Gastrointestinal Cytomegalovirus Infection Research Articles

Severe gastrointestinal cytomegalovirus infection in a patient diagnosed with late onset combined immunodeficiency

Late onset combined immunodeficiency (LOCID) is a rare variant of common variable immunodeficiency (CVID), typically affecting adult patients who present with opportunistic infections (OI) and/or low CD4+ T lymphocytes. Diagnostic delay is common due to the rareness of this entity, increasing morbidity and mortality. We report on a 66-year-old male who developed a severe gastrointestinal cytomegalovirus (CMV) infection, refractory to antiviral treatment and anti-cytomegalovirus specific human immunoglobulin administration, with a fatal outcome due to an undiagnosed LOCID.

Severe gastrointestinal cytomegalovirus infection with underlying common variable immunodeficiency in a middle aged lady

Cytomegalovirus is a common herpes virus infection found worldwide and by adulthood majority become seropositive. In immunosuppressed state it may reactivate to cause tissue invasive disease in gastro intestinal tract, liver, lungs, brain and retina with or without viremia. It is commonly seen in bone marrow transplant, organ transplant, AIDS and autoimmune disease requiring intense immunosuppressive therapy. Common variable immunodeficiency is a condition that affects both arms of the immune system and can lead to opportunistic infections. Chance is more when CD4 counts falls below 50 cells/microlt.

An Unexpected Cause of Acute Abdomen Late After Heart Transplantation—A Case Report

Cytomegalovirus (CMV) infection is a frequent complication after a solid organ transplant, and in 86% of the cases, CMV disease occurred during the first 6 months after transplantation. Invasive CMV infections may be present as ulcerative infections of the upper gastrointestinal tract with esophagitis, gastritis, and ulcerations of the duodenum and the small bowel; however, CMV infections of the pancreatobiliary system, especially papillitis, are rarely observed. We present a case report of a man who underwent a heart transplant 6 years before, with a clinical picture of duodenitis and a simultaneous pseudotumor of major duodenal papilla who developed signs of acute abdomen caused by gastrointestinal CMV infection, successfully treated with medical therapy with valganciclovir. There is an urgent need for developments in CMV and solid organ transplantation to stratify the risk of late-onset CMV disease.

Gastrointestinal cytomegalovirus disease secondary to measles in an immunocompetent infant: A case report

BACKGROUNDGastrointestinal cytomegalovirus (CMV) disease occurs commonly in immunocompromised/immunodeficient patients with advanced human immunodeficiency virus infection, neoplasm, solid organ transplantation, hematopoietic stem cell transplantation, or treatment with immunosuppressants, but is rarely reported in association with measles infection.CASE SUMMARYWe describe a case of extensive gastrointestinal CMV disease secondary to measles infection in a 9-mo-old boy who presented with persistent fever and bloody diarrhea. His condition was improved after ganciclovir treatment. Serological analysis of CMV showed negative immunoglobulin (Ig) M and positive IgG. Blood CMV-DNA was 9.26 × 103 copies/mL. The diagnosis of gastrointestinal CMV disease was confirmed by histopathological findings of intranuclear and intracytoplasmic inclusions and Owl’s eye inclusion. This case highlights the differential diagnosis and histopathological characteristics of gastrointestinal CMV infection and laboratory tests.CONCLUSIONExtensive gastrointestinal CMV lesions can be induced by the immune suppression secondary to measles infection. Rational, fast, and effective laboratory examinations are essential for suspected patients.

COVID-19 and Cytomegalovirus Co-infection: A Challenging Case of a Critically Ill Patient with Gastrointestinal Symptoms

We describe a case of COVID-19 and cytomegalovirus (CMV) co-infection in a critically ill patient.Clinical symptoms simulated mesenteric vascular involvement and intestinal obstruction.The successful management of invasive CMV colitis in a patient with COVID-19 with atypical symptoms is described.

Colon perforation due to cytomegalovirus infection in a patient with idiopathic hypereosinophilic syndrome: a case report

BackgroundHypereosinophilic syndrome (HES) is a very rare disease and usually treated with corticosteroids. Gastrointestinal (GI) cytomegalovirus (CMV) infection is also rare but frequent in patients with immunocompromised status. These two related diseases present with similar manifestations, and may result in a life-threatening complication: perforation. However, the treatment strategies differ greatly. Here, we report a case of colon perforation due to cytomegalovirus infection in a patient with idiopathic HES.Case presentationA 41-year-old man with a history of HES was transferred to our hospital due to an acute onset of abdominal pain. During the treatment course of HES, this patient received CMV-DNA test with a result of < 2000 copies/ml. Computed tomography (CT) suggested colon perforation. An emergency surgery was performed immediately. Pathological diagnosis revealed CMV infection and infiltration of eosinophils. This patient received both anti-CMV therapy and immunosuppression therapy. Subsequently, the patient recovered and was discharged 25 days after the operation.ConclusionDuring the course of HES treatment, CMV infection should be reconsidered if digestive symptoms relapse.

