Acute EBV Infection Research Articles

Donʼt Ask, Donʼt Tell: A Lesson on Evaluating Acute Hepatitis

Acute hepatitis A virus (HAV) infection is common in developing countries. It can range from asymptomatic to fulminant hepatitis. The mean peak of total bilirubin in acute HAV infection is usually less than 10 mg/dL with mean jaundice lasting about 4 weeks. Cases of prolonged or relapsing cholestatic HAV were reported at a global incidence of 5-10%. Acute HAV infection with prolonged cholestatic jaundice (PCJ) is rare. We present a severe prolonged cholestatic HAV infection likely complicated by concurrent Chikungunya virus infection and drug induced liver injury. A 39 year old female, born in India, presented to our hospital with subjective fevers, malaise, and myalgias for 3 weeks. She returned from a trip to India 1 month ago. On admission she had a temperature of 100.1°F. Her physical exam was within normal limits with no documented hepatomegaly. Her initial blood work showed elevated transaminases (aspartate aminotransferase (AST u/L) 122, alanine aminotransferase (ALT u/L) 143)with normal alkaline phosphatase (ALP) and total bilirubin (TB). Three days into her admission she showed some clinical improvement but with worsening of AST to 1958 and ALT to 1605 reaching a peak of AST 3804 and ALT 3335; ALP remained normal and TB increased to 4.0 mg/dL. US of abdomen showed hepatic steatosis. Viral markers were positive for HAV IgM but negative for acute EBV, CMV, HBV, HCV and HEV infection. Her autoimmune panel was negative. She was discharged 1 week later with clinical improvement; AST 556 and ALT 1418, ALP 77 and INR 1.58. Her TB remained elevated to 7.6. She was readmitted to the hospital 2 weeks later with pruritus and worsening fatigue. Her AST was 88 and ALT 59, with ALP of 148 and a TB of 23.4. Her INR was 2.09. A repeat US showed no biliary ductal dilation or stones. She tested positive for Chikungunya IgM. She admitted to ingesting multiple herbal products. Her liver tests normalized at 4 months with positive HAV and Chikungunya IgG.FigureFigureFigureWe present a severe prolonged cholestatic HAV infection likely complicated by concurrent Chikungunya infection and drug induced liver injury. Acute HAV infection with prolonged cholestatic jaundice (PCJ) is rare. Acute Chikungunya has been documented as a cause of acute cholestatic hepatitis. A thorough history of drug exposure is essential in the evaluation of cholestatic liver injury. Furthermore, CDC recommendation for HAV vaccination for travelers should be reinforced even on immigrants from endemic countries.

THE IMPORTANCE OF HERPESVIRUSES IN THE ETIOLOGY OF A NUMBER OF INFECTIOUS AND SOMATIC DISEASES OF CHILDREN

The article is devoted to study the etiological role of herpes viruses in infectious and somatic pathology of children (n = 770) using the complex of methods of laboratory diagnostics. Determined the leading etiological role of HSV in children with neuroinfections (12,7%) during primary infection and in children with intrauterine infection (29,0%) during its reactivation. It is shown that in 50,9% of cases, the diagnosis of «infectious mononucleosis» confirmed by the detection of markers of acute EBV-infection, and 20,0%, it was replaced by mononucleotides syndrome was discovered markers of acute CMV-infection, and 18,1% — markers of acute HHV-6-infection. The role of HHV-6 as the primary etiologic agent of the disease is established at 36,3% of children admitted with convulsive syndrome on the background of febrile, at 29,1% — a sudden exanthema and 25,5% — with fever of unknown origin.

