RESUMEN
We studied laboratory parameters of patients with COVID-19 against the background of chronic pathologies (cardiovascular pathologies, obesity, type 2 diabetes melitus, and cardiovascular pathologies with allergy to statins). A decrease in pH and a shift in the electrolyte balance of blood plasma were revealed in all studied groups and were most pronounced in patients with cardiovascular pathologies with allergy to statin. It was found that low pH promotes destruction of lipid components of the erythrocyte membranes in patients with chronic pathologies, which was seen from a decrease in Na+/K+-ATPase activity and significant hyponatrenemia. In patients with cardiovascular pathologies and allergy to statins, erythrocyte membranes were most sensitive to a decrease in pH, while erythrocyte membranes of obese patients showed the greatest resistance to low pH and oxidative stress.
Asunto(s)
COVID-19/complicaciones , Hiponatremia/etiología , Hipoxia/complicaciones , ATPasa Intercambiadora de Sodio-Potasio/fisiología , Anciano , COVID-19/metabolismo , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/virología , Estudios de Casos y Controles , Enfermedad Crónica , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/virología , Hipersensibilidad a las Drogas/complicaciones , Hipersensibilidad a las Drogas/metabolismo , Hipersensibilidad a las Drogas/virología , Membrana Eritrocítica/metabolismo , Eritrocitos/metabolismo , Femenino , Transferencias de Fluidos Corporales/fisiología , Humanos , Concentración de Iones de Hidrógeno , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hiponatremia/metabolismo , Hiponatremia/virología , Hipoxia/metabolismo , Peroxidación de Lípido/fisiología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad/virología , Estrés Oxidativo/fisiología , SARS-CoV-2/fisiología , Sodio/metabolismo , Estrés Fisiológico/fisiologíaAsunto(s)
Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Nanotecnología , SARS-CoV-2/efectos de los fármacos , Anafilaxia/inducido químicamente , COVID-19/inmunología , COVID-19/patología , COVID-19/virología , Hipersensibilidad a las Drogas/patología , Hipersensibilidad a las Drogas/virología , Humanos , Polietilenglicoles/efectos adversos , SARS-CoV-2/patogenicidad , Vacunación/efectos adversosRESUMEN
The proinflammatory cytokine interleukin-17A (IL-17A) is known to mediate antimicrobial activity, but its role during rhinovirus (RV) infections and in asthma needs further investigation. Therefore, we addressed the role of IL-17A during allergic asthma and antiviral immune response in human and murine immunocompetent cells. In this study we found that asthmatic children with a RV infection in their upper airways have upregulated mRNA levels of the antiviral cytokine interferon type I (IFN)-ß and the transcription factor T-box 21 (TBX21) and reduced levels of IL-17A protein in their peripheral blood mononuclear cells (PBMCs). We also found that IL-17A inhibited RV1b replication in infected human lung epithelial cells A549. Furthermore, by using gene array analysis we discovered that targeted deletion of Il17a in murine lung CD4(+) T cells impaired Oas1g mRNA downstream of Ifnß, independently from RV infection. Additionally, in PBMCs of children with a RV infection in their nasalpharyngeal fluid OAS1 gene expression was found downregulated. Finally RV1b inhibited IL-17A production in lung CD4(+) T cells in a setting of experimental asthma. These results indicate that the RV1b inhibits IL-17A in T helper type 17 cells and IL-17A clears RV1b infection in epithelial cells. In both cases IL-17A contributes to fend off RV1b infection by inducing genes downstream of interferon type I pathway.