Patient characteristics, clinical manifestations, prognosis, and factors associated with gastrointestinal cytomegalovirus infection in immunocompetent patients

BackgroundGastrointestinal (GI) cytomegaloviral (CMV) infection is common among patients with immunocompromised status; however, data specific to GI-CMV infection in immunocompetent patients are comparatively limited.MethodsThis retrospective study included patients diagnosed with GI-CMV infection at Siriraj Hospital (Bangkok, Thailand) during 2008–2017. Baseline characteristics, presentations, comorbid conditions, endoscopic findings, treatments, and outcomes were compared between immunocompetent and immunocompromised.ResultsOne hundred and seventy-three patients (56 immunocompetent, 117 immunocompromised) were included. Immunocompetent patients were significantly older than immunocompromised patients (73 vs. 48.6 years, p < 0.0001). Significantly more immunocompetent patients were in the ICU at the time of diagnosis (21.0% vs. 8.6%, p = 0.024). GI bleeding was the leading presentation in immunocompetent, while diarrhea and abdominal pain were more common in immunocompromised. Blood CMV viral load was negative in significantly more immunocompetent than immunocompromised (40.7% vs. 12.9%, p = 0.002). Ganciclovir was the main treatment in both groups. Significantly more immunocompetent than immunocompromised did not receive any specific therapy (25.5% vs. 4.4%, p ≤ 0.01). Six-month mortality was significantly higher among immunocompetent patients (39.0% vs. 22.0%, p = 0.047). Independent predictors of death were old age and inpatient or ICU clinical setting. Treatment with antiviral agents was the only independent protective factor.ConclusionGI-CMV infection was frequently observed among immunocompetent elderly patients with comorbidities or severe concomitant illnesses. GI bleeding was the most common presentation. Blood CMV viral load was not diagnostically helpful. Significantly higher mortality was observed in immunocompetent than in immunocompromised patients, but this could be due to more severe concomitant illnesses in the immunocompetent group.

A case report of late-onset gastrointestinal cytomegalovirus infection 17 years post kidney transplantation

Cytomegalovirus (CMV) infection, one of the most common viral infections seen post-transplantation, is rarely known to occur after 15 years. Here, we report a 59-year-old male on minimum immunosuppressive agents who presented with abdominal pain and was found to have CMV infection of the distal ileum with concurrent high CMV viral load 17 years post kidney transplantation.

Routine Hematoxylin and Eosin Stain Is Specific for the Diagnosis of Cytomegalovirus Infection in Gastrointestinal Biopsy Specimens.

Gastrointestinal cytomegalovirus (CMV) infection is a serious complication in immunocompromised patients; clinicians often expect expedited results for biopsy specimens. Our goal is to determine the accuracy of identification of CMV on hematoxylin and eosin (H&E) stain. A total of 361 biopsy specimens from 273 patients with suspicion for CMV infection were retrieved. CMV was detected by immunohistochemistry (IHC) in 37 specimens acquired from 33 individual patients (average age = 54 years). Among the CMV-positive patients, 29 (88%) were reported to be immunosuppressed. Colon was the most common affected location. Of 37 CMV-positive specimens by IHC, 28 were positive by H&E (76%), 6 were negative (16%), and 3 were suspicious (8%). Of the 29 positive specimens on H&E, 28 were confirmed by IHC (97%) and 1 was indeterminate (3%). The sensitivity and specificity of H&E were 84% and 94%, respectively; the positive predictive value was 97%, and the negative predictive value was 93% ( P < .00001). Our results show that a preliminary diagnosis of CMV infection, based on H&E stains, can be reported with high specificity and low risk for false-positive results. Suspicious cases should be deferred pending the result of IHC stains.

