Systemic Cytomegalovirus Infection Research Articles

TCR CDR3-CMV Antigen Chemical Complementaries Are Associated With a Worse Outcome for Renal Cell Carcinoma.

Due to still unresolved questions regarding viruses as either a primary cause or a comorbidity in cancer, we examined a potential immune response to cytomegalovirus (CMV) in the renal cell carcinoma (RCC) setting using genomics and bioinformatics approaches. Specifically, we assessed chemical complementarity scores (CSs) for solid tissue normal resident, T-cell receptor (TCR) complementarity determining region 3 (CDR3s) and CMV antigens and determined whether higher or lower CS groups were associated with a higher or lower survival probability. This was indeed the case, with all such analyses consistently indicating a lower overall and progression-free survival for the cases representing the higher TCR CDR3-CMV antigen chemical CSs. This basic result was obtained for two separate RCC datasets and multiple CMV antigens. The results raise the question, to what extent a systemic CMV infection may represent an important co-morbidity for RCC.

Cytomegalovirus infection among people living with HIV in Sweden: Case profiles, treatment strategies and patient outcomes at Karolinska University Hospital 2010-2020.

In countries with access to early antiretroviral treatment (ART), opportunistic infections caused by cytomegalovirus (CMV) in people living with HIV (PLWH) are becoming increasingly rare. As potential complications are severe, it is critical to remain aware of this important diagnosis. However, clinical characteristics and prognosis of CMV infection in PLWH in the era of modern ART have not been well described. Here, we compiled the clinical presentation, management and outcome of CMV infection in PLWH treated at the infectious diseases clinic of Karolinska University Hospital during 2010-2020. We identified 51 cases of active CMV infection, based on detection of CMV-DNA, mainly diagnosed in patients with CD4 T-cell count <200 cells/μL (86%). Median time from HIV diagnosis to detection of CMV infection was 16 days. In 20 cases (39%), CMV infection was symptomatic with retinitis identified as a manifestation in 70% of cases. Symptomatic CMV infection was treated for 73 (20-313) days upon diagnosis, mostly using valganciclovir. One-year mortality was 22% and was associated with longer time to ART initiation from HIV diagnosis and with comorbidities, but not with CMV-DNA levels or CD4 count. Immune reconstitution was not significantly compromised in patients with symptomatic CMV, although CD4/8 ratio tended to be lower in patients with systemic CMV infection. Retinitis remains the most common manifestation of symptomatic CMV infection in PLWH. Recognizing CMV infection is important, especially in the management of 'late presenters'. Adequate duration of antiviral therapy and appropriate follow-up must be ensured to avoid complications.

Transcriptome Analysis of Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic Neonatal Murine Cytomegalovirus Infection.

Our previous studies have shown that systemic neonatal murine cytomegalovirus (MCMV) infection of BALB/c mice spread to the eye with subsequent establishment of latency in choroid/RPE. In this study, RNA sequencing (RNA-Seq) analysis was used to determine the molecular genetic changes and pathways affected by ocular MCMV latency. MCMV (50 pfu per mouse) or medium as control were injected intra-peritoneally (i.p.) into BALB/c mice at <3 days after birth. At 18 months post injection, the mice were euthanized, and the eyes were collected and prepared for RNA-Seq. Compared to three uninfected control eyes, we identified 321 differentially expressed genes (DEGs) in six infected eyes. Using the QIAGEN Ingenuity Pathway Analysis (QIAGEN IPA), we identified 17 affected canonical pathways, 10 of which function in neuroretinal signaling, with the majority of DEGs being downregulated, while 7 pathways function in upregulated immune/inflammatory responses. Retinal and epithelial cell death pathways involving both apoptosis and necroptosis were also activated. MCMV ocular latency is associated with upregulation of immune and inflammatory responses and downregulation of multiple neuroretinal signaling pathways. Cell death signaling pathways are also activated and contribute to the degeneration of photoreceptors, RPE, and choroidal capillaries.

