Cytomegalovirus Antigenemia Assay Research Articles

Prolonged Epstein-Barr Virus DNA Detection in a Case of Infantile Infectious Mononucleosis

Abstract Infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) is a relatively common disease in adolescents and children. There have been few reports on serial changes in EBV DNA load in IM infants, and we herein describe the precise clinical course as well as the kinetics of EBV DNA load in a case of infantile IM. An 11-month-old girl presented with persistent fever, splenomegaly, and rash and was diagnosed with IM on the basis of her EBV DNA load despite the absence of a significant increase in anti–viral capsid antigen-IgM. The result of a cytomegalovirus antigenemia assay was also positive during the acute phase, but this quickly changed to negative. However, despite the spontaneous resolution of symptoms and seroconversion, the EBV DNA load result remained positive for more than 1 year. Although the potential impact from cytomegalovirus infection is uncertain, we speculate that prolonged EBV DNA load may occur in immunocompetent infantile IM patients.

Adult T-cell leukemia/lymphoma with multiple intracranial masses and CMV and HHV-6 reactivation at initial presentation

A 55-year-old male was referred to our hospital after complaining of a sore throat for a month. Physical examination revealed a disturbance in consciousness, nuchal rigidity, painful multiple ulcers in the oral cavity, and erythema, the size of rice grains on the body. Hematological examination showed the following results: white blood cells, 7,910/µl (abnormal lymphocytes 2%), LDH, 203 U/l, corrected calcium, 11.2 mg/dl, soluble IL-2 receptor, 11,800 U/ml, and cytomegalovirus antigenemia assay (C10, C11) 43/49. Abnormal lymphocytes (CD4+CD25+) were discovered in the peripheral blood, bone marrow, and skin samples. Southern blotting of peripheral blood revealed monoclonal integration of human T-cell leukemia virus type 1 (HTLV-1) provirus DNA; and consequently, he was diagnosed with adult T-cell leukemia/lymphoma (ATLL). Multiple tumors with ringed contrast effect were observed in the brain parenchyma using contrast-enhanced computed tomography. The cell number in the cerebrospinal fluid was 1,320/mm3 (ATLL cells were 79% in flow cytometry), and the protein level was 244 mg/dl; moreover, the examination revealed a positive result for human herpesvirus 6 DNA. Despite herpesvirus genus treatment and modified LSG15 therapy combined with intrathecal chemotherapy, the patient became comatose and died on day 21 of hospitalization. A better understanding of the pathogenesis of ATLL, and the involvement with the central nervous system is needed along with the development of standard treatment.

Factors associated with cytomegalovirus antigenemia in patients with rheumatic disease: A retrospective study

IntroductionThis study aimed to examine the factors associated with cytomegalovirus (CMV) antigenemia and the time of onset of CMV antigenemia among patients with rheumatic diseases. MethodsA single-center, retrospective, observational study was conducted in our institution from January 2009 to December 2017. This study included patients with rheumatic diseases who had at least one CMV antigen measurement. Multivariate analysis and receiver operating characteristic analysis was performed. ResultsA total of 249 patients underwent CMV antigenemia assay, and 84 (33.7%) patients tested positive. When the association between CMV antigenemia and possible associated factors was investigated, multivariate analysis showed that daily steroid dose increased the odds of having CMV [odds ratio 16.25, 95% confidence interval (CI), 5.360–49.253]. In this study, the cutoff value of daily steroid dose found in this study (0.45 mg/kg/day) was reasonable in clinical practice, and the area under the curve of the steroid dose was 0.838 [95% CI 0.781–0.882], which was the largest of the known indicators. Moreover, the median time from the start of immunosuppressive therapy to the onset of CMV antigenemia was 30 (interquartile range, 21–44) days, and most of the daily steroid users (85.7%) developed CMV antigenemia within 60 days. ConclusionsThe daily steroid dose is the most important factor associated with CMV antigenemia. Therefore, monitoring and treatment strategies based on the steroid dose, especially in the initial 2 months, are important.