Cytomegalovirus Disease of the Upper Gastrointestinal Tract: A 10-Year Retrospective Study

Background and Aims: Cytomegalovirus (CMV) disease of the gastrointestinal (GI) tract is a major cause of morbidity and mortality in immunocompromised patients. The colon is the most commonly affected site, and the literature is scarce regarding CMV disease of the upper GI tract. Therefore, our study aimed to evaluate the clinical and endoscopic features of upper GI CMV disease. Methods: This 10-year retrospective study included all patients with a histopathological diagnosis of upper GI CMV infection. Patients' clinical, endoscopic, therapy, and follow-up data were collected from medical records. Results: Twelve patients with histopathologically proven upper GI CMV disease were identified (age 61 ± 18 years, 50% men). Most of the patients were immunocompromised (75%) due to acquired immunodeficiency syndrome (AIDS), malignancy, and/or immunosuppressive therapy. In the remainder (25%), the disease occurred in the absence of immunodeficiency and immunosuppression. Three patients (all with AIDS) presented with disseminated CMV infection. In the majority of the cases (83%), upper GI CMV disease was symptomatic, and the most common clinical presentations were odynophagia/dysphagia (25%) and nausea/vomiting (25%). Endoscopically, there were 5 cases of esophagitis (42%) and 7 cases of gastritis (58%). The lower esophagus (33%) and the gastric antrum (42%) were the most frequently affected GI sites. Regardless of the location, mucosal ulceration was the most common endoscopic finding (75%) and was associated with very deep ulceration resembling cavitation in 2 cases. Other endoscopic features were mucosal edema, hyperemia, and nodularity (25%). Eleven patients (92%) received antiviral treatment (duration 26 ± 12 days). The 1-month and 1-year mortality rates were 16.7 and 25%, respectively. Conclusions: Upper GI CMV disease can occur in the absence of immunodeficiency and immunosuppression. It is usually symptomatic, and mucosal ulceration is often evident at endoscopy. It is associated with significant mortality; therefore, early diagnosis and adequate antiviral treatment are essential.

Histologic detection of cytomegalovirus and its application in gastrointestinal cytomegalovirus infection

To investigate the clinical and pathologic features of gastrointestinal cytomegalovirus (CMV) disease, and the histological detection of CMV. Forty-one gastrointestinal tissues were obtained from 35 patients suspected for gastrointestinal CMV disease. The pathologic changes of these specimens were evaluated by immunohistochemistry and in situ hybridization for CMV, and these were compared to serologic detection methods. CMV was detected in 23/41 tissues. There were 32 serologic CMV DNA tests at the time of biopsies or operations. Compared with histological detection, the sensitivity and specificity of serologic CMV DNA tests were 73.7% and 69.2% respectively. Gastrointestinal histological detection of CMV has important clinical application. HE staining combined with immunohistochemistry and/or in situ hybridization detection is a reliable method to detect CMV.

Surgical manifestations of gastrointestinal cytomegalovirus infection in children: Clinical audit and literature review

IntroductionGastrointestinal sequelae of cytomegalovirus are rare, usually associated with significant immune compromise, and carry a high morbidity and mortality. Gastrointestinal disease frequently requires surgical intervention for diagnosis and management. AimThe aim of the study is to evaluate the incidence, presentation and management of gastrointestinal cytomegalovirus disease in a pediatric population. MethodBetween January 2003 and June 2011, a retrospective folder review was conducted of all symptomatic children with proven CMV disease, presenting to the surgical service. Eligible patients were identified using the surgical, histopathology and serology databases. ResultsThirty-eight patients (1.8/1000 surgical admissions) were identified with a median presenting age of 5months (range 3days–12years). Esophagitis (n=18) and small bowel disease (n=16) predominated, but CMV was seen throughout the gastrointestinal tract. Risk factors included HIV infection (n=21, 55%) and recent gastrointestinal surgery or infection (n=10, 26%). Characteristic multiple jejunoileal perforations were seen in six patients. Compared to upper GIT disease, intestinal involvement was associated with younger age and doubled mortality. In HIV-infected children, median CD4 (%) was lower in intestinal compared to upper gastrointestinal disease. Morbidities included anastomotic breakdowns (5), anastomotic strictures (3), relook laparotomies (10), resistant esophageal strictures (5) and prolonged parenteral nutrition (5). Anti-CMV drugs were given in 63%. Overall mortality was 32% (12/38) and was associated with lower GIT disease. ConclusionInvasive CMV gastrointestinal disease in our children was predominantly HIV-associated, or followed a major lower gastrointestinal inflammatory insult in infants younger than 6months. Successful therapy requires a high index of suspicion of active CMV disease to allow early implementation of CMV viral load control and aggressive treatment of the underlying immune impairment. Multiple surgical interventions are often required for both tissue diagnosis and management of acute and chronic complications. CMV-viral-load-tailored anti-CMV therapy is supported by recent literature.