Frosted branch angiitis as an immune recovery response in newly diagnosed acquired immunodeficiency syndrome and systemic cytomegalovirus infection

Frosted branch angiitis (FBA) is an uncommon form of severe retinal perivasculitis associated with systemic inflammatory/infectious diseases. In this report, we describe a case of FBA and macular edema as a result of immune recovery response in a patient newly diagnosed with HIV infection and cytomegalovirus viremia.

Complement-Mediated Thrombotic Microangiopathy and Spontaneous Splenic Rupture Associated With Cytomegalovirus Infection.

This is a case report of a previously healthy female patient with complement-mediated thrombotic microangiopathy (TMA) caused by a systemic cytomegalovirus infection that was successfully treated with plasmapheresis, steroids, and parenteral valganciclovir. Complement-mediated TMA is the result of various genetic mutations leading to complement abnormalities with overactivation of alternate complement pathway in response to a triggering infection. She also had splenic rupture without splenomegaly and was managed successfully without splenectomy.

Oral Cytomegalovirus Infection in a Systemic Lupus Erythematosus Patient: Case Report and Review of Literature

Systemic manifestations of cytomegalovirus (CMV) are varied, and include pneumonitis, hepatitis and retinitis. Oral ulcers due to CMV infection are rare lesions, most often seen in immunocompromised hosts, typically HIV positive patients, transplant recipients, patients on chemotherapy or patients receiving immunosuppressive therapy for associated conditions. Despite a suspected relationship between childhood onset of systemic lupus erythematosus (SLE) and CMV infection, oral CMV ulcerations have not previously been reported in patients being treated for SLE. Here, we present a case of widespread CMV infected oral ulcers in an 18-year-old woman with SLE. The lack of unique distinguishing clinical features of CMV related oral ulcers often leads to delayed diagnosis. Because CMV oral ulcers are often associated with an unfavorable prognosis, early detection is imperative to prevent disseminated disease and increased morbidity. We hope that this case, by describing the manifestations of oral CMV in a patient with SLE, will lead to heightened levels of suspicion and more timely diagnosis and treatment.

Comparable anti-CMV responses of transplant donor and third-party CMV-specific T cells for treatment of CMV infection after allogeneic stem cell transplantation.

Adoptive transfer of cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CMV-CTLs) from original transplant donors or third-party donors was effective for the treatment of CMV infection after allogenic stem cell transplantation (allo-SCT), but the antiviral activity of CMV-CTL types has not been compared. To determine whether third-party CMV-CTLs provide comparable long-term antiviral efficacy to transplant donor CMV-CTLs, we first compared the antiviral abilities of transplant donors and third-party CMV-CTLs for treatment of CMV infection in two mouse models, compared the in vivo recovery of CMV-specific immunity, and analyzed the underlying mechanisms driving sustained antiviral immunity. The results showed that both donor and third-party CMV-CTLs effectively combated systemic CMV infection by reducing CMV pathology and tumor burden 28 days postinfusion. The in vivo recovery of CMV-specific immunity after CMV-CTL infusion was comparable in both groups. A detailed analysis of the source of recovered CMV-CTLs showed the proliferation and expansion of graft-derived endogenous CMV-CTLs in both groups. Our clinical study, which enrolled 31 patients who received third-party CMV-CTLs and 62matched pairs of individuals who received transplant donor CMV-CTLs for refractory CMV infection, further showed that adoptive therapy with donor or third-party CMV-CTLs had comparable clinical responses without significant therapy-related toxicity. We observed strong expansion of CD8+ tetramer+ T cells and proliferation of recipient endogenous CMV-CTLs after CMV-CTL infusion, which were associated with a reduced or cleared viral load. Our data confirmed that adoptive therapy with third-party or transplant donor CMV-CTLs triggered comparable antiviral responses to CMV infection that might be mediated by restoration of endogenous CMV-specific immunity.