The understanding of Epstein-Barr virus associated lymphoproliferative disorder

In recent years, there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+ LPD), and the name of EBV+ LPD is used widely. However, the meaning of EBV+ LPD used is not the same, which triggered confusion of the understanding and obstacles of the communication. In order to solve this problem. Literature was reviewed with combination of our cases to clarify the concept of EBV+ LPD and to expound our understanding about it. In general, it is currently accepted that EBV+ LPD refers to a spectrum of lymphoid tissue diseases with EBV infection, including hyperplasia, borderline lesions, and neoplastic diseases. According to this concept, EBV+ LPD should not include infectious mononucleosis (IM) and severe acute EBV infection (EBV+ hemophagocytic lymphohistiocytosis, fatal IM, fulminant IM, fulminant T-cell LPD), and should not include the explicitly named EBV+ lymphomas (such as extranodal NK/T cell lymphoma, aggressive NK cell leukemia, Burkitt lymphoma, and Hodgkin lymphoma, etc.) either. EBV+ LPD should currently include: (1) EBV+ B cell-LPD: lymphomatoid granulomatosis, EBV + immunodeficiency related LPD, chronic active EBV infection-B cell type, senile EBV+ LPD, etc. (2) EBV+ T/NK cell-LPD: CAEBV-T/NK cell type, hydroa vacciniforme, hypersensitivity of mosquito bite, etc. In addition, EBV+ LPD is classified, based on the disease process, pathological and molecular data, as 3 grades: grade1, hyperplasia (polymorphic lesions with polyclonal cells); grade 2, borderline (polymorphic lesions with clonality); grade 3, neoplasm (monomorphic lesions with clonality). There are overlaps between EBV+ LPD and typical hyperplasia, as well as EBV+ LPD and typical lymphomas. However, the most important tasks are clinical vigilance, early identification of potential severe complications, and treating the patients in a timely manner to avoid serious complications, as well as the active treatment to save lives when the complications happened.

P.060 A case of mononeuritis multiplex complicating Epstein-Barr virus infection

Background: Mononeuritis multiplex is a painful, asymmetrical peripheral neuropathy involving motor and sensory nerves. This neurological condition is classically associated with systemic diseases such as connective tissue disorders, vasculitis, hematologic diseases including cryoglobulinaemia and amyloidosis. It has also been reported infrequently as a paraneoplastic or post infectious disorder. Methods: Case report Results: We are reporting a case of a 35-year-old man who presented with mononeuritis multiplex following an infectious mononucleosis associated with a mixed cryoglobulinemia. He was treated with IVIG, IV pulse steroid and a prednisone taper over 7 months. Later on, he had a nerve transfer from FCR (flexor carpi radialis) to ECRB (extensor carpi radialis brevis) and PIN (posterior interosseous nerve) due to complete denervation of the PIN without evidence of spontaneous recovery. Conclusions: Acute EBV infection should be suspected in the setting of mononeuritis multiplex. This is the first reported case of nerve transfer for this type of nerve injury.

Acute EBV Infection and HIV Antibody Cross-Reactivity in a First Time Donor

An 18-years-old female college student was screened as a first-time blood (plateletpheresis) donor and was found to have a highly positive HIV Ab ChLIA (duplicate) test. Negative Western Blot (WB), HIV p24 antigen and NAT HCV RNA/HIV RNA/HBV DNA assays confirmed that the donor was not infected with HIV. The use of other laboratory tests revealed an acute Epstein Barr infection with positive EBV Viral Capsid Antigen (VCA IgM and VCA IgG) antibodies and also positive Heterophile antibodies. Nonspecific reactivity (false-positive) results of HIV infection, by serological tests, may represent a cross-reaction with other human viruses.

Splenic Infarction Induced By Epstein-Barr Virus Infection in a Patient with Sickle Cell Trait