Cytomegalovirus management after allogeneic hematopoietic stem cell transplantation: A mini-review

Because of the high incidence of cytomegalovirus (CMV) seropositivity in the population, CMV infection is a common and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Taiwan. Here we propose a CMV management strategy for patients undergoing allo-HSCT from the Taiwanese perspective, which focuses on the epidemiology, diagnosis, monitoring, prophylaxis, and treatment of CMV infection after allo-HSCT. In terms of CMV monitoring, weekly CMV monitoring with the COBAS® AmpliPrep system is the standard approach because the pp65 CMV antigenemia assay has a lower sensitivity than CMV monitoring with the COBAS® AmpliPrep system. However, pp65 CMV antigenemia assay has a better correlation with clinical symptoms in immunocompromised patients. A 14-week prophylactic course of letermovir is recommended for allo-HSCT recipients in Taiwan, especially for recipients of hematopoietic stem cells from mismatched unrelated and haploidentical donors. Preemptive ganciclovir therapy should be initiated when the CMV viral load exceeds 1000 copies/mL, and should not be discontinued until CMV DNA is no longer detected in the blood. For allo-HSCT recipients who have CMV-related diseases, ganciclovir with or without CMV-specific intravenous immunoglobulin is the standard of care. The limited availability of foscarnet, an alternative for patients who are not responsive to or cannot tolerate ganciclovir, is a crucial issue in Taiwan. For pediatric allo-HSCT recipients, more data are needed to propose a CMV management recommendation.

Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy.

Cytomegalovirus (CMV) antigenemia assays have been widely used as adjunct tests to diagnose tissue invasive CMV diseases, including cytomegalovirus retinitis (CMVR). In this study, we examined CMVR cases to assess the presence of CMV in sera and aqueous humor and antiviral therapy received prior to the onset of CMVR. A total of 37 eyes from 26 different cases of CMVR in patients who visited Hokkaido University Hospital between 2007 and 2015 were enrolled. The diagnosis of CMVR was established based on characteristic ophthalmoscopic findings and the presence of local and/or systemic CMV infection. Among the 26 cases, 3 cases (12%) were HIV-positive, while the other 23 cases (88%) were HIV-negative. The records of clinical and laboratory results were reviewed from clinical charts retrospectively. CMV antigenemia was positive at the onset of CMVR in 14 cases (53.8%) and negative in the other 12 cases. In 9 cases among the antigenemia-negative cases (75.0%), the antigenemia had been previously positive and had turned negative before the onset of CMVR. In 12 of the 14 antigenemia-positive cases (85.7%) and in 8 of the 9 antigenemia-negative cases (88.9%) that were previously positive, systemic antiviral therapies had never been used or had been used before but had been discontinued prior to the onset of CMVR. Even if viremia turns negative, the risk of developing CMVR exists for more than several weeks after the completion of systemic therapy.

Low-Level Cytomegalovirus Antigenemia Promotes Protective Cytomegalovirus Antigen-Specific T Cells after Allogeneic Hematopoietic Cell Transplantation.

Previous studies have reported a beneficial effect from cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (alloHCT) on immune reconstitution. We determined the CMV antigenemia level associated with increased CMV antigen-specific T cells (CASTs) at day +100 and decreased CMV reactivation after day +100. CMV reactivation and CASTs were measured with CMV antigenemia and CMV-specific major histocompatibility complex multimers. The analysis consisted of 775 CAST measurements obtained before and 30, 100, and 365 days post-alloHCT from 327 consecutive patients treated between 2008 and 2016. Detectable CASTs correlated with recipient (P < .0001) and donor (P < .0001) CMV seropositivity pre-alloHCT. CMV reactivation before day +100 was associated with a higher proportion of patients who achieved ≥3 CASTs/µL by day +100 (61% with versus 39% without reactivation, P < .001). In alloHCT recipients at high risk for CMV reactivation (R+D±) with a maximum of grade II acute graft-versus-host-disease, reactivating CMV before day +100 and achieving ≥3 versus <3 CASTs/µL at day +100 was associated with reduced CMV reactivation from day +100 to +365 (27% versus 62%, P=.04). This protective effect was observed with low-level but not high-level CMV reactivation (<5 versus ≥5/50,000 polymorphonuclear leukocytes+pp65, respectively). These findings suggest low-level CMV reactivation may be beneficial and that treatment may be delayed until progression. These findings will need validation in prospective clinical trials using CMV PCR and antigenemia assays.