Asunto(s)
Asma/inmunología , Linfocitos T CD4-Positivos/inmunología , Hipersensibilidad a las Drogas/inmunología , Interleucina-17/inmunología , Infecciones por Picornaviridae/inmunología , Rhinovirus/inmunología , 2',5'-Oligoadenilato Sintetasa/genética , 2',5'-Oligoadenilato Sintetasa/inmunología , Células A549 , Animales , Asma/genética , Asma/virología , Linfocitos T CD4-Positivos/virología , Niño , Preescolar , Hipersensibilidad a las Drogas/genética , Hipersensibilidad a las Drogas/virología , Femenino , Regulación de la Expresión Génica , Humanos , Interferón beta/genética , Interferón beta/inmunología , Interleucina-17/genética , Pulmón/inmunología , Pulmón/virología , Masculino , Ratones , Ratones Noqueados , Ovalbúmina/administración & dosificación , Infecciones por Picornaviridae/genética , Infecciones por Picornaviridae/virología , Cultivo Primario de Células , ARN Mensajero/genética , ARN Mensajero/inmunología , Rhinovirus/crecimiento & desarrollo , Transducción de Señal , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/inmunologíaRESUMEN
Reactivation of certain latent viruses has been linked with a more severe course of drug-induced hypersensitivity reaction (HSR). For example, reactivation of human herpes virus (HHV)-6 is associated with severe organ involvement and a prolonged course of disease. The present study discusses an HSR developed in a previously healthy male exposed to ceftriaxone, doxycycline, vancomycin, and trimethoprim/sulfamethoxazole (co-trimoxazole; TMP/SMX). Initially, the patient presented clinical manifestations of HSR, as well as clinical and laboratory measurements compatible with liver and renal failure. Moreover, the patient presented skin desquamation compatible with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis. During the reaction, it was observed HHV-6 reactivation. The severity of clinical symptoms is correlated with HHV-6 titer, as well as with results of the in vitro lymphocyte toxicity assay (LTA). Serum levels of a large panel of cytokines are compared between the patient, a large population of SJS patients, and a cohort of healthy controls, using data collected by our laboratory over the years. HHV-6 was measured in the cell culture media from lymphocytes incubated with each of the 4 drugs. Moreover, we describe a new assay using cytokines released by patient lymphocytes following in vitro exposure to the incriminated drugs as biomarkers of HSR. Based on LTA results, HHV-6 reactivation and cytokine measurements, we establish that only doxycycline and TMP/SMX were involved in the HSR. As result of this analysis, the patient could continue to use the other 2 antibiotics safely.
Asunto(s)
Antibacterianos/efectos adversos , Herpesvirus Humano 6/efectos de los fármacos , Herpesvirus Humano 6/patogenicidad , Activación Viral/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/virología , Citocinas/sangre , Citocinas/metabolismo , Doxiciclina/efectos adversos , Erupciones por Medicamentos/inmunología , Erupciones por Medicamentos/virología , Hipersensibilidad a las Drogas/inmunología , Hipersensibilidad a las Drogas/virología , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Masculino , Infecciones por Roseolovirus/etiología , Infecciones por Roseolovirus/inmunología , Síndrome de Stevens-Johnson/inducido químicamente , Síndrome de Stevens-Johnson/inmunología , Síndrome de Stevens-Johnson/virología , Investigación Biomédica Traslacional , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Adulto JovenRESUMEN
BACKGROUND/AIM: Drug-induced hypersensitivity syndrome (DIHS) is a severe reaction to drugs which characteristically occurs after a long latency period. In addition, human herpes virus 6 (HHV-6) reactivation is a characteristic finding in DIHS, which has been known to be related to disease severity. Because DIHS has generally been treated by systemic corticosteroids, the natural clinical course is not clear. METHODS: Data for patients with both DIHS and HHV-6 reactivation were retrospectively collected from four hospitals. RESULTS: Data were collected on 12 patients ranging in age from 21 to 76 years (median, 65.5). All cases had been suspected of DIHS at their initial visit, and the elevation of serum anti-HHV-6 antibody had been confirmed (4-256 times: median; 32). The culprit drugs were carbamazepine (6), salazosulfapyridine (4), mexiletine (1) and zonisamide (1). The period of latency from the first administration of the drug ranged from 15 to 50 days (median, 30). All patients were treated conservatively for DIHS without systemic corticosteroids. The peaks of the patients' symptoms and laboratory findings were as follows (days from the onset of skin lesions): fever, 4-16 (median, 10.5); liver abnormality, 3-22 (median, 7.5); leukocytosis, 7-20 (median, 9). All patients recovered without pneumonia, myocarditis, nephritis or other systemic disease, from 7 to 37 days (median, 18) after withdrawal of the drug and from 11 to 44 days (median, 21) after the onset of skin lesions. CONCLUSION: It might be unnecessary to give systemic corticosteroids immediately to all patients suspected of having DIHS.
