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2.
Molecules ; 24(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505853

RESUMO

Complement (C) activation can underlie the infusion reactions to liposomes and other nanoparticle-based medicines, a hypersensitivity syndrome that can be partially reproduced in animal models. However, the sensitivities and manifestations substantially differ in different species, and C activation may not be the only cause of pathophysiological changes. In order to map the species variation of C-dependent and -independent pseudoallergy (CARPA/CIPA), here we used known C activators and C activator liposomes to compare their acute hemodynamic, hematological, and biochemical effects in rats. These C activators were cobra venom factor (CVF), zymosan, AmBisome (at 2 doses), its amphotericin B-free vehicle (AmBisombo), and a PEGylated cholesterol-containing liposome (PEG-2000-chol), all having different powers to activate C in rat blood. The pathophysiological endpoints measured were blood pressure, leukocyte and platelet counts, and plasma thromboxane B2, while C activation was assessed by C3 consumption using the Pan-Specific C3 assay. The results showed strong linear correlation between C activation and systemic hypotension, pointing to a causal role of C activation in the hemodynamic changes. The observed thrombocytopenia and leukopenia followed by leukocytosis also correlated with C3 conversion in case of C activators, but not necessarily with C activation by liposomes. These findings are consistent with the double hit hypothesis of hypersensitivity reactions (HSRs), inasmuch as strong C activation can fully account for all symptoms of HSRs, but in case of no-, or weak C activators, the pathophysiological response, if any, is likely to involve other activation pathways.


Assuntos
Ativação do Complemento/efeitos dos fármacos , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Leucocitose/sangue , Lipossomos/farmacologia , Anfotericina B/química , Anfotericina B/farmacologia , Animais , Colesterol/química , Convertases de Complemento C3-C5/química , Convertases de Complemento C3-C5/farmacologia , Proteínas do Sistema Complemento/química , Proteínas do Sistema Complemento/metabolismo , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/patologia , Venenos Elapídicos/química , Venenos Elapídicos/farmacologia , Humanos , Hipotensão/sangue , Hipotensão/induzido quimicamente , Leucocitose/induzido quimicamente , Leucopenia/sangue , Leucopenia/induzido quimicamente , Lipossomos/química , Nanopartículas/química , Polietilenoglicóis/química , Ratos , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Zimosan/química , Zimosan/farmacologia
3.
Pediatr Dermatol ; 36(4): e99-e101, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31132165

RESUMO

Lymphadenopathy is a common sign for drug reaction and eosinophilia with systemic symptoms (DRESS) syndrome, but hilar and mediastinal lymphadenopathy may be underreported. We describe a 7-year-old boy who started taking ethosuximide for absence seizures and presented with diffuse rash, fever, elevated transaminases, facial swelling, and hilar and mediastinal lymphadenopathy. His mediastinal lymphadenopathy was concerning for lymphoma, which led to more invasive testing to rule out malignancy. This report highlights an unusual and likely underreported presenting sign of DRESS syndrome in children.


Assuntos
Corticosteroides/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/efeitos adversos , Linfadenopatia/induzido quimicamente , Biópsia por Agulha , Criança , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/patologia , Eosinofilia/induzido quimicamente , Eosinofilia/fisiopatologia , Epilepsia Tipo Ausência/diagnóstico , Etossuximida/uso terapêutico , Seguimentos , Humanos , Imuno-Histoquímica , Linfadenopatia/patologia , Linfadenopatia/fisiopatologia , Masculino , Mediastino/patologia , Recidiva , Medição de Risco
5.
Allergol Int ; 68(3): 301-308, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31000444

RESUMO

The aim of this review was to provide an updated overview of drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS). Several new insights have been made, particularly with regards to the diagnosis, pathogenesis and care of some important complications and sequelae. The indication of herpesvirus reactivations in diagnosis in the assessment of disease severity is now better specified. Nevertheless, because fatal complications and autoimmune sequelae have been under-recognized, there is a clear need to identify effective parameters for assessing disease severity and predicting prognosis of the disease in the early phase. In this regard, we have established a scoring system that can be used to monitor severity, predict prognosis and stratify the risk of developing severe complications including fatal cytomegalovirus (CMV) disease. Regulatory T cells are likely to be central to the mechanism and would represent potential targets for therapeutic approaches that can ameliorate inflammatory responses occurring at the acute phase while preventing the subsequent development of harmful outcomes, such as CMV disease and autoimmune diseases.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/patologia , Corticosteroides/uso terapêutico , Doenças Autoimunes/etiologia , Doenças Autoimunes/prevenção & controle , Síndrome de Hipersensibilidade a Medicamentos/complicações , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Herpesviridae/fisiologia , Humanos , Prognóstico , Índice de Gravidade de Doença , Linfócitos T Reguladores/fisiologia , Ativação Viral
8.
J Am Acad Dermatol ; 80(3): 670-678.e2, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30240780