Usefulness of quantitative PCR in biopsy specimens for early therapeutic intervention in gastro-intestinal cytomegalovirus infections after allogeneic stem cell transplantation

Gastro-intestinal cytomegalovirus infection (GI-CMV), which occurs after allogeneic stem cell transplantation (allo-SCT), is diagnosed by immunostaining of biopsied tissues obtained using a fiberscope. However, the sensitivity of this pathological diagnostic test is poor. We evaluated the suitability of using quantitative polymerase chain reaction (qPCR) to test GI-mucosal tissues for CMV. We analyzed adult patients who had undergone allo-SCT at our institute. Twenty-seven specimens were collected from patients undergoing GI-fibers-copy for upper GI-symptoms after allo-SCT. Of these patients, 9 tested positive for CMV by qPCR; their symptoms resolved soon after receiving antiviral therapies for CMV. Pathological procedures detected GI-CMV in only 3 cases. In contrast, CMV qPCR was positive for 12 of 30 specimens collected from patients with lower GI-symptoms by using colon fibers-copy. Antiviral therapies were effective in all but one case. GI-CMV was diagnosed pathologically in only 5 cases. Therefore, CMV qPCR is effective for early therapeutic intervention in CMV-GI patients after allo-SCT.

Clinical significance of isolated cytomegalovirus-infected gastrointestinal cells.

Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract is associated with high mortality in immunosuppressed patients. However, few studies have correlated blood CMV load with GI histopathological findings. Furthermore, there have been few studies determining the clinical significance of isolated CMV infection. Cases were selected for the diagnosis of GI CMV infection by searching the information system of a tertiary hospital. The electronic medical record was reviewed for each case to determine blood viral load, clinicopathological features at the time of diagnosis and clinical outcomes after discharge. In all, 30 patients with CMV-positive intestinal biopsies confirmed by immunohistochemistry (IHC) were identified. All were immunosuppressed. CMV inclusions were also recognized by hematoxylin and eosin stain in 27% of the cases, and the remaining cases were identified by IHC alone. CMV blood load was only positive in 17% of the cases; 8 cases had only isolated CMV-infected cells (0.1-0.5 IHC count/high-power field), with the following outcomes: worsening symptoms that responded to antiviral therapy (n = 5); clinical improvement without treatment (n = 1); death without treatment (n = 2). CMV infection of the intestines is clinically significant but will not always present with classic viral cytopathic changes. IHC should be considered in any case where there is a clinical suspicion for CMV infection. Identification of isolated CMV infection by IHC should be considered clinically significant. Current blood viral load tests have poor sensitivity in detecting CMV intestinal infection. Future studies will investigate the predictive value of positive peripheral blood viral load in patients with intestinal symptoms.

Debilitating chronic diarrhea caused by generalized gastrointestinal cytomegalovirus infection in an immunocompetent adult.

Gastrointestinal cytomegalovirus (CMV) infection is a common opportunistic infection in immunocompromised patients, especially patients with acquired immunodeficiency syndrome and transplant recipients. In contrast, CMV infection of the gastrointestinal tract is rare in immunocompetent individuals. We report a case of severe, protracted, and debilitating diarrhea caused by generalized CMV infection of the gastrointestinal tract in an elderly woman with no apparent immunosuppression. An extensive diagnostic investigation demonstrated CMV-associated disease affecting both the upper and lower gastrointestinal tracts (esophagus, small intestine, and colon). Such extensive simultaneous involvement of the alimentary tract in an immunocompetent patient is rare and presents a diagnostic and therapeutic challenge. The diagnosis was based on a combination of endoscopic, histopathological, serological, and polymerase chain reaction analysis findings and our patient was successfully treated with intravenous ganciclovir. Our case demonstrates that gastrointestinal CMV infection should be considered in the differential diagnosis of severe chronic diarrhea in immunocompetent patients and that antiviral treatment may be justified in this setting.

Jejunal stricture in a premature infant: Is cytomegalovirus the causative pathogen or a superinfection?

Cytomegalovirus infection can cause gastrointestinal disease, especially in immunocompromised patients and premature infants. In the neonatal period, however, gastrointestinal involvement is infrequent. A case of cytomegalovirus enteritis and jejunal stricture in a preterm neonate is presented. The diagnosis was established after the histopathology of the surgical specimen demonstrated the presence of cytomegalovirus inclusion bodies. Every neonatal gastrointestinal cytomegalovirus infection case has been described in the literature as a necrotizing enterocolitis-like illness, but none of them clearly identifies whether cytomegalovirus was the pathogen responsible for causing necrotizing enterocolitis or whether cytomegalovirus occured as an infection during the course of necrotizing enterocolitis.