Asunto(s)
Hipersensibilidad a las Drogas/tratamiento farmacológico , Corticoesteroides , Adulto , Anciano , Hipersensibilidad a las Drogas/virología , Femenino , Herpesvirus Humano 6/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Activación Viral , Adulto JovenRESUMEN
The DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), also known as DIHS (drug-induced hypersensitivity syndrome), presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, producing damage in several systems, especially kidney, heart, lungs, and pancreas. The pathogenesis is related to specific drugs (especially the aromatic anticonvulsants), altered immune response, sequential reactivation of herpes virus, and association with some HLA alleles. Glucocorticoids are the basis for the treatment of the syndrome, which may be given with intravenous immunoglobulin and, in selected cases, ganciclovir. This article reviews current concepts regarding the interaction of drugs, viruses and immune responses during this complex adverse-drug reaction.
Asunto(s)
Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/inmunología , Hipersensibilidad a las Drogas/virología , Eosinofilia/inducido químicamente , Eosinofilia/inmunología , Eosinofilia/virología , Herpesviridae/inmunología , Hipersensibilidad a las Drogas/terapia , Eosinofilia/terapia , Humanos , Factores de Riesgo , SíndromeRESUMEN
Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe multiorgan disorder. The reactivation of human herpesvirus-6 (HHV-6) and other human herpesviruses has been reported to be associated with its pathogenesis. We herein report a case of 14-year-old female who developed DIHS during the treatment with lamotrigine, a novel antiepileptic drug. She initially presented with fever, skin rash, cervical lymphadenopathy, leukocytosis with eosinophilia and atypical lymphocytosis, liver dysfunction and hypogammaglobulinemia. Discontinuation of the drug and administration of prednisolone led to improvement;however, tapering of prednisolone and administration of midazolam and ketamine thereafter triggered clinical deterioration. She subsequently developed hyperthyroidism followed by hypothyroidism. Herpesviral loads were determined in her peripheral blood by real-time PCR during the course of the treatment, and sequential reactivation of Epstein-Barr virus (EBV), HHV-6 and cytomegalovirus was demonstrated. EBV viremia was detected throughout the course, except for a short period when HHV-6 viremia was at the peak. HHV-6 viremia developed after the secondary deterioration. Cytomegalovirus viremia appeared transiently before the hyperthyroidic state reversed and became hypothyroidic. Although this syndrome should be regarded as a systemic reaction induced by a complex interplay among herpesviruses and the immune responses against viral infections and drugs, it remains unknown how such a sequential reactivation is related to the pathogenesis of the condition.
Asunto(s)
Anticonvulsivantes/efectos adversos , Hipersensibilidad a las Drogas/etiología , Triazinas/efectos adversos , Adolescente , Citomegalovirus/fisiología , Hipersensibilidad a las Drogas/inmunología , Hipersensibilidad a las Drogas/virología , Femenino , Herpesvirus Humano 4/fisiología , Herpesvirus Humano 6/fisiología , Humanos , Lamotrigina , Reacción en Cadena de la Polimerasa , Síndrome , Linfocitos T Reguladores/inmunología , Activación ViralAsunto(s)
Antiarrítmicos/efectos adversos , Artritis/inducido químicamente , Hipersensibilidad a las Drogas/diagnóstico , Exantema/diagnóstico , Mexiletine/efectos adversos , Artralgia/tratamiento farmacológico , Artralgia/virología , Artritis/tratamiento farmacológico , Artritis/virología , Celecoxib , Enfermedad Crónica , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , ADN Viral/sangre , Hipersensibilidad a las Drogas/tratamiento farmacológico , Hipersensibilidad a las Drogas/virología , Quimioterapia Combinada , Exantema/inducido químicamente , Exantema/tratamiento farmacológico , Exantema/virología , Femenino , Herpesvirus Humano 6/aislamiento & purificación , Humanos , Metaloproteinasa 3 de la Matriz/sangre , Persona de Mediana Edad , Prednisolona/uso terapéutico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Resultado del TratamientoRESUMEN
Drug-induced hypersensitivity syndrome (DIHS) is caused by a limited number of specific drugs and is characterized by late onset, infectious mononucleosis-like symptoms, and herpesvirus 6 (HHV-6) reactivation. Recently, the involvement of herpes viruses other than HHV-6, such as Epstein-Barr virus and cytomegalovirus, has been reported. Many approaches have been used to analyze the pathological mechanism, and have revealed new aspects of DIHS. Here, we focused on three key recent findings regarding DIHS: (i) overlap between DIHS and Stevens-Johnson syndrome/toxic epidermal necrolysis; (ii) the relevance of Epstein-Barr virus in the development of infectious mononucleosis-like symptoms of DIHS; and (iii) roles of monomyeloid precursors increased in the blood and plasmacytoid dendritic cells increased in the lesion skin in HHV-6 reactivation.
