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1.
J Drugs Dermatol ; 18(10): 1049-1052, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603634

RESUMO

Drug re-exposure resulting in Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) is a rare phenomenon and has scarcely been reported. With an aging population, polypharmacy, and a lack of a unified electronic medical record, standard recommendations to prevent or minimize the risk of re-exposure are necessary. We identified five patients, with diagnosis confirmed SJS/TEN, and determined the clinical characteristics and contributing risk factors leading to re-exposure. Polypharmacy, multiple prescribers, advanced age, medical illiteracy, retention of discontinued medications and self-prescribing all contributed to re-exposure in this cohort of patients. This case series demonstrates the potentially deadly effect of drug re-exposure, and the need for both streamlined and integrated medication allergy documentation systems. J Drugs Dermatol. 2019;18(10):1049-1052.


Assuntos
Anamnese , Reconciliação de Medicamentos , Síndrome de Stevens-Johnson/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento/efeitos adversos , Fatores de Risco , Índice de Gravidade de Doença , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Adulto Jovem
2.
Braz J Infect Dis ; 23(5): 363-367, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562853

RESUMO

Erythema multiforme (EM), Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (TEN) have been reported as possible adverse effects of some classes of first-line antiretroviral drugs (ART) for HIV treatment. Herein we report an unusual presentation of TEN lesions associated with ART in an HIV-infected patient. The patient presented disseminated cutaneous eruption and oral lesions from the lips to the oropharynx region, causing odynophagia and dysphagia. In the tongue, circular, atypical erythematous lesions appeared, increasing in diameter over seven days and coalescing since then to complete remission. TEN treatment included efavirenz interruption, use of methylprednisolone, prophylactic antibiotic, and daily laser therapy with low-intensity red light. The circular oral lesions have not been described yet. Reporting our findings and clinical management may help diagnosing other similar cases and guide the clinical conduct. Analgesia and acceleration of oral ulcer repair with red laser therapy are recommended.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Benzoxazinas/efeitos adversos , Infecções por HIV/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia , Adulto , Benzoxazinas/uso terapêutico , Feminino , Humanos , Síndrome de Stevens-Johnson/diagnóstico
4.
Nat Commun ; 10(1): 3569, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395875

RESUMO

Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αßTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02. This public αßTCR has binding affinity for carbamazepine and its structural analogs, thereby mediating the immune response. Adoptive transfer of T cell expressing this public αßTCR to HLA-B*15:02 transgenic mice receiving oral administration of carbamazepine induces multi-organ injuries and symptoms mimicking SCAR, including hair loss, erythema, increase of inflammatory lymphocytes in the skin and blood, and liver and kidney dysfunction. Our results not only demonstrate an essential role of TCR in the immune synapse mediating SCAR, but also implicate potential clinical applications and development of therapeutics.


Assuntos
Carbamazepina/efeitos adversos , Complexo Receptor-CD3 de Antígeno de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Síndrome de Stevens-Johnson/imunologia , Linfócitos T Citotóxicos/imunologia , Transferência Adotiva , Adulto , Idoso , Animais , Modelos Animais de Doenças , Feminino , Antígeno HLA-B15/genética , Antígeno HLA-B15/imunologia , Humanos , Masculino , Camundongos Transgênicos , Pessoa de Meia-Idade , Complexo Receptor-CD3 de Antígeno de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Índice de Gravidade de Doença , Pele/imunologia , Pele/patologia , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/patologia , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Citotóxicos/transplante
5.
BMJ Case Rep ; 12(8)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434673

RESUMO

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered variants of a disease continuum that results in a life-threatening exfoliative mucocutaneous disease. These are categorised as type IV cell-mediated delayed hypersensitivity reactions, and antibiotics are often implicated as a cause. Penicillins and other beta-lactam antibiotics are known to cause both immediate and delayed hypersensitivity reactions. While immediate IgE-mediated cross-reactivity between penicillins and carbapenems is well studied, less information on the risk of type IV delayed cell-mediated cross-reactivity between the two is available. We present a case of meropenem-induced SJS in a patient with documented history of SJS from amoxicillin. There are few cases of cross-reactivity with carbapenems reported in the literature, but based on the potential for life-threatening reaction, it is likely prudent to avoid the use of any beta-lactams in a patient with a history of SJS, TEN or any other severe cutaneous adverse reactions to another beta-lactam antibiotic.