Management of cytomegalovirus infection after hematopoietic stem cell transplantation

In a highly immunodeficient state following allogeneic hematopoietic stem cell transplantation (HSCT), the reactivation of cytomegalovirus (CMV) is occasionally uncontrollable, which leads to various clinical symptoms, such as pneumonia, enteritis, and hepatitis and finally to lethal outcomes. Although preemptive anti-CMV therapy based on monitoring of CMV infection by quantitative polymerase chain reaction and CMV antigenemia assays has reduced lethal CMV disease, CMV infection is associated with increased non-relapse mortality and reduced survival. A new antiviral drug, letermovir, which exhibited high tolerability and preventive effect on CMV infection, was approved as a prophylactic agent for CMV infection. In the future, it is expected that survival after allogeneic HSCT will be improved by preventing CMV infection. However, further investigations are warranted to solve problems, such as the establishment of the appropriate prophylaxis for CMV infection and the management of late-onset and drug-resistant CMV infection.

Persistent Primary Cytomegalovirus Infection After Deceased Donor Kidney Transplant: Ganciclovir Susceptibility of Human Cytomegalovirus With UL97 D605E Mutation: A Case Report

BackgroundCytomegalovirus (CMV) could cause rejection in immunocompromised patients during early post-renal transplant stage. The American Transplant Society guidelines recommend prophylactic therapy with ganciclovir (GCV) for 3 to 6 months to prevent CMV infections in adult renal transplant patients. However, there is no recommended CMV treatment regimen for pediatric patients. Main FindingsWe performed deceased donor kidney transplant from an anti-CMV antibody-positive donor to an anti-CMV antibody-negative 15-year-old female recipient with end-stage renal disease caused by bilateral renal hypoplasia. One month after transplant, increase in positive cells in the CMV antigenemia assay indicated a primary CMV infection in the patient, who immediately received GCV. She was switched to foscarnet after 4 months of anti-CMV therapy because of clinical GCV resistance. CMV was isolated from the peripheral blood mononuclear cells but neutralizing antibody was not detected. Isolated CMV was susceptible to GCV and foscarnet, although it carried the UL97 D605E mutation, assumed to be associated with GCV resistance. ConclusionsThe primary CMV infection presented a phenotypic clinical drug resistance, but all recovered CMV isolates were drug-susceptible even if isolated after prolonged anti-CMV therapy, indicating that immune status was more important for recovery from primary CMV infection than anti-CMV therapy.

Cytomegalovirus Infection after Renal Transplantation: Occurrence, Clinical Features, and the Cutoff for Antigenemia in a University Hospital in Brazil.

BackgroundCytomegalovirus (CMV) is the main infectious agent causative of morbidity and mortality in transplant recipients. This study aimed to describe the occurrence and clinical features of CMV infection, and the optimum antigenemia assay cutoff associated with symptomatic infection.Materials and MethodsThis was a cohort study that investigated 87 patients undergoing renal transplantation. The patients were monitored with the CMV antigenemia assay performed weekly for the first 3 months post-transplantation and subsequently, when CMV infection was suspected clinically.ResultsCMV infection was observed in 63.2% (55/87) of the recipients during the follow-up. Of the 65 episodes observed, 75% (49/65) occurred until 100 days after transplantation (D+100) and 25% (16/65) after D+100 with a median of 60 days. CMV infection was associated with age of the transplant recipients (P = 0.001) and use of deceased donor organ (P = 0.009). There were asymptomatic (34%) and symptomatic (66%) episodes of CMV infection, in which diarrhea was the most common symptom (22.6%), followed by elevated creatinine levels (14.5%), fever (12.9%) and leukopenia (10.5%). The optimum cutoff point associated with symptomatic infection was 5 positive cells/200,000 leukocytes (area under the curve = 0.87, positive predictive value = 88% and negative predictive value= 71%).ConclusionsThe high occurrence and the risk factors for CMV infection such as the age of recipients, the number of positive cells in the antigenemia assay, and use of a deceased donor organ should be considered for appropriate monitoring and management of kidney recipients during the post-transplant period.

Sensitivity of the Cytomegalovirus Antigenemia Assay to Diagnose Cytomegalovirus Retinitis.