Asunto(s)
Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Herpesviridae/complicaciones , Síndrome de Stevens-Johnson/diagnóstico , Células Dendríticas/virología , Herpesvirus Humano 4/patogenicidad , Herpesvirus Humano 6/fisiología , Humanos , Mononucleosis Infecciosa/complicaciones , Células Mieloides/virología , Síndrome , Activación ViralAsunto(s)
Hipersensibilidad a las Drogas/etiología , Edema/etiología , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , ADN Viral/sangre , Hipersensibilidad a las Drogas/sangre , Hipersensibilidad a las Drogas/virología , Edema/sangre , Edema/virología , Cara , Herpesvirus Humano 6/fisiología , Humanos , Masculino , Cuello , Síndrome , Activación ViralRESUMEN
Drug-induced hypersensitivity syndrome (DIHS) is characterized by a serious adverse systemic reaction that usually appears after a 3-6-week exposure to certain drugs, for example, anticonvulsants. Many different precipitating factors have been reported, but the pathophysiology of DIHS remains unknown. However, reactivation of members of the human herpesvirus (HHV) family, and of HHV-6 in particular, has been reported in patients with DIHS. We report the case of a 64-year-old man who developed a generalized erythematous rash, fever, hepatic failure, lymphadenopathy and an increased number of atypical lymphocytes. In addition, reactivation of HHV-6 and cytomegalovirus (CMV) was demonstrated by real-time quantitative amplification by polymerase chain reaction. The patient was given a diagnosis of DIHS due to carbapenem antibiotics based on his clinical course, laboratory data, and results of lymphocyte-stimulation tests with various drugs. This is the first report, to our knowledge, of DIHS induced by carbapenem antibiotics.
Asunto(s)
Carbapenémicos/efectos adversos , Infecciones por Citomegalovirus/etiología , Citomegalovirus/efectos de los fármacos , Hipersensibilidad a las Drogas/virología , Herpesvirus Humano 6/efectos de los fármacos , Infecciones por Roseolovirus/etiología , Activación Viral/efectos de los fármacos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carbapenémicos/administración & dosificación , Ciclofosfamida/administración & dosificación , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/patología , Doxorrubicina/administración & dosificación , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/patología , Exantema/diagnóstico , Exantema/patología , Exantema/virología , Fiebre/diagnóstico , Fiebre/virología , Humanos , Fallo Hepático/diagnóstico , Fallo Hepático/patología , Fallo Hepático/virología , Enfermedades Linfáticas/diagnóstico , Enfermedades Linfáticas/patología , Enfermedades Linfáticas/virología , Linfoma de Células del Manto/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prednisolona/administración & dosificación , Rituximab , Infecciones por Roseolovirus/diagnóstico , Infecciones por Roseolovirus/patología , Síndrome , Vincristina/administración & dosificaciónRESUMEN
Drug-induced hypersensitivity syndrome (DIHS) is an adverse reaction with clinical signs of fever, rash, and internal organ involvement. The culprit drugs of DIHS are limited to several drugs such as carbamazepine, phenytoin, phenobarbital, zonisamide, allopurinol, salazosulfapyridine, diaphenylsulphone, and mexiletine. The association of HHV-6 reactivation with DIHS has been known. Flaring of symptoms such as fever and hepatitis is closely related to HHV-6 reactivation. A combination of immunologic reaction to a drug and HHV-6 reactivation results in the severe course of DIHS.
