Successful treatment of severe aplastic anemia associated with human parvovirus B19 and Epstein-Barr virus in a healthy subject with allo-BMT.

Several reports have noted pancytopenia associated with Human parvovirus B19 (PVB19) or Ebstein-Barr virus (EBV) infections in patients who have no history of immunodeficiency. To our knowledge, we report the first case of severe aplastic anemia associated with both EBV and PVB19 infections in a previously healthy 22-year-old man. He was admitted to our hematology service due to anemia and thrombocytopenia. He had no symptoms or signs of infections of these viruses. His bone marrow biopsy revealed a hypocellular marrow. Specific IgM and IgG antibodies to EBV and PVB19 were elevated. EBV and PVB19 virus genomes were detected by PCR in the bone marrow nucleated cells and the peripheral blood lymphocytes. Two months after treatment with prednisone, acyclovir, and intravenous immune globulin (IVIg), the genomes of both these viruses disappeared. However, his transfusion requirement for platelet suspensions and packed red blood cells persisted. The patient underwent allogeneic bone marrow transplant (allo-BMT) and has had an enduring complete hematological response for 8 months.     

Prospective monitoring of Epstein–Barr virus and other herpesviruses in patients with juvenile idiopathic arthritis treated with methotrexate and tocilizumab

Abstract

Methotrexate (MTX) is widely used for the treatment of articular-type juvenile idiopathic arthritis (JIA), but patients receiving MTX for rheumatoid arthritis have been reported to be at increased risk of reactivation of Epstein–Barr virus (EBV) and the development of lymphoproliferative disorder. The association between MTX and reactivation of herpesviruses in pediatric patients is not yet understood. We prospectively monitored the viral load of EBV, cytomegalovirus (CMV), and herpesvirus 6 (HHV-6) in four JIA patients treated with MTX for 12–24 months. Tocilizumab, an anti-interleukin 6 receptor monoclonal antibody, was added to the therapeutic regimen in three patients during the observation period. Prior to the administration of MTX, EBV and HHV-6 were detected by PCR in two patients. Significant increases in EBV and HHV-6 load were not observed following the administration of MTX or tocilizumab. In one patient, a relatively high EBV load remained detectable during 21 months of observation in the absence of clinical symptoms. CMV was not detected throughout the observation period in any patient. This is the first report monitoring the longitudinal DNA loads of EBV and other herpesviruses in JIA patients. EBV and HHV-6 were often detectable, but treatment with MTX and tocilizumab did not appear to influence the viral load.     

Pure red cell aplasia associated with cytomegalovirus and Epstein–Barr virus infection in seven cases of Chinese children

Abstract

Pure red cell aplasia (PRCA) associated with cytomegalovirus (CMV) and Epstein–Barr virus (EBV) infection is uncommon. Here, we describe the clinical features and management of seven cases of Chinese children with PRCA associated with viral infections. The patients presented with pallor on admission. Blood cell counts and marrow smears showed anemia, reticulocytopenia, and aplasia of erythroblasts. Serological investigation and DNA polymerase chain reactions for CMV were positive in four patients and those tests for EBV were positive in other three patients. All patients received blood transfusion, corticosteroids treatment, and ganciclovir injection. Two patients had a complete response and one had a partial response after the treatments. The other three patients had a complete response to second-line therapies, including high-dose methylprednisolone, cyclosporin A, and intravenous immunoglobulin. Only one patient had no response to the therapies. Our results indicated that it might be important to combine immunosuppressive drugs with an antiviral drug in the management of PRCA associated with CMV and EBV infection.     

Seroprevalence of parvovirus B19 in fibromyalgia syndrome

This study was aimed to evaluate the seroprevalence of parvovirus B19 in patients with fibromyalgia syndrome (FS). Seventy-five patients with FS (44.3 ± 8.3) and 75 healthy controls (44.2 ± 8.1) were evaluated. Serum anti-B19 IgM and IgG antibodies were measured by ELISA technique. Patients were questioned about duration of symptoms, characteristic features of FS, and symptoms related with viral infection preceding the onset of FS. No significant difference was found regarding the prevalence of anti-B19 IgM antibodies between the groups (p = 0.494). Seropositivity of anti-B19 IgG of the patients was significantly higher than control group (81.3% vs. 64% respectively, p = 0.027). No statistically significant differences were found regarding to the clinical features between fibromyalgia patients with IgG antibody compared to those without IgG antibody. Parvovirus B19 IgG seropositivity was found to be significantly higher in patients with FS. Parvovirus B19 infection might have a role in the etiopathogenesis of FS or might act as a triggering factor.     

