RESUMO
Human herpesviruses are enveloped viruses with double-stranded linear DNA genomes highly prevalent in the human population. These viruses are subdivided into three subfamilies, namely alphaherpesvirinae (herpes simplex virus type 1, HSV-1; herpes simplex virus type 2, HSV-2; and varicella-zoster virus, VZV), betaherpesvirinae (human cytomegalovirus, HCMV; human herpesvirus 6, HHV-6; and human herpesvirus 7, HHV-7) and gammaherpesvirinae (Epstein-Barr virus, EBV; and Kaposi's sarcoma-associated herpesvirus, KSHV). Besides encoding numerous molecular determinants to evade the host antiviral responses, these viruses also modulate cellular metabolic processes to promote their replication. Here, we review and discuss existing studies describing an interplay between carbohydrate metabolism and the replication cycle of herpesviruses, altogether highlighting potentially new molecular targets based on these interactions that could be used to block herpesvirus infections.
RESUMO
Pityriasis rosea (PR) has been manifested in patients suffering from COVID-19 as well as after vaccine protocols against SARS-CoV-2. It has a possible association with the HHV-6B virus (roseola infantum) and can be controlled by antivirals such as acyclovir as well as by the amino acid l-Lysine that showed a positive result in reducing the number of lesions and healing time. The aim of this study was to report a case of PR after a second dose of Oxford-AstraZeneca, the adopted therapy and a brief literature review. A 53-year-old woman, phototype II, presented an erythematous lesion in the posterior right thigh 15 days after the second dose of Oxford-AstraZeneca vaccine. Eight days after the initial injury, new injuries appeared in the calf, buttocks and thighs. The diagnosis was PR with a 5-week eruption cycle. The treatment consisted of the use of l-Lysine, 3 grams loading dose and 500 mg for 30 days and moisturizing/healing lotion, starting 14 days after the herald patch. After the 5th week of the disease cycle, there were no new eruptions and the repair cycle continued for up to 8 weeks leaving some residual skin spots. It is concluded that the patient may be a carrier a latent virus, HHV-6, and the vaccine administration with immune system stimulation, would have activated the possible virus causing PR. l-Lysine helped to control the manifestation by limiting the number of lesions and their location, which were restricted to the legs, thighs and buttocks.
Assuntos
COVID-19 , Herpesvirus Humano 7 , Pitiríase Rósea , Vacinas , Feminino , Humanos , Pessoa de Meia-Idade , Pitiríase Rósea/induzido quimicamente , Pitiríase Rósea/diagnóstico , SARS-CoV-2RESUMO
La reacción a drogas con eosinofilia y síntomas sistémicos es una reacción adversa cutánea rara, potencialmente grave. Puede presentar fiebre, erupción cutánea polimorfa, edema facial y/o linfoadenopatías. La reactivación del virus herpes humano tipo 6 se asocia a un curso más grave y/o prolongado.Un lactante de 22 meses en tratamiento con fenobarbital presentó lesiones eritematopapulares, fiebre, leucocitosis, proteína C reactiva elevada y alteración de pruebas hepáticas. Se realizó biopsia de piel compatible con reacción adversa a drogas. Se trató con corticoides sistémicos e inmunoglobulina intravenosa sin respuesta. La reacción en cadena de la polimerasa para virus herpes humano tipo 6 resultó positiva. Se inició ciclosporina más prednisona, con buena respuesta. Existe poca evidencia del uso de ciclosporina en adultos, cuando los corticoides sistémicos son inefectivos. Este es el primer reporte pediátrico Podría ser una alternativa efectiva o un complemento de los corticosteroides sistémicos cuando no responde a tratamientos convencionales.
Drug reaction with eosinophilia and systemic symptoms is a rare and potentially serious skin adverse reaction, with fever, polymorphous skin rash, facial edema, and/or lymphadenopathy. Reactivation of human herpes virus type 6 has been associated with a more severe and/or prolonged course. A 22-month-old infant under phenobarbital treatment developed erythematous-papular lesions, fever, leukocytosis, elevated C-reactive protein, and abnormal liver tests. The skin biopsy was compatible with an adverse drug reaction. Treatment with systemic corticosteroids and intravenous immunoglobulin had no response. Polymerase chain reaction for human herpesvirus type 6 was positive, and cyclosporine plus prednisone was started with a good response. There is little evidence for the use of cyclosporine in adults when systemic corticosteroids are ineffective. This is the first report of pediatric drug reaction with eosinophilia and systemic symptoms treated with cyclosporine, which could be an effective alternative or an adjunct to systemic corticosteroid therapy unresponsive to conventional treatments.