IntroductionAlthough sickle cell trait (SCT) is considered a benign condition, evidence has been accumulating for related complications, including isothenuria, hematuria, exercise-induced death and splenic infarction.Most splenic infarctions are reported during a hypoxic state.Non-hypoxic related splenic infarction in a patient with SCT and EBV infection has been reported once.Here we present the second case of such association.Case ReportAn otherwise healthy 7-year-old African American male presented with worsening LUQ abdominal pain associated with emesis, dark-colored urine and low-grade fever. There was no history of trauma. Family history was positive for SCD.On presentation, the patient had a temperature of 38.2 °C and was tachycardic. Physical examination revealed scleral icterus and conjunctival pallor. Abdomen was soft, but the spleen was tender and palpable 6 cm below the costal margin.Laboratory studies showed hemoglobin of 7.2 g/dL, MCV 72.6 fL, leukocytes 14 X 109/L with 73% neutrophils, platelet count 136 X 109/L, and reticulocyte count 8%. Peripheral blood smear didn't reveal sickling, spherocytosis nor elliptocytosis. Total bilirubin was 3.5 mg/dL, direct bilirubin 0.6 mg/dL, ALT 13 U/L, AST 57 IU/L, LDH 476 IU/L. The Direct Coombs were negative. The D-dimer was positive. The Abdominal X-ray was negative, however abdominal ultrasound showed an enlarged spleen, 13.1 cm in longitudinal diameter.An Abdominal MRI showed splenic enlargement, 13 cm in longitudinal diameter, with non-enhancing 4 cm density in anterior aspect and minimal left pleural effusion.The thrombophilia work-up was negative. EB VCA IgG and IgM antibodies levels were high (> 8 and 1 AI, respectively), consistent with late acute infection. The CMV serology was negative. G6PD screening was negative. Hemoglobin electrophoresis revealed HbA 63.9%, HbA2 3.1%, HbF 0.0%, and HbS 33%. Patient was managed conservatively with RBCs transfusion, hydration and pain control and discharged home once stable.DiscussionSCT is generally considered a benign hematological condition, still evidence has been accumulating for related complications. In United States, SCT affects 6-9% of the African American population, and 0.01-0.05% of the remaining population.Splenic infarction is commonly associated with SCD, but rarely with SCT. Reported cases of splenic infarction in SCT have been predominantly related to hypoxic states, primarily in a high altitude setting. Still there have been limited reports in non-hypoxic conditions. (Kark JA and Ward FT Semin Hematol1994).One case of non-hypoxic related splenic infarction in a patient with SCT and acute EBV infection was reported (Symeonidis A et al Acta Haematol 2001). Here we report the second case.We present a non-obese, previously healthy male with no evidence of hypoxia, high altitude setting, or intensive exercise. He suffered a splenic infarction during the acute phase of EBV infection. His initial presentation was consistent with hemolytic anemia and indirect hyperbilirubinemia, which led to further work-up and the diagnosis of SCT. We postulate that hemolysis resulted from hypersplenism.Possible factors leading to infarction in SCT are the induction of sickling and the presence of a hypercoagulable state. The exposure of these HbAS erythrocytes to lower pH and hypoxia in the splenic circulation likely promotes sickling and, as a consequence, splenic infarcts. Subjects with HbAS have significantly increased levels of D-dimer, thrombin-antithrombin TAT complexes, prothrombin fragment 1.2 (F1.2) and absolute monocytosis. The African American population has a 7% risk of VTE attributable to HbAS compared to an attributable risk of 3% for prothrombin G20210A mutation in the Caucasian population.Contributing factors to splenic infarction in the presence of acute EBV infection can be thrombophilia, thrombotic microangiopathy and rapid splenic enlargement. Moreover, during an EBV infection, acute expansion of splenic red and white pulp, as well as increased blood flow and loosening of the reticular network, make the organ friable. HbS existing under such conditions may be quite unstable, which can induce sickling. DisclosuresNo relevant conflicts of interest to declare.

A Gene Expression Signature That Correlates with CD8+ T Cell Expansion in Acute EBV Infection.