Assuntos
Antibacterianos/efeitos adversos , Meropeném/efeitos adversos , Penicilinas/efeitos adversos , Síndrome de Stevens-Johnson/diagnóstico , beta-Lactamas/efeitos adversos , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Síndrome de Stevens-Johnson/imunologia , Resultado do Tratamento
6.
J Am Acad Dermatol ; 81(3): 749-757, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31150704

RESUMO

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions that may present with similar findings to other severe dermatologic diseases. OBJECTIVE: The primary objective of this exploratory study was to explore factors associated with SJS/TEN and develop a model that provides the predicted probability of SJS/TEN for patients for whom the diagnosis of SJS/TEN is considered. METHODS: Retrospective review of consultations for patients with suspected SJS, TEN, or overlap at 4 academic dermatology consultation services. RESULTS: Overall, 208 patients were included; 59 (28.4%) had a final diagnosis of SJS/TEN, and 149 (71.6%) were given a different diagnosis. The most common mimickers were drug hypersensitivity syndrome (n = 21, 10.1%), morbilliform drug eruption (n = 18, 8.7%), erythema multiforme (n = 15, 7.2%), and acute generalized exanthematous pustulosis (n = 13, 6.2%). Nikolsky sign, atypical targets, fever, and lymphopenia were included in a model for predicting the probability of SJS/TEN. LIMITATIONS: All cases were obtained from academic centers, which may limit the generalization of findings to community-based settings. This was an exploratory study with a small number of cases, and external validation of the model performance is needed. CONCLUSION: Early dermatologic evaluation of patients with suspected SJS/TEN is key to separating patients with this condition from those who ultimately receive diagnoses of other serious skin diseases.


Assuntos
Modelos Biológicos , Encaminhamento e Consulta , Síndrome de Stevens-Johnson/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos
7.
J Am Acad Dermatol ; 81(3): 686-693, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31195022

RESUMO

BACKGROUND: Sepsis is the main cause of death in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVES: Our aim was to identify admission risk factors predictive of bacteremia and the accompanying clinical or biochemical markers associated with positive blood cultures. METHODS: A retrospective cohort study over a 14-year period (2003-2016) was performed. RESULTS: The study included 176 patients with SJS (n = 59), SJS-TEN overlap (n = 51), and TEN (n = 66). During hospitalization, bacteremia developed in 52 patients (29.5%), who experienced poorer outcomes, including higher intensive care unit admission (P < .0005), longer length of stay (P < .0005), and higher mortality (P < .0005). There were 112 episodes of bacteremia, and isolates included Acinetobacter baumannii (27.7%, n = 31) and Staphylococcus aureus (21.4%, n = 24). On multivariate analysis, clinical factors present at admission that were predictive of bacteremia included hemoglobin ≤10 g/dL (odds ratio [OR] 2.4, confidence interval [CI] 2.2-2.6), existing cardiovascular disease (OR 2.10, CI 2.0-2.3), and body surface area involvement ≥10% (OR 14.3, CI 13.4-15.2). The Bacteremia Risk Score was constructed with good calibration. Hypothermia (P = .03) and procalcitonin ≥1 µg/L (P = .02) concurrent with blood culture sampling were predictive of blood culture positivity. LIMITATIONS: This is a retrospective study performed in a reference center. CONCLUSION: Hemoglobin ≤10 g/dL, cardiovascular disease, and body surface area involvement ≥10% on admission were risk factors for bacteremia. Hypothermia and elevated procalcitonin are useful markers for the timely detection of bacteremia.