Assuntos
Humanos , Masculino , Lactente , Herpesvirus Humano 6 , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Ciclosporina/uso terapêutico , Corticosteroides/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Eosinofilia , Síndrome de Hipersensibilidade a Medicamentos/complicações , Síndrome de Hipersensibilidade a Medicamentos/terapiaRESUMO
Drug reaction with eosinophilia and systemic symptoms syndrome associated with human herpesvirus 6. A pediatric case treated with cyclosporine and corticosteroids elevated C-reactive protein, and abnormal liver tests. The skin biopsy was compatible with an adverse drug reaction. Treatment with systemic corticosteroids and intravenous immunoglobulin had no response. Polymerase chain reaction for human herpesvirus type 6 was positive, and cyclosporine plus prednisone was started with a good response. There is little evidence for the use of cyclosporine in adults when systemic corticosteroids are ineffective. This is the first report of pediatric drug reaction with eosinophilia and systemic symptoms treated with cyclosporine, which could be an effective alternative or an adjunct to systemic corticosteroid therapy unresponsive to conventional treatments.
La reacción a drogas con eosinofilia y síntomas sistémicos es una reacción adversa cutánea rara, potencialmente grave. Puede presentar fiebre, erupción cutánea polimorfa, edema facial y/o linfoadenopatías. La reactivación del virus herpes humano tipo 6 se asocia a un curso más grave y/o prolongado. Un lactante de 22 meses en tratamiento con fenobarbital presentó lesiones eritematopapulares, fiebre, leucocitosis, proteína C reactiva elevada y alteración de pruebas hepáticas. Se realizó biopsia de piel compatible con reacción adversa a drogas. Se trató con corticoides sistémicos e inmunoglobulina intravenosa sin respuesta. La reacción en cadena de la polimerasa para virus herpes humano tipo 6 resultó positiva. Se inició ciclosporina más prednisona, con buena respuesta. Existe poca evidencia del uso de ciclosporina en adultos, cuando los corticoides sistémicos son inefectivos. Este es el primer reporte pediátrico Podría ser una alternativa efectiva o un complemento de los corticosteroides sistémicos cuando no responde a tratamientos convencionales.
Assuntos
Herpesvirus Humano 6 , Adulto , Criança , Humanos , SíndromeRESUMO
Resumen Introducción: Las manifestaciones clínicas más frecuentes causadas por el Herpes Virus Humano Tipo 6 (HHV-6) ocurren en niños menores de 2 años, presentan lesiones en piel tipo roséola o exantema súbito. En adultos, las manifestaciones clínicas relacionadas a HHV-6 son muy variables, y pueden sobreponerse con otras afecciones. Objetivo: Presentar una serie de casos de pacientes diagnosticados con infección activa por HHV-6, quienes mostraban manifestaciones neurológicas, dermatológicas y de fatiga crónica. Materiales y métodos: Se realizó análisis de historias clínicas de 6 pacientes que fueron diagnosticados con infección activa por HHV-6, a través de métodos moleculares. Resultados: Se reportan 6 pacientes que fueron diagnosticados con infección activa por HHV-6 mediante métodos moleculares, quienes presentaron manifestaciones clínicas comunes tales como: fiebre, cefalea, depresión, decaimiento, pérdida de memoria y concentración, dolor fibromuscular, dolor poliarticular, sueño no reparador, exantema, nevus rubí, liquen plano y parestesias. Conclusiones: A través de esta serie de casos se espera resaltar la importancia de identificar la infección activa por HHV-6 a través de métodos moleculares, y sensibilizar a la comunidad médica sobre el papel que juega el virus en la evolución de diversas patologías.