BackgroundCytomegalovirus (CMV) retinitis is one of the most important tissue-invasive CMV diseases in immunocompromised patients. Since 1980, non-invasive diagnostic methods, notably the CMV antigenemia assay, have been widely used as adjunct tests to diagnose tissue-invasive CMV diseases. However, there are limited data on the diagnostic value of the CMV antigenemia assay for diagnosing CMV retinitis.Materials and MethodsWe performed a retrospective review of all cases of CMV retinitis at Asan Medical Center, Seoul, South Korea over a 9-year period. The diagnosis of CMV retinitis was made by experienced ophthalmologists according to medical history and an ophthalmoscopic appearance of typical retinopathy, together with absence of an alternative diagnosis.ResultsWe analyzed 44 patients with CMV retinitis (affecting 57 eyes) for whom the CMV antigenemia assay was performed. Of the 44 patients, 31 (70%) were HIV-uninfected and 13 (30%) were HIV-infected. The overall sensitivity of the CMV antigenemia assay was 66% (95% confidence interval [CI] 50–80%). The test’s sensitivity showed a non-significant trend towards being higher in HIV-infected patients than in HIV-uninfected patients (sensitivity 85% vs 58%, respectively, P = 0.16). In a subgroup analysis of the 35 patients without other concurrent tissue-invasive CMV disease, the sensitivity of the CMV antigenemia assay was 57% (95% CI 40–74%).ConclusionsThe CMV antigenemia assay has limited value as a non-invasive diagnostic adjunct test for CMV retinitis. Therefore, the results of the assay need to be interpreted in the context of underlying disease, clinical presentation, and ophthalmoscopic findings.

A clinical significance of assessing cytomegalovirus infection status in patients with ulcerative colitis.

A clinical significance of assessing cytomegalovirus infection status in patients with ulcerative colitis.

Usefulness of the cytomegalovirus antigenemia assay in patients with ulcerative colitis.

Background/AimsPatients with ulcerative colitis (UC) are at high risk for cytomegalovirus (CMV) reactivation. The usefulness of the CMV antigenemia assay in active UC patients has rarely been studied. We assessed whether the assay detects CMV colitis and predicts clinical outcomes in patients with UC.MethodsWe retrospectively reviewed the medical records of patients hospitalized for moderate-to-severe UC from 2003 to 2012. Positive CMV antigenemia was defined as ≥1 pp65-positive cell per 2×105 polymorphonuclear neutrophils. CMV colitis was defined as the presence of inclusion bodies and/or positive immunohistochemistry in the colonic mucosa. The primary outcome was steroid refractoriness, defined as the absence of clinical improvement after intravenous high-dose steroid administration.ResultsA total of 43 patients were enrolled. CMV antigenemia was detected in 12 (27.9%) patients. Positive CMV antigenemia was significantly associated with CMV colitis (P =0.001). The sensitivity and specificity of positive CMV antigenemia for diagnosing CMV colitis were 66.7% and 87.1%, respectively. Steroid refractoriness was found in 11 of 12 (91.7%) and 12 of 31 (38.7%) patients with positive and negative CMV antigenemia, respectively (P =0.002). The independent predictors for steroid refractoriness were positive CMV antigenemia (adjusted odds ratio [OR], 7.73; 95% confidence interval [CI], 1.22-49.19; P =0.030) and a shorter duration from the diagnosis of UC (adjusted OR, 0.99; 95% CI, 0.98-0.99; P =0.025).ConclusionsThe CMV antigenemia assay shows low sensitivity but high specificity for detecting CMV colitis and may predict steroid-refractory UC. Early rescue therapy might be considered in UC patients positive for CMV antigenemia.

When is an Assay of Cytomegalovirus Antigenemia Useful in Detecting Cytomegalovirus Colitis?

