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Síndrome de Hipersensibilidad a Medicamentos , Herpesvirus Humano 6 , Infecciones por Roseolovirus , Activación Viral , Humanos , Herpesvirus Humano 6/aislamiento & purificación , Infecciones por Roseolovirus/diagnóstico , Infecciones por Roseolovirus/complicaciones , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/virología , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/diagnóstico , Eosinofilia/inducido químicamente , Eosinofilia/virología , Eosinofilia/diagnóstico , Infección LatenteAsunto(s)
Síndrome de Hipersensibilidad a Medicamentos , Herpesvirus Humano 6 , Infecciones por Roseolovirus , Activación Viral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/virología , Eosinofilia/inducido químicamente , Eosinofilia/diagnóstico , Eosinofilia/virología , Herpesvirus Humano 6/aislamiento & purificación , Infección Latente , Infecciones por Roseolovirus/diagnóstico , Infecciones por Roseolovirus/complicacionesAsunto(s)
COVID-19/sangre , COVID-19/complicaciones , Síndrome de Hipersensibilidad a Medicamentos/etiología , Eosinofilia/tratamiento farmacológico , Eosinofilia/etiología , Anciano , Comorbilidad , Enfermedad Crítica , Síndrome de Hipersensibilidad a Medicamentos/sangre , Síndrome de Hipersensibilidad a Medicamentos/virología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2/efectos de los fármacosAsunto(s)
COVID-19 , Síndrome de Down , Síndrome de Hipersensibilidad a Medicamentos , Enfermedades Renales/inducido químicamente , COVID-19/complicaciones , Síndrome de Down/complicaciones , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/virología , Humanos , Riñón/efectos de los fármacosRESUMEN
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe type of adverse drug eruption associated with multiorgan involvement and the reactivation of human herpesvirus 6, which arises after prolonged exposure to certain drugs. Typically, two waves of disease activity occur during the course of DIHS/DRESS; however, some patients experience multiple waves of exacerbation and remission of the disease. Severe complications, some of which are related to cytomegalovirus reactivation, can be fatal. DIHS/DRESS is distinct from other drug reactions, as it involves herpes virus reactivation and can lead to the subsequent development of autoimmune diseases. The association between herpesviruses and DIHS/DRESS is now well established, and DIHS/DRESS is considered to arise as a result of complex interactions between several herpesviruses and comprehensive immune responses, including drug-specific immune responses and antiviral immune responses, each of which may be mediated by distinct types of immune cells. It appears that both CD4 and CD8 T cells are involved in the pathogenesis of DIHS/DRESS but play distinct roles. CD4 T cells mainly initiate drug allergies in response to drug antigens, and then herpesvirus-specific CD8 T cells that target virus-infected cells emerge, resulting in tissue damage. Regulatory T-cell dynamics are also suggested to contribute to the diverse symptoms of DIHS/DRESS. However, the pathomechanisms of this complex disease remain largely unknown. In particular, how viral infections contribute to the pathogenesis of DIHS/DRESS and why autoimmune sequelae arise in DIHS/DRESS are yet to be elucidated. This review describes the clinical features of DIHS/DRESS, including the associated complications and sequelae, and discusses recent advances in our understanding of the immunopathogenic mechanisms of DIHS/DRESS.
Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos/inmunología , Síndrome de Hipersensibilidad a Medicamentos/patología , Eosinofilia/complicaciones , Presentación de Antígeno/inmunología , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/virología , Antígenos HLA/metabolismo , Humanos , Linfocitos T/inmunologíaRESUMEN
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug induced hypersensitivity (DiHS) syndrome is a severe delayed hypersensitivity reaction with potentially fatal consequences. Whilst recognised as T cell-mediated, our understanding of the immunopathogenesis of this syndrome remains incomplete. Here, we discuss models of DRESS, including the role of human leukocyte antigen (HLA) and how observations derived from new molecular techniques adopted in key studies have informed our mechanism-based understanding of the central role of Herpesviridae reactivation and heterologous immunity in these disorders.
Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos/etiología , Eosinofilia/inducido químicamente , Infecciones por Herpesviridae/inmunología , Linfocitos T/efectos de los fármacos , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/virología , Eosinofilia/inmunología , Antígenos HLA/inmunología , Herpesviridae/efectos de los fármacos , Herpesviridae/fisiología , Infecciones por Herpesviridae/complicaciones , Humanos , Receptores de Antígenos de Linfocitos T , Linfocitos T/inmunología , Replicación Viral/efectos de los fármacosRESUMEN
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous drug reaction characterized by fever, lymphadenopathy, hematologic abnormalities, multisystem involvement, and viral reactivation. Although most patients with DRESS syndrome are able to fully recover, a subset of patients go on to have a prolonged course with recurrence, and/or autoimmune complications. Severe systemic involvement is associated with significant morbidity and mortality. Viral reactivation, especially of human herpes virus 6, Epstein-Barr virus, and cytomegalovirus, is a common feature of DRESS, with a high viral load and antibody titers being associated with poor outcomes. Aside from prompt discontinuation of the offending drug, treatment for patients with significant disease consists of systemic therapy with corticosteroids.
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Síndrome de Hipersensibilidad a Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Eosinofilia/inducido químicamente , Preparaciones Farmacéuticas , Corticoesteroides/uso terapéutico , Citomegalovirus , Síndrome de Hipersensibilidad a Medicamentos/terapia , Síndrome de Hipersensibilidad a Medicamentos/virología , Femenino , Herpesvirus Humano 4/fisiología , Herpesvirus Humano 6 , Humanos , Masculino , Pronóstico , Índice de Severidad de la Enfermedad , Carga Viral , Activación ViralAsunto(s)
Citomegalovirus/inmunología , Dermatitis Exfoliativa/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Herpesvirus Humano 6/inmunología , Administración Oral , Anciano , Citomegalovirus/aislamiento & purificación , Dermatitis Exfoliativa/tratamiento farmacológico , Dermatitis Exfoliativa/inmunología , Dermatitis Exfoliativa/virología , Diagnóstico Diferencial , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Síndrome de Hipersensibilidad a Medicamentos/virología , Femenino , Herpesvirus Humano 6/aislamiento & purificación , Humanos , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Prednisolona/administración & dosificación , Carga Viral , Activación Viral/inmunologíaRESUMEN
PURPOSE: Occupational trichloroethylene hypersensitivity syndrome (OTHS) clinically manifests as generalized severe rash resembling drug-induced hypersensitivity syndrome (DIHS) and afflicts predominantly HLA-B*13:01 gene carriers after their exposure to trichloroethylene. Meanwhile, OTHS may also be associated with human herpesvirus such as herpesvirus-6 (HHV6) and cytomegalovirus (HCMV) reported to participate in the pathology of DIHS. This study explored the association of carrying HHV6 and HCMV, and the joint association of carrying HLA-B*13:01 and HHV6 and HCMV with OTHS. METHODS: We recruited 30 OTHS patients and 40 trichloroethylene-exposed healthy workers as cases and controls, respectively. HLA-B*13:01 was genotyped and HHV6 and HCMV DNA were detected in the DNA extracted from whole-blood sample of each participant with PCR techniques. Positive rates of HLA-B*13:01 gene and HHV6 and HCMV DNA and their association with OTHS were then analyzed. RESULTS: The OTHS cases showed significantly higher positive rates of HLA-B*13:01 gene and HHV6 DNA, but not HCMV DNA, than the controls (83.3% vs. 25.0% and 56.7% vs. 10.0%, respectively, both P < 0.001). Positive rate of HHV6 DNA was significantly higher in HLA-B*13:01 carriers than in non-carriers in the cases (68.0% vs. 0, P = 0.005), but not in the controls. Carrying HLA-B*13:01 and HHV6 had an interactive effect on OTHS (OR = 91.80, P < 0.001). CONCLUSIONS: Carrying HLA-B*13:01 and HHV6 may be associated with OTHS; furthermore, carrying HLA-B*13:01 and HHV6 may be jointly associated with OTHS.