Virus-specific CD8(+) T cells expand dramatically during acute EBV infection, and their persistence is important for lifelong control of EBV-related disease. To better define the generation and maintenance of these effective CD8(+) T cell responses, we used microarrays to characterize gene expression in total and EBV-specific CD8(+) T cells isolated from the peripheral blood of 10 individuals followed from acute infectious mononucleosis (AIM) into convalescence (CONV). In total CD8(+) T cells, differential expression of genes in AIM and CONV was most pronounced among those encoding proteins important in T cell activation/differentiation, cell division/metabolism, chemokines/cytokines and receptors, signaling and transcription factors (TF), immune effector functions, and negative regulators. Within these categories, we identified 28 genes that correlated with CD8(+) T cell expansion in response to an acute EBV infection. In EBV-specific CD8(+) T cells, we identified 33 genes that were differentially expressed in AIM and CONV. Two important TF, T-bet and eomesodermin, were upregulated and maintained at similar levels in both AIM and CONV; in contrast, protein expression declined from AIM to CONV. Expression of these TF varied among cells with different epitope specificities. Collectively, gene and protein expression patterns suggest that a large proportion, if not a majority of CD8(+) T cells in AIM are virus specific, activated, dividing, and primed to exert effector activities. High expression of T-bet and eomesodermin may help to maintain effector mechanisms in activated cells and to enable proliferation and transition to earlier differentiation states in CONV.

Emergency splenectomy during gastroenteritis and primary EBV infection

We describe the case of a 11 year-old girl with splenic rupture in the course of an acute EBV infection. The patient is brought to the Emergency Department with dehydration secondary to vomit and diarrhoea; when she arrives she has already undergone a 4 days treatment with Amoxicillin/Clavulanic acid for pharyngotonsillitis with fever.

Lymphoprolifération systémique T liée à l’EBV chez l’enfant

Systemic EBV+ T-cell lymphoproliferative disease of childhood is a recent entity described in the 2008 World Health Organisation tumours of haematopoietic system and lymphoid tissues as a clonal T-cell EBV+ systemic proliferation. It occurs after acute or chronic active EBV infection. We report the case of a caucasian, immunocompetent 12-year-old girl, with no particular history, who presented with hemophagocytic lymphohistiocytosis in the aftermath of an infectious mononucleosis. Main symptoms were multiple organ failure, hepatosplenomegaly and pancytopenia. Histopathology of peripheral lymph node and bone marrow revealed a T-cell, CD8+, EBV+ lymphoproliferation. An elevated viral load was detected in blood by PCR. The patient died within 3 weeks. Since most of the cases have been reported in Asia and South America, few cases still have been described in Europe. Unlike B-cell lymphoproliferation in immunocompromised individuals, T-cell EBV+ lymphoproliferation occurs in immunocompetent patients and seems to be the consequence of a proliferative disorder of EBV-infected T-cells, attributed to a cytotoxic T-cell response deficiency. These T-cell proliferations are more frequently immunoreactive for CD8 than CD4. A key feature of the diagnosis might be EBV viral load.

Clinical and laboratory characteristic and age features of the patients with Epstein-Barr virus infection

123 patients with acute and chronic EBV infection were under observation. The aim of this study was to determine differences in clinical course of acute and chronic diseases. Diagnosis in all patients was confirmed by serologic tests results. We described 3 most common variants of chronic EBV infection: reactivation, incomplete remission and atypical reactivation. The most frequent in patients with chronic EBV infection weretoxical, lymphoproliferative, cardiac and arthralgic syndromes.

PD33 ‐ Drug Reaction and Eosinophilia with Systemic Symptoms (DRESS): a 10‐year review in a pediatric population

Results 7 patients with DRESS were identified. Patients ranged from 8 to 16 years old at the time of presentation. Inciting drugs were: Bactrim (3 cases), augmentin (1), carbamazepine (1), phenobarbitone (1), sulfasalazine (1), traditional chinese medication (1). Symptom onset ranged from 10 days to 6 weeks from the start of the inciting drug. All patients had high fever and generalized pruritic exanthematous rash. Two patients also had desquamative rashes, and one patient had purpuric papules. 4 patients had facial oedema, 4 patients had oral mucositis. Most patients had lymphadenopathy and hepatomegaly. 6 patients had significant eosinophilia, 5 had atypical lymphocytosis, and two had leucopenia. All patients had transaminitis, most at least 10x normal. Peak ALT was 1172IU/L in one patient. None suffered liver failure. One patient developed drowsiness and persistent rotatory nystagmus. Another patient had myositis. 3 patients were tested for HHV6; only one was positive. None had acute EBV infection or reactivation. All patients were treated with systemic corticosteroids. Doses ranged from 0.3mg/kg/day to 1.6mg/kg/day prednisolone equivalent. Most patients were weaned off steroids by 2 months. 5 patients had worsening symptoms despite oral steroids, with 2 patients requiring readmission. There were no fatalities. One patient developed TRAb+ hyperthyroidism 6 months later.