Asunto(s)
Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/virología , Herpesvirus Humano 6/fisiología , Activación Viral , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , ADN Viral/sangre , Femenino , Herpesvirus Humano 6/inmunología , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Síndrome , Adulto JovenAsunto(s)
Hipersensibilidad a las Drogas/virología , Herpesvirus Humano 6/fisiología , Células Mieloides/patología , Activación Viral/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Hipersensibilidad a las Drogas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome , Adulto JovenAsunto(s)
Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Hipersensibilidad a las Drogas/virología , Herpesvirus Humano 6/aislamiento & purificación , ARN Viral/análisis , Piel/virología , Adulto , Anciano , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/patología , Femenino , Herpesvirus Humano 6/genética , Humanos , Hibridación in Situ , Masculino , Persona de Mediana Edad , Piel/patología , Síndrome , Transcripción GenéticaRESUMEN
Viral infections are most likely triggering factors of autoimmune diseases, although a single vial infection is not sufficient to cause clinically evident autoimmune diseases. Any disease that profoundly alters the immune system may cause perturbed viral infections, thereby rendering otherwise refractory patients susceptible to autoimmune diseases. In this regard, drug-induced hypersensitivity syndrome (DIHS), a drug rash characterized by sequential reactivations of herpesviruses and the subsequent development of autoimmune diseases, offers a unique opportunity to investigate the mechanism of how autoimmunity is elicited after viral infections. Indeed, several autoimmune diseases have been reported to occur at intervals of several months to years after clinical resolution of DIHS. Two representative cases who developed autoimmune diseases three to four years after DIHS are shown. Our recent analyses of the kinetics of a developing disease have shown that fully functional FoxP3(+) regulatory T (Treg) cells are expanded at the acute stage thereby allowing viral reactivations but lose their suppressive function coincident with their contraction upon clinical resolution. The functional defect of Treg cells would be responsible for the subsequent development of autoimmune diseases. Patients with DIHS need close monitoring because of possible progression to autoimmune diseases even after the complete resolution.
Asunto(s)
Enfermedades Autoinmunes/virología , Hipersensibilidad a las Drogas/virología , Infecciones por Herpesviridae/inmunología , Herpesviridae/fisiología , Linfocitos T Reguladores/inmunología , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/fisiopatología , Autoinmunidad , Hipersensibilidad a las Drogas/complicaciones , Hipersensibilidad a las Drogas/fisiopatología , Exantema , Factores de Transcripción Forkhead , Herpesviridae/patogenicidad , Infecciones por Herpesviridae/complicaciones , Humanos , Tolerancia Inmunológica , Linfocitos T Reguladores/patología , Factores de Tiempo , Activación ViralRESUMEN
A case of severe hypersensitivity syndrome, triggered by carbamazepine in the presence of a concomitant active human herpes virus (HHV) 6 and 7 infection is described. To further understand the molecular mechanism of this adverse reaction, analyses of the genetic variants of human leukocyte antigen (HLA) and of the epoxide hydrolase gene (EPHX1), previously associated with carbamazepine hypersensitivity, were performed. A lymphocyte transformation test (LTT) was conducted in order to detect drug-specific lymphocytes. In the hypersensitive patient, 2 genetic factors previously associated with intolerance to carbamazepine were detected: the allele HLA-A*3101 and homozygosity for the variant allele of SNP rs1051740 in EPHX1. Drug-specific lymphocytes could be detected by LTT when the HHV was active (positive PCR for viral DNA and increased anti-HHV 6 IgG titer), but not when it was no longer active. In conclusion, we document a case of severe carbamazepine hypersensitivity triggered by viral reactivation in a patient presenting the interaction of 2 unfavorable genetic factors.
Asunto(s)
Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Hipersensibilidad a las Drogas/virología , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 6 , Herpesvirus Humano 7 , Células Cultivadas , Niño , Hipersensibilidad a las Drogas/genética , Epóxido Hidrolasas/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA-A/genética , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Polimorfismo de Nucleótido Simple , Síndrome , Activación Viral/genética , Activación Viral/inmunologíaRESUMEN
Drug-induced hypersensitivity syndrome (DIHS) is a severe form of drug eruptions associated with viral reactivations. Autoimmune diseases have been reported to develop several months or years after the resolution of DIHS. We describe a 36-year-old man with cervical lymphadenopathy and an erythematous eruption affecting the face and neck, which evolved into clinically evident systemic lupus erythematosus. He had had an episode of DIHS 4 years previously, in which human herpesvirus-6 and Epstein-Barr virus (EBV) were reactivated. Expression of EBV-encoded RNA was detected in the lymph node. On the basis of findings in this patient, we suggest that EBV is pathogenically important in the sequence of events leading to the onset of systemic lupus erythematosus and that patients with a history of DIHS may be at a risk of eventually developing autoimmune diseases.