Clinical Characteristics of Peripheral Lymphocyte Subtypes in Chronic Active Epstein-Barr Virus Infection.

BACKGROUND: We aimed to analyze the clinical characteristics of peripheral Epstein-Barr virus (EBV)-infected lymphocyte subtypes in children with chronic active EBV infection (CAEBV). METHODS: The levels of peripheral EBV infection of CD4+ T cells, CD8+ T cells, and CD56+ natural killer (NK) cells were determined by flow cytometry and quantitative polymerase chain reaction (qPCR) in patients with CAEBV from July 2017 to July 2022. RESULTS: In total, 112 children with CAEBV were evaluated. Of these, CD4+ type, CD8+ type, and CD56+ type were defined in 44, 21, and 47 patients, respectively. Patients with CD8+ T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4+ T-cell type. Generally, patients with CD8+ T-cell type had the lowest overall survival rate (P = .017). Patients treated with chemotherapy and hematopoietic stem cell transplantation (HSCT) had a better prognosis (P = .001). In multivariate analysis, rash, hemophagocytic lymphohistiocytosis, CD8+ T-cell type, and no decrease of plasma EBV-DNA after treatment were independent indicators of poor prognosis (P = .002, .024, .022, and .012, respectively). CONCLUSIONS: In children with CAEBV, rash was more frequent in patients with CD8+ T-cell type, whereas patients with CD4+ T-cell type were more likely to develop hepatomegaly. Patients with CD8+ T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT.

Clinical characteristics of peripheral lymphocyte subtypes in chronic active Epstein-Barr virus infection.

PURPOSE: To analyze the clinical characteristics of peripheral Epstein-Barr virus(EBV)-infected lymphocyte subtypes in children with chronic active EBV infection(CAEBV). METHODS: The levels of peripheral EBV infection of CD4 + T cells, CD8 + T cells, and CD56 + NK cells were determined by flow cytometry and qPCR in patients with CAEBV from July 2017 to July 2022. RESULTS: A total of 112 children with CAEBV were evaluated in the study. Of them, CD4 + type, CD8 + type, and CD56 + type were defined in 44, 21, and 47 patients, respectively. Patients with CD8 + T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4 + T-cell type. Generally, patients with CD8 + T-cell type had the lowest overall survival(OS) rate(P = 0.017). As for treatment, patients treated with chemotherapy and hematopoietic stem cell transplantation had a better prognosis(P = 0.001). In multivariate analysis, rash, HLH, CD8 + T-cell type, and no decrease of plasma EBV-DNA after treatment were indicated as independent factors of poor prognosis(P = 0.002, 0.024, 0.022, and 0.012, respectively). CONCLUSION: In children with CAEBV, the rash was more frequent in patients with CD8 + T-cell type, whereas patients with CD4 + T-cell type were more likely to develop hepatomegaly. Patients with CD8 + T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT.

Epstein-Barr virus-associated B-cell lymphoproliferative disorder meeting the definition of CAEBV B cell disease: a case report.

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) is a systemic EBV-positive lymphoproliferative disorder (EBV-LPD) considered to be associated with a genetic immunological abnormality, although its cause is still unclear. EBV is usually detected in T cells or NK cells in CAEBV patients with only a few cases involving B cells described in East Asia, which may be due to differences in genetic and environmental factors. CASE DESCRIPTION: A 16-year-old boy who seemed to be diagnosed as CAEBV of B cell type was studied. The patient had IM-like symptoms persisting for more than 3 months, high levels of EBV DNA in the PB, and positive EBER in situ hybridization in B cells. In addition, to exclude underlying genetic disorders, we performed next-generation sequencing (NGS) and whole-exome sequencing (WES), which identified the missense mutation in PIK3CD (E1021K), ADA (S85L) and CD3D (Q140K) in the patient while no same genetic mutation was detected in his parents and sister. However, there is no diagnosis of CAEBV of B cell type in the most recent World Health Organization classification of tumors of hematopoietic and lymphoid tissues, therefore we finally diagnosed this patient as EBV-B-LPD. CONCLUSIONS: This study shows a rare case of a patient meeting the definition of CAEBV B-cell disease in East Asia. Meanwhile, the case indicates that the missense mutation and the disease are related.