Multifocal EBV-associated smooth muscle tumors in a patient with cytomegalovirus infection after liver transplantation: a case report from Shiraz, Iran

IntroductionImmunodeficient patients, including the recipients of solid organs, exhibit an increase in the incidence of neoplasms. Post-transplant smooth muscle tumor (PTSMT) is a distinct and infrequent entity of these groups of neoplasms. Epstein–Barr virus (EBV) is considered to be involved in the etiology of this neoplasm.Case reportA 28-year-old man who underwent liver transplantation presented with abdominal pain and diarrhea for several months. He had a history of resistant systemic cytomegalovirus (CMV) infection after transplantation. Radiologic evaluation and colonoscopy revealed multiple liver, spleen, lung, and colon lesions. Microscopic assessment of colon and liver lesions using IHC study were in favor of spindle cell proliferation with mild atypia and a mild increase in mitotic rate without any necrosis, with features of smooth muscle tumor. Considering the transplantation history, EBER chromogenic in situ hybridization (CISH) study on paraffin blocks was requested, which demonstrated EBV RNA in tumor cell nuclei, suggesting EBV-associated smooth muscle tumor. In addition, PCR for CMV on paraffin blocks was positive. PCR for EBV and CMV viremia were negative. The dosage of immunosuppressive agents was reduced, and currently, he is being followed, with slow expansion in the size of the lesions.ConclusionAlthough the incidence of post-transplant smooth muscle tumors (PTSMTs) is low, it should be remained in the differential diagnosis in post-transplantation patients, especially dealing with multifocal tumors. As strong stimulant for smooth muscle tumors, close follow-up and screening for EBV and CMV infection and early treatment at the time of diagnosis are recommended to avoid these virus-induced tumors.

Range and Consistency of Infection Outcomes Reported in Trials Conducted in Kidney Transplant Recipients: A Systematic Review.

Infection remains a leading cause of death in kidney transplant recipients. This study aimed to assess the scope and consistency of infection outcomes reported in contemporary trials conducted in kidney transplant recipients. A literature review of all randomized trials and trial protocols reporting infection outcomes in adult kidney transplant recipients was identified in the Cochrane Kidney and Transplant Specialized Register from January 2014 to July 2019. Characteristics and infection outcomes from the trials were analyzed. From 102 included trials, 772 outcome measures were extracted and categorized into 216 unique measures with a median of 3.2 outcome measures per trial (range: 1-9). Measures were further grouped into 32 outcomes based on site of infection (14 outcomes) and organism (18 outcomes). The most commonly reported site-specific outcome and organism-specific outcome were systemic infection (71% trials) and cytomegalovirus infection (62% trials), respectively. Outcome metric and methods of aggregation included mean, median, proportion, proportional change, and number of patients with at least 1 episode. Across all trials, measures were assessed at 55 different time points with a range of 1-11 time points per trial. Infection outcomes in kidney transplant recipients were frequently reported by site and organism but varied widely in terms of outcome, metrics, method of aggregation, and time point of measurement. Establishment of core outcomes for infection based on the shared priorities of patients/caregivers and health professionals may improve the consistency, comparability, and usefulness of trial evidence.

Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic Neonatal Murine Cytomegalovirus Infection

Although pathologies associated with acute virus infections have been extensively studied, the effects of long-term latent virus infections are less well understood. Human cytomegalovirus, which infects 50% to 80% of humans, is usually acquired during early life and persists in a latent state for the lifetime. The purpose of this study was to determine whether systemic murine cytomegalovirus (MCMV) infection acquired early in life disseminates to and becomes latent in the eye and if ocular MCMV can trigger in situ inflammation and occurrence of ocular pathology. This study found that neonatal infection of BALB/c mice with MCMV resulted in dissemination of virus to the eye, where it localized principally to choroidal endothelia and pericytes and less frequently to the retinal pigment epithelium (RPE) cells. MCMV underwent ocular latency, which was associated with expression of multiple virus genes and from which MCMV could be reactivated by immunosuppression. Latent ocular infection was associated with significant up-regulation of several inflammatory/angiogenic factors. Retinal and choroidal pathologies developed in a progressive manner, with deposits appearing at both basal and apical aspects of the RPE, RPE/choroidal atrophy, photoreceptor degeneration, and neovascularization. The pathologies induced by long-term ocular MCMV latency share features of previously described human ocular diseases, such as age-related macular degeneration.

