CLINICAL AND LABORATORY OBSERVATIONS
Fatal disseminated infection with human herpesvirus-6 Paula J. Prezioso, MD, J o a n C a n g i a r e l l a , MD, M o d e s t u s Lee, MD, G e r a r d J. N u o v o , MD, William Borkowsky, MD, Seth J. O r l o w , MD, PhD, a n d M A l b a G r e c o , MD From the Departments of Pediatrics, Pathology (Division of Pediatric Pathology), and Dermatology, New York University School of Medicine, New York, and the Departments of Pathology and Obstetrics and Gynecology, State University of New York at Stony Brook
A 13-month-old immunocompetent girl had fever, rash, and multisystem disease, and she eventually died of cardiac failure. Autopsy revealed intracellular viral inclusions of the herpesvirus group, with results of in situ hybridization positive for human herpesvirus-6. This is apparently the first case of fatal disseminated herpesvirus-6 infection. (J PEDIATR1992;120:921-3)
Recent reports have described the association of roseola (exanthem subitum) with a newly classified h e r p e s v i r u s - h u m a n herpesvirus-6.1 Several studies have also a t t e m p t e d to link H H V - 6 with other diseases, such as infectious mononucleosis,2 Kawasaki syndrome, 3 and viral hepatitis. 4 We present a case of fatal disseminated H H V - 6 infection in a child. CASE R E P O R T A 13-month-old Vietnamese girl was seen in the emergency department of a community hospital because of fever and poor feeding. She was the product of a 32-week gestation twin pregnancy, had an uncomplicated neonatal course, and had been well before this illness. Her diagnosis was mild dehydration and bilateral otitis media, and she was admitted to the hospital for intravenous hydration and ampicillin therapy. After the first dose of medication, an eruption developed on her trunk and face, and the ampicillin therapy was discontinued. She remained febrile and was transferred to our care. At the time of admission to our facility, her temperature was 40.6 ~ C, heart rate 130 beats/min, and capillary refill poor. She was awake but irritable, had dry, erythematous mucous membranes, shotty cervical lymphadenopathy, and nonpitting edema of her hands and feet. Her abdomen was soft and nontender, with liver edge 8 cm below the right costal margin and spleen tip 2 cm below Submitted for publication Aug. 28, 1991; accepted Dec. 20, 1991. Reprint requests: Paula J. Prezioso, MD, Department of Pediatrics, New York University Medical C.enter, 550 First Ave., New York, NY 10016. 9/22/35838
the left costal margin. Scaly, erythematous oval papules, 3 to 4 mm in diameter, with areas of telangiectasia and mottled hyperpigmentation, were present on the face, trunk, and proximal extremities; there were areas of coalescence. Hemorrhagic crusting was present on the lips, and ulcerations with purulent bases were noted in the perineal area. Laboratory evaluation at this time was significant for a leukocyte count of 50 • 106/L, with 14% atypical lymphocytes, a platelet count of 20 • 109/L, hematocrit of 0.24, with prolonged coagulation times and low serum fibrinogen values. Disseminated intravascular coagulation, possibly caused sepsis, was suspected. In addition, the history and physical findings suggested Kawasaki syndrome or an acute viral illness. Graft-versus-host disease was also considered, but the infant had received only one transfusion, 12 months previously. She was treated with clindamycin, gentamicin, and chloramphenicol, as well as a 3-day course of intravenously administered immune globulin. The echocardiogram showed no abnormalities. Supportive care with blood, fresh frozen CMV EBV HHV-6 HSV
Cytomegalovirus Epstein-Barr virus Human herpesvirus-6 Herpes simplex virus
plasma, and platelets was given. A skin biopsy specimen revealed a lichenoid infiltrate of lymphoid and histiocytic cells with interface changes of the basal cell layer, scattered necrotic keratinocytes, and epidermal hyperplasia, thought to be most consistent with a viral infection. Additional laboratory findings included cultures of blood, urine, and cerebrospinal fluid that were negative for bacteria and fungi, negative results on serologic studies for cytomegalovirus and leptospirosis, negative results on antibody screens for hepatitis A
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Clinical and laboratory observations
The Journal of Pediatrics June 1992
Fig. 1. A, Atypical lymphoid cells, some with intranuclear viral inclusions (arrows) are seen in the spleen. (Hematoxylineosin stain; original magnification, x 100.) B, Electron micrograph showing intranuclear particles of viral nucleocapsids (arrows), similar to herpesvirus group. (Uranyl acetate-lead citrate stain; • C, In situ DNA hybridization with biotinylated DNA probe for HHV-6 virus. Specific nuclear staining is present (arrowheads) (Nuclear fast red counterstain; original magnification, x40.)