[Delayed diagnosis of hydroa vacciniforme-like lymphoproliferative disorder in a patient with skin rashes].

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent EBV infection and can lead to fatal conditions such as hemophagocytic syndrome and malignant lymphoma through the clonal expansion of EBV-infected T or natural killer (NK) cells. Hydroa vacciniforme lymphoproliferative disorder (HV) and hypersensitivity to mosquito bites (HMB) have been identified as skin diseases in EBV-associated T- or NK-cell lymphoproliferative diseases. We present the case of a 33-year-old man. The patient had frequent episodes of a facial rash for three years before he visited our hospital, he visited several dermatologists but did not receive a diagnosis of HV. He was referred to the hematology department of our hospital for assessment of atypical lymphocytes in peripheral blood. Based on routine blood and bone marrow test we were unable to diagnose HV. However, when the patient's liver function deteriorated six months later, we considered the possibility of HV after reevaluating the skin rash. After performing EBV-related tests, we were able to definitively diagnose CAEBV with HV. It is crucial to be able to connect clinical observations to EBV-related tests when diagnosing CAEBV. Hematologists must be knowledgeable of the EBV-associated skin conditions of HV and HMB.

Acute fibrinous and organizing pneumonia complicated with hemophagocytic lymphohistiocytosis caused by chronic active Epstein-Barr virus infection: a case report.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare lung condition that is associated with acute lung injury. Its etiology may be idiopathic or secondary to a series of conditions, including immune-related diseases, unclassified connective tissue diseases, hematopoietic stem cell transplantation, infections, hematological diseases and drug induced lung toxicity. We report for the first time a case of AFOP complicated with hemophagocytic lymphohistiocytosis (HLH) caused by chronic active Epstein-Barr virus (CAEBV) infection. CASE PRESENTATION: A 64-year-old man was admitted with a complaint of fever and dyspnea for 2 weeks. The patient presented with elevated serum aminotransferase levels, splenomegaly, progressive decrease of red blood cells and platelets, hyperferritinemia, hypofibrinogenemia, and elevated of Soluble interleukin-2 receptor (sCD25). His chest computed tomography (CT) scan revealed multiple patchy consolidation in both lungs and multiple lymphadenopathy in the mediastinum and hilum. The serology for antibodies of VCA-IgG was positive, EBV-DNA in peripheral blood was elevated, and EBV nucleic acid was detected in the alveolar lavage fluid. Histopathology of the lung tissue showed a dominant of intra-alveolar fibrin and organizing pneumonia. Hemophagocytic cells was found in the bone marrow smear and biopsy. EBV-DNA was detected in lung tissue and bone marrow using in situ hybridization with an EBV-encoded RNA (EBER) probe. After 50 days of hospitalization, he was improved in lung and hemogram. CONCLUSION: We report a case of AFOP with HLH caused by CAEBV in an immunocompetent adult, suggesting that AFOP may be a rare but serious complication caused by CAEBV, and glucocorticoid therapy may improve short-term prognosis.

[The road to treating chronic active Epstein-Barr viral infection].

Chronic active Epstein-Barr virus (CAEBV) infection is a progressive disease characterized by persistent inflammatory symptoms accompanied by clonally proliferating EBV-positive T or NK cells. The optimal medical treatment for CAEBV to eradicate EBV-infected T or NK cells has not yet been established, with allogeneic hematopoietic stem cell transplantation as the only strategy currently available. Patients with CAEBV have been reported mainly from limited area of Japan and East Asia. However, CAEBV is drawing a global attention, and the number of reports is increasing worldwide after its definition was added to the EBV-positive T- or NK-cell neoplasms in the 2017 World Health Organization classification. We had previously discovered that STAT3 was constitutively activated in EBV-infected tumor cells in CAEBV inducing the immortalization and production of inflammatory cytokines. Based on these findings, an investigator-initiated clinical research of a JAK1/2 inhibitor ruxolitinib for CAEBV infection was initiated in January 2019. Japanese researchers have been expected to elucidate pathological mechanisms and to establish an effective treatment.