Assuntos
Bacteriemia/diagnóstico , Bactérias/isolamento & purificação , Hipotermia/diagnóstico , Índice de Gravidade de Doença , Síndrome de Stevens-Johnson/complicações , Adulto , Idoso , Bacteriemia/sangue , Bacteriemia/etiologia , Hemocultura , Superfície Corporal , Feminino , Hemoglobinas/análise , Humanos , Hipotermia/sangue , Hipotermia/etiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Singapura , Síndrome de Stevens-Johnson/sangue , Síndrome de Stevens-Johnson/diagnóstico
8.
J. Health NPEPS ; 4(1): 319-329, jan.-jun. 2019.
Artigo em Português | LILACS | ID: biblio-999710

RESUMO

Objetivo: identificar as manifestações clínicas da necrólise epidérmica tóxica (NET) e síndrome de Stevens Johnson (SSJ). Método: trata-se de uma revisão narrativa. A busca dos artigos utilizou a ferramenta Publish or Perish, que ranqueia os trabalhos com base no número de citações recebidas. Foram realizadas duas buscas, pois apesar das doenças se relacionarem, possuem diagnósticos diferentes. Na primeira, os descritores utilizados foram: "necrólise epidérmica tóxica" e "manifestações clínicas", e na segunda os descritores foram: "Síndrome de Stevens-Johnson" e "manifestações clínicas". Resultados: após a leitura dos 12 artigos selecionados, entendeu-se que a patogênese da necrólise epidérmica tóxica e Síndrome de Stevens Johnson se dá pela hipersensibilidade tardia a fármacos. As manifestações clínicas se dão pelo aparecimento do eritema cutâneo com formação de máculas, pápulas, vesículas e bolhas associadas ou isoladas, como placas de urticária ou eritema extenso. Na NET é possível notar desprendimento extenso da epiderme maior que 30% da superfície corpórea, conhecido como sinal de Nikolsky, com acometimento de mucosas. Conclusão: A NET e SSJ são farmacodermias graves, com baixas incidências, mas elevada mortalidade. O reconhecimento precoce das doenças e a retirada do fármaco causador são essenciais para conduzir o tratamento, diminuindo por sua vez a taxa de mortalidade.(AU)


Objective: to identify the clinical manifestations of toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS). Method: the articles search was done using the Publish or Perish computational tool, which ranks the articles based on the number of citations. Two separate searches were performed, because although the diseases are related, they have different diagnoses. In the first, the descriptors used were "Toxic Epidermal Necrolysis" and "clinical manifestations", and in the second the descriptors were "Stevens-Johnson Syndrome" and "clinical manifestations". Results: in total, 12 articles constituted the present revision. It was understood that the pathogenesis of TEN and SJS is due to late drugs hypersensitivity. The clinical manifestations are due to the appearance of cutaneous erythema with the formation of macules, papules, vesicles and associated or isolated blisters, such as urticaria plaques or extensive erythema. In the TEN it is possible to notice extensive detachment of the epidermis greater than 30% of the body surface, known as Nikolsky's signal, with mucous involvement. Conclusion: TEN and SJS are serious skin diseases, with low incidences but high mortality. Early recognition of disease and withdrawal of the causative drug are essential for conducting treatment, thus decreasing the mortality rate. Descriptors: Nursing; Dermatology; Signs and Symptoms; Treatment; Health Management.(AU)


Objectivo: identificar las manifestaciones clínicas de la necrólisis epidérmica tóxica (NET) y el síndrome de Stevens Johnson (SSJ). Método: la selección de los artículos consideró el número de citas recibidas por otras publicaciones. Se realizaron dos búsquedas, pues a pesar de las enfermedades se relacionan, poseen diferentes diagnósticos. En la primera, los descriptores utilizados fueron: "Toxic Epidermal Necrolysis" y "clinical manifestations", y en los segundos los descriptores fueron: "Stevens-Johnson Syndrome" y "clinical manifestations". Resultados: en total, 12 artículos constituyeron la presente revisión. Se ha comprobado que la patogénesis de TEN y SJS se debe a las drogas de larga duración. Las manifestaciones clínicas se deben a la apariencia de cutánea erythema con la formación de macules, papules, vesicles y asociados, o blister, tales como urticaria plaquetas o extensión erythema. En el TEN es posible que tenga un detalle detallado de las epidermis mayor que el 30% de la superficie del cuerpo, conocidas la Nikolsky de la señal, con mucous. Conclusión: la NET y SSJ son farmacodermias graves, con bajas incidencias pero elevada mortalidad. El reconocimiento precoz de las enfermedades y la retirada del fármaco causante son esenciales para conducir el tratamiento, disminuyendo a su vez la tasa de mortalidad. Descriptores: Enfermería; Dermatología; Signos y Síntomas; Tratamiento; Gestión en Salud.(AU)


