Pediatr Nephrol (2004) 19:569 DOI 10.1007/s00467-004-1416-1 LETTER TO THE EDITORS Toru Watanabe Hemolytic uremic syndrome associated with Epstein-Barr virus infection Published online: 3 March 2004  IPNA 2004 Sirs, I read with interest the article, entitled “Hemolytic uremic syndrome linked to infectious mononucleosis” by Simon- etti et al. in this journal [1]. Several viruses are known to cause hemolytic uremic syndrome (HUS), including hu- man immunodeficiency virus, enterovirus [2], influenza virus [3], and human parvovirus B19 [4]. Although interstitial nephritis has sometimes been reported as a renal complication of Epstein-Barr virus (EBV) infection [5], HUS associated with EBV infection is extremely rare, with only two patients with the disease having been pre- viously reported [6, 7]. The rarity of this association may be due to an absence of CD21 antigen, which is the cel- lular receptor for EBV, on glomerular endothelial cells [8]. On the other hand, virus-associated hemophagocytic syndrome (VAHS) induced by EBV is a well-known disease [9, 10]. VAHS is a reactive disorder of the mononuclear phagocytic system, characterized by a non-malignant, generalized histiocytic proliferation with marked hemophagocytosis, and is caused by hypercy- tokinemia resulting from viral infections [10]. Patients with VAHS exhibit fever, cytopenia, liver dysfunction, jaun- dice, and disseminated intravascular coagulation (DIC), and may develop acute renal failure [11, 12] as part of a multiple organ dysfunction syndrome [13, 14]. Therefore, EBV-induced VAHS may also manifest as anemia with red blood cell fragmentation due to hemophagocytosis and DIC, liver dysfunction, jaundice, and renal dysfunction, thereby mimicking the clinical characteristics of HUS. In order to differentiate HUS from VAHS in EBV infection, the renal histological findings of thrombotic microangiopathy, such as glomerular endothelial cell swelling or a widened subendothelial space, are required [2]. In addition, there should be an absence of hemo- phagocytic histiocytosis in the bone marrow and the presence of laboratory findings of hemolysis such as reticulocytosis or decreased levels of serum haptoglobin. References 1. Simonetti GD, Santos KDD, Pachlopnik JM, Ramelli G, Bianchetti MG (2003) Hemolytic uremic syndrome linked to infectious mononucleosis. Pediatr Nephrol 18:1193–1194 2. Laszik Z, Silva FG (1998) Hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, and systemic sclerosis (systemic scleroderma). In: Jennette JC, Olson JL, Schwartz MM, Silva FG (eds) Heptinstall’s pathology of the kidney, 5th edn. Lippincott-Raven, Philadelphia, pp 1003–1057 3. Watanabe T (2001) Hemolytic uremic syndrome associated with influenza A virus infection. Nephron 89:359–360 4. Watanabe T (2003) Renal involvement in human parvovirus B19 infection. Pediatr Nephrol 18:966–967 5. Norwood VF, Sturgill BC (2002) Unexplained acute renal failure in a toddler: a rare complication of Epstein-Barr virus. Pediatr Nephrol 17:628–632 6. Shashaty GG, Atamer MA (1974) Hemolytic uremic syndrome associated with infectious mononucleosis. Am J Dis Child 127: 720–722 7. Lee MH, Cho KS, Kahng KW, Kang CM (1998) A case of hemolytic uremic syndrome associated with Epstein-Barr virus infection. Korean J Intern Med 13:131–135 8. Becker JL, Miller F, Nuovo GJ, Josepovitz C, Schubach WH, Nord EP (1999) Epstein-Barr virus infection of renal proximal tubule cells: possible role in chronic interstitial nephritis. J Clin Invest 104:1673–1681 9. Reisman RP, Greco MA (1984) Virus-associated hemophago- cytic syndrome due to Epstein-Barr virus. Hum Pathol 15:290– 293 10. Imashuku S, Hibi S, Todo S (1997) Hemophagocytic lympho- histiocytosis in infancy and childhood. J Pediatr 130:352–357 11. Tsai JD, Lee HC, Lin CC, Liang DC, Chen SH, Huang FY (2003) Epstein-Barr virus-associated acute renal failure: diag- nosis, treatment, and follow-up. Pediatr Nephrol 18:667–674 12. Gauvin F, Toledano B, Champagne J, Lacroix J (2000) Reactive hemophagocytic syndrome presenting as a component of multiple organ dysfunction syndrome. Crit Care Med 28:3341–3345 13. Watanabe T (1998) Serum ferritin levels in acute renal failure. Clin Nephrol 50:336 14. Watanabe T, Okazaki E, Shibuya H (2003) Influenza A virus- associated encephalopathy with haemophagocytic syndrome. Eur J Pediatr 162:799–800 T. Watanabe ( ) ) Department of Pediatrics, Niigata City General Hospital, 2–6-1 Shichikuyama, Niigata 950–8739, Japan e-mail: twata@hosp.niigata.niigata.jp Tel.: +81-25-2415151 Fax: +81-25-2483507