Chronic active Epstein-Barr virus infection manifesting as coronary artery aneurysm and uveitis.

BACKGROUND: Chronic active Epstein-Barr virus (CAEBV) infection is a type of lymphoproliferative disorder characterized by chronic or recurrent infectious mononucleosis (IM)-like symptoms, which can have less-frequent clinical presentations. The prognosis of CAEBV is poor, and hematopoietic stem cell transplantation (HSCT) has been shown to be the only potentially effective treatment. In this article, we present a special CAEBV case of a patient who had no typical IM-like symptoms at the early stage, but manifested with severe and progressive coronary artery aneurysm (CAA), abdominal aortic lesions, and severe uveitis. These manifestations were uncommon features and could only be blocked by HSCT. CASE PRESENTATION: A 4-year-old girl with no special medical history complained of decreased vision for 10 months and cough after physical activities for three months. The blurred vision grew rapidly worse within one month, until only light perception remained. She was diagnosed with uveitis and cataract, and received prednisone and ciclosporin A treatment. However, her vision did not improve. Physical examination showed slight hepatosplenomegaly. Ultrasonic cardiogram showed bilateral CAA (5.0 mm and 5.7 mm for inner diameters), and abdominal CT scan revealed a thickened aortic wall, as well as stenosis and dilation of the segmental abdominal aorta. Other significant findings were increased EBV-DNA (3.29 × 104 copies/mL) from peripheral blood, positive EBV antibodies (EBV-CA-IgG, EBV-EA-IgA, and EBV-NA-IgG), and positive EBV-encoded small RNAs found by bone marrow biopsy. Based on her clinical manifestations and evidence for EBV infection, we diagnosed CAEBV. She received allogeneic HSCT, and the cataract operation was performed after HSCT. EBV-DNA could not be detected in peripheral blood after HSCT. Her CAAs did not progress, and uveitis was well controlled. Her vision recovered gradually over the 3 years after HSCT. CONCLUSIONS: We present a rare CAEBV case of a patient who suffered from uncommon and severe cardiovascular and ocular involvement that was relieved by HSCT. Therefore, early recognition and diagnosis of CAEBV are of vital importance to improve its prognosis. In summary, this atypical CAEBV case could help us recognize similar cases more easily, make the right diagnosis as early as possible, and deliver proper and timely treatment.

Impact of melphalan dose during reduced-intensity conditioning on engraftment of cord blood transplantation for chronic Epstein-Barr virus-associated T or NK cell lymphoproliferative diseases.

The rejection rate in cord blood transplants for chronic Epstein-Bar virus-associated T or natural killer cell lymphoproliferative diseases using our standard reduced-intensity conditioning "LPAM140 regimen," which includes fludarabine, melphalan (LPAM), etoposide, and antithymocyte globulin, has been high. To ensure better engraftment, we increased the LPAM dose to 210 mg/m2 ("LPAM210 regimen"). Patient data (n = 22; LPAM140, n = 7; LPAM210, n = 15) were analyzed retrospectively. The engraftment rate after the LPAM210 regimen (100.0%) was significantly higher than that after the LPAM140 regimen (57.1%; P = .002). Fludarabine combined with melphalan (210 mg/m2 ) had a favorable impact on engraftment.

Chronic active Epstein-Barr virus infection involving gastrointestinal tract mimicking inflammatory bowel disease.