Вивчення апоптозстимулюючого впливу похідних ізонікотинової кислоти на моделях латентної та гострої ВЕБ інфекцій

Вивчення апоптозстимулюючого впливу похідних ізонікотинової кислоти на моделях латентної та гострої ВЕБ інфекцій

Acute viral hepatitis – Should the current screening strategy be modified?

BackgroundThe epidemiology of viral hepatitis has changed. Since the introduction of safe and effective vaccines for hepatitis A and B in 1980s, the incidence of acute infections caused by these viruses has been declining in the UK. At the same time, hepatitis E virus (HEV) has been recognised as an increasingly important cause of acute hepatitis, but testing is not widely available. ObjectivesThe aim of this study was to establish the viral causes of acute hepatitis, and use that data to modify the current diagnostic algorithm. Study designA Cognos search was performed to collate subjects tested for HAV, HBV, HCV, HEV, EBV and CMV between June 2010 and December 2012. Information included virological result and their ALT level if done within 5 days from virological testing. ResultsFrom 3462 subjects with suspected acute viral hepatitis, only 25% had biochemical evidence of acute hepatitis (n=854; ALT>100IU/l). The frequency of detection of acute HEV infection (25/409) was over 31-times higher than that of HAV (6/3462), and 7-times higher than that of HBV (24/3462). Most cases of acute HAV, HEV, EBV and CMV infections presented with abnormal ALT levels. Most EBV infections were associated with lymphadenopathy (23/34); in comparison most of CMV infections were not associated with lymphadenopathy (18/22). ConclusionsHEV screening should be included in the initial testing panel for acute hepatitis and screening at least for HAV and HEV might be limited to those with abnormal ALT levels.

Clinical and paraclinical aspects of infectious mononucleosis

Results The incidence of infectious mononucleosis was highest in the age group 15 to 24. The age of the patient has a profound influence on the clinical expression of EBV infection. The incidence of EBV infection is higher in urban environment, where the interhuman contact is closer, and also the addressability to health-care services is better and the laboratory diagnosis is more easily available to the population. The clinical forms of the disease have been grouped according to the severity of illness into the following: light forms – 44 cases (25%), medium forms – 122 cases (69%), and severe forms – 10 cases (6%). A number of 64 cases, considered severe forms, presented mononucleosic hepatitis (36%), 112 cases (64%) were anicteric. 75 cases (42.6%) presented disorders of protein synthesis, factors of coagulation and albumin, hypoglycemia, and dyslipidemia. The most frequent complications during the acute EBV infection were: hepatic (64 cases – 36%); hematologic (19 cases – 11%) anemia, thrombocytopenia; neurologic (5 cases – 3%) meningitis, neuritis; pulmonary (2 cases – 1%) interstitial pulmonary infiltrate, and chronic fatigue syndrome (7 cases – 4%). The therapy consisted in drugs for sustaining the liver functions, corticotherapy accompanied by antibiotic-therapy in the 10 severe cases of central nervous system involvement (15%) and in 15 other cases with hematologic or other complications (20%). Altogether, the combination was utilized in 25 cases (47%), while the rest of 151 cases (65%) didn’t receive corticotherapy.