and B, and the absence of antinuclear antibodies. Liver function tests revealed elevated liver enzyme activities (aspartate aminotransferase, 272 IU/L; alananine aminotransferase, 144 IU/L). Because of the rash temporally associated with the administration of ampicillin, the hepatosplenomegaly, and the atypical lymphocytosis, Epstein-Barr virus infection was considered. Serologic studies revealed EBV capsid IgG 1:160, EB nuclear antigen 1:32, E antigen 1:10, and EBV capsid IgM
Fatal disseminated infection with human herpesvirus-6 Paula J. Prezioso, MD, J o a n C a n g i a r e l l a , MD, M o d e s t u s Lee, MD, G e r a r d J. N u o v o , MD, William Borkowsky, MD, Seth J. O r l o w , MD, PhD, a n d M A l b a G r e c o , MD From the Departments of Pediatrics, Pathology (Division of Pediatric Pathology), and Dermatology, New York University School of Medicine, New York, and the Departments of Pathology and Obstetrics and Gynecology, State University of New York at Stony Brook
A 13-month-old immunocompetent girl had fever, rash, and multisystem disease, and she eventually died of cardiac failure. Autopsy revealed intracellular viral inclusions of the herpesvirus group, with results of in situ hybridization positive for human herpesvirus-6. This is apparently the first case of fatal disseminated herpesvirus-6 infection. (J PEDIATR1992;120:921-3)
Recent reports have described the association of roseola (exanthem subitum) with a newly classified h e r p e s v i r u s - h u m a n herpesvirus-6.1 Several studies have also a t t e m p t e d to link H H V - 6 with other diseases, such as infectious mononucleosis,2 Kawasaki syndrome, 3 and viral hepatitis. 4 We present a case of fatal disseminated H H V - 6 infection in a child. CASE R E P O R T A 13-month-old Vietnamese girl was seen in the emergency department of a community hospital because of fever and poor feeding. She was the product of a 32-week gestation twin pregnancy, had an uncomplicated neonatal course, and had been well before this illness. Her diagnosis was mild dehydration and bilateral otitis media, and she was admitted to the hospital for intravenous hydration and ampicillin therapy. After the first dose of medication, an eruption developed on her trunk and face, and the ampicillin therapy was discontinued. She remained febrile and was transferred to our care. At the time of admission to our facility, her temperature was 40.6 ~ C, heart rate 130 beats/min, and capillary refill poor. She was awake but irritable, had dry, erythematous mucous membranes, shotty cervical lymphadenopathy, and nonpitting edema of her hands and feet. Her abdomen was soft and nontender, with liver edge 8 cm below the right costal margin and spleen tip 2 cm below Submitted for publication Aug. 28, 1991; accepted Dec. 20, 1991. Reprint requests: Paula J. Prezioso, MD, Department of Pediatrics, New York University Medical C.enter, 550 First Ave., New York, NY 10016. 9/22/35838
the left costal margin. Scaly, erythematous oval papules, 3 to 4 mm in diameter, with areas of telangiectasia and mottled hyperpigmentation, were present on the face, trunk, and proximal extremities; there were areas of coalescence. Hemorrhagic crusting was present on the lips, and ulcerations with purulent bases were noted in the perineal area. Laboratory evaluation at this time was significant for a leukocyte count of 50 • 106/L, with 14% atypical lymphocytes, a platelet count of 20 • 109/L, hematocrit of 0.24, with prolonged coagulation times and low serum fibrinogen values. Disseminated intravascular coagulation, possibly caused sepsis, was suspected. In addition, the history and physical findings suggested Kawasaki syndrome or an acute viral illness. Graft-versus-host disease was also considered, but the infant had received only one transfusion, 12 months previously. She was treated with clindamycin, gentamicin, and chloramphenicol, as well as a 3-day course of intravenously administered immune globulin. The echocardiogram showed no abnormalities. Supportive care with blood, fresh frozen CMV EBV HHV-6 HSV
Cytomegalovirus Epstein-Barr virus Human herpesvirus-6 Herpes simplex virus
plasma, and platelets was given. A skin biopsy specimen revealed a lichenoid infiltrate of lymphoid and histiocytic cells with interface changes of the basal cell layer, scattered necrotic keratinocytes, and epidermal hyperplasia, thought to be most consistent with a viral infection. Additional laboratory findings included cultures of blood, urine, and cerebrospinal fluid that were negative for bacteria and fungi, negative results on serologic studies for cytomegalovirus and leptospirosis, negative results on antibody screens for hepatitis A
921
922
Clinical and laboratory observations
The Journal of Pediatrics June 1992
Fig. 1. A, Atypical lymphoid cells, some with intranuclear viral inclusions (arrows) are seen in the spleen. (Hematoxylineosin stain; original magnification, x 100.) B, Electron micrograph showing intranuclear particles of viral nucleocapsids (arrows), similar to herpesvirus group. (Uranyl acetate-lead citrate stain; • C, In situ DNA hybridization with biotinylated DNA probe for HHV-6 virus. Specific nuclear staining is present (arrowheads) (Nuclear fast red counterstain; original magnification, x40.)
and B, and the absence of antinuclear antibodies. Liver function tests revealed elevated liver enzyme activities (aspartate aminotransferase, 272 IU/L; alananine aminotransferase, 144 IU/L). Because of the rash temporally associated with the administration of ampicillin, the hepatosplenomegaly, and the atypical lymphocytosis, Epstein-Barr virus infection was considered. Serologic studies revealed EBV capsid IgG 1:160, EB nuclear antigen 1:32, E antigen 1:10, and EBV capsid IgM