Cytomegalovirus (CMV) in patients with moderate-to-severe UC can worsen colitis and be associated with corticosteroid refractoriness.1,2,3,4 Early diagnosis and proper intervention is therefore very important. However, the clinical diagnosis of CMV colitis is very difficult. The diagnosis of CMV colitis in UC patients can be confirmed by histology, which comprises either PCR or immunohistochemistry (IHC).5 However, tissue PCR for CMV is controversial because of the possibility for false positives.6 Although IHC staining may be the best method to confirm CMV colitis,7,8,9 it takes several days for this test to yield results, and could be associated with hemorrhage or perforation.10,11,12 Many clinicians have tried to identify the best method of diagnosing CMV colitis. With this in mind, I read the study of Chun et al.13 with great interest. They assessed the clinical utility of the CMV antigenemia assay for the diagnosis of CMV colitis and predicting the outcomes of patients with UC. According to their results, CMV colitis was more common in patients with positive CMV antigenemia (eight patients, 66.7%), and this association was statistically significant (P=0.001). The results were consistent with other similar studies, which showed low sensitivity and high specificity.12,14 They suggested 2 pp65-positive cells per 2×105 polymorphonuclear leukocytes as a cut-off value, and this is very meaningful. However, among patients with positive antigenemia assay results, three did not have CMV colitis and four with negative results had CMV colitis. In addition, ganciclovir was considered only in tissue-confirmed cases with steroid refractoriness. I am therefore curious as to whether these results have any clinical significance in the diagnosis of CMV colitis. Can the antigenemia assay substitute histologic evaluation? I believe that Chun et al. did not clearly demonstrate the significance of the CMV antigenemia assay without histology in the diagnosis of CMV colitis. Even in cases where the antigenemia assay was negative, they considered antiviral therapy if tissues showed CMV colitis. Therefore, I think we eventually need endoscopy and tissue confirmation in steroid refractory UC patients to decide upon antiviral therapy. One study suggested that the CMV antigenemia assay has a diagnostic role only in conjunction with endoscopic findings.14 I agree with this opinion; however, considering the high rate of false positive results of PCR for CMV, it could be helpful for diagnosis only when tissue PCR is positive and IHC staining is negative. The role of CMV in the exacerbation of UC is still under debate.6 Several studies have reported that CMV reactivation could be improved without antiviral treatment,15,16 and others have suggested that in patients who are resistant to corticosteroids, antiviral therapy should be considered if they are positive for CMV in tissue studies.17 Chun et al. also demonstrated a significant association of CMV antigenemia with steroid refractoriness, and suggested early rescue therapy.13 CMV antigenemia could be a good predictor of clinical outcomes such as steroid refractoriness. However, it is limited in the diagnosis of CMV colitis. Despite these limitations, I think it could be very helpful in some cases. Therefore, we need to define the proper indication of the CMV antigenemia assay in the diagnosis of CMV colitis.

Clinical utility of cytomegalovirus antigenemia assay and blood cytomegalovirus DNA PCR for cytomegaloviral colitis patients with moderate to severe ulcerative colitis

Background and aimsClinical usefulness of cytomegalovirus (CMV) antigenemia assay and blood CMV polymerase chain reaction (PCR) in patients with ulcerative colitis (UC) needs to be evaluated. MethodsMedical records of moderate to severe UC patients between January 2001 and December 2012 were reviewed retrospectively. Diagnostic performances of CMV antigenemia assay and blood PCR to predict CMV colitis, and clinical outcome according to the results were analyzed. CMV colitis was diagnosed by H&E staining and/or CMV immunohistochemistry. ResultsOf the 229 study subjects, 83 patients (36.2%) had CMV colitis. The sensitivity and specificity of CMV antigenemia assay were 47.0% and 81.7%, and those of blood CMV DNA PCR were 44.3% and 87.9%, respectively. If either CMV antigenemia or PCR was positive in the presence of significant ulcers, the sensitivity and specificity of having CMV colitis were 67.3% and 75.7%, respectively, with the area under the receiver operating characteristic curve value of 0.717. Among patients with significant ulcers, positive CMV antigenemia (33/50 [66.0%] vs. 31/102 [30.4%]; p<0.001) and positive blood CMV PCR (25/37 [67.6%] vs. 24/86 [27.9%]; p<0.001) showed significantly higher probability of CMV colitis than blood test-negative patients. UC-CMV colitis patients with positive CMV antigenemia showed significantly higher rate of colectomy than those with negative antigenemia (13/39 [33.3%] vs. 5/44 [11.4%]; p=0.015). ConclusionsAlthough CMV antigenemia and blood CMV PCR showed low sensitivity for diagnosing CMV colitis, the specificity values were high. Among UC-CMV colitis patients, CMV antigenemia showed significant association with subsequent colectomy.

Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status

To clarify the impact of cytomegalovirus (CMV) activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis (UC) patients. UC patients with flare-up were divided into CMV-positive and -negative groups according to the CMV antigenemia assay. The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir. The median number of days to initial remission was significantly greater for the patients in the CMV-positive group (21 d vs 16 d, P = 0.009). However, the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups. Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group. CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy.

