Comparison of clinical features between chronic active Epstein-Barr virus infection and infectious mononucleosis in adult patients / 中华临床感染病杂志

Objective:To compare the clinical features between chronic active Epstein-Barr virus infection(CAEBV) and infectious mononucleosis(IM)in adult patients.Methods:Clinical data from 56 adult IM patients and 14 adult CAEBV patients admitted in the First Affiliated Hospital of Nanjing Medical University during January 2011 to December 2019 were enrolled. Clinical manifestations, laboratory indicators, treatment and outcomes were compared between two groups. Chi-square test and Mann-whitney U test were used to analyze data. Results:The average age of CAEBV patients was higher than that of IM patients [36.0(23.8, 50.5)years vs. 19.0(17.3, 22.8) years; U=90.0, P<0.05]. The symptoms of sore throat, throat congestion, tonsilla enlargement and lymphadenopathy in IM group were more common than those in CAEBV group( χ2=14.088, 16.875, 31.855 and 10.938, all P<0.01). However, the incidence of pulmonary infection, sleepiness/dysphoria and splenomegaly in CAEBV group were significantly higher than those in IM group( χ2=17.217, 5.809 and 6.254, P<0.05 or <0.01). The white blood cell counts, hemoglobin levels, platelet counts, alanine aminotransferase(ALT) and albumin in CAEBV group were significantly lower than those in IM group( U=47.0, 49.5, 158.5, 173.0 and 263.5, all P<0.01). The levels of neutrophil ratio, C-reactive protein, serum ferritin and EBV DNA load in CAEBV group were significantly higher than those in IM group( U=145.0, 140.0, 128.5 and 115.0, P<0.05 or <0.01). The proportions of CD3 + T cell counts and CD8 + T cell counts in CAEBV group were significantly lower compared to those in IM group( U=42.0 and 24.5, P<0.01); the proportions of CD4 + T cell counts, the CD4 + T/CD8 + T cell counts ratio and B lymphocytes in CAEBV group were significantly higher compared to those in IM group( U=29.0, 23.5 and 34.5, P<0.01). Fifty-six IM patients were all cured and discharged from hospital. In CAEBV group, 8 cases died, 3 cases were improved and 3 cases lost follow-up. Conclusions:Patients with IM represent a favorable prognosis, while the prognosis of CAEBV is relatively poor and complication with HLH may occur. For older patients with EBV infection complicated with pulmonary infection, lethargy/irritability, attention should be paid to monitor blood routine, liver function, serum EBV DNA load and peripheral blood lymphocyte subsets.

Clinical characteristics of 111 patients with chronic active Epstein-Barr virus infection / 中华传染病杂志

Objective:To analyze the clinical features of chronic active Epstein-Barr virus infection (CAEBV) in order to reduce the rates of underdiagnosis and misdiagnosis of this disease.Methods:The CAEBV related literatures of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, WanFang Database and Chongqing VIP since the first literature published (May 1987) until August 29, 2020 were searched. The clinical characteristics, laboratory examinations, outcome and causes of death of CAEBV patients were retrospectively analyzed. Statistical analysis was performed by Mann-Whitney U test, chi-square test or Fisher′s exact probability test. Results:A total of 111 patients aged 22.0 (10.0, 39.0) years were included from 46 articles. There were 64 cases (57.7%) in the age ≥18 years group and 47 cases (42.3%) in the age <18 years group. Fever, splenomegaly, hepatomegaly, and lymph node enlargement were common clinical manifestations, with incidences of 95.5%(106/111), 84.7%(94/111), 57.7%(64/111) and 56.8%(63/111), respectively. The incidences of rash and hepatomegaly in the age ≥18 years group were 3.1%(2/64) and 45.3%(29/64), respectively, which were both lower than those in patients aged <18 years group (27.7%(13/47) and 74.5%(35/47), respectively), while the incidence of abnormal liver biochemical indexes was higher (45.3%(29/64) vs 23.4%(11/47)). The differences were all statistically significant ( χ2=13.957, 9.436 and 5.643, respectively, all P<0.05). Of the 70 patients with follow-up outcomes, 38(54.3%) died and 32(45.7%) survived. The causes of death included gastrointestinal bleeding, severe infection, respiratory failure, liver failure, etc. The incidences of splenomegaly in the death and survival groups were 92.1%(35/38) and 68.8%(22/32), respectively. The difference was statistically significant ( χ2=6.266, P<0.05). Of 21 death and 17 survival cases in the age <18 years group, 15(71.4%) and two cases were combined hemophagocytic lymphohistiocytosis (HLH), respectively, with statistical significance ( χ2=13.527, P<0.01). Of the 90 patients whose HLH-related information was available, 38(42.2%) combined HLH and 52(57.8%) without HLH, with 36.8%(14/38) and 65.4% (34/52) of males, respectively. The difference of gender distribution was statistically significant ( χ2=7.187, P=0.007). The treatment regimens of the 111 CAEBV patients during the course of disease were various, but the detailed information was lacking. Conclusions:The clinical manifestations of CAEBV are diverse. CAEBV can be complicated with fatal complications, lacks of effective treatment, and shows poor prognosis. It is necessary to actively carry out related research to improve the understanding of the disease, and explore effective treatment and reduce mortality.