Splenic infarction as a complication of infectious mononucleosis in a patient with no significant comorbidity

Aims: Splenic infarction represents a very rare complication of infectious mononucleosis encountered mostly in patients with underlying hematologic abnormalities. The aim of the present report is to describe a case of splenic infarction during infectious mononucleosis in an otherwise healthy individual. Case report: A 17-year old boy was admitted to our department due to persistent febrile exudative tonsillitis. Routine laboratory results showed a white blood cell count of 6.70 × 103/μL with 60% lymphocytes including 8% of atypical lymphocytes, elevated aspartate aminotransferase, alanine aminotransferase (AST 134 IU/L and ALT 114 IU/L with a normal range of 10–37 IU/L) and lactate dehydrogenase (LDH 1159 IU/L with a normal range of 240–480 IU/L) levels. Splenomegaly was found in the physical examination and abdominal ultrasound (spleen diameter 20 cm). Monospot test and EBV antibodies (both IgM and IgG) were positive. Two days after admission the patient complained of left upper quadrant pain. Ultrasound examination revealed a hypoechogenic area in the enlarged spleen. Abdominal MRI scan was carried out and showed a splenic infarct (size 4.5 × 4.25 cm). Other causes of splenic infarction were excluded, based on the history, clinical examination, peripheral blood smear, negative Coombs' tests, thrombophilic screen and cardiac echocardiography. Discussion and conclusion: Acute EBV infection may cause splenic infarction in patients without other comorbidities. Underlying pathophysiology remains to be investigated, as several mechanisms have been proposed (hypoxemia, thrombotic microangiopathy, impaired fibrinolysis). Beyond that, we should always bear in mind that complications of infectious mononucleosis, such as splenic infarction, may be a cause of acute abdominal pain in otherwise healthy young patients.

EBV infection and anti-CD3 treatment for Type 1 diabetes: bad cop, good cop?

EBV infection and anti-CD3 treatment for Type 1 diabetes: bad cop, good cop?

Concurrent and Fatal HHV-8 Positive Multicentric Castlemanʼs Disease and Kaposiʼs Sarcoma in a HIV Negative Kidney Transplant Recipient

Castleman's disease is a rare lymphoid disorder. It comprises two pathological entities. These are the hyaline-vascular type, which is usually localized (uni-centeric), and the plasma cell type which is usually multicenteric and rather aggressive. Castleman's disease has been described thrice after kidney transplantation. A 62-year-old Caucasian male with a history of kidney transplant presented high fever, night sweats, dyspnoea, coughing, weakness, hepatosplenomegaly, peripheral lymphadenopathy and symptoms of renal failure within 6 years of the transplantation. Laboratory findings revealed anaemia (haemoglobin = 4.6 mmol/l), thrombocytopenia (101 × 109/L), normal WBC total and differential count, renal function impairment (creatinine = 218 μmol/l), hypoalbuminemia (24 g/l), and elevated CRP (133 mg/l). Diagnostic assays for HIV-1 were performed with repeatedly negative results. No acute CMV or EBV infection was detected (by serology and PCR analysis). The clinical diagnosis at this stage was post-transplant lymphoproliferative disorder, therefore dosage of cyclosporin immunosuppression was decreased. CT-scans revealed hepatosplenomegaly and enlarged abdominal lymph nodes. A bone marrow biopsy showed an active haematopoiesis in all cell lineages without any abnormalities. Histological examination of an axillary lymph node biopsy showed a multifocal proliferation of spindle cells. The diagnosis of Kaposi's sarcoma was confirmed by positive staining of these spindle cells with antibodies against factor VIII-related antigen (not shown) and HHV-8. The remainder of the lymph node showed partly involuted germinal centres, surrounded by small lymphocytes. A number of these lymphocytes also stained positive for HHV-8, as seen in multicentric Castleman's disease. The clinical syndrome and the histological findings were compatible with KS and MCD caused by HHV-8 infection in a long-term immunocompromised patient. HHV-8 DNA load in serum or plasma was determined by real-time quantitative PCR (15 × 105 copies/ml). His condition deteriorated rapidly and he died despite therapy. The unicentric Castelman's disease, histopathologically described as the hyaline-vascular subtype, is more common, it is not associated with HHV8-infection, and can mostly be treated effectively with radiotherapy or surgery. The multicentric form is not well understood: it is an atypical lymphoproliferative disorder of a plasma cell type, and is related to immune dysfunction. Patients with MCD often develop malignancies like Kaposi's sarcoma and non-Hodgkin's lymphoma. Clinically, HHV8-positive MCD is more aggressive, and has a poorer prognosis with a median survival of less than 30 months. MCD, whether or not HHV8-associated, is generally treated with combination chemotherapy and steroids.

