 5 patients; 1 had 15.3 U/mL anti-cardiolipin IgM antibodies (elevated >7), 2 others were not evaluated for genetic procoagulant tendency. The exact nature of the procoagulant effect of CMV has not yet been clarified. Even though these mechanistic studies are incomplete, we suggest that from the clinical perspective, the presence of CMV infection should be considered a possible risk factor for thrombophilia, justifying a high index of suspicion for possible thrombotic events and subsequent decisions regarding prophylactic anticoagulation.     

Cytomegalovirus cholangitis and pancreatitis in an immunocompetent patient

Cholangitis and pancreatitis associated with cytomegalovirus (CMV) infection in an immunocompetent patient is reported. Endoscopic retrograde cholangiography performed on a 55-year-old man for evaluation of the cause of jaundice and liver dysfunction revealed a distal focal irregular narrowing of the common bile duct. Microscopic findings of the resected specimen showed chronic cholangitis and CMV pancreatitis. Immunohistochemistry disclosed that epithelial cells in the inflamed bile duct were positive for CMV antigen, which was compatible with CMV cholangitis. Inflammation of the biliary tract or pancreas by CMV has been commonly reported as a complication in immunocompromised patients. Our report appears to be a rare case, but suggests that CMV cholangitis or pancreatitis should be considered in the differential diagnoses of common bile duct stenosis or pancreatitis even in immunocompetent individuals.     

Portal hypertension caused by acute cytomegalovirus infection with liver involvement in an immunocompetent patient

Primary infection by cytomegalovirus in immunocompetent patients is usually unapparent. We report a case of severe acute cytomegalovirus infection in a young immunocompetent male with pulmonary and hepatic involvement and portal hypertension who recovered without specific antiviral therapy with complete resolution of sonographic signs of portal hypertension after 6 months.     

Cytomegalovirus infection of bile duct epithelial cells, hepatic artery and portal venous endothelium in relation to chronic rejection of liver grafts

BACKGROUND/AIM: Chronic rejection is an important cause of graft loss following liver transplantation. A number of risk factors for chronic rejection have been identified previously, albeit inconsistently. These include cytomegalovirus infection detected by a number of different techniques, including immunohistochemical staining and in situ hybridisation of liver grafts. However, tissue-based techniques for the detection of CMV have not been applied to grafts lost to conditions other than chronic rejection. The purpose of this study was to investigate the relationship between the presence of cytomegalovirus infection detected by in situ hybridisation and immunohistochemistry with respect to graft outcome, the presence of cytomegalovirus infection detected by other techniques and in addition, the type of infected cell. METHODS: The 29 patients studied included 15 patients who lost their primary liver graft to chronic rejection in 8 cases, to hepatic artery thrombosis in 4 cases and to causes other than chronic rejection or hepatic artery thrombosis in 3 further cases. In each case, sections containing septal or large ducts and vessels were selected (usually blocks) since these may be more representative. Needle biopsies from 14 further patients who ultimately achieved satisfactory graft function served as control tissue. Of these, ten had evidence of cytomegalovirus infection at the time of study by serum/urine PCR, DEAFF testing or seroconversion, while 4 patients had no evidence of cytomegalovirus infection according to these techniques. RESULTS: Cytomegalovirus infection was detected in the liver of 12 of the 29 patients. These included 8/15 grafts lost, which comprised 3/8 with chronic rejection, 2/3 with hepatic artery thrombosis and 3/4 with grafts lost to other causes, as well as 4/14 who retained grafts. CMV was detected most commonly in association with symptomatic infection and notably was detected only by in situ hybridisation in two cases. Predominant cell types that contained cytomegalovirus were hepatocytes and mononuclear cells. However, bile duct epithelial cells, hepatic artery endothelial cells and portal venous endothelial cells also contained cytomegalovirus in some cases. CONCLUSIONS: These data support previous studies that cytomegalovirus infection is detectable in patients with chronic rejection and are consistent with the theory that CMV is involved in chronic rejection. However, cytomegalovirus infection was detected in explanted grafts lost to conditions other than chronic rejection, and the association may not be causal but a consequence of graft injury.     

Cytomegalovirus colitis--an unusual cause for diarrhoea in an elderly woman

BACKGROUND: Clinically apparent cytomegalovirus (CMV) disease is uncommon in the immunocompetent host, despite the high seroprevalence rate of CMV in the general population. CASE REPORT: Here, we report the case of CMV colitis in an immunocompetent elderly woman who developed a large pulmonary embolism during her illness. DISCUSSION: The diagnosis of CMV colitis is made on histological examination of biopsy specimens obtained at sigmoidoscopy or colonoscopy. Extensive CMV disease can be accompanied by vascular thrombosis.     

Cytomegalovirus related fatal duodenal diverticular bleeding: Case report and literature review

Involvement of gastrointestinal tract by cytomegalovirus(CMV) is common. CMV infections mainly run their course without any clinical signs in immunocompetent hosts. In contrast, CMV can cause severe infections with serious consequences in a immunocompromised state typically associated with organ transplants, highly immunosuppressive cancer chemotherapy, advanced HIV infection or treatment with corticosteroids. The incidence and severity of these manifestations of CMV is directly proportional with the degree of cellular immune dysfunction, i.e., CD8+ Cytotoxic T-cell response. Clinical manifestations of CMV can become apparent in different situations including reactivation of CMV from latency, primary infection in a seronegative host, or exposure of a seropositive host to a new strain of CMV. As the clinical signs of CMV in immunodeficient patients are usually sparse, physicians should be highly vigilant about CMV infection, a treatable condition that otherwise is associated with significant mortality. Here we report a rare case of severe gastrointestinal CMV infection with sustained immunodeficiency secondary to treatment with steroids manifesting as fatal duodenal diverticular bleeding.     

Cytomegalovirus colitis mimicking ischemic colitis in an immunocompetent host

Cytomegalovirus (CMV) causes infections in healthy individuals and compromised hosts. In compromised hosts, CMV may cause encephalitis, pneumonia, hepatitis, colitis, and so forth. In immunocompetent hosts, CMV mononucleosis is the most common clinical manifestation and CMV colitis is rare. We present a case of an 82-year-old immunocompetent man who presented with community-acquired bloody diarrhea. A computed tomography scan of the abdomen revealed pan-colitis. His age and abdominal pains suggested ischemic colitis as the cause of his bloody diarrhea. Workup for Clostridium difficile and all enteric pathogens were negative. The patient remained febrile with abdominal pain. During the second week, he underwent sigmoidoscopy for biopsy, which revealed viral inclusions of the Cowdry owl eye inclusion bodies characteristic of CMV. CMV colitis was diagnosed in the patient; he was successfully treated with a course of oral valganciclovir and made an uneventful recovery.     

Fulminant varicella infection complicated with acute respiratory distress syndrome, and disseminated intravascular coagulation in an immunocompetent young adult

Primary varicella infection in immunocompetent adults is very rare, but it has a high mortality rate because of serious complications. We describe a case of varicella infection in a previously healthy young adult complicated with acute respiratory distress syndrome (ARDS), rhabdomyolysis, acute hepatitis and disseminated intravascular coagulation (DIC). Acyclovir was administered for varicella infection and the ARDS was successfully treated with steroidpulse therapy, hemofiltration and a mechanical respiratory support with a positive end-expiratory pressure. Early administration of antiviral agents and extensive management were thought to be necessary for such patients with severe complications.