Assuntos
Humanos , Síndrome de Stevens-Johnson/diagnóstico , Gestão em Saúde , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Síndrome de Stevens-Johnson/mortalidade , Erupção por Droga
10.
J Dermatol ; 46(6): 540-543, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31106904

RESUMO

Toxic epidermal necrolysis (TEN) is a rare condition, causing life-threatening adverse cutaneous reactions. TEN occurrence after bone marrow transplantation (BMT) is a well-known phenomenon; however, to date, only a few cases have been reported in the published work. Here, we describe the case of a 53-year-old woman who experienced TEN after undergoing allogenic BMT for malignant lymphoma. Skin erosion spread across a maximum of 70% of the body surface area and severe mucosal lesions developed. Steroid pulse therapy, plasma apheresis and immunoglobulin therapy were administrated, which resulted in the complete resolution of TEN. However, she developed hemophagocytic lymphohistiocytosis and died 38 days after BMT, owing to rupture of the lower digestive tract complicated by multi-organ failure. In our case, engraftment failure occurred, and the peripheral white blood cell count was less than 100/µL during the TEN course, suggesting that the presence of only a few immune cells could cause TEN. Our findings showed that high mortality rates and widespread skin erosion could be regarded as the most important characteristics of TEN occurring after BMT.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Rejeição de Enxerto/imunologia , Síndrome de Stevens-Johnson/imunologia , Evolução Fatal , Feminino , Rejeição de Enxerto/complicações , Rejeição de Enxerto/prevenção & controle , Humanos , Enteropatias/etiologia , Linfo-Histiocitose Hemofagocítica/etiologia , Linfoma/terapia , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Ruptura Espontânea/etiologia , Síndrome de Stevens-Johnson/complicações , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/terapia
11.
Medicine (Baltimore) ; 98(19): e15553, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083216

RESUMO

RATIONALE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are 2 rare but life-threatening diseases characterized by detachment of epidermis, bullous skin lesions, and mucous membrane erosions. Drugs are highly suspected to be the causative agents. We report a case of SJS/TEN induced by oseltamivir, which is a very rare event. PATIENT CONCERNS: A 9-year-old girl with upper respiratory tract infections presented with generalized maculopapular rash the second day after taking oseltamivir. DIAGNOSIS: The diagnosis of SJS/TEN was made based on cytotoxic skin lesions and mucous membrane involvement. INTERVENTIONS: After discontinuing of the drug and combination therapy of corticosteroid and human immunoglobulin initiation, the lesions were improved. Human leukocyte antigen (HLA) gene sequencing was done. OUTCOMES: The girl was followed-up for 1 year. The skin and mucous membranes symptoms were relieved. LESSONS: We report this case to attract attention to the rare but serious side effect of this antiviral drug.


Assuntos
Antivirais/efeitos adversos , Oseltamivir/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Antivirais/uso terapêutico , Criança , Feminino , Antígeno HLA-A2/genética , Humanos , Oseltamivir/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/genética , Síndrome de Stevens-Johnson/terapia
12.
Brain Nerve ; 71(4): 401-406, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-30988229

RESUMO

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug induced hypersensitivity syndrome (DIHS) are severe cutaneous adverse reactions, which can be life-threatening and lead to severe sequelae. Antiepileptic drugs frequently cause severe adverse reactions in the form of. It is important to understand the characteristics of each disease and attempt at early diagnosis.