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) is a rare disease, which is difficult to be differentiated from inflammatory bowel disease (IBD). To cause the attention, we present twelve cases of CAEBV in immunocompetent patients with gastrointestinal tract involvement. METHODS: Twelve patients who fulfilled the diagnostic criteria of CAEBV were enrolled in this retrospective study. The control group was consisted of twenty-four IBD patients with EBV-DNA value increased in peripheral blood. The clinicopathologic and endoscopic characteristics were reviewed and analyzed. RESULTS: The major clinical presentations of CAEBV patients were intermittent fever (100%), hepatomegaly/splenomegaly (58%), lymphadenopathy (50%), diarrhea (50%) and hematochezia (50%). Compared with IBD patients, the incidence of intermittent fever and increased level of ferritin were significantly higher among CAEBV patients. The median values for EBV detected in peripheral blood were significantly higher in CAEBV group (1.42*10^6 copies/µg) than in IBD group (3.2*10^3 copies/µg, p<0.05). The main endoscopic findings of CAEBV included multifocal or isolated, irregular, multiform ulcers and diffuse inflammation, lacking of typical cobblestone appearance. Ten patients died within 5 years of disease onset. The average survival time is 21 months. CONCLUSIONS: Symptoms such as intermittent fever, increased level of ferritin and atypical endoscopic findings could be a sign for CAEBV. Early detections of EBV-DNA in serum and EBV-encoded small nuclear RNA (EBER) by in situ hybridization in intestinal tissue are essential for differential diagnosis between CAEBV and IBD.

Chronic active Epstein-Barr virus infection with intrapulmonary shunting: A case report.

Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is a high-mortality form of EBV infection. However, chronic hypoxemia is rare in these patients. We herein reported a case of severe hypoxemia due to intrapulmonary shunting in CAEBV. A 17-year-old girl presented with fever, dyspnea, cyanosis, and hepatosplenomegaly. Laboratory tests showed mild liver dysfunction and high copy numbers of EBV-DNA in the peripheral blood. A left supratrochlear lymph node biopsy showed infiltration of highly proliferative T lymphocytes with positive EBV encoded small RNA by in situ hybridization. Technetium-99m-labeled macroaggregated albumin and contrast-enhanced echocardiography confirmed the existence of intrapulmonary shunting, which was probably related to hepatopulmonary syndrome. The final diagnosis was CAEBV with intrapulmonary shunting. The patient was treated with cyclosporine A, etoposide, and dexamethasone. Finally, the patient died of respiratory failure. Intrapulmonary shunting is a rare complication of CAEBV. Early recognition and exploring the cause of hypoxemia should be highlighted in patients with CAEBV.

[Chronic active Epstein-Barr virus infection with multiple vascular lesions successfully treated by cord blood transplantation].

An 18-year-old woman presented with fever and liver dysfunction. Computed tomography showed lymphadenopathy, hepatosplenomegaly, and vascular lesions such as aneurysms and irregularities at multiple arteries, including coronary arteries. Based on the high copy number of Epstein-Barr virus (EBV)-DNA in the peripheral blood, EBV-infected CD4+T cells, and the proliferation of EBER-positive cells in the bone marrow, chronic active EBV infection (CAEBV) was diagnosed. Although the fever and liver dysfunction improved as a result of the initial immunosuppressive therapy and multiagent chemotherapy, EBV-DNA remained high. Moreover, she experienced repeated episodes of angina pectoris due to coronary arterial lesions. Therefore, cord blood transplantation was performed after reduced-intensity conditioning. EBV-DNA decreased quickly after initiating the conditioning and became undetectable at day 7 after the transplant. Vascular lesions did not progress after the transplant, and the patient's angina pectoris resolved. At 2.5 years after the transplant, she is alive without disease recurrence. The prognosis of CAEBV with vascular lesions is especially poor. Although the indication for allogeneic hematopoietic stem cell transplantation (HSCT) is difficult to determine in such cases, the clinical course of our case suggests that allogenic HSCT could be safely performed under appropriate management and could successfully control not only CAEBV but also vascular lesions.

Novel mutations of STXBP2 and LYST associated with adult haemophagocytic lymphohistiocytosis with Epstein-Barr virus infection: a case report.