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Síndrome de Hipersensibilidad a Medicamentos/genética , Síndrome de Hipersensibilidad a Medicamentos/virología , Antígenos HLA-B/genética , Herpesvirus Humano 6/aislamiento & purificación , Enfermedades Profesionales/inducido químicamente , Tricloroetileno/efectos adversos , Adulto , Estudios de Casos y Controles , China , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , ADN Viral , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Enfermedades Profesionales/genética , Enfermedades Profesionales/virología , Exposición Profesional/efectos adversos , Reacción en Cadena en Tiempo Real de la Polimerasa , Infecciones por Roseolovirus/inducido químicamente , Activación Viral/efectos de los fármacosAsunto(s)
MicroARN Circulante/sangre , Síndrome de Hipersensibilidad a Medicamentos/virología , Herpesvirus Humano 6/genética , ARN Viral/sangre , Activación Viral , Estudios de Casos y Controles , MicroARN Circulante/genética , Síndrome de Hipersensibilidad a Medicamentos/sangre , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Marcadores Genéticos , Herpesvirus Humano 6/patogenicidad , Humanos , ARN Viral/genética , Factores de Tiempo , Regulación hacia ArribaAsunto(s)
Infecciones por Citomegalovirus/complicaciones , Síndrome de Hipersensibilidad a Medicamentos/complicaciones , Eosinofilia/complicaciones , Hepatitis/complicaciones , Adulto , Citomegalovirus , Síndrome de Hipersensibilidad a Medicamentos/virología , Eosinofilia/virología , Resultado Fatal , Femenino , Gota/tratamiento farmacológico , Hepatitis/virología , Humanos , Hígado/fisiopatología , ViremiaRESUMEN
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, potentially life-threatening idiosyncratic drug reaction that may result in skin eruption, mucous membrane involvement, eosinophilia, atypical lymphocytosis and lymphadenopathy, with wide-ranging internal organ involvement. The authors report the case of a 21-year-old man who was prescribed lamotrigine for anxiety disorder. After 2 weeks of treatment, he developed a pruritic morbilliform rash on his trunk and upper extremities that was associated with fever, sore throat, bilateral scleral injection, nausea, vomiting and abdominal pain. A laboratory work-up revealed elevated transaminases and atypical lymphocytosis. He was found to have an active Epstein-Barr virus infection. Lamotrigine was discontinued due to suspicion of DRESS; the patient received pulsed intravenous methylprednisolone followed by oral prednisone taper, which resulted in a significant improvement of symptoms. At follow-up 3 weeks later, signs and symptoms had completely resolved. Follow-up laboratory tests revealed that liver dysfunction had normalised.
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Trastornos de Ansiedad/tratamiento farmacológico , Fármacos del Sistema Nervioso Central/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Infecciones por Virus de Epstein-Barr/psicología , Triazinas/efectos adversos , Trastornos de Ansiedad/virología , Síndrome de Hipersensibilidad a Medicamentos/virología , Humanos , Lamotrigina , Masculino , Adulto JovenRESUMEN
Drug-induced hypersensitivity syndrome (DIHS) is a severe systemic adverse drug reaction. Previous studies showed that DIHS is associated with the onset of fulminant type 1 diabetes mellitus (FT1D). Although genetic background and abnormalities in immune response or viral infection are considered to be associated with pathogenesis of FT1D, it remains unclear whether virus infection and specific human leukocyte antigen (HLA) typing are involved in DIHS-associated FT1D. Here, we report a case of a 78-year-old female patient with FT1D after DIHS treatment. She was diagnosed as DIHS caused by carbamazepine, and treatment with predonisolone was initiated. After 46 days from the occurrence of DIHS, she was admitted to our hospital because of type 1 diabetes mellitus and diabetic ketoacidosis. Although her Hemoglobin A1c (HbA1c) was elevated by predonisolone treatment (HbA1c: 9.2%), we diagnosed her as fulminant type 1 diabetes mellitus considering the abrupt onset of the ketoacidosis. Her general condition was improved by treatment with fluid infusion and insulin administration. During her clinical course, the infection of coxsackie B4 virus was observed. In addition, the examination of HLA typing showed HLA-A24 haplotype. These findings suggest that the coxsackie B4 virus infection may be involved in the pathogenesis of DIHS-induced FT1D, and that HLA-A24 haplotype might relate to DIHS-associated FT1D.
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Infecciones por Coxsackievirus/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Síndrome de Hipersensibilidad a Medicamentos/complicaciones , Enterovirus Humano B/aislamiento & purificación , Antígeno HLA-A24/sangre , Anciano , Antiinflamatorios/uso terapéutico , Anticonvulsivantes/efectos adversos , Blefaroespasmo/complicaciones , Blefaroespasmo/tratamiento farmacológico , Carbamazepina/efectos adversos , Terapia Combinada , Infecciones por Coxsackievirus/sangre , Infecciones por Coxsackievirus/virología , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/virología , Cetoacidosis Diabética/prevención & control , Síndrome de Hipersensibilidad a Medicamentos/sangre , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/virología , Monitoreo de Drogas , Femenino , Humanos , Japón , Prednisolona/uso terapéutico , Resultado del TratamientoRESUMEN
DRESS is one of the most severe drug reactions. The aim of this retrospective study was to summarize the clinical presentation, genetic predisposition and prognostic factors of DRESS. A total of 52 patients with DRESS, who were inpatients at a medical referral centre in Shanghai, China, from January 2011 to December 2016, were analysed retrospectively. All the patients had skin eruption, 83% had liver involvement, and ≤10% had other organ involvement. Mean cost of hospitalization was US$5,511±3,050. The 3 most common causative agents were allopurinol (18/52; 35%), salazosulphapyridine (11/52; 21%) and carbamazepine (5/52; 10%). HLA-B*5801 and HLA-B*1302 were associated with allopurinol-induced DRESS. HLA-B*1301 was related to salazosulphapyridine-induced DRESS. The mortality rate was 6% (3/52). Epstein-Barr virus DNA was found in 10 patients (19%) and indicated a poor prognosis. Human herpes virus 6 DNA was detected in 17 patients (33%) and was associated with autoimmune sequelae. Due to its high medical cost and sometimes poor prognosis, prevention of DRESS should be a high priority.