Assuntos
Anticonvulsivantes/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Síndrome de Stevens-Johnson/diagnóstico , Hipersensibilidade a Drogas/patologia , Humanos , Pele/patologia , Síndrome de Stevens-Johnson/patologia
13.
Cornea ; 38(8): 938-942, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30998617

RESUMO

PURPOSE: To evaluate the microbiological profile and outcome in cases with infective keratitis in Stevens-Johnson syndrome (SJS). METHODS: Eighty-three eyes of 68 patients with SJS presenting with microbial keratitis were recruited and managed with standard antimicrobial therapy. RESULTS: Microbial keratitis developed in 34% of patients with SJS (83 eyes, 68 patients) over a period of 5 years. Four eyes (4.8%) had a history of concurrent topical steroid use at the onset of keratitis. Mean baseline best-corrected visual acuity was 1.8 ± 0.9 logMAR units. The site of corneal ulceration was central in 52 eyes (62.6%), paracentral in 17 eyes (20.5%), and peripheral in 14 eyes (16.8%). The mean ulcer area was 3.9 ± 2.7 mm. Approximately 15 of 24 (62.5%) culture-positive eyes had bacterial infection, most of which (80%) were caused by Gram-positive bacteria. Polymicrobial infection was noted in 7 of 24 eyes (29.1%). Although 57 of 83 (68.6%) eyes healed with medical therapy, 26 of 83 (31.3%) eyes had corneal perforation and were managed with cyanoacrylate glue application (30.7%) or therapeutic keratoplasty (69.3%). Systemic infection as an inciting factor of SJS and an early presentation for keratitis were the major risk factors associated with corneal perforation. Large mean ulcer size, paracentral ulcers, and punctal involvement were associated with a good visual outcome. CONCLUSIONS: Infective keratitis in SJS is common, and unlike routine cases, surgical intervention is often required. However, the antibiotic sensitivity pattern suggests that resistance is not that high.


Assuntos
Úlcera da Córnea/microbiologia , Infecções Oculares Bacterianas/microbiologia , Síndrome de Stevens-Johnson/microbiologia , Adolescente , Adulto , Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Criança , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamento farmacológico , Resultado do Tratamento , Acuidade Visual/fisiologia , Adulto Jovem
14.
Clin Dermatol ; 37(2): 148-158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30981295

RESUMO

We have explored the rash that appears as target lesions, with the central and dominant diseases belonging to the Stevens-Johnson syndrome/toxic epidermal necrolysis group. After presenting the clinical patterns of an individual target lesion and classifying them into different types of lesions, the contribution has been organized with groups characterized by such specific findings according to the type of lesion: flat or raised, typical or atypical, presence or absence of fever, presence or absence of mucosal ulcerations, presence or absence of arthralgias, and/or internal organ involvement. Other specific features, such as histologic appearance, immunofluorescence findings, and laboratory changes, are considered. We provide clinicians with an algorithmic, systematic, and logical approach to diagnose the condition of the patients who present with targetoid lesions, and enable them to differentiate between those with serious systemic and life-threatening diseases from others with ordinary skin ailments.


Assuntos
Eritema Multiforme/complicações , Eritema Multiforme/diagnóstico , Exantema/diagnóstico , Exantema/etiologia , Pele/patologia , Síndrome de Stevens-Johnson/complicações , Síndrome de Stevens-Johnson/diagnóstico , Artralgia , Diagnóstico Diferencial , Eritema Multiforme/patologia , Exantema/patologia , Feminino , Febre , Imunofluorescência , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/patologia , Humanos , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/patologia , Membrana Mucosa , Penfigoide Bolhoso/complicações , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/patologia , Gravidez , Complicações na Gravidez , Choque Séptico/complicações , Choque Séptico/diagnóstico , Choque Séptico/patologia , Síndrome de Stevens-Johnson/patologia , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/patologia , Úlcera , Urticária/complicações , Urticária/diagnóstico , Urticária/patologia
16.
Eur J Clin Pharmacol ; 75(8): 1135-1141, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30918988