RESUMO

BACKGROUND: The prognosis of drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is highly unpredictable. Severe complications, either related or unrelated to cytomegalovirus (CMV) reactivation, are a highly probable cause of death. OBJECTIVES: The aim was to establish a scoring system for DiHS/DRESS that can be used to monitor severity, predict prognosis, and stratify the risk of developing CMV disease and complications. METHODS: A retrospective analysis of 55 patients with DiHS/DRESS was performed. A composite score was created using clinical data. DiHS/DRESS patients were also stratified into 3 groups based on the scores to predict the risk of CMV reactivation and complications. RESULTS: This scoring system made it possible to predict CMV disease and complications. Scores ≥4 were associated with the later development of CMV disease and complications, while no patients with scores <4 developed complications. LIMITATIONS: This was a single-institution study with a relatively small patient cohort that lacked a validation cohort. CONCLUSIONS: Our scoring system may be useful for predicting CMV-related complications, and early intervention with anti-CMV agents should be considered in patients with scores ≥4 or with evidence of CMV reactivation.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/complicações , Índice de Gravidade de Doença , Adolescente , Corticosteroides/uso terapêutico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Antivirais/administração & dosagem , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Feminino , Ganciclovir/uso terapêutico , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco , Tempo para o Tratamento , Valganciclovir/uso terapêutico , Ativação Viral , Adulto Jovem
11.
Cutis ; 102(5): 322-326, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30566546

RESUMO

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome), also known as drug-induced hypersensitivity syndrome, is an uncommon severe systemic hypersensitivity drug reaction. It typically develops 2 to 6 weeks after exposure to a culprit medication and presents with widespread rash, facial edema, systemic symptoms (eg, fever, rigors, hypotension), lymphadenopathy, evidence of visceral organ involvement, and often eosinophilia. The clinical myths and pearls presented here highlight some of the commonly held assumptions regarding DRESS syndrome in an effort to illuminate subtleties of managing patients with this condition.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Humanos
13.
BMJ Case Rep ; 20182018 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-30368475

RESUMO

We experienced a 6-year-old case of drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) with subsequent development autoimmune thyroiditis (Hashimoto's thyroiditis), type 1 diabetes with antithyroglobulin, thyroid peroxidase, insulinoma-associated antigen and anti-insulin antibodies at 4 months, alopecia at 7 months, vitiligo, uveitis due to Vogt-Koyanagi-Harada disease at 8 months after clinical resolution of the DiHS/DRESS. He was diagnosed as type III polyglandular autoimmune syndrome (PASIII) after DiHS/DRESS. Prompted by this case, we sought to determine which triggering factors were responsible for later development of PASIII in previously published cases with autoimmune sequelae. In the literature review, five patients with DIHS/DRESS were found to develop autoimmune sequelae consistent with PASIII. All cases with PASIII were much younger than those without them. Four out of the five patients were treated with intravenous immunoglobulin or pulsed prednisolone in the acute stage, although effective in short-term outcomes.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Poliendocrinopatias Autoimunes/etiologia , Antibacterianos/efeitos adversos , Criança , Glucocorticoides/efeitos adversos , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Masculino , Prednisolona/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
14.
Pan Afr Med J ; 30: 120, 2018.
Artigo em Francês | MEDLINE | ID: mdl-30364443

RESUMO

We report the case of a 60-year old patient with a 1-month history of hyperuricemia treated with allopurinol. The patient presented to the Department of Dermatology with acute rash on the face and the lower limbs associated with fever, arthralgias and myalgias. Clinical examination showed symmetric macular erythema on the face at the level of the cheeks with discreet edema (A), erythematous plaques at the level of both legs with healthy skin areas extending progressively from the bottom-up. Lesions were very itchy with burning sensation (B). The examination of the oral cavity showed very painful erosive lesions at the level of the internal face of the cheeks. Lymph nodes were free. Paraclinical tests showed leukocyte counts at 20000, elevated transaminases > 100 IU, eosinophil counts at 1500, HHV6 serology was negative. The diagnosis of DRESS syndrome was retained. The patient underwent corticosteroid therapy at a dose of 1 mg/kg/day associated with symptomatic treatment. Treatment evolution was marked by spectacular improvement after 06 days (C and D) with regression of skin lesions and gradual normalization of laboratory results.


