Case report A previously healthy
Case report A previously healthy 37-year-old man was referred to our hospital in September 2015 with fever (between 37 and 38°C) for 10 days and general malaise. There was no history of recent travel, and the patient had no animals in his home. There were no remarkable features in the heart, lungs, or abdomen. A neurological examination revealed no abnormalities. Initial laboratory data showed anemia (hemoglobin, 10.5g/dl), including red cell fragmentation (schistocytes) and thrombocytopenia (platelets, 1.4×109/l), and the Coombs test was negative. Further evidence of intravascular hemolysis included a lactate dehydrogenase (LDH) level of 748 U/L (normal range: 106–211 U/L) and decreased haptoglobin level of <10mg/dL (normal range: 36–195mg/dL). However, renal function was normal, with a blood urea nitrogen level of 12mg/dL (normal range: 8–20mg/dL) and creatinine level of 0.98mg/dL (normal range: 0.6–1.1mg/dL). His ADAMTS13 level was decreased (<0.5%, normal range: 50–150%), and autoantibodies against ADAMTS13 were positive (0.5 Bethesda unit/ml, normal range: <0.5 Bethesda unit/ml) in chromogenic act-ELISA . All cultures were negative. Tests for a series of autoantibodies related to collagen diseases were negative. Hepatitis virus B and C and human immunodeficiency virus infections were ruled out. Cytomegalovirus DNA was absent and herpes simplex virus serology was negative. Anti-EBV viral Y-27632 antigen IgG and IgM, early antigen IgM, and nuclear antigen IgG were positive, and the detection of a viral load of 7500 copies/ml suggested EBV reactivation. The features of MAHA, thrombocytopenia, decreased ADAMTS13, positivity for autoantibodies against ADAMTS13, fever, and altered sensorium without any evidence of disseminated intravascular coagulation (DIC) strongly suggested TTP associated with EBV reactivation. The patient recovered spontaneously without any treatment (Fig. 1). An ADAMTS13 activity assay was performed, and autoantibodies against ADAMTS13 were tested approximately one month after his discharge and gradually normalized (Table 1). Three months later, EBV IgM was no longer detectable and EBV-DNA in his serum had decreased. The remission of TTP has been maintained, and the condition of the patient has remained stable for 20 months with no recurrence of acquired TTP. TTP is a rare but life-threatening disease that is typically characterized by MAHA, profound peripheral thrombocytopenia, and a severe deficiency in the von Willebrand factor-cleaving protease ADAMTS13 . A low baseline ADAMTS13 activity of <10%, with or without the presence of anti-ADAMTS13 autoantibodies, in a patient with thrombocytopenia and MAHA strongly supports a diagnosis of TTP [2,9,10]. In some cases, acquired TTP occurs in association with specific conditions that have to be identified for appropriate management: collagen disease, pregnancy, malignancies, treatment with antiplatelet agents, and infections . Infections are well-known triggers of TTP episodes, and Shigera toxin-producing Escherichia coli, HIV, human parvovirus B19, hepatitis C virus, and influenza infection or vaccination are known to be associated with TTP [4,5]. However, it currently remains unclear whether TTP is associated with EBV reactivation. EBV is a human herpes virus with primary infections occurring in most adults in childhood. EBV mainly persists in B lymphocytes and shows four phases (types) of latency (latency 0–3) based on viral antigen expression. EBV causes persistent infection with a tight latency program in memory B-cells, which enables evasion from immune defenses. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV . These immune-modulating functions make EBV a good candidate for the initiation of autoimmune diseases and exacerbation of disease progression. EBV has long been associated with the induction of various cancers, including lymphoid malignancies and epithelial cell malignancies.