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Alopurinol/efectos adversos , Carbamazepina/efectos adversos , ADN Viral/genética , Síndrome de Hipersensibilidad a Medicamentos/genética , Síndrome de Hipersensibilidad a Medicamentos/virología , Antígenos HLA-B/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 6/genética , Sulfasalazina/efectos adversos , Corticoesteroides/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , China , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/mortalidad , Femenino , Predisposición Genética a la Enfermedad , Cadenas HLA-DRB1/genética , Herpesvirus Humano 4/patogenicidad , Herpesvirus Humano 6/patogenicidad , Costos de Hospital , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Tiempo de Internación/economía , Masculino , Persona de Mediana Edad , Admisión del Paciente/economía , Fenotipo , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Activación Viral , Adulto JovenAsunto(s)
Antibacterianos/efectos adversos , Azitromicina/efectos adversos , Cromonas/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/virología , Antagonistas de Leucotrieno/efectos adversos , Virus BK/fisiología , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/virología , Femenino , Humanos , Lactante , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/virología , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/virología , Activación ViralRESUMEN
AIMS: Lymphadenopathy, haematological abnormalities and constitutional symptoms are among the non-specific manifestations seen in drug rash with eosinophilia and systemic symptoms (DRESS), an uncommon but potentially fatal cutaneous adverse drug reaction. The ubiquitous human herpesvirus 6 (HHV-6) plays a unique role in the pathogenesis of DRESS, with emerging data suggesting that reactivation occurs in most cases and contributes to the clinical manifestations, including lymphadenopathy. Further, in the appropriate clinical context, demonstration of HHV-6 reactivation may lend support to a diagnosis of DRESS. The histopathology of DRESS-associated HHV-6 lymphadenitis is reported rarely, with morphologic and immunophenotypic characteristics concerning for T cell lymphoma. The aim is to characterize the histopathology of HHV-6 lymphadenitis in the context of DRESS and to highlight this as an important cause of lymphadenopathy that may be a clinical, morphologic and immunophenotypic mimic of lymphoma. METHODS AND RESULTS: We describe a case of lymphoma-mimicking lymphadenitis in which the histopathological demonstration of reactivation of HHV-6 infection lent support to the clinical diagnosis of DRESS. CONCLUSION: Lymph node biopsies concerning for T cell lymphoma should be evaluated for HHV-6 involvement in a clinical context suggestive of DRESS.
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Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Linfadenitis/virología , Linfoma de Células T/diagnóstico , Infecciones por Roseolovirus/complicaciones , Adulto , Diagnóstico Diferencial , Síndrome de Hipersensibilidad a Medicamentos/virología , Femenino , Herpesvirus Humano 6 , HumanosRESUMEN
Acute infection with viral pathogens in the herpesviridae family can trigger acute urticaria, and reactivation of herpesviridae is associated with cutaneous urticarial-like syndromes such as drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS). Reactivation of latent herpesviridae has not been studied systematically in chronic idiopathic/spontaneous urticaria (CIU). This review proposes that CIU is an inflammatory disorder with autoimmune features (termed 'CVU' for chronic viral urticaria), based on serology consistent with the hypothesis that reactivation of a latent herpesvirus or -viruses may play a role in CIU. Serology obtained from a cohort of omalizumab (Xolair)-dependent patients with severe CIU was consistent with previous HHV-6 infection, persistent viral gene expression and replication. CIU patients also exhibited serological evidence of increased immune response to HHV-4 (Epstein-Barr virus, or EBV) but not all CIU patients were infected with EBV. These observations, combined with case reports of CIU response to anti-viral therapy, suggest that HHV-6, possibly interacting with HHV-4 in cutaneous tissues, is a candidate for further prospective study as a co-factor in CIU.