Chronic active Epstein‐Barr virus infection in children in Japan

Abstract

The patients with chronic active Epstein-Barr virus infection (CAEBV) in childhood in Japan are described. Among 39 registered cases, 20 patients were males and 19 were females. Unlike the X-linked lymphoproliferative syndrome, there was no hereditary background. The incidence of hypersensitivity to mosquito bites was high (31.3%) as a past history. Most patients exhibited hepatomegaly (92.3%), splenomegaly (87.2%) and fever (84.6%). The incidence of absent anti-EB virus nuclear antigen titres was unexpectedly low (17.1%). Lymphoreticular disorders and cardiovascular diseases were major complications. Twenty-four (61.5%) patients died 6 months to 8 years after the onset, mainly of hepatic failure (eight cases), cardiac failure (five cases), virus-associated haemophagocytic syndrome (three cases) and haematological malignancies (two cases). This study reveals the CAEBV in Japan has several clinical features and should be informative for the pathogenesis of EB virus.

Proposed guidelines for diagnosing chronic active Epstein‐Barr virus infection

“…The following clinical features are commonly noted in patients with CAEBV [19][20][21]. Symptoms are persistent and chronic and generally consist of prolonged or intermittent fever, lymphadenopathy, and/or hepatosplenomegaly.…”

“…Caution should be exercised in diagnosing CAEBV initially in the presence of these diseases. Skin lesions such as hypersensitivity to mosquito bites were characteristic in some patients with CAEBV who may suffer from the granular lymphocyte proliferative disorder or clonal T-cell lymphoproliferation [21,[24][25][26], and various cutaneous manifestations, including hydroa vacciniforme-like eruptions, were recently reported to be associated with T-cell or NK-cell LPDs having chronic activated EBV infections [27].…”

Successful treatment of natural killer (NK) cell leukemia following a long-standing chronic active Epstein–Barr virus (CAEBV) infection with allogeneic bone marrow transplantation

“…13 It was reported that NK cell leukemia/lymphoma occasionally occurred after CAEBV infection and the prognosis was very poor. 3,4 Here we describe a first such patient, who was successfully treated with allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling donor.…”

“…3,4 An effective treatment has yet to be established partly because CAEBV infection is rare. 3 Recently, allogeneic blood stem cell transplantation was reported to be effective in eradicating EBV-infected cells. 5,6 Kuzushima et al 7 described that an adoptive transfer of anti-EBV cytotoxic T lymphocytes (CTLs) from an HLA-matched sibling to a patient with severe CAEBV infection transiently reduced the amount of EBV DNA, but was not able to completely eradicate the EBV infection.…”

“…[1][2][3] The prognosis for CAEBV infection is very poor and half of all patients die of multiorgan failure, infection, lymphoid malignancy and /or hemophagocytic syndrome within a few years. 3,4 An effective treatment has yet to be established partly because CAEBV infection is rare. 3 Recently, allogeneic blood stem cell transplantation was reported to be effective in eradicating EBV-infected cells.…”