BACKGROUND: Haemophagocytic lymphohistiocytosis is a life-threatening disease resulting from primary or secondary hyper-inflammatory disorders. The typical symptoms include persistent fever, splenomegaly, cytopenia and significant elevation of serum ferritin. CASE PRESENTATION: We report a 30-year-old Chinese female patient who was diagnosed with chronic active Epstein-Barr virus infection more than 9 months prior and has since been presenting with cutaneous lymphoproliferative disorders mimicking hydroa vacciniforme and subsequent haemophagocytic lymphohistiocytosis. Exome sequencing suggested novel digenic heterozygous STXBP2 (c.592A > C, p.Thr198Pro) and LYST (c.830A > T, p.His277Leu) mutations. CONCLUSIONS: This is the first case report in which adult HLH was associated with novel digenic mutations of STXBP2 and LYST combined with Epstein-Barr virus infection. It could also be the first polygenic model report, given that the pathogenicity of other mutated genes still remains unclear. We additionally conducted an in-depth, two-generation pedigree analysis to further illustrate the mode of inheritance in this case.

A fatal case of Exophiala dermatitidis disseminated infection in an allogenic hematopoietic stem cell transplant recipient during micafungin therapy.

Exophiala dermatitidis is a dematiaceous fungus that is increasingly becoming the cause of fungal infection in immunocompromised patients. However, the risk factors and optimal treatment modality for E. dermatitidis infection are unknown to date. Herein, we present a fatal case of E. dermatitidis infection in an adult patient that developed after allogeneic hematopoietic stem cell transplantation for chronic active Epstein-Barr virus infection. The dematiaceous fungus caused a breakthrough fungemia despite prophylactic administration of micafungin. Although the patient was intensively treated with liposomal-amphotericin B and voriconazole, serum level of beta-D-glucan continuously increased, and the patient eventually died because of cerebral hemorrhage. An autopsy found multiple involvements of the fungal infection at the bilateral lungs, thoracic cavities, diaphragm, and thyroid. To the best of our knowledge, this is the first reported case of E. dermatitidis infection involving these tissues as determined via autopsy. This case highlights the importance of attention for Exophiala infection in immunocompromised individuals in those given antifungal therapy with echinocandins.

Bilateral granulomatous panuveitis in two patients with T-cell type of chronic active Epstein-Barr virus infection.

BACKGROUND: To report 2 cases of bilateral granulomatous panuveitis accompanied by chronic active Epstein-Barr virus infection (CAEBV). CASE PRESENTATION: Case 1 was a 38-year-old man who had a history of bilateral mild panuveitis who was diagnosed with CAEBV. Fifteen months later, a severe bilateral granulomatous panuveitis developed. White infiltrates covered the optic disc and all the retinal vessels of the right eye, and white nodules were seen along the retinal veins and arteries of the left eye. Case 2 was a 34-year-old man with bilateral panuveitis showing mutton-fat keratic precipitates and diffuse vitreous opacity in both eyes. A snow ball-like vitreous opacity was present in the right eye. Systemic investigations revealed the presence of CAEBV. In both cases, a comprehensive polymerase chain reaction (PCR) analyses of the aqueous humor detected significant copy numbers of EBV-DNA. The intraocular inflammation did not respond to steroid, methotrexate, and other immunosuppressive therapies, but was ameliorated after hematopoietic stem cell transplantation with preceding chemotherapy and low-dose total body irradiation in both cases. CONCLUSION: Granulomatous panuveitis can develop in eyes with CAEBV as a primary symptom. Ophthalmologists should rule out CAEBV when EBV-DNA is positive in the intraocular fluids of steroid-resistant panuveitis.

[Clinical features of adult-onset chronic active Epstein-Barr virus infection].

