Encefalitis por virus herpes humano tipo 6 en una adolescente con lupus eritematoso sistémico. Primer caso reportado en el ecuador / First case reported in ecuador: human herpes virus type 6 encephalitis in adolescents with systemic lupus erythematosus. First case reported in ecuador

Se describe el caso de una paciente de catorce años con Lupus Eritematoso Sistémico (LES) con índice de actividad severo y en tratamiento inmunosupresor. Acudió al servicio de Urgencias Pediátricas del Hospital de Especialidades Carlos Andrade Marín, por presentar fiebre, cefalea, náuseas, alucinaciones auditivas y paresia en extremidades inferiores. Se realizó estudio de líquido cefalorraquídeo por Reacción en Cadena de la Polimerasa, en el cual se detectó la presencia de Virus Herpes Humano tipo 6 o también llamado Roseolovirus. Se inició ganciclovir con respuesta clínica favorable en 72 horas. Conclusiones: Se debe considerar la presencia de encefalitis por HHV-6 en pacientes inmunocomprometidos con encefalopatía y el uso de ganciclovir como terapia dirigida.

The case of a fourteen-year-old patient with Systemic Lupus Erythematosus with severe activity index and immunosuppressive treatment is described. He went to the Pediatric Emergency Department of the Carlos Andrade Marín Specialty Hospital, for presenting fever, headache, nausea, auditory hallucinations and paresis in the lower extremities. Cerebrospinal fluid was studied by Polymerase Chain Reaction, in which the presence of Human Herpes Virus type 6 or also called Roseolovirus was detected. Ganciclovir was started with a favorable clinical response in 72 hours. Conclusions: The presence of HHV-6 encephalitis should be considered in immunocompromised patients with encephalopathy and use of ganciclovir as directed therapy.

Infección por virus herpes humano 6 en un paciente inmunocompetente con síndrome DRESS secundario a carbamazepina / Human herpes virus 6 infection in an inmunocompetent patient with carbamazepine-induced DRESS syndrome

El síndrome DRESS (drug reaction with eosinophilia and systemic symptoms) constituye una reacción adversa a fármacos, potencialmente mortal, caracterizada por una erupción cutánea polimorfa asociada a fiebre, linfadeno-patías y compromiso multiorgánico con eosinofilia. Presentamos el caso clínico de un hombre inmunocompetente con un síndrome DRESS secundario a carbamazepina que cursó concomitantemente con una meningoencefalitis por virus herpes humano 6 (VHH-6). El rol patogénico del VHH-6 en el síndrome DRESS sigue siendo controversial; sin embargo, dada la importancia diagnóstica y eventualmente pronóstica de la infección por VHH-6, su tamizaje sería recomendable dentro del estudio de estos pacientes.

DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is an adverse life-threatening drug reaction characterized by a polymorphous rash associated with fever, lymphadenopathy and multiorgan involvement with eosinophilia. We present the case of an immunocompetent man with DRESS syndrome secondary to carbamazepine, that developed concomitantly meningoencephalitis caused by human herpes virus 6 (HHV-6), and a review of literature. The pathogenic role of HHV-6 in DRESS syndrome remains controversial. Given the diagnostic and possibly prognostic significance of HHV-6, the screening seems to be a good measure to use in the clinical management of these patients.

Human Herpes Virus 6 Encephalitis Following Bone Marrow Transplantation with Uncommon Magnetic Resonance Imaging Findings

BACKGROUND: Human Herpes Virus 6 (HHV6) is commonly associated with encephalitis following bone marrow transplantation. However, hippocampal atrophy and global hypometabolism are rare findings in HHV6 encephalitis. CASE REPORT: A 41-year-old right-handed woman with acute lymphoblastic leukemia presented with fever and mental changes 2 weeks after receiving a sibling bone marrow transplant. The patient's cerebrospinal fluid (CSF) was positive for HHV-6 deoxyribonucleic acid (DNA), but was negative for other viral DNA. Brain magnetic resonance imaging revealed atrophic changes in bilateral medial temporal lobes. Following 4 weeks of ganciclovir therapy, a CSF exam was negative for HHV-6 DNA and the patient's neurological symptoms partially improved. However, she was disoriented and had severe retrograde and anterograde amnesia. 18F-fluorodeoxyglucose-positron emission tomography indicated global hypometabolism in the medial temporal lobes and the fronto-parietal cortices. CONCLUSIONS: This is a rare and unusual case of hippocampal atrophy in the acute stage of HHV6 encephalitis. Our imaging findings may reflect the chronic indolent course of HHV6 encephalitis.