Assuntos
Alopurinol/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Supressores da Gota/efeitos adversos , Corticosteroides/administração & dosagem , Alopurinol/administração & dosagem , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Feminino , Supressores da Gota/administração & dosagem , Humanos , Hiperuricemia/tratamento farmacológico , Pessoa de Meia-Idade , Prurido/induzido quimicamente
15.
BMJ Case Rep ; 20182018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30301732

RESUMO

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon drug hypersensitivity reaction caused by a wide variety of agents. It has a characteristic latent period between 2 and 8 weeks from the onset of drug ingestion followed by a slow resolution with the potential for relapse. Despite being a potentially fatal disease, little is understood about its variable clinical presentation and why it can present long after removal of the offending drug. Visceral organ involvement typically occurs, but rarely results in clinically manifested cardiac injury. In its most aggressive form, acute necrotizing eosinophilic myocarditis (ANEM) can present with DRESS. We present an unusual case of DRESS syndrome due to lamotrigine with confirmed ANEM showing both eosinophils and rare giant cell infiltrates on endomyocardial biopsy. Although lamotrigine has been reported to cause DRESS, it has not been previously implicated as a cause of ANEM.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Miocardite/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Diagnóstico Diferencial , Síndrome de Hipersensibilidade a Medicamentos/complicações , Eletrocardiografia , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Miocardite/complicações , Miocardite/diagnóstico por imagem , Miocardite/fisiopatologia , Recidiva
17.
BMJ Case Rep ; 20182018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30275021

RESUMO

We present a case report of an early-onset drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) induced by vemurafenib (BRAF inhibitor) in a middle-age man affected by a metastatic, BRAF mutant melanoma who was started on first-line metastatic treatment with vemurafenib and cobimetinib.After initiating the treatment, the patient presented an extensive cutaneous rash with eosinophilia and renal impairment. Due the constellation of signs and symptoms, a diagnosis of DRESS syndrome was made which strongly contraindicated the reintroduction of vemurafenib due to its hypersensibility reaction. Thus, vemurafenib was stopped immediately, and we started corticoid treatment with clinical improvement.Due to the contraindication to start vemurafenib again, after multidisciplinary view of the case and having balanced the risks and benefits, we successfully performed a switch to another BRAF inhibitor in a progressively ascending pattern, without any skin toxicity and with a good response of the metastatic melanoma.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Melanoma/tratamento farmacológico , Vemurafenib/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Azetidinas/administração & dosagem , Azetidinas/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/complicações , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Eosinofilia/induzido quimicamente , Exantema/induzido quimicamente , Humanos , MAP Quinase Quinase 1/antagonistas & inibidores , Masculino , Melanoma/patologia , Melanoma/secundário , Pessoa de Meia-Idade , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundário , Resultado do Tratamento , Vemurafenib/uso terapêutico
20.
Clin Exp Allergy ; 48(11): 1453-1463, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30112775

RESUMO

BACKGROUND: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS) is a distinct phenotype of severe drug eruptions characterized by sequential reactivations of herpesviruses. Although a progressive loss of suppressive function in regulatory T cells (Tregs) occurred during the course of DiHS/DRESS, but not in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), no previous studies investigated the mechanism. Given the recent finding that Treg development could be differentially regulated by CD16+ patrolling monocytes (pMOs) and CD14+ classical monocytes (cMOs), we can hypothesize that a differential fine-tuned interaction between Tregs and monocytes is the driving force behind the possible shift from Tregs to Th17 cells over a prolonged period of time in DiHS/DRESS. OBJECTIVE: To investigate whether the shift from Treg to Th17 could specifically occur during the course of DiHS/DRESS and to elucidate which subsets of monocytes could be involved in the shift. METHODS: We performed a prospective longitudinal study on the frequencies of Tregs, Th17 cells and monocyte subsets after onset of DiHS/DRESS and SJS/TEN, and long after their clinical resolutions. We next examined whether pMOs and cMOs could have a strong impact on the Th17/Treg differentiation and which cytokines could be crucial for the interaction between Th17/Tregs and MO subsets, by in vitro cocultures. RESULTS: Selective depletion of pMOs occurring at the acute stage of DiHS/DRESS was associated with the relative increase in the frequencies of cMOs producing IL-10 and it did drive Treg expansions. After clinical resolution, pMOs producing IL-6 were alternatively recruited and contributed to the eventual shift from a Treg to Th17 responses. CONCLUSIONS AND CLINICAL RELEVANCE: The gradual shift from Treg to Th17 cell development observed during the clinical course of DiHS/DRESS is mediated by the predominance of cMOs at the acute stage and alternatively recruited pMOs at the resolution stage, respectively.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Adulto , Biomarcadores , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Estudos Longitudinais , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Índice de Gravidade de Doença
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