A Rare Case of Cytomegalovirus Infection Induced Hemophagacytic Lymphohistocytosis Syndrome (HLH)

Introduction:Haemophagocytic Lymphohistiocytosis (HLH) is a rare immunopathological syndromes of excessive immune activation which results in multiorgan dysfunction and haemophagocytosis. Persistent stimulation of lymphocytes and histiocytes results in hypercytokinemia, leading to characteristic symptoms of HLH. Primary HLH is caused by the genetic mutation and secondary HLH occurs in autoinflammatory and autoimmune disease(macrophage activation syndrome), lymphoma, Iatrogenic immunosupression and healthy persons with infections. HLH is rare disease but has garnered increaed attension over past 10 years.Case description:This is 50 year old female patient with significant past medical history of autoimmune hepatitis controlled on Azathioprine for 2 years. She presented to the emergency room with worsening cough, fevers, chills and shortness of breath, and admitted to the Intensive Care Unit (ICU) due to acute respiratory failure and suspicious for septic shock. She was found to have new onset pancytopenia with White Blood Cell count of 0.7 x10 9, Hemoglobin of 6.9, and platelet 77,000. She did not improved with antibiotics and clinical deteriorating with worse hypoxia and suspicion for Acute Respiratory Distress Syndrome. She was Intubated and on pressor support. Mean while patient also developed Dissiminated Intravascular Coagulation which required multiple platelets, packed red blood cell and cryoprecipitate transfusions. Diagnostic bronchoscopy was done. Bronchial washing is positive for Cytomegalovirus (CMV). Serum CMV Polymerase chain reaction(PCR)test shows high viral load. Computed Tomogram (CT) of abdomen also showed splenomegaly. Patient was started on Valganlciclovir, CT guided bone marrow (BM) biopsy showed secondary hemophagocytosis, Consideration with immunosuppression along with systemic CMV infection, pancytopenia, fever, low fibrinogen (<70 mg/dl) and high ferritin (2292 ng/ml), the diagnosis of the hemophagocytic lymphohistocytosis was made. Steroid was added into treatment regimen. Lab works shows gradually decreasing CMV viral load, till undetectable before discharge. Patient clinically improved with the treatment. She was extubated and discharge with Valganciclovir 900mg 3 times daily for 3 months with weekly CMV PCR.Discussion:Disseminated CMV associated with HLH is uncommon in adults, this case is a type of secondary HLH. Early recognition and treatment is important. The clinical features raised the suspicion of HLH were fever, cytopenia, organomegaly, coagulopathy, elevated ferritin and hemophagocytic lymphohistocytic in the BM and not responded to initial antibiotics and Granulocyte colony stimulating factor. In this case patient met the 5 of 8 criteria and showed improvement of symptoms after treatment of the primary infection. DisclosuresNo relevant conflicts of interest to declare.

Severe Complication of Thiopurine Treatment in a Young Woman with Crohn's Disease.

A 28-year old woman receiving thiopurine treatment for Crohn's disease presented with a systemic primo cytomegalovirus (CMV) infection affecting the gut (colitis), liver (hepatitis), lungs (pneumonitis) and eyes (retinitis). Secondary to this systemic infection, she developed splenomegaly, pancytopenia and lymphadenopathy. Anti-viral treatment resulted in complete resolution of clinical, biochemical and radiological abnormalities within 6 weeks. Early recognition is crucial since CMV infection in a patient receiving thiopurine treatment may result in serious complications. Cytomegalovirus (CMV) infection in patients receiving thiopurine treatment may result in serious complications.This case report describes extensive primo CMV infection causing colitis, hepatitis, pneumonitis and retinitis in a patient receiving thiopurine treatment.Early recognition and treatment of the infection is crucial.