Abstract Introduction: The most frequent clinical manifestations of Human Herpesvirus 6 (HHV-6) in children under 2 years of age are roseola-like skin lesions and sudden rash. In adults, the clinical manifestations associated with HHV-6 are highly variable and can overlap with other conditions. Objective: To present a case series of patients diagnosed with active HHV-6 infection, who showed neurological, dermatological and chronic fatigue manifestations. Materials and methods: An analysis of medical records of 6 patients who were diagnosed with active HHV-6 infection through molecular methods was performed. Results: 6 patients were diagnosed with active HHV-6 infection using molecular methods, who had common clinical manifestations such as fever, headache, depression, tiredness, loss of memory and concentration, fibromuscular pain, polyarticular pain, nonrestorative sleep, rash, ruby nevus, lichen planus and paresthesia. Conclusions: This case series highlights the importance of identifying active HHV-6 infection through molecular methods and creating awareness in the medical community of the role that the virus plays on the development of diverse pathologies.
Assuntos
Herpesvirus Humano 6 , Dermatopatias , Síndrome de Fadiga Crônica , Carga ViralRESUMO
Pityriasis rosea (PR) is a dermatological disease with an erythemato-papulosquamous manifestation, distributed on the trunk and extremities affecting healthy people, especially children and young people between 10 and 35 years of age. The evolution is 6 to 8 weeks and may remain for 3 to 6 months. It regresses spontaneously and can leave changes in the skin color but reversibly. Acyclovir is indicated to minimize clinical manifestations with the suspected of viral association (HHV-6 and 7). Another group of the human herpesvirus family (HHV-1 and 2), causes herpes simplex that is controlled with the antivirals, including acyclovir, as well as the amino acid L-lysine, both showing positive and similar results in reducing the number of annual manifestations and the healing time of the lesions. The aim of this study is to report a case of PR in a child, to review the literature on the etiopathogenesis of the disease and on the effects of L-lysine as well as another amino acid in the treatment. An 11-year-old girl, phototype II, presented lesions diagnosed as PR. The cycle would be 6 to 8 weeks on average. A solution of L-lysine was prescribed for 30 days, on an empty stomach. After the fourth day of therapy, the cycle of new eruptions was interrupted, initial lesions regressed, accelerating the repair of larger lesions resulting in an improvement of the clinical condition. We concluded that the administration of L-lysine, in therapeutic doses, can be a safe alternative for the PR control.
Assuntos
Herpesvirus Humano 6 , Herpesvirus Humano 7 , Pitiríase Rósea , Aciclovir/uso terapêutico , Adolescente , Criança , Feminino , Humanos , Lisina , Pitiríase Rósea/diagnóstico , Pitiríase Rósea/tratamento farmacológicoRESUMO
In recent years, extreme attention has been focused on the role of human herpesvirus-6 (HHV-6) in multiple sclerosis (MS) pathogenesis. However, the pathogenesis of MS associated with HHV-6 infection remains unknown. In this study, we measured the serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection. Five hundred sixty (including 300 females and 260 males) MS patients along with 560 healthy subjects were analyzed for HHV-6 seropositivity using enzyme-linked immunosorbent assay (ELISA). Subsequently, we measured the serum levels of MMP-2, MMP-9, and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection by ELISA. About 90.7% of MS patients (508/560) were seropositive for HHV-6, while 82.3% (461/560) of healthy subjects were seropositive for this virus (pâ¯=â¯0.001). Moreover, there was a significant increase in the levels of MMP-2, MMP-9, and lower vitamin D in the serum samples of MS patients when compared with healthy subjects. Additionally, we demonstrated that the MMP-9 levels in seropositive MS patients were significantly higher than seronegative MS patients (pâ¯=⯠0.001). Finally, our results demonstrated that the mean of expanded disability status scale (EDSS) in seropositive MS patients was significantly higher in comparison to seronegative MS patients (pâ¯<â¯0.05). In conclusion, we suggest that the HHV-6 infection may play a role in MS pathogenesis.