Linfohistiocitosis hemofagocítica secundaria a infección crónica activa por virus de Epstein-Barr en un hospital pediátrico en México: series de casos y revisión de la literatura / Hemophagocytic lymphohistiocytosis secondary to chronic active Epstein-Barr virus infection in a pediatric hospital in Mexico: case series and literature review

INTRODUCCIÓN: La linfohistiocitosis hemofagocitica (HLH) secundario está asociada a enfermedades malignas, genéticas o autoinmunes, pero también a infecciones principalmente EBV hasta en un 70%, sin embargo hay poca información. Esta entidad se caracteriza por un curso variable y recurrente que conlleva a una alta morbimortalidad con complicaciones potencialmente mortales. OBJETIVO: Describir las características clínicas y evolución de los pacientes pediátricos con diagnóstico de HLH secundario a CAEBV. RESULTADOS: Se incluyeron 7 pacientes, edad media al diagnóstico fue 52 meses con predilección al sexo masculino. Todos los pacientes fueron tratados con un régimen quimioterapéutico multiagente, que incluye corticosteroide, etopósido y Ciclosporina. Después del tratamiento 6 pacientes presentaron remisión y uno de ellos reactivación. La media de seguimiento fue 19 meses y la supervivencia libre de enfermedad (SLE) 16 meses. CONCLUSIÓN: Podemos observar que el curso clínico es variable en ocasiones fulminantes y con pobre respuesta al tratamiento. Un diagnóstico temprano, así como detectar los factores pronóstico podría ayudar a adaptar estrategias de tratamiento que cambiaría la evolución clínica.

INTRODUCTION: Secondary hemophagocytic lymphohistiocytosis (HLH) is associated with malignant, genetic or autoimmune diseases but also with infections mainly EBV in up to 70%, however there is little information. This entity is characterized by a variable and recurrent course that leads to high morbidty and mortality with life-threatening complications. OBJECTIVE: To describe the clinical characteristics and evolution of pediatric patients with a diagnosis of HLH secondary to CAEBV. RESULTS: 7 patients were included, mean age at diagnosis was 52 months with a predilection for males. All patients were treated with a multiagent chemotherapeutic regimen, including corticosteroid, etoposide, and cyclosporine. After treatment, 6 patients presented remission and one of them had reactivation. The mean follow-up was 19 months and disease-free survival (DFS) 16 months. CONCLUSION: We can observe that the clinical course is variable, sometimes fulminant and with poor response to treatment. An early diagnosis as well as detecting prognostic factors could help to adapt treatment strategies that would change the clinical course.

A Boy with Chronic Active EBV Infection Presented as Mosquito Bite Hypersensitivity Progressed to Fatal Hemophagocytic Lymphohistiocytosis due to NK Cell Neoplasm / 임상소아혈액종양

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by recurrent infectious mononucleosis (IM)-like symptoms and an unusual pattern of anti-EBV antibodies. We report a boy with CAEBV who progressed to aggressive hemophagocytic lymphohistiocytosis (HLH) with NK cell neoplasm. A 19-year-old adolescent boy was admitted with fever and a history of recurrent IM-like symptoms following mosquito bites since the age of 6 years. His condition was diagnosed as CAEBV with atypical lymphocytosis and an unusual pattern of anti-EBV antibodies. His symptoms subsided during treatment with steroids and cyclosporine, although the EBV genome load kept increasing for several years. He was re-admitted after follow-up loss for 8 years, and his clinical and laboratory findings confirmed HLH and high titer of the EBV genome. Bone marrow analysis with flow cytometry showed hemophagocytosis with compatible NK cell neoplasm. He rapidly progressed to pulmonary infection and expired soon after. We conclude that hematopoietic stem cell transplantation may be a potential therapeutic modality for treating CAEBV before serious EBV manifestations.

Clinical features of adult patients with chronic active Epstein-Barr virus infection / 中华内科杂志

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.