Successful umbilical cord blood transplantation for severe chronic active Epstein-Barr virus infection after the double failure of hematopoietic stem cell transplantation

An 11-year-old boy with severe chronic active Epstein-Barr virus infection (CAEBV) underwent successful cord blood transplantation (CBT) after consecutive failure of peripheral blood and bone marrow transplantation from his HLA-mismatched mother. CB cells from an unrelated donor were infused after conditioning with total body irradiation (12 Gy), melphalan (120 mg/m(2)), and etoposide (600 mg/m(2)). Complete remission without circulating EBV-DNA has continued for 15 months after a delayed hematologic recovery. This is the first successful report of CBT for CAEBV. CB may therefore be an alternate source of stem cells for the curative treatment of CAEBV, despite the absence of EBV-specific cytotoxic T lymphocytes.     

Epstein–Barr virus and methotrexate-related CNS lymphoma in a patient with rheumatoid arthritis

Abstract

Patients with rheumatoid arthritis (RA), especially those treated with methotrexate (MTX), might have an increased risk of lymphoproliferative disorders that are associated with Epstein–Barr virus (EBV). We describe a case of EBV-associated central nervous system (CNS) lymphoma (diffuse large B-cell lymphoma) in a patient with RA on a short course of MTX treatment. The neoplastic cells express the B-cell surface markers (CD20, Pax-5 and CD30), and EBV-encoded RNA was demonstrated by in situ hybridization. The patient’s lymphoma did not recur for the 8-year follow-up period after the tumor resection and cessation of MTX. MTX may promote EBV-positive CNS lymphoma in RA patient due to its immunosuppressive properties as well as reactivating latent EBV infection.     

Hepatitis due to Epstein–Barr virus and cytomegalovirus: clinical features and outcomes

Objective: To determine the frequency of cytomegalovirus (CMV) and Epstein–Barr virus (EBV) hepatitis among those with acute CMV and EBV infection in a population based setting and to compare these two types of hepatitis and analyze the outcomes.

Methods: A retrospective search was undertaken on all patients with IgM antibodies to CMV and EBV during the period of 2006–2015 in the virological database of the University Hospital of Iceland covering the metropolitan area of Reykjavík (population 202,255). Patients with available liver tests at the University Hospital and/or admitted to this institution were included and relevant clinical data obtained from medical records.

Result: Overall, 190 patients had acute EBV infection during the study period and 118 patients were diagnosed with acute CMV. Overall, 82% of patients with acute EBV infection had hepatitis, males 43%, median age 17 years, 15% had jaundice and 26% hospitalized. Among those with acute CMV infection, 69% had elevated liver tests, 63% males, median age 33 years, 9% had jaundice and also 26% hospitalized. Overall, 17% of those with CMV hepatitis were immunosuppressed, 6% were pregnant and 4% developed Guillain–Barré syndrome following the infection.

Conclusion: A high proportion of patients with acute CMV and EBV developed hepatitis and jaundice, most of those patients have good prognosis. Patients with CMV hepatitis were more often immunosuppressed, required hospitalization or were pregnant in comparison with patients with EBV hepatitis.     

人细小病毒B19感染在心肌病发病中的作用

目的 :探讨人细小病毒B19(HPVB19)感染在心肌病发病中的作用。方法 :病理诊断确诊为炎症性心肌病患者 30例 ,扩张型心肌病 (DCM)患者 36例 ,肥厚型心肌病 (HCM)患者 13例 ,无心肌炎、DCM或近期感染者 (对照 ) 36例。所有被研究者均行心肌组织活检 ,用于病理组织学检查和巢式聚合酶链反应 (PCR)检测分析HPVB19 DNA。结果 :炎症性心肌病中有 4例HPVB19 DNA阳性 (占 13.3% ) ,DCM中有 3例HPVB19 DNA阳性 (占 8.3% ) ,HCM中有 2例HPVB19 DNA阳性 (占 15 .4 % ) ,而对照组HPVB19 DNA均为阴性。结论 :心肌病患者中HPVB19感染率较高 ,HPVB19感染可能是心肌病的重要病因之一。     

Heterogeneity in clinical course of EBV-associated lymphoproliferative disorder after allogeneic stem cell transplantation

Objective and Importance

Post-transplant lymphoproliferative disorder (PTLD) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) associated with Epstein–Barr virus (EBV).