Diagnosis of GATA2 Deficiency in a Young Woman with Hemophagocytic Lymphohistiocytosis Triggered by Acute Systemic Cytomegalovirus Infection.

Patient: Female, 22-year-oldFinal Diagnosis: GATA2 deficiency • hemophagocytic lymphohistiocytosisSymptoms: Chest pain • cough • fever • malaise • shortness of breathMedication: —Clinical Procedure: Bone marrow biopsy • bronchoscopySpecialty: ImmunologyObjective:Rare diseaseBackground:Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by an intense immunologic response that results in multiorgan dysfunction. It typically manifests as a result of a familial genetic immunodeficiency disorder or secondary to a trigger such as an infection, malignancy, or autoimmune disease. The major factors involved in the development of the disease are an individual’s genetic propensity to develop HLH, such as rare associated mutations, or inflammatory processes that trigger the immune system to go haywire.Case Report:Before the COVID-19 pandemic, a 22-year-old woman with a history of congenital absence of the right kidney, right-sided hearing loss, and leukopenia presented with a 3-week history of generalized malaise, fever, chest pain, cough, and shortness of breath. She developed an acute systemic cytomegalovirus infection further complicated by HLH. Based on her history and clinical course, an underlying primary immunodeficiency was suspected. An immunodeficiency gene panel revealed a monoallelic mutation in GATA2, a gene that encodes zinc-transcription factors responsible for the regulation of hematopoiesis.Conclusions:GATA2 deficiency encompasses a large variety of mutations in the GATA2 gene and leads to disorders associated with hematologic and immunologic manifestations of monocytopenia and B-, and natural killer-cell deficiency. Over time, affected individuals are at high risk of developing life-threatening infections and serious hematologic complications, such as myelodysplastic syndromes and/or leukemias. We aimed to illustrate the importance of identifying an underlying genetic disorder associated with secondary HLH to help guide acute and long-term management.

Lower CMV and EBV Exposure in Children With Kawasaki Disease Suggests an Under-Challenged Immune System.

Background: Kawasaki Disease (KD) is a pediatric vasculitis of which the pathogenesis is unclear. The hypothesis is that genetically pre-disposed children develop KD when they encounter a pathogen which remains most often unidentified or pathogen derived factors. Since age is a dominant factor, prior immune status in children could influence their reactivity and hence the acquisition of KD. We hypothesized that systemic immune responses early in life could protect against developing KD. With this study we tested whether the incidence of previous systemic cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection is lower in children with KD compared to healthy age-matched controls.Methods and Results: We compared 86 KD patients with an age-matched control group regarding CMV and EBV VCA IgG measurements (taken before or 9 months after IVIG treatment). We found that both CMV and EBV had an almost 2-fold lower seroprevalence in the KD population than in the control group.Conclusions: We suggest that an under-challenged immune system causes an altered immune reactivity which may affect the response to a pathological trigger causing KD in susceptible children.

Comparison of Transplant Donor- and Third-Party Donor-Derived CMV-Specific T Cells for CMV Infection After Allogenic Stem Cell Transplantation