Assuntos
Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Esclerose Múltipla/sangue , Infecções por Roseolovirus/sangue , Vitamina D/sangue , Adulto , Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Herpesvirus Humano 6/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Infecções por Roseolovirus/complicaçõesRESUMO
ABSTRACT In recent years, extreme attention has been focused on the role of human herpesvirus-6 (HHV-6) in multiple sclerosis (MS) pathogenesis. However, the pathogenesis of MS associated with HHV-6 infection remains unknown. In this study, we measured the serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection. Five hundred sixty (including 300 females and 260 males) MS patients along with 560 healthy subjects were analyzed for HHV-6 seropositivity using enzyme-linked immunosorbent assay (ELISA). Subsequently, we measured the serum levels of MMP-2, MMP-9, and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection by ELISA. About 90.7% of MS patients (508/560) were seropositive for HHV-6, while 82.3% (461/560) of healthy subjects were seropositive for this virus (p = 0.001). Moreover, there was a significant increase in the levels of MMP-2, MMP-9, and lower vitamin D in the serum samples of MS patients when compared with healthy subjects. Additionally, we demonstrated that the MMP-9 levels in seropositive MS patients were significantly higher than seronegative MS patients (p = 0.001). Finally, our results demonstrated that the mean of expanded disability status scale (EDSS) in seropositive MS patients was significantly higher in comparison to seronegative MS patients (p < 0.05). In conclusion, we suggest that the HHV-6 infection may play a role in MS pathogenesis.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina D/sangue , Infecções por Roseolovirus/sangue , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Esclerose Múltipla/sangue , Ensaio de Imunoadsorção Enzimática , Herpesvirus Humano 6/imunologia , Infecções por Roseolovirus/complicações , Anticorpos Antivirais/sangue , Esclerose Múltipla/complicaçõesRESUMO
ABSTRACT Background: Hypothyroidism due to Hashimoto's thyroiditis (HT) is the commonest autoimmune endocrine illness in which antibodies against thyroid organ result in inflammation. The disease has a complex etiology that involves genetic and environmental influences. Viral infections may be involved in triggering of the disease as their molecular mimicry enhance autoimmune responses. Human herpesvirus-6 (HHV-6) is recognized for its contribution to some autoimmune diseases. Objective: In the current study, the prevalence of HHV-6 active infection in patients with HT and with non-autoimmune thyroid disorders were compared with patients with euthyroidism. In addition, a correlation between presence of HHV-6 infections and HT was investigated. Methods: A total of 151 patients with clinically and laboratory confirmed HT, 59 patients with non-autoimmune thyroid disorders, and 32 patients with normal thyroid function were included in the study. For further confirmation of HT disease, all the precipitants were tested for anti-thyroid peroxidase (TPO), and anti-thyroglobulin (TG) antibodies. For detection of both HHV-6 types A and B, nested PCR and restriction enzyme digestion were used. HHV-6 DNA positive samples were further investigated by DNA sequencing analysis. Results: HHV-6A DNA was found in serum sample of 57 out of 151 patients (38%) with HT, which was significantly more often than in patients with non-autoimmune thyroid disorders (p = 0.001). However, HHV-6 DNA was not detected in serum samples of euthyroid subjects. Conclusions: The results support a possible role for active HHV-6A infection, demonstrated by the presence of HHV-6 DNA in sera, in the development of HT.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Herpesvirus Humano 6/genética , Infecções por Roseolovirus/virologia , Doença de Hashimoto/virologia , Glândula Tireoide/virologia , DNA Viral/análise , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Hypothyroidism due to Hashimoto's thyroiditis (HT) is the commonest autoimmune endocrine illness in which antibodies against thyroid organ result in inflammation. The disease has a complex etiology that involves genetic and environmental influences. Viral infections may be involved in triggering of the disease as their molecular mimicry enhance autoimmune responses. Human herpesvirus-6 (HHV-6) is recognized for its contribution to some autoimmune diseases. OBJECTIVE: In the current study, the prevalence of HHV-6 active infection in patients with HT and with non-autoimmune thyroid disorders were compared with patients with euthyroidism. In addition, a correlation between presence of HHV-6 infections and HT was investigated. METHODS: A total of 151 patients with clinically and laboratory confirmed HT, 59 patients with non-autoimmune thyroid disorders, and 32 patients with normal thyroid function were included in the study. For further confirmation of HT disease, all the precipitants were tested for anti-thyroid peroxidase (TPO), and anti-thyroglobulin (TG) antibodies. For detection of both HHV-6 types A and B, nested PCR and restriction enzyme digestion were used. HHV-6 DNA positive samples were further investigated by DNA sequencing analysis. RESULTS: HHV-6A DNA was found in serum sample of 57 out of 151 patients (38%) with HT, which was significantly more often than in patients with non-autoimmune thyroid disorders (p=0.001). However, HHV-6 DNA was not detected in serum samples of euthyroid subjects. CONCLUSIONS: The results support a possible role for active HHV-6A infection, demonstrated by the presence of HHV-6 DNA in sera, in the development of HT.