Clinical presentations

Among 263 individuals treated with allo-HSCT for severe aplastic anemia, pure white cell aplasia, T-prolymphocytic leukemia, and relapsed Hodgkin lymphoma, we diagnosed EBV-PTLD in 5 patients. Median age was 29 years (range 19–70 years) and four of five patients were EBV-seropositive prior to HSCT. All five had unrelated EBV-positive donors. In all cases, PTLD occurred within the first year post-transplant (median 4 months).

Intervention

There were two rapidly fatal courses with extensive organ involvement. Both patients showed lymphopenia and thrombocytopenia. In contrast, the three surviving patients had higher lymphocytes and normal platelet counts, while PTLD was restricted to one site and resolved after 2–4 cycles of rituximab.

Conclusion

In this case series courses of PTLD showed substantial diversity.     

Prevalence of Markers of Hepatotrophic Viruses in Alcoholics with Symptomatic Liver Cirrhosis or Pancreatitis

The reason why similar amounts of alcohol consumption cause different types of organ damage in alcoholics is obscure. Recent studies indicate that hepatitis B virus infection may influence the development of liver cirrhosis in alcoholics. We investigated the prevalence of markers of viruses known to cause hepatitis (HAV, HBV, EBV, CMV) in two groups of patients, one with alcoholic pancreatitis without known liver cirrhosis and one with alcoholic liver cirrhosis without known pancreatitis. We found signs of past infection with HAV and HBV more often in alcoholics with liver cirrhosis than in patients with alcoholic pancreatitis or in age-matched controls.     

An elderly patient with chronic active Epstein–Barr virus infection with mixed cryoglobulinemia and review of the literature

A 76-year-old woman was diagnosed with chronic active Epstein–Barr virus (EBV) infection (CAEBV) with sustained fever, anemia, numbness of the lower limbs, and liver dysfunction. The patient had an unusual anti-EBV antibody profile and high viral load, positive rheumatoid factor, and cryoglobulinemia. She suffered from recurrent hemosputum with pleural effusion and thrombocytopenia caused by CAEBV infection, and she died in July 2008. Here, we present a rare case of CAEBV infection with cryoglobulinemia in an elderly patient.     

Simultaneous presentation of hemophagocytic syndrome and mesenteric vasculitis in a patient with systemic lupus erythematosus

Abstract

We report an 18-year old female patient with systemic lupus erythematosus (SLE), who developed fever, pancytopenia, abdominal pain, and watery diarrhea. Computed tomography (CT) and bone marrow aspirate revealed lupus mesenteric vasculitis (LMV) and hemophagocytic syndrome (HPS). Serologic tests for Epstein–Barr virus (EBV) indicated its reactivation. This case demonstrates that HPS and concomitant LMV associated with viral reactivation can occur as clinical manifestations of SLE flare.     

CMV和EBV感染与儿童ITP的关系

目的 :探讨巨细胞病毒 (CMV)和Epstein Barr病毒 (EBV)感染与儿童特发性血小板减少性紫癜 (ITP)的关系。方法 :采用基础PCR方法检测了 44例ITP患儿外周血白细胞中CMV和EBV的感染情况 ,并结合实验室及临床特征进行分析。结果 :①ITP患儿CMV感染阳性率较高 ,达 6 1.4% ;在慢性反复发作的患儿中 ,CMV阳性率更高 (71.9% ) ,显著高于急性ITP患儿 (33.3% ) (χ2 =5 .47,P <0 .0 5 )。CMV阳性患儿血小板自身抗体阳性率较高 ,血小板及巨核细胞数均较低 ,出血症状明显 ,激素治疗效果较差。② 5 0 %的ITP患儿外周血EBVDNA阳性 ,急性患儿较多见 ,但与慢性患儿比差异无显著性意义。EBV阳性患儿血小板自身抗体阳性率也较高 ,以抗GPⅡb/Ⅲa升高最明显 ,显著高于EBV阴性患儿 (χ2 =4.96 ,P <0 .0 5 )。与CMV阳性患儿相比 ,EBV阳性患儿血小板减少多为轻、中度 ,骨髓中巨核细胞数正常或增多 ,出血症状少见 ,预后较好。结论 :CMV和EBV感染与部分儿童ITP的发病有关 ,不同的病毒感染有不同的发病机制和临床特征。     