Chronic active Epstein-Barr virus infection (CAEBV) presents with mononucleosis-like symptoms such as chronic persistent or recurrent pyrexia, lymphadenopathy, and hepatosplenomegaly because of the reactivation of Epstein-Barr virus (EBV) as demonstrated by the recurrence of EBV-infected cells. The mechanism of CAEBV remains obscure, and CAEBV can lead to fatal conditions such as hemophagocytic syndrome and malignant lymphoma by clonal expansion of EBV-infected T- or NK-cells. Without hematopoietic stem cell transplantation, CAEBV has a poor prognosis. CAEBV is listed in the revised 2016 World Health Organization classification as a chronic active EBV infection of T- and NK-cell types, systemic form, among EBV-positive T- and NK-cell lymphoproliferative diseases of childhood. However, similar clinical conditions have been reported in adult patients. Therefore, we investigated the clinical features of adult patients with CAEBV-like features (adult-onset CAEBV) in a relatively small number of cases. Additionally, genetic alterations related to CAEBV development have also been reported. Along with these results, we reviewed the clinical characteristics of adult-onset CAEBV.

[Fatal exacerbations of chronic active Epstein-Barr virus infection subsequent to cytotoxic chemotherapy].

Chronic active Epstein-Barr virus infection (CAEBV) is critical owing to lethal complications such as hemophagocytic lymphohistiocytosis (HLH), multiple organ failure, and malignant lymphoma. Here we present two cases of CAEBV who developed rapid and life-threatening disease progression after cytotoxic chemotherapy. Case 1: In a 34-year-old male, CAEBV recurred after 4-month remission obtained by initial therapy with etoposide, cyclosporine, and prednisolone. Accordingly, cord blood transplantation was planned. A day after administering high-dose melphalan as the conditioning, he developed respiratory failure, pancytopenia, and hyperferritinemia. He died 3 days later. Case 2: A 53-year-old female attained remission after initial therapy for CAEBV. After 1 month, she relapsed, and high-dose cytarabine (HDAC) was administered. A day after HDAC administration, she suddenly developed respiratory failure, which was followed by multiple organ failure. She died 3 days later. Thus, planned strategy for prompt allogeneic hematopoietic stem cell transplantation is necessary to prevent disease progression and control cytokinemia before cytotoxic chemotherapy for CAEBV.

Chronic active Epstein-Barr virus infection of T-cell type, systemic form in an African migrant: case report and review of the literature on diagnostics standards and therapeutic options.

BACKGROUND: Chronic active Epstein-Barr virus (EBV) infection (CAEBV) of the T-/NK-cell type, systemic form is a rare and potentially life-threatening illness caused by persistent EBV infection. The highest incidence is found in children and adolescents with increased frequency among Asians and Native Americans, while the disease is uncommon in Western countries. Typically patients present with unspecific symptoms, like fever, lymphadenopathy, hepatosplenomegaly and liver dysfunction. Due to fatal complications including hemophagocytic syndrome, coagulopathy, multiple organ failure and development of EBV-positive lymphoproliferative disease (LPD) or lymphoma early diagnosis is critical for successful treatment. However, in consequence of the lack of experience due to the low incidence in Europe, a broad spectrum of clinical manifestations and a particularly unexpected group of patients, diagnosis can be challenging. Inhere we describe the clinicopathological findings of an African adult with CAEBV associated LPD with a brief review of the literature. CASE PRESENTATION: A 42-year-old African man with fever, enlargement of the spleen and a suspected epileptic seizure was referred to our hospital. Diagnostic testing repeatedly revealed a massive EBV-DNA load in peripheral blood. Whole-body PET-CT-scan presented a strong uptake at multiple bone marrow sites, the thyroid and the adrenal glands. Histopathological analysis of bone marrow and thyroid gland revealed a highly proliferating, atypical and predominantly intravascular cytotoxic T-cell population with intracellular EBV-encoded RNA. Clonality analysis revealed the presence of polyclonal T-cell-receptor. Based on these findings a CAEBV of the T-/NK-cell type, systemic form was diagnosed. Subsequent therapy including three cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisolone resulted in decreased EBV load, clinical improvement and ongoing complete remission. CONCLUSION: Adult-onset CAEBV of T/NK-cell type usually comprises a poor prognosis and is extremely rare in Western countries. Therefore, our case highlights the need for a clinical awareness of this disease in patients with systemic illness and for a comprehensive multidisciplinary diagnostic approach to facilitate diagnosis. Treatment options include antiviral drugs, immunosuppressive agents and systemic chemotherapy with or without allogeneic stem cell transplantation. Given the limited data these options need to be decided upon in each patient individually considering severity of the disease, comorbidities and response.