Assuntos
Doença de Hashimoto/virologia , Herpesvirus Humano 6/genética , Infecções por Roseolovirus/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Viral/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Glândula Tireoide/virologia , Adulto JovemRESUMO
BACKGROUND: DRESS syndrome (rash with eosinophilia and systemic symptoms) is an uncommon and severe drug-induced reaction. CLINICAL CASE: An 8-year-old boy was diagnosed with tonsillopharyngitis, and treatment with amoxicillin was started. One day later, he presented bilateral malar rash which evolved to generalized erythroderma in two days. He was referred to the emergency room and then he was discharged after the treatment with amoxicillin was discontinued. Five days later, he still had fever, progressive facial and acral edema, and ecchymotic lesions. The laboratory studies showed 6220 leukocytes/mm3 (970 eosinophils/mm3). The pharyngeal culture tested positive to human herpesvirus 6 (HHV-6). The fever, rash and edema disappeared with supportive measures. Based on the results of the allergy tests, a diagnosis of delayed reaction to aminopenicillin associated to HHV-6 mimicking DRESS syndrome was made, with the recommendation to avoid penicillin antibiotics. CONCLUSION: The diagnosis of delayed reactions to aminopenicillin and DRESS syndrome requires a high index of suspicion in order to promptly withdraw the offending medication and to avoid delays in the diagnosis.
Antecedentes: El síndrome DRESS (erupción que cursa con eosinofilia y síntomas sistémicos) es una reacción inducida por fármacos poco frecuente y grave. Caso clínico: Niño de ocho años a quien se prescribió tratamiento con amoxicilina debido a diagnóstico de amigdalofaringitis. Un día después del inicio del medicamento, el paciente presentó erupción malar bilateral que evolucionó a eritrodermia generalizada en dos días. Fue derivado al servicio de urgencias donde se interrumpió el tratamiento con amoxicilina y fue dado de alta. Cinco días después, todavía tenía fiebre, edema facial y acral progresivo y lesiones equimóticas. Los estudios de laboratorio mostraron 6220 leucocitos/mm3 (970 eosinófilos/mm3). El cultivo faríngeo fue positivo al virus de herpes humano 6. La fiebre, la erupción y el edema desaparecieron con medidas de apoyo. Con base en los resultados de las pruebas de alergia, se realizó un diagnóstico de reacción tardía a la aminopenicilina asociada con herpesvirus de humano 6 que simulaba síndrome DRESS. La recomendación fue evitar los antibióticos con penicilina. Conclusiones: El diagnóstico de reacciones tardías a la aminopenicilina y el síndrome DRESS requieren un alto índice de sospecha para retirar rápidamente la medicación desencadenante y evitar retrasos en el diagnóstico.
Assuntos
Antibacterianos/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Herpesvirus Humano 6 , Penicilinas/efeitos adversos , Criança , Humanos , Masculino , Infecções por Roseolovirus/diagnóstico , Fatores de TempoRESUMO
La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.
The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.
Assuntos
Humanos , Feminino , Pré-Escolar , Herpesvirus Humano 6/isolamento & purificação , Encefalite Viral/diagnóstico , Exantema Súbito/diagnóstico , Encefalite Viral/virologia , Exantema Súbito/complicaçõesRESUMO
The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.
La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.
Assuntos
Encefalite Viral/diagnóstico , Exantema Súbito/diagnóstico , Herpesvirus Humano 6/isolamento & purificação , Pré-Escolar , Encefalite Viral/virologia , Exantema Súbito/complicações , Feminino , HumanosRESUMO
Human herpesvirus 6 (HHV-6) may cause severe complications after haematopoietic stem cell transplantation (HSCT). Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR) has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-106 copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance.