Evaluation of the Validity of Preemptive Therapy against Cytomegalovirus Disease Based on Antigenemia Assay with a Cutoff of 20 Positive Cells per Two Slides

BackgroundPreemptive therapy with ganciclovir (GCV) based on the results of a cytomegalovirus (CMV) antigenemia assay is a standard strategy for preventing CMV disease after allogeneic hematopoietic cell transplantation (HCT). However, the appropriate threshold of antigenemia-positive cells for deciding when to start GCV remains unclear.PatientsThis retrospective study included 80 recipients who received HCT from an alternative donor between 2007 and 2011. In 2009, we switched the threshold from 3 (3A group, n=24) to 20 (20A group, n=56) antigenemia-positive cells per two slides for preemptive therapy after HCT from an alternative donor.ResultsEarly CMV disease within 100 days after HCT was observed in one patient in the 20A group. Antiviral agents including GCV, val-GCV, and foscarnet were given in 17 (71%) and 36 (64%) patients in the 3A and 20A groups, respectively (p=0.23). In 13 (23%) patients in the 20A group, the initiation of preemptive therapy was avoided because of the change in the cutoff value for CMV antigenemia. However, the total dose of GCV was not different between the two groups. The use of steroid was significantly associated with CMV antigenemia of at least 20 positive cells among patients with low-level antigenemia at the first detection.ConclusionThe increased threshold up to 20 positive cells for starting preemptive therapy was not associated with a significant increase in CMV disease, but the total dose of GCV was not reduced and there was one early CMV disease in the 20A group. We should explore how to identify patients who are at high risk for increased antigenemia among patients with low-level antigenemia, but at least, preemptive therapy should not be withheld in patients who are already receiving systemic steroid.

Cytomegalovirus disease of the upper gastrointestinal tract in patients with rheumatic diseases: a case series and literature review

Cytomegalovirus disease of the upper gastrointestinal tract (CMV-UGT) is a rare but significant complication in patients with rheumatic diseases. We reviewed records for January 2004 to December 2012 and investigated the occurrence of CMV-UGT in patients with rheumatic diseases to evaluate clinical characteristics, the value of the CMV antigenemia assay, and the association between immunosuppressive therapy and CMV-UGT. Ten CMV-UGT events (six gastric ulcer, two esophagitis, one gastritis, and one duodenal ulcer) in nine patients (three rheumatoid arthritis, three systemic lupus erythematosus, one dermatomyositis, one systemic sclerosis, and one overlap syndrome) were identified based on pathology. Mean age was 66.5 (range, 53-76) years. The CMV antigenemia assay was negative in five cases (50 %). All ten cases received glucocorticoids and six (60 %) received pulsed glucocorticoids. Mean prednisolone dose was 31.3 (range, 7.5-40) mg/day at diagnosis. Concomitant immunosuppressive agents were used in eight cases (80 %). Considering other published cases, the most common immunosuppressive drug was cyclophosphamide (ten cases; 45 %). Notably, two of our patients who were treated with low-dose glucocorticoids plus other milder immunosuppressive drugs (methotrexate and cyclosporine) also developed CMV-UGT. Life-threatening complications such as massive bleeding or perforated ulcer occurred in two patients. These results suggest that patients receiving intensive immunosuppressive therapy such as high-dose glucocorticoids and cyclophosphamide are at higher risk for developing CMV-UGT. Moreover, CMV-UGT can occur even with low-dose glucocorticoid therapy and relatively mild immunosuppressive agents. The value of the CMV antigenemia assay for predicting CMV-UGT appears to be limited.

Severe eosinophilic pneumonia presenting during gemcitabine adjuvant chemotherapy