Background: Adoptive transfer of cytomegalovirus (CMV)-specific T cells (CTLs) from original transplant donors or third-party donors was effective for CMV infection after allogenic stem cell transplantation (allo-SCT), but the safety and antiviral activity of CTL types have not been compared. Additionally, mechanisms driving sustained antiviral immunity induced by these CTLs need to be established and compared. Methods: i) We compared antiviral abilities of transplant donor and third-party CTLs for CMV infection in two mouse models, compared the in vivo recovery of CMV-specific immunity and analyzed underlying mechanisms driving sustained antiviral immunity induced by these CTLs therapies. ii) We collected data from 31 patients receiving third-party CTLs and selected matched pairs of 62 individuals who received donor CTLs for refractory CMV infection after allo-SCT, compared the safety and efficacy of the CTLs types for CMV infection, and evaluated the recovery of virus-specific immunity in patients. Findings: i) In mouse models, we observed that both donor and third-party CTLs effectively combated systemic CMV infection by reducing CMV pathology and tumor burden 28 days post-infusion. The in vivo recovery of CMV-specific immunity after CTLs infusion was comparable in both groups. A detailed analysis of the source of recovered CTLs showed the proliferation and expansion of graft-derived endogenous CTLs in both groups. ii) In patients, adoptive therapy with donor or third-party CTLs had comparable clinical responses without significant therapy-related toxicity. We observed strong expansion of CD8 + tetramer + T cells and the proliferation of recipient’s endogenous CTLs after CTLs infusion, which were associated with a reduced or cleared of viral load. Interpretation: Adoptive therapy with transplant donor or third-party CTLs triggered comparable antiviral responses to CMV infection by helping to restore CMV-specific immunity. Funding: National Key Research and Development Program of China, National Natural Science Foundation of China. Declaration of Interest: The authors have no competing financial interests to declare. Ethical Approval: This study was approved by the ethics committee of Peking University People's Hospital

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.

Частота обов’язкових для використання клінічних і лабораторних діагностичних критеріїв системного червоного вовчака за наявності активної цитомегаловірусної та вірус М. Е. Епштейна – І. Барр інфекції, їх діагностична цінність

Introduction. Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology, in the origin and pathogenesis of which cytomegalovirus (CMV) and M. A. Epstein – Y. Barr virus (EBV) play an important role. There is a need to find in patients with SLE such clinical and laboratory markers identified from the obligatory diagnostic criteria of the disease, which would allow in such conditions to inform about the presence of this active viral infection. The aim of the study. To determine the frequency of necessary clinical and laboratory diagnostic criteria for systemic lupus erythematosus in the presence of active cytomegalovirus and M. A. Epstein – Y. Barr virus, their diagnostic value. Materials and methods. 120 patients with SLE were included in the study. To diagnose CMV and EBV infection, antibodies to viruses and their deoxyribonucleic acid (DNA) were detected. All patients were divided into four groups, namely: with active CMV infection, active EBV, active CMV and EBV and without active CMV and EBV. Results. We found that patients with SLE and active CMV infection are significantly more likely than patients with SLE without active infections to have arthritis, psychosis, leukopenia, increased antibody titers to double-stranded DNA (anti-DNA) and antiphospholipid antibodies; and arthritis, psychosis, leukopenia and increased titer of antiphospholipid antibodies have the highest diagnostic value for the diagnosis of active CMV infection. The patients with SLE and active EBV infection significantly more often than in patients without active infections to have photosensitization, ulcers of mucous membranes, thrombocytopenia and increased titer of anti-DNA, and photosensitization, mucosal ulcers and thrombocytopenia have the highest diagnostic value for the diagnosis of active EBV infection. The patients with SLE and a combination of active CMV and EBV are significantly more likely than patients with SLE and without active infections to have “butterfly” erythema, lymphopenia, detection of lupus anticoagulant and increased titer of antinuclear antibodies, and “butterfly” erythema, lymphopenia and the appearance of lupus anticoagulant have the highest diagnostic value of active CMV and EBV. Conclusions. In patients with systemic lupus erythematosus and active cytomegalovirus infection, among the necessarily diagnostic criteria for systemic lupus erythematosus clinical and laboratory markers are significantly more often arthritis, psychosis, leukopenia, increased antibody titer to double-stranded deoxyribonucleic acid and antiphospholipid antibodies than in patients with systemic lupus erythematosus without these active infections. In patients with active M. A. Epstein – Y. Barr virus there are significantly more often photosensitization, ulcers of mucous membranes, thrombocytopenia and increased titer of antibodies to double-stranded deoxyribonucleic acid than in patients with systemic lupus erythematosus without these active infections.. In patients with a combination of active cytomegalovirus and M. A. Epstein – Y. Barr virus are significantly more often “butterfly” erythema, lymphopenia, the appearance of lupus anticoagulant and increased titer of antinuclear antibodies than in patients with systemic lupus erythematosus without these active infections. Such clinical and laboratory markers as arthritis, or psychosis, or leukopenia or increase in the titer of antiphospholipid antibodies allow to suspect patients with the presence of active cytomegalovirus; photosensitization, or ulcers of mucous membranes, or thrombocytopenia – active M. A. Epstein – Y. Barr virus; “butterfly” erythema, or lymphopenia, or the appearance of lupus anticoagulant – a combination of active cytomegalovirus and M. A. Epstein – Y. Barr virus, the final verification of which requires the use of direct serological tests.