Romiplostim (AMG531, Nplate®) for Secondary Failure of Platelet Recovery After Allogeneic Stem-Cell Transplantation

Abstract 1994Romiplostim (Rm), a protein that binds to and stimulates the thrombopoietin receptor, has been shown to increase and maintain platelet counts in splenectomised and non-splenectomised adult patients with chronic immune thrombocytopenic purpura (ITP), and few adverse events have been reported. Thrombocytopenia after allogeneic stem cell transplantation (allo-SCT) is a common complication which can sometimes be severe. All patients are thrombocytopenic until the primary recovery of platelet counts at engraftment, although some patients present with secondary failure of platelet recovery (SFPR) defined by the Seattle group as a decline of platelet counts below 20,000/μL for 7 consecutive days or requiring transfusion support after achieving sustained platelet counts ≥50,000/μL without transfusions for 7 consecutive days after allo-SCT. SFPR is associated with a greater number of complications and a worse outcome indicating that rapid correction of severe thrombocytopenia in these patients is essential.We report on seven patients treated with Rm after allo-SCT for a SFPR not due to disease relapse. The first day of the 7 consecutive days when platelet counts were <20,000/μL was considered the day of SFPR onset. Our therapeutic strategy was to start Rm at 1μg/kg and to increase dose weekly by 1μg/kg until platelet count had reached 50,000/μL. The dose was then reduced as quickly as possible until discontinuation, providing platelet counts remained >50,000/μL, to avoid unnecessary Rm exposure.Transplantations were performed between January 2009 and January 2011. The median age of the patients was 57 years (range, 25 to 60). There were 4 males and 3 females. Diseases were distributed as follow: acute myeloid leukemia (n=2), acute lymphoid leukemia (n=1), myelodysplastic syndrome (n=1), non-Hodgkin lymphoma (n=2), severe aplastic anemia (n=1). Conditioning regimes were reduced in 5 patients. Donors were siblings in 2 cases, matched unrelated in 4 cases and mismatched unrelated in 1 case (C mismatch). The sources of stem cells were peripheral blood in 4 patients and bone marrow in 3 patients. At the onset of SFPR, all patients had severe thrombocytopenia (<10,000/μL) that required transfusion support. At bone marrow aspiration, 2 patients had numerous megakaryocytes while they were rare in the other 4 patients. The median time between allo-SCT and onset of SFPR was 3 months (range, 2 to 18). The median time between onset of SFPR and start of Rm was 27 days (range, 7 to 61). Thrombocytopenia was corrected in all patients. There was a median time of 54 days (range, 24 to 84) between onset of Rm and the first day when platelet count was >50,000/μL. Median duration of treatment was 13 weeks (range, 4 to 16). Maximum dose ranged from 1 to 10μg/kg. Rm was well tolerated and no patient needed to discontinue drug treatment because of adverse events. Four patients developed SFPR within 2 months of developing acute GvHD II-IV. Another patient had an acute GvHD II-IV at 15 months before the onset of SFPR. He also had 2 episodes of CMV infection at 16 and 4 months before SFPR and 2 episodes of EBV infection at 12 and 1 month before SFPR. Moreover, the same patient developed bronchiolitis obliterans organizing pneumonia (BOOP) not due to infection at 1 month before SFPR. Another patient developed acute GvHD II-IV 6 months before SFPR. She also had 2 episodes of CMV infection at 5 and 3 months before the onset of SFPR. The last patient did not develop acute GvHD II-IV or chronic GvHD but had a CMV infection at 1 month before SFPR. Taken together, these observations underline the occurrence of SFPR shortly after episodes of acute GvHD II-IV, BOOP, EBV or CMV infections. At the last follow-up, one patient had died of a relapse of acute myeloid leukemia while others were alive and in remission without recurrence of SFPR after discontinuation of Rm.We conclude that Rm can be a therapeutic option after allo-SCT for patients with severe thrombocytopenia caused by SFPR. However, these preliminary data need to be confirmed in larger studies with a longer follow-up time to improve assessment of efficacy and safety profiles within this setting. In the meantime, if Rm is prescribed, it seems reasonable to use it at the minimally effective dose and to avoid unnecessary prolonged exposure. Disclosures:No relevant conflicts of interest to declare.