Gemcitabine is widely accepted as the standard treatment for pancreatic cancer, but it can cause unpredictable side effects. Acute respiratory distress syndrome is a rare complication with gemcitabine, but is sometimes fatal. We describe a cured case of acute, severe gemcitabine-induced pulmonary toxicity. The patient was a 76-year-old man with pancreatic cancer who was receiving adjuvant gemcitabine chemotherapy after surgery. The patient received gemcitabine 1,000 mg/m2 on days 1, 8, and 15 for three 4-week cycles, with intervals of 1 week. He developed severe general fatigue on day 1 of the third cycle. Computed tomography showed diffuse ground-glass opacity with pleural effusion. There was no increase in β-D-glucan, and cytomegalovirus antigenemia assays were negative. No bacteria or acid-fast bacilli were found. The number of eosinophils in bronchoalveolar lavage fluid was increased. Considering these data, we diagnosed eosinophilic pneumonia induced by gemcitabine. The patient was immediately treated with a steroid and neutrophil elastase inhibitor under respiratory supportive therapy. After 4 weeks, his pulmonary symptoms were markedly improved. Physicians should be cognizant of the possible association of serious pulmonary toxicity with gemcitabine treatment. A delay in diagnosis and treatment could lead to a fatal outcome.

Assessment of Antigenemia Assay for the Diagnosis of Cytomegalovirus Gastrointestinal Diseases in HIV-Infected Patients

We conducted a single-center prospective study to evaluate the utility of cytomegalovirus (CMV) antigenemia assay for the diagnosis of CMV-gastrointestinal disease (GID). The study subjects were HIV-infected patients with CD4 count ≤200 μL/cells who had undergone endoscopy. A definite diagnosis of CMV-GID was made by histological examination of endoscopic biopsied specimen. CMV antigenemia assay (C10/C11 monoclonal antibodies), CD4 count, HIV viral load, history of HAART, and gastrointestinal symptoms as measured by 7-point Likert scale, were assessed on the same day of endoscopy. One hundred cases were selected for analysis, which were derived from 110 cases assessed as at high-risk for CMV-GID after endoscopy screening of 423 patients. Twelve patients were diagnosed with CMV-GID. Among the gastrointestinal symptoms, mean bloody stool score was significantly higher in patients with CMV-GID than in those without (2.5 vs. 1.7, p=0.02). The area under the receiver-operating characteristic curve of antigenemia was 0.80 (95%CI 0.64-0.96). The sensitivity, specificity, positive likelihood ratio (LR), and negative LR of antigenemia were 75.0%, 79.5%, 3.7, and 0.31, respectively, when the cutoff value for antigenemia was ≥1 positive cell per 300,000 granulocytes, and 50%, 92.0%, 5.5, and 0.55, respectively, for ≥5 positive cells per 300,000 granulocytes. In conclusion, CMV antigenemia seems a useful diagnostic test for CMV-GID in patients with HIV infection. The use of ≥5 positive cells per 300,000 granulocytes as a cutoff value was associated with high specificity and high positive LR. Thus, a positive antigenemia assay with positive endoscopic findings should allow the diagnosis of CMV-GID without biopsy.

十二指腸乳頭部腫瘍が疑われた HIV 感染合併 CMV 感染症の 1 例

We present herein a case report of a 59-year-old patient with HIV-1 infection who developed a CMV-induced pseudotumor of the duodenum. The patient presented with oral pain and dysphagia. Physical examination revealed oral thrush. An EIA and a Western blot assay for antibodies to HIV were positive. His CD4-positive lymphocyte count was initially 49/microL with an HIV viral load of 2.6 x 10(5) copies/mL. Cytomegalovirus (CMV) reactivation was detected with the CMV antigenemia assay. He had CMV retinitis in both eyes with unilateral blurring. An endoscopic study revealed candida esophagitis, and a tumor-like lesion with an irregular ulcer at the papilla of Vater. Histological and immunohistochemical studies revealed a CMV-induced pseudotumor and severely inflamed duodenal mucosa with infiltration of CMV-positive cells. The patient was treated with oral valganciclovir and fluconazole for three weeks. As the oral thrush and retinitis showed improvement, he began antiretroviral therapy (ART), consisting of raltegravir and TDF/ FTC. One month later the patient's CD4-positive cells increased to 130/microL and the level of HIV-RNA decreased to 160 copies/mL, The CMV retinitis had transiently worsened because of an ART-induced inflammatory response, immune reconstitution inflammatory syndrome (IRIS). Six months after the ART initiation, an endoscopic study revealed that the esophagitis and the lesion at the papilla had improved. Biopsy showed no CMV-positive cells in the epithelium. The patient was now in a relatively healthy condition. CMV-induced pseudotumors of the duodenum are rare, and sometimes resemble malignancy. However, because this tomor responds to medical treatment physicians treating severely immunocompromised patients should be aware of its presentation and treatment.