Clinical analysis of chronic active epstein-barr virus infection in children / 中国综合临床

Objective To study the clinical characteristics of chronic active Epstein-Barr virus (EBV) infection (CAEBV) in children and to provide a basis for the diagnosis and treatment of CAEBV.Methods Clinical data,laboratory serology,pathological examination,treatment and follow-up results of 10 cases with CAEBV infection who were treated in Xijing Hospital of the Fourth Military Medical University from January 2008 to January 2016 were analyzed retrospectively.Results CAEBV major manifestations were continuous or intermittent fever,hepatomegaly,splenomegaly and lymphadenopathy,and others,including general fatigue,cough,hematemesis,diarrhea,skin rash,jaundice,sore throat,muscle joint pain,and so on.And with liver dysfunction,hematologic abnormality,and so on.All patients in anti-EB virus capsid antigen IgG (EBVCA-IgG)antibodies and EBEA-IgG antibodies had positive,while all patients in EBVCA-IgM antibodies had negative.The median load of EBV-DNA detected by real-time polymerase chain reaction(PCR) in the peripheral blood was 7.15× 105 copies/ml.Six of 10 cases CAEBV patients presented a poor clinical course,1 case died from intracranial hemorrhage,2 cases from respiratory failure,1 case from gastrointestinal bleeding,1 case from liver failure,1 case from severe multiple pathogens infection,rest 3 cases showed an improvement and 1 cases had a recurrence.Conclusion CAEBV infection has varieties of clinical features,with poor prognosis and high mortality.If the patients had unexplained fever,hepatomegaly,splenomegaly and lymphadenectasis,we should be timely detect virology and histopathological to diagnosis as early as possible.

Severe Chronic Active Epstein-Barr Virus Infection Presenting as Fever of Unknown Origin / 감염과화학요법

Epstein-Barr virus (EBV) is one of eight human herpesvirus. Primary infection with EBV in childhood is generally asymptomatic or mild, however, often causes overt diseases such as infectious mononucleosis (IM) and lymphoproliferative disorder (LPD), the latter occursing in immunologically compromised individuals. Historically, EBV has been considered to be etiologically linked to human malignancies such as EBV genome positive Burkitt's lymphoma and nasopharyngeal carcinoma. Recently, however, another category of EBV-related disease, "chronic active EBV infection", has been made to describe persons without a clearly defined underlying disease. We report 4 cases of patients, presented with episodic fever of unknown origin (FUO), who were diagnosed as severe chronic active EBV infection. A combined application of serology for EBV and in-situ hybridization established the diagnosis of the EBV infection.

Severe Chronic Active Epstein-Barr Virus Infection Presenting as Fever of Unknown Origin / 감염과화학요법

Epstein-Barr virus (EBV) is one of eight human herpesvirus. Primary infection with EBV in childhood is generally asymptomatic or mild, however, often causes overt diseases such as infectious mononucleosis (IM) and lymphoproliferative disorder (LPD), the latter occursing in immunologically compromised individuals. Historically, EBV has been considered to be etiologically linked to human malignancies such as EBV genome positive Burkitt's lymphoma and nasopharyngeal carcinoma. Recently, however, another category of EBV-related disease, "chronic active EBV infection", has been made to describe persons without a clearly defined underlying disease. We report 4 cases of patients, presented with episodic fever of unknown origin (FUO), who were diagnosed as severe chronic active EBV infection. A combined application of serology for EBV and in-situ hybridization established the diagnosis of the EBV infection.

A Case of Chronic Active Epstein-Barr Virus Infection with Coronary Aneurysm

Chronic active Epstein-Barr virus infection(CAEBV) is a nonfamilial syndrome that shows a specific immunodeficiency for the Epstein-Barr virus(EBV). CAEBV is characterized by fever, lymphadenopathy, splenomegaly, hepatitis, interstitial pneumonitis, interstitial nephritis, and uveitis. Cardiovascular complications are rare in EBV infection. Patients with CAEBV show characteristically high titers of anti-viral capsid antigen(VCA) IgG antibody and anti-early antigen(EA) antibody, as well as relatively low titer of anti-EB nuclear antigen(EBNA) antibody. We experienced a case of CAEBV with giant coronary aneurysms, who was a 6-year-old boy. He had 5 episodes of high fever and cervical lymphadenopathy and hepatosplenomegaly. The 6 mm sized bilateral coronary aneurysms were detected by echocardiography at second admission. IgG antibodies to EBV was positive, whereas negative for IgM antibody. Antibodies to EA and EBNA were also positive. The EBV was detected in lymph node tissue by in situ hybridization, and in the peripheral blood and bone marrow by the PCR. Treatment has been done with ganciclovir and interferon (IFN)-alpa for 5 weeks. The EBV-PCR of peripheral blood was converted to negative from 12th day of treatment. At present he has followed well for two years without fever and enlargements of lymphnode, except large coronary aneurysm.