CRESCENTIC GLOMERULONEPHRITIS AND LEUCOCYTOCLASTIC VASCULITIS ASSOCIATED WITH ACUTE EBV INFECTION

We report a case of leucocytoclastic vasculitis with crescentic glomerulonephritis in association with acute EBV infection. nep_1440 617..618 A 14 year old male presented to us with history of sudden onset of fever and skin rashes initially over the trunk and gradually involving the entire body including the face for 10 days. He was febrile and breathless with a blood pressure of 110/60 mmHg. He had conjunctival suffusion with a diffuse erythematous maculopapular rash. Systemic examination revealed hepatosplenomegaly with pulmonary congestion. His laboratory investigations revealed thrombocytopenia (87000/cmm) with acute renal failure (creatinine 1.7 mg/dL). Urinalysis showed 2+ proteinuria, haematuria and red blood cell casts with spot urine protein to creatinine ratio of 1.74. His blood and urine culture was negative and 2-D echocardiography was normal. Serum complement 3 and 4 levels were low and vasculitis work-up was negative. Serum for EBV capsid antigen (VCA) was highly positive with increasing titres. He had normal bone marrow studies and skin biopsy suggestive of leucocytoclastic vasculitis. He was treated with i.v. ceftriaxone and other supportive measures but he continued to have high grade fever with worsening azotemia (creatinine 5.2 mg/dL). Percutaneous kidney biopsy revealed severe proliferative glomerulonephritis with cellular crescents in more than 50% of the glomeruli (Fig. 1). He was treated with i.v. methyl prednisolone 500 mg once daily on 3 consecutive days followed by 1 mg/kg day p.o. Following this, his respiratory symptoms subsided, rashes started fading and his urine output improved. His serum creatinine dropped to 0.8 mg/dL with disappearance of proteinuria and haematuria. The finding of leucocytoclastic vasculitis on skin biopsy is suggestive of small-vessel vasculitis. The possible pathophysiological mechanism is either direct invasion of endothelial cells by EBV or by immune complex-mediated inflammation. Renal involvement in EBV infection is predominantly interstitial, 2 overt renal failure is uncommon 3 and crescentic glomerulonephritis has never been reported. Crescentic glomerulonephritis and small-vessel vasculitis in the presence of Ig M VCA antibodies in our patient may have resulted from an intense immune response to the EBV infection. Simultaneous decrease in C3 and C4 indicating classical complement activation along with prompt response to immunosuppressive therapy supports this possibility. Thus, we hypothesize that EBV infection should be included in the differential diagnosis while treating a patient with crescentic glomerulonephritis.

The clinical pathological analysis of Epstein-Barr virus active infection during the middle-late pregnancy

Objective To explore the relationship of acute infections of Epstein-Barr virus and hydrops fetalis and explore the harm to fetuses and the affection on pregnancy outcomes caused by acute EBV infection during pregnancy. Methods 40 cases hydrops fetalis were diagnosed by ultrasonography. The difference between the EBEA-IgM positive and negative patients blood were studied. 101 cases over the same period of pregnant women with normal fetuses were enrolled as a control group. Results The positive rate of EBEA-IgM in pregnant women (95%) was significantly higher than that of control group(48.5%,P＜0.01). And the differences of the ratio of still birth and live birth and abnormal fetuses induction of labor between the groups were statistically significant（P＜0.01）. Premature birth among the live birth (40%) was obviously higher than that of control group (10.9%,P＜0.05). Conclusions Active infection of EBV in pregnancy was relevant to the hydrops fetalis and there need to pay attention to the detection of EBV during pregnancy. Key words: Herpesvirus 4,human; Herpesviridae infections; Hydrops fetalis/ET; Pregnancy trimester,third; Pregnancy outcome