Historical Comparison of Prophylactic Ganciclovir for Gastrointestinal Cytomegalovirus Infection in Kidney Transplant Recipients

BackgroundCytomegalovirus (CMV) can cause morbidity in kidney transplant recipients. The gastrointestinal (GI) tract is a major target for CMV disease. The aim of this study was to evaluate the benefit of ganciclovir prophylaxis on GI CMV infection in intermediate-risk CMV seropositive transplant recipients. MethodsSince January 2009, intravenous ganciclovir (5 mg/kg, twice daily) was administered for 14 days after kidney transplantation in 41 patients. The historical control group consisted of 45 patients who received kidney transplantations between January 2007 and December 2008. To evaluate the effects of prophylaxis on GI CMV infection, we performed routine endoscopic examinations with mucosal biopsies at the time of transplantation as well as 1, 3, and 6 months thereafter. ResultsThe average age of the 86 studied patients was 43.7 ± 10.6 years (range = 14–63) and the male-to-female ratio 1:1.3. Forty-three (50%) patients underwent deceased donor transplantations and 84 (97.7%) patients were CMV seropositive at that time. The incidence of GI CMV infection was significantly lower among the prophylaxis than the historical control group (24.4% vs 48.9%, P = .026). Patient age, numbers of deceased donors, and tacrolimus trough levels at 1 and 3 months posttransplant were significantly lower in the prophylaxis than the historical control group. Logistic regression analysis revealed ganciclovir prophylaxis to be the only significant risk factor for GI CMV infection. ConclusionProphylactic treatment with ganciclovir decreased the incidence GI CMV infection among seropositive kidney transplant recipients.

Update on Cytomegalovirus Infections of the Gastrointestinal System in Solid Organ Transplant Recipients

Cytomegalovirus (CMV) infection of the gastrointestinal tract is the most common manifestation of tissue-invasive CMV disease, and is a significant cause of morbidity and mortality in the solid organ transplantation (SOT) recipient. In addition to the direct effects of the infection, its indirect effects on allograft function, risk for other opportunistic infections, and mortality are significant in this population. The most common clinical syndromes are esophagitis, colitis, and hepatitis; however, infection can occur anywhere in the gastrointestinal tract. Diagnosis is usually by histopathology or viral culture of tissue specimens; molecular assays also often have a role. Antivirals are the cornerstone of therapy for gastrointestinal tract CMV disease and complications such as recurrent infection and antiviral resistance are not uncommon. Prevention with antiviral prophylaxis or preemptive therapy is important. This review summarizes recent data regarding the clinical manifestations, diagnosis, treatment, and prevention of gastrointestinal tract CMV infection in the SOT population.

Cytomegalovirus infection presenting as isolated inflammatory polyps of the gastrointestinal tract

Gastrointestinal involvement by cytomegalovirus (CMV) infection is a well recognised complication in patients taking steroid/immunosuppressive therapy or suffering from immunodeficiency and debilitating diseases. Rarely, CMV may affect immunocompetent healthy individuals. However, CMV infection presenting as isolated inflammatory polyps is unusual. We describe five patients (1 infant and 4 adults 56-80 years of age) with CMV-associated polyps that posed diagnostic difficulty. Four lesions were initially misdiagnosed as inflammatory fibroid polyp (n = 2), atypical/suspicious lymphoproliferative (n = 1) and mesenchymal (n = 1) lesion. Underlying diseases were kidney transplantation (1), ulcerative colitis (1), and HIV infection (1). One elderly patient had pseudomembranous colitis but no significant co-morbidity. One patient had no relevant diseases. The lesions affected the colon (3), small intestine (1) and gastric antrum (1); one was multifocal. The size ranged from 0.3 cm to 2.0 cm. Histologically, all lesions showed extensive surface ulceration and abundant capillary-rich granulation tissue containing activated lymphoid cells, plasma cells, granulocytes, enlarged histiocytes and atypical fibroblasts. Eosinophils were prominent in two cases. Immunohistochemistry showed unequivocal intranuclear CMV inclusions. These cases widen the spectrum of endoscopic and histological appearance of gastrointestinal CMV infection. Awareness of these unusual lesions should enhance detection and proper classification of this probably under-recognised CMV presentation.

Cytomegalovirus duodenitis, pseudotumour and cholangiopathy in advanced HIV

Gastro-intestinal cytomegalovirus (CMV) infection manifests as oesophagitis, gastritis, enteritis and colitis. Reports of duodenal involvement are rare. We found only one reported CMV-induced pseudotumour of the duodenum and 14 CMV-induced gastrointestinal pseudotumours.