Polymorphisms in Interleukin-2 and Interleukin- 7 Receptor α-Chain Genes and Human Herpes Virus-6 as Risk Factors for Multiple Sclerosis.

Aim: The aim of this study was to examine whether a Human herpes virus-6 (HHV-6) infection increases the risk of MS in individuals harboring particular cytokine receptor α- chain gene alleles. Study Design: MS patients and controls were assessed for HHV-6 DNA and for single nucleotide polymorphisms (SNPs) in their IL7RA and IL2RA genes. Place and Duration of Study: The study was carried out at the Department of Experimental Pathology, Microbiology and Immunology, American University of Beirut, between March 2011 and March 2013. Methodology: Blood samples from 100 MS patients and 100 controls were investigated for the presence of HHV-6 by nested PCR. Single nucleotide polymorphisms (SNPs) in the IL7RA and IL2RA genes were examined by restriction fragment length polymorphism. Results: HHV-6 was detected in 58% of MS patients and 32% of controls (OR = 2.935, 95% CI = 1.582-5.463, p=0.000). We did not detect a statistically significant correlation between MS and the studied rs2104286, rs12722489 SNPs in the IL2RA gene and rs6897932 SNP in the IL7RA gene. Concomitant presence of rs2104286 and HHV-6 was detected in 56% of patients and 30% of controls (OR=2.970, 95% CI=1.594-5.53, P=0.000). Similarly, rs6897932 and HHV-6 were observed in 57% of patients and 28% of controls (OR=3.409, 95% CI= 1.815-6.428, P=0.000). Therefore, double positivity moderately increased the risk of MS compared to either factor alone. HHV-6 and rs12722489 double positivity did not increase the risk of MS. Conclusion: HHV-6 infections may enhance the risk of MS in subjects with particular genetic determinants.

Optimization of the Sybr Green real time PCR for the detection of Human Herpes Virus type 6 (HHV-6) / Otimização da PCR em tempo real - Sybr Green para detecção do Herpes Vírus Humano tipo 6 (HHV-6)

HHV-6 is the etiological agent of Exanthem subitum which is considered the sixth most frequent disease in infancy. In immuno-compromised hosts, reactivation of latent HHV-6 infection may cause severe acute disease. We developed a Sybr Green Real Time PCR for HHV-6 and compared the results with nested conventional PCR. A 214 pb PCR derived fragment was cloned using pGEM-T easy from Promega system. Subsequently, serial dilutions were made in a pool of negative leucocytes from 10-6 ng/µL (equivalent to 2465.8 molecules/µL) to 10-9 (equivalent to 2.46 molecules/µL). Dilutions of the plasmid were amplified by Sybr Green Real Time PCR, using primers HHV3 (5' TTG TGC GGG TCC GTT CCC ATC ATA 3)'and HHV4 (5' TCG GGA TAG AAA AAC CTA ATC CCT 3') and by conventional nested PCR using primers HHV1 (outer): 5'CAA TGC TTT TCT AGC CGC CTC TTC 3'; HHV2 (outer): 5' ACA TCT ATA ATT TTA GAC GAT CCC 3'; HHV3 (inner) and HHV4 (inner) 3'. The detection threshold was determined by plasmid serial dilutions. Threshold for Sybr Green real time PCR was 24.6 molecules/µL and for the nested PCR was 2.46 molecules/µL. We chose the Real Time PCR for diagnosing and quantifying HHV-6 DNA from samples using the new Sybr Green chemistry due to its sensitivity and lower risk of contamination.

HHV-6 é o agente etiológico do Exantema Súbito e considerado a sexta doença mais comum na infância. Em indivíduos imunocomprometidos, a reativação da infecção latente pode causar doença aguda ou morte. Padronizamos PCR em Tempo Real utilizando a química Sybr Green na detecção do HHV-6 e comparamos os resultados com a PCR convencional. Um fragmento de 214 pb foi clonado através do kit pGEM-T do sistema Promega. Com este clone, foram feitas diluições seriadas em um pool de leucócitos negativos a partir de 10-6 ng/µL (equivalente a 2465,8 moleculas/µL) até 10-9 (equivalente a 2,46 moleculas/µL). As diluições foram amplificadas por PCR em Tempo Real utilizando Sybr Green, com primers HHV3 5' TTG TGC GGG TCC GTT CCC ATC ATA 3' e HHV4 5' TCG GGA TAG AAA AAC CTA ATC CCT 3' e pelo método convencional, PCR nested usando primers HHV1 (externo): 5' CAA TGC TTT TCT AGC CGC CTC TTC 3'; HHV2 (externo): 5' ACA TCT ATA ATT TTA GAC GAT CCC 3', HHV3 (interno) e HHV4 (interno): 5' TCG GGA TAG AAA AAC CTA ATC CCT 3'. O limite de detecção foi determinado pelas diluições seriadas do plasmídio contendo um fragmento de HHV6: para o ensaio com Sybr Green, foi de 24,6 moleculas/µL e para a PCR nested, 2,46 moleculas/µL. Elegemos o PCR em Tempo Real - Sybr Green como método diagnóstico e quantitativo do HHV-6 devido a sua boa sensibilidade e menor risco de contaminação.

