Hemophagocytic Syndrome Revealing Primary HHV-6 Infection

Abstract

Figure. Bone marrow smears during hemophagocytic syndrome concurrent to HHV-6 primary infection. A, Hemophagocytosis of 7 red blood cells into a single macrophage. B, Activated macrophages and lymphocytes destroying red blood cells (lymphohistiocytosis). O n day 7 after a course of vincristin-actinomycin for bilateral nephroblastomatosis, a 14-monthold girl with Wiedemann-Beckwith syndrome presented at our hospital with pyrexia, asthenia, and hepatomegaly. She had severe pancytopenia (hemoglobin, 58 g/L; lymphopenia, 1.7 g/L; thrombocytopenia, 21 g/L), but she also had acute hepatic insufficiency (prothrombin time, 19.8 seconds; factor V, 40%; ALAT, 1922 UI/L; ASAT, 3327 UI/L; LDH, 7465 UI/L) without cholestasis. She had a high serum ferritin level (1237 mg/L) and low serum triglyceride level (0.75g/L) at admission (2.96 g/L 7 days later). Serum C-reactive protein level was 28 mg/L. Abdominal ultrasound examination found a normal biliary tract and heterogeneous hepatomegaly with moderate ascites but normal Doppler on both portal and sushepatic veins. The suspicion of hemophagocytic syndrome was confirmed on bone marrow smears (Figure). She received transfusion of platelets and red blood cells and methylprednisolone at 1 mg/kg twice a day. Clinical and biological examinations resolved within 48 hours. No septicemia could be documented. Legionella urinary antigens were negative, as was the PCR for search of Mycoplasma pneumoniae. Antigenemia for Cryptococcus was negative. On day 1 of the episode, human herpes virus (HHV)-6 serologies were negative for both immunoglobulin (Ig)M and IgG. On day 3, PCR HHV6 was positive, whereas IgM was negative and IgG positive, with a weak intensity. On day 7, PCR, IgM, and IgG were positive for HHV6. Three weeks later, IgM HHV6 became negative and IgG had a stronger positivity, and PCR was still positive. All other virus searches remained negative (hepatitis A, B, C, E; human immunodeficiency virus; cytomegalovirus; herpes simplex virus; varicella-zoster virus; Epstein-Barr virus; HHV8; parvovirus B19; influenza A, B; rhinoviruses), except for Respiratory Syncytial Virus (positive on PCR and cultures of nasal secretions). Despite the high rate of HHV-6 primary infection in childhood, it is a rare cause of hemophagocytic syndromes in children. n