An adult-onset case of chronic active Epstein-Barr virus infection with fulminant clinical course.

A 56-year-old Japanese male with chronic active Epstein-Barr virus (EBV) infection (CAEBV) who developed systemic gamma-delta T-cell lymphoproliferative disease (LPD) is reported. Although immune cooling therapy was effective, he died of sudden and severe hypoxia and anemia soon after the initiation of cytotoxic chemotherapy that had been previously recommended. There might remain a difficulty to control fulminant adult-onset CAEBV. Additionally, we describe three types of lymphoid cells that were observed in his peripheral blood: morphologically normal lymphocytes, large blastic cells and mature ones with rough granules. Morphological observation appeared to be useful to estimate clinical manifestations. Since CAEBV is extremely rare disease in adult population, it is important to accumulate clinical data to more understand the pathogenesis or to establish treatment strategy.

[Clinical features of adult patients with chronic active Epstein-Barr virus infection].

Objective: To investigate the clinical features of adult-onset chronic active Epstein-Barr virus infection (CAEBV). Methods: A total of 21 adult patients with CAEBV who were admitted to the department of General Internal Medicine at Peking Union Medical College Hospital from January 2006 to January 2016 were retrospectively analyzed. Demographic data, disease duration, clinical manifestations, laboratory findings, treatments and prognosis were reviewed. Results: Eighteen females and 3 males were enrolled with a mean age of 39 years. The most common clinical manifestations included fever in 20 patients, splenomegaly in 20 patients, lymphadenopathy in 18 patients, and hepatomegaly in 10 patients, followed by laryngopharyngeal disorders in 6 patients, pleural effusion and peritoneal effusion each in 5 patients, rash in 4 patients, interstitial lung disease in 3 patients, gastrointestinal hemorrhage in 2 patients, and peripheral neuropathy and pulmonary hypertension each in 1 patient. Six patients were complicated with hemophagocytic lymphohis-tioncytosis(HLH) that developed 5-17 (mean: 9) months following CAEBV onset, all of whom experienced hyperpyrexia, pancytopenia, lymphadenopathy, splenomegaly, and liver dysfunction, 3 with hepatomegaly. Nineteen of the 21 patients had received steroid therapy including 10 combined with immunosuppressive agents, 11 with antiviral therapy, and 8 with intravenous immunoglobulin. Thirteen patients died, including 10 of multiple organ failure, (including 6 of HLH) 2 of severe pulmonary infection, and 1 of lymphoma. Six patients remained on follow-up, yet 2 were missing. Conclusions: CAEBV is expected with severe condition and poor prognosis, which is likely to be complicated with HLH. Clinical physicians should pay attention to adult patients with fever, hepatosplenomegaly and lymphadenopathy, which suggests possible CAEBV.

[Ovum collection following ovarian stimulation in patients with chronic active Epstein-Barr virus infection].

The only curative treatment for chronic active Epstein-Barr virus infection (CAEBV) is hematopoietic stem cell transplantation. For young female patients, ovulation induction and oocyte cryopreservation may be performed prior to transplantation to provide for future pregnancies. However, the effects of this ovum treatment on CAEBV and EBV infections have not been reported. Attempts were made to collect ova from three female CAEBV patients before transplantation conditioning, but this was only successful in two cases. Ovarian stimulation did not induce disease progression, and there was no change in the peripheral blood EBV DNA load. In one patient, 460 copies/ml of EBV DNA were detected in the follicular fluid by real-time PCR. Red blood cells were also present in the follicular fluid but not mononuclear cells. EBV protein mRNA was not detected in the RNA extracted from the same fluid, suggesting that the EBV DNA resulted from peripheral blood contamination. Moreover, there were no EBV-infected cells in the follicular fluid. Therefore cryopreservation of oocytes from CAEBV patients is possible and may be used to provide for future pregnancies.