Two Cases of Antituberculosis Drug-induced Hypersensitivity Syndrome / 대한피부과학회지

Drug-induced hypersensitivity syndrome is a rare, but severe, life-threatening disease with multiorgan failure. Aromatic antiepileptic drugs are frequent causes of this syndrome. The association of the human herpes virus-6 has been recently reported in patients with drug-induced hypersensitivity syndrome. We report two patients who were diagnosed as having antituberculosis drug-induced hypersensitivity syndrome based on clinical course and laboratory data. In addition, human herpes virus-6 DNA was detected by polymerase chain reaction in peripheral blood mononuclear cells and the serum. There was a favorable outcome after discontinuation of the causative drug, plus corticosteroid therapy. After the treatment, human herpes virus-6 DNA was not detected by polymerase chain reaction. This is the first report of antituberculosis drug-induced hypersensitivity syndrome associated with reactivation of human herpes virus-6.

Haemophilus influenzae and Human Herpes Virus-6 Detection by EIA and PCR in CSF from Young Hospitalized Children with Aseptic Meningitis

There are various microbial agents which causing meningitis in children. It is well known that Haemophilus influenzae (HI) are the most frequent bacterial agents. In Korea, it is hard to find studies detecting HI in cerebrospinal fluid (CSF) from pediatric patients with aseptic meningitis by PCR. It has been also reported that human herpes virus-6 (HHV-6) causes meningitis, meningoencephalitis, neuroinvasion and persistent infection of the central nervous system in children. In this study we also detected HHV-6 in the same CSF by EIA and PCR. We used 85 CSF specimens from 85 aseptic meningitis patients (mean age 6.6 years) taken from the Department of pediatrics at Ewha Womans University MokDong Hospital from June 2001 to August 2002. Detection rate of HI by EIA method was 12.9% (11/85) and by PCR was 16.5% (14/85). Detection rate of HHV-6 by EIA and by PCR was 18.8% (16/85) and 21.2% (18/85), respectively. Co-detection rate of HI and HHV-6 was 7.1% (6/85) by EIA and 12.9% (11/85) by PCR. In conclusion, by PCR in combination with EIA, HI infection could be proved in the aseptic meningitis CSF from which no bacterium was cultivated.

Detection by PCR of Adenovirus and Human Herpes Virus 6 in Peripheral Blood Monocyte from Young Children who were Hospitalized with Lower Respiratory Tract Infection

There are reports that the second most causative viral agent which causes lower respiratory tract infection (LRTI) in young children is adenovirus (ADV). Human herpes virus 6 (HHV-6) is also reported as a rare agent of LRTI in young children. But there is no report of simultaneous detection of ADV and HHV-6 in LRTI using the same peripheral blood monocyte (PBM) by nested-polymerase chain reaction (PCR) or PCR. Firstly, we detected ADV antigen (Ag) and HHV-6 Ag in serum by each monoclonal antibody with enzyme immunoassay (EIA). Secondly we tested two viruses in peripheral blood monocyte by nested-PCR or PCR. Twenty nine cases of young hospitalized children with LRTI (mean age 11.3 months, mean hospitalization period 5.7 days) had bronchiolitis or viral pneumonia and were confirmed by X-ray findings. Positivity of ADV Ag in serum by EIA was 75% (21/28) and positivity of HHV-6 Ag in serum by EIA was 10.7% (3/28). ADV in PBM by nested-PCR positivity was 89.7% (26/29) and HHV-6 in PBM by PCR positivity was 42.9% (12/28). ADV and HHV-6 dual infection in PBM by PCR was 11/29 (37.9%). Young children with dual infection were hospitalized (mean 6.3 days) with severe bronchiolitis.