Isolated thrombotic microangiopathy of the small intestine in a patient with atypical hemolytic uremic syndrome \u2013 a case report

BackgroundAtypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by systemic thrombotic microangiopathy (TMA) reflected by hemolysis, anemia, thrombocytopenia and systemic organ injury. The optimal management of aHUS-patients when undergoing kidney transplantation to prevent recurrence in the allograft is eculizumab, an approved recombinant antibody targeting human complement component C5.Case presentationA 39 year-old woman presented with severe abdominal pain, diarrhea and emesis for 3 days. In her past medical history she had experienced an episode of aHUS leading to end stage renal disease (ESRD) in 2007 and a genetic workup revealed a heterozygous mutation in the membrane cofactor protein gene. In 2014 she underwent cadaveric kidney transplantation. Four years later she had to go back on hemodialysis due to allograft failure following a severe systemic cytomegalovirus infection resulting in transplant failure. At presentation she still received calcineurin-inhibitor therapy and reported subfebrile temperatures and pain projecting over the transplant prior to the current symptoms. A contrast enhanced CT-scan of the abdomen revealed inflammatory wall thickening of the small intestine. Diagnostic endoscopy discovered fresh blood in the small intestine without a clear source of bleeding. Histopathology of the small intestine biopsies showed severe thrombotic microangiopathy. Of note, the patient persistently had no signs of systemic hemolysis. Since the TMA of the small intestine was most likely due to aHUS, eculizumab treatment was initiated which abolished the symptoms.ConclusionHere we report a patient with thrombotic microangiopathy with predominant manifestation in a single organ, the small intestine, due to aHUS with absence of systemic signs and symptoms. aHUS patients usually require a secondary trigger for the disease to manifest. In this case, the trigger may be attributed to the dysfunctional renal transplant, which was subsequently explanted. Histology of the explanted kidney showed severe inflammation due to purulent nephritis and signs of cellular rejection. After nephrectomy, we continued eculizumab therapy until the patient completely recovered. No signs of TMA recurred after discontinuation of eculizumab, further supporting the concept of the renal transplant as the main trigger of TMA of the small intestine in our patient.