Hypersensitivity to mosquito bites: A versatile Epstein–Barr virus disease with allergy,inflammation, and malignancy

Hypersensitivity to mosquito bites (HMB) is a rare disease characterized by transient intense skin reaction and systemic inflammation. Clinical presentation of HMB resembles other mosquito allergic responses, and it can also be difficult to clinically distinguish HMB from other severe allergic reactions. However, a distinctive pathophysiology underlies HMB.HMB belongs to a category of Epstein–Barr virus (EBV)-associated natural killer (NK) cell lymphoproliferative disorders (LPD). Hence, HMB may progress to systemic diseases, such as hemophagocytic lymphohistiocytosis, chronic active EBV disease, and EBV-associated malignancies.A triad of elevated serum IgE, NK lymphocytosis, and detection of EBV DNA in peripheral blood is commonly observed, and identification of EBV-infected NK cells usually facilitates the diagnosis. However, the effective treatment is limited, and its precise etiology remains unknown.Local CD4+ T cell proliferation triggered by mosquito bites appears to help induce EBV reactivation and EBV-infected NK-cell proliferation. These immunological interactions may explain the transient HMB signs and symptoms and the disease progression toward malignant LPD.Further research to elucidate the mechanism of HMB is warranted for better diagnosis and treatment of HMB and other forms of EBV-associated LPD.     

Monitoring of Epstein–Barr virus load and killer T cells in patients with juvenile idiopathic arthritis treated with methotrexate or tocilizumab

Objectives: Methotrexate (MTX) is used for the treatment of polyarticular juvenile idiopathic arthritis (JIA), and an anti-interleukin-6 receptor monoclonal antibody (tocilizumab: TCZ) is also used and added for the treatment of intractable JIA. It has been reported that MTX might induce Epstein–Barr virus (EBV)-associated lymphoma, but the discussion about the effect of MTX and/or TCZ against reactivation of EBV in pediatric patients has been incomplete.

Methods: The EBV loads in four polyarticular JIA and three systemic arthritis JIA patients treated with MTX and/or TCZ, and the percentage of EBV-specific killer T cells (EBV-CTLs) in some patients were prospectively monitored.

Results: No patients had EBV-associated symptoms during the observation period. EBV loads in all patients were not significantly increased, and the levels of EBV loads were the same as EBV-seropositive healthy children following the administration of MTX and/or TCZ. EBV-CTLs were detectable during the observation period, but some patients had slightly low levels of EBV-CTLs.

Conclusion: Treatment with MTX and/or TCZ did not severely affect EBV load and prevent induction of EBV-CTLs in JIA patients.     

EBV-associated lymphoma and chronic inflammatory demyelinating polyneuropathy in an adult without overt immunodeficiency

Epstein-Barr virus (EBV)-associated lymphoproliferative disease occurs almost exclusively in immunocompromised states. This type of malignancy nevertheless developed in a woman without overt immunocompromise. She presented with rapidly progressive lower extremity weakness that was consistent with a chronic inflammatory demyelinating polyneuropathy (CIDP). CIDP has been documented in Hodgkin's disease but rarely in non-Hodgkin's disease. Diagnosis was confirmed by lymph node and sural nerve biopsies and by nerve conduction studies. Prednisone, rituximab, cyclophosphamide, doxorubicin, and etoposide were administered with regression of lymphadenopathy and improvement in neurologic symptoms. EBV-associated lymphoproliferative disease can thus develop in the absence of overt immunodeficiency and may trigger a demyelinating polyneuropathy.