Assuntos
Humanos , DNA Viral/análise , Transplante de Células-Tronco Hematopoéticas , /genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções por Roseolovirus/diagnóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Transplante Homólogo , Carga ViralRESUMO
Status epilepticus after allogeneic hematopoietic cell transplantation (alloHCT) is rare. The authors report a case involving a 65-year-old man with nonconvulsive status epilepticus 34 days after umbilical cord blood transplantion for chronic lymphocytic leukemia. Cerebrospinal fluid and serum were positive for human herpesvirus 6 (HHV6). Magnetic resonance imaging of the brain showed symmetric T2 hyper-intensity bilaterally in the mesial temporal lobes, and T2 hyperintensi-ties and restricted diffusion of bilateral putamina. Despite aggressive anticonvulsive therapy, his seizures only abated with initiation of ganciclovir therapy. The patient completed six weeks of combination antiviral therapy (ganciclovir and foscarnet). His cognitive function gradually improved and, after prolonged rehabilitation, the patient was discharged home with residual intermittent memory loss but otherwise functional. HHV6 should be considered in the differential diagnosis of nonconvulsive status epilepticus after alloHCT, especially in patients with hyponatremia. Empirical antiviral therapy targeting HHV6 should be administered to these patients.
L'état de mal épileptique est rare après une greffe de cellules souches hématopoïétiques allogéniques (GCSallo). Les auteurs rendent compte du cas d'un homme de 65 ans présentant un état de mal épileptique non convulsif 34 jours après avoir subi une greffe de sang de cordon pour soigner une leucémie lymphocytaire chronique. Le liquide céphalorachidien et le sérum étaient positifs à l'herpèsvirus humain type 6 (HVH6). L'imagerie par résonance magnétique du cerveau a révélé un signal hyperintense symétrique et bilatéral des lobes temporaux mésiaux en T2, ainsi que des signaux hyperintenses en T2 et une diffusion bilatérale restreinte du putamen. Malgré un traitement énergique aux anticonvulsivants, les convulsions n'ont diminué qu'après l'amorce d'un traitement au ganciclovir. Le patient a été mis sous bithérapie antivirale (ganciclovir et foscarnet) pendant six semaines. Sa fonction cognitive s'est améliorée graduellement et, après une réadaptation prolongée, il a obtenu son congé à domicile. Il présentait une perte de mémoire résiduelle intermittente, mais était autrement fonctionnel. Il faut envisager un HVH6 dans le diagnostic différentiel de l'état de mal épileptique non convulsif après une GCSallo, particulièrement chez les patients présentant une hyponatrémie. Il faut administrer une anti-virothérapie empirique qui cible l'HVH6 chez ces patients.
RESUMO
UNLABELLED: Herpesvirus reactivation is common after liver transplantation. OBJECTIVE: Analyze the presence of cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6) DNA in liver donor biopsies, seeking to better understand issues involving human donor leukocyte antigens (HLA)-A, B and DR, as well as correlations with acute cellular rejection. METHODS: Fifty-nine liver transplantation patients were investigated for the presence of HCMV and HHV-6 DNA in liver donor biopsies, using the Nested-PCR technique. The clinical donor information and HLA matches were obtained from the São Paulo State Transplant System. The recipients' records regarding acute cellular rejection were studied. RESULTS: Seven (11.8%) biopsies were positive for HCMV DNA and 29 (49%) were positive for HHV-6 DNA. In 14 donors with HLA-DR 15 nine had HHV-6 DNA positive liver biopsy with a tendency for significant association (p=0.09), 22 recipients developed acute cellular rejection and 9/22 were positive for HLA-DR 15 (p=0.03; χ(2)=4.51), which was statistically significant in univariate analysis and showed a tendency after multivariate analysis (p=0.08). CONCLUSION: HHV-6 DNA was prevalent in liver donors studied as well as HLA-DR 15. These findings suggest that patients with HLA-DR 15 in liver donor biopsies develop more rejection after liver transplantation.
Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/genética , Rejeição de Enxerto/virologia , Antígenos HLA-DR/imunologia , Herpesvirus Humano 6/genética , Transplante de Fígado/efeitos adversos , Fígado/virologia , Infecções por Roseolovirus/virologia , Doença Aguda , Adulto , Biópsia , Estudos de Coortes , Infecções por Citomegalovirus/diagnóstico , DNA Viral/isolamento & purificação , Feminino , Rejeição de Enxerto/diagnóstico , Humanos , Fígado/patologia , Masculino , Reação em Cadeia da Polimerase , Estudos Prospectivos , Infecções por Roseolovirus/diagnóstico , Ativação ViralRESUMO
INTRODUCTION: Exanthem subitum is a classical rash disease of early childhood caused by human herpesvirus 6B (HHV-6B). However, the rash is frequently misdiagnosed as that of either measles or rubella. METHODS: In this study, a nested multiplex polymerase chain reaction (PCR) was used to diagnose HHV-6B primary infection, differentiate it from infections caused by HHV-6A and compare it to antibody avidity tests. The samples were separated into case group and control group according to the results of the indirect immunofluorescence assay (IFA) technique. RESULTS: From the saliva samples analyzed, HHV-6A DNA was detected in 3.2 percent of the case group and in 2.6 percent of the control group. Regarding HHV-6B, PCR detected viral DNA in 4.8 percent of the case group and in 1.3 percent of the control group. Among the serum samples studied, a frequency of 1.7 percent was determined for HHV-6A in the case group and 1.2 percent in the control group. PCR did not detect HHV-6B DNA in serum samples. The sensitivity and specificity of the PCR technique ranged from 0 percent to 4.8 percent and 97.5 percent to 100 percent, respectively, compared to IFA. CONCLUSIONS: The PCR technique was not suitable for diagnosing primary infection by HHV-6B in children with exanthematic disease and should not substitute the IFA.
INTRODUÇÃO: O exantema súbito é uma doença comum durante a infância e pode ser causada pela infecção por herpesvirus humano tipo 6B (HHV-6B). No entanto, a erupção cutânea característica dessa doença, é frequentemente confundida com outras viroses como sarampo ou rubéola. MÉTODOS: Foi utilizada a técnica de reação em cadeia da polimerase (PCR) no formato nested multiplex para o diagnóstico de infecção primária por HHV-6B, diferenciação entre as infecções causadas pelo HHV-6A e comparação com testes de avidez de anticorpos. As amostras foram separadas em grupo caso e grupo controle, de acordo com os resultados do teste de imunofluorescência indireta (IFA). RESULTADOS: Nas amostras de saliva analisadas, o DNA do HHV-6A foi detectado em 3,2 por cento no grupo caso e em 2,6 por cento das amostras do grupo controle. Em relação ao HHV-6B, o DNA viral foi observado em 4,8 por cento no grupo caso e em 1,3 por cento no grupo controle. Após a realização da PCR nas amostras de soro, o DNA do HHV-6A foi detectado em 1,7 por cento no grupo caso e em 1,2 por cento no grupo controle, enquanto o DNA do HHV-6B não foi detectado. A sensibilidade e a especificidade da técnica de PCR variaram de 0 por cento a 4,8 por cento e de 97,5 por cento a 100 por cento, respectivamente, quando comparado com a IFA. CONCLUSÕES: A técnica de PCR não se mostrou adequada para o diagnóstico de infecção primária pelo HHV-6B em crianças com doença exantemática e não deve substituir a IFA.
Assuntos
Criança , Humanos , Anticorpos Antivirais/sangue , DNA Viral/análise , Exantema Súbito/diagnóstico , /genética , Afinidade de Anticorpos , Diagnóstico Diferencial , Exantema Súbito/virologia , Técnica Indireta de Fluorescência para Anticorpo , /imunologia , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Saliva/virologiaRESUMO
El objetivo es el de efectuar una revisión de aquellos padecimientos de baja frecuencia que son adquiridos por el neonato a través de la vía transplacentaria, con la finalidad de alertar al médico pediatra sobre su existencia, el probable incremento de algunos de ellos, y en forma breve exponer algunos de sus elementos clínicos más distintivos, como es el caso de los herpesvirus 6 y 7, así como 1 y 2; dengue, papilomavirus, Coxsackie virus, Plasmodium, Leishmania, Mycobacterium tuberculosis, Candida y Treponema pallidum. En función de su conocida frecuencia de transmisión, se anota al final el número de mujeres que las presentaron en México en el año 2004, con la finalidad de sensibilizar al médico para que se investigue con mayor intencionalidad su presencia en el neonato.
The objective of this review is to list some of the important, albeit less frequent, causes of vertical infections in the newborn infant in order to alert pediatricians and other physicians that care for children on their existence. A brief summary of the most salient features of the following diseases is provided: herpes-virus 6 and 7 as well as 1 and 2; dengue, papillomavirus, coxsackie virus, Plasmodium, Leishmania, Mycobacterium tuberculosis, Candida and Treponema pallidum. Based on its well-known transmission frequency, the number of women who presented/displayed them in Mexico in 2004 is presented.