AN ATYPICAL PRESENTATION OF CYTOMEGALOVIRUS PNEUMONIA

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Cytomegalovirus (CMV) is a viral pathogen that is seen in 40-100% of adults by the fourth decade (1). Infection in an immunocompetent individual is usually subclinical, with severe life-threatening infection seen in immunocomprised individuals. Steroid use has a weak association for infection reactivation in an immunocompetent host. We present the case of a chronic kidney disease (CKD) patient on steroids who was diagnosed and treated for CMV interstitial pneumonia. CASE PRESENTATION: 78-year-old female with a past medical history of interstitial lung disease, idiopathic thrombocytopenia purpura on steroids, CKD stage III who presented from a nursing facility where she was recuperating from a recent hospitalization due to pneumonia. During her prior admission, she was treated with steroids, vancomycin and cefepime for a presumed bacterial pneumonia. Patient presented with shortness of breath. Vital signs were notable for a temperature of 98.4 F, heart rate 102 bmp, RR 24/min, and SaO2 90% on 7L NC. Physical exam revealed bibasilar rales. Labs showed a white blood cell count of 10.1 Thou/uL, creatinine of 1.5 mg/dL, lactic acid 2.8 mmol/L, procalcitonin of 0.12 ng/mL, lactate dehydrogenase (LDH) of 544 U/L. Computed tomography (CT) of the chest showed increasing ground glass changes compared to previous admission imaging. Patient was started on steriods, vancomycin and cefepime. Given worsening radiographical findings, history of ILD, and elevated LDH in the setting of chronic steroids, there was a suspicion for pneumocystis pneumonia. She underwent a video-assisted thoracoscopic surgery lung biopsy, bronchoalveolar lavage and wedge resection of the right lung. Pathology showed microscopic honey combing and extensive subpleural fibrosis, consistent with interstitial pneumonia. CMV cytopathic effect was confirmed with immunoperoxidase staining. PCR testing and tissue culture also returned positive for CMV; viral load was 81,581 IU/mL. Patient was started on a six-week course of valganciclovir with a plan to taper steroids as an outpatient. Patient was unfortunately lost to follow up thereafter. DISCUSSION: Severe life threatening CMV infection is seen in immunocomprised risk groups particularly transplant recipients, patients affected with AIDS, malignancy and neonates. Steroid use has a weak association with CMV reactivation; CKD also has been postulated as a risk factor for reactivation due to malfunctioning white cells. CONCLUSIONS: Although CMV pneumonia targets a subtype of immunosuppressed patients, it should be considered a differential in patient’s on chronic steroid treatment and CKD. This case emphasizes the importance of having a high degree of suspicion of CMV pneumonia in a patient on chronic high dose steroids, in clinical setting, such as this one. Without the correct diagnosis, obtained by PCR of a BAL sample, treatment opportunities will be missed, leading to poor outcomes. Reference #1: Grilli, Elisabetta, et al. “Cytomegalovirus Pneumonia in Immunocompetent Host: Case Report and Literature Review.” Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology, U.S. National Library of Medicine, Dec. 2012. Reference #2: Al-Omari, A., Aljamaan, F., Alhazzani, W., Salih, S., & Arabi, Y. (2016). Cytomegalovirus infection in immunocompetent critically ill adults: literature review. Annals of intensive care, 6(1), 110 Reference #3: Carpani, G., Foresti, S., Dell'Oro, R., Grassi, G., & Bombelli, M. (2019). Severe systemic cytomegalovirus infection in an immunocompetent patient outside the intensive care unit: a case report. BMC infectious diseases, 19(1), 34. https://doi.org/10.1186/s12879-018-3621-8 DISCLOSURES: No relevant relationships by Antonie Auguste, source=Web Response No relevant relationships by Amreet Aujla, source=Web Response No relevant relationships by Sarah Banks, source=Web Response No relevant relationships by Manmeet Grewal, source=Web Response No relevant relationships by Ann Palmer, source=Web Response

Severe systemic cytomegalovirus infection in an immunocompetent patient outside the intensive care unit: a case report

BackgroundCytomegalovirus is responsible for an opportunistic infection that can be life threatening in immunocompromised patients, while it is usually mild or completely asymptomatic in immunocompetent subjects. In the recent years, however, some cases of severe cytomegalovirus infection in immunocompetent patients have been reported, showing this to be a less rare occurrence than previously reported.Case presentationWe report the case of an 83-year-old man, admitted to our hospital for gastroenteritis, complicated by dehydration and severe prothrombin time prolongation due to oral anticoagulant therapy accumulation, who developed hospital-acquired pneumonia; neither of these illnesses responded to several lines of antibiotic therapy. All microbiologic tests were negative, except cytomegalovirus DNA test in blood, which showed high viral load. Antiviral therapy with ganciclovir was then started and a quick favourable response followed. A state of immunodeficiency was excluded, based on normal CD4 count and patient’s clinical history.ConclusionDifferent risk factors for severe cytomegalovirus disease in immunocompetent patients may exist, besides the ones already known, which could be responsible for severe cytomegalovirus disease in immunocompetent patients; thus, these patients should be tested for cytomegalovirus infection, if the clinical picture is compatible, to avoid delay in diagnosis and allow prompt start of specific therapy.