RESUMO

PURPOSE: Establishment of causality between drug exposure and adverse drug reactions (ADR) is challenging even for serious ADRs such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Several causality assessment tools (CAT) exist, but the reliability and validity of such tools is variable. The objective of this study was to compare the reliability and validity of existing ADR CATs on SJS/TEN cases. METHODS: Seven investigators completed three CAT (ALDEN, Naranjo, Liverpool) for 10 SJS/TEN cases. Each CAT categorized the causality of 30 potential drugs as definite/very probable, probable, possible, or doubtful/unlikely. An additional reviewer provided expert opinion by designating the implicated drug(s) for each case. A Kappa score was generated to compare CAT responses both by method (reliability of all 7 reviewers, by CATs) and by reviewer (reliability of the 3 CAT, by reviewer). A c statistic was calculated to assess validity. RESULTS: Inter-rater reliability by CAT was poor to fair: ALDEN 0.22, Naranjo 0.11, and Liverpool 0.12. Reliability was highest when causality classification was definite/very probable (0.16-0.41). Similarly, intra-rater reliability by reviewer was poor. When comparing the validity of the overall CAT to expert reviewer, area under the curve was highest for ALDEN (c statistic 0.65) as compared to Liverpool (0.55) or Naranjo (0.54). CONCLUSION: Available CAT have poor reliability and validity for drug-induced SJS/TEN. Due to the importance of determining ADR causality for research, industry, and regulatory purposes, development of an enhanced tool that can incorporate data from immunological testing and pharmacogenetic results may strengthen CAT usefulness and applicability for drug-induced SJS/TEN.


Assuntos
Causalidade , Farmacovigilância , Síndrome de Stevens-Johnson/diagnóstico , Algoritmos , Humanos , Probabilidade , Reprodutibilidade dos Testes , Medição de Risco/métodos , Fatores de Risco , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia
17.
Adv Emerg Nurs J ; 41(1): 56-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30702535

RESUMO

Stevens-Johnson syndrome and toxic epidermal necrolysis represent a spectrum of severe cutaneous adverse reactions that carry the potential for severe, long-term adverse effects, including death. Although medications are most commonly implicated in the development of these diseases, other factors, including infection and genetics, play a role. Management is generally supportive in nature and includes maintenance of the patient's airway, breathing, and circulation. Special disease considerations include the use of skin barrier management, unique infection prevention measures, and systemic immunomodulatory therapies.


Assuntos
Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/terapia , Diagnóstico Diferencial , Humanos , Síndrome de Stevens-Johnson/epidemiologia
18.
Clin Drug Investig ; 39(4): 363-368, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30689189

RESUMO

BACKGROUND AND OBJECTIVE: Adverse cutaneous drug reactions associated with antiepileptic drugs (AEDs) are a serious problem in the clinical setting. New-generation AEDs have been reported to be better tolerated than old-generation forms; however, information about the risks of adverse cutaneous drug reactions to new-generation AEDs is limited. OBJECTIVE: The purpose of this study was to clarify the association of AEDs with adverse cutaneous drug reactions using a spontaneous reporting database. METHODS: We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between April 2004 and January 2017 were analyzed. Based on reports of all adverse events, we obtained 4805 reports of adverse cutaneous drug reactions associated with AEDs, and calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for drug rash, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). RESULTS: Individual AEDs had variable signals for drug rash, SJS, and TEN. The strongest signals were detected for drug rash caused by lamotrigine (ROR 9.18, 95% CI 8.65-9.74), SJS caused by zonisamide (ROR 9.85, 95% CI 8.23-11.78), and TEN caused by phenobarbital (ROR 14.08, 95% CI 11.28-17.57). CONCLUSION: There are clear differences in the risk of cutaneous reactions among AEDs, and further studies are needed to confirm these findings.


Assuntos
Anticonvulsivantes/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Exantema/induzido quimicamente , Exantema/epidemiologia , Farmacovigilância , Bases de Dados Factuais/tendências , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Exantema/diagnóstico , Feminino , Humanos , Japão/epidemiologia , Lamotrigina/efeitos adversos , Masculino , Fenobarbital/efeitos adversos , Estudos Retrospectivos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/epidemiologia , Zonisamida/efeitos adversos
20.
Pediatr Dermatol ; 36(1): e27-e30, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30474865

RESUMO

Drug-induced reactions are complications associated with high mortality and significant morbidity. Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of these conditions, which are characterized by skin and mucous lesions. Here, we report a case of a 9-year-old girl who presented with blisters associated with an extensive vesicular rash and multiple ulcerations on the lips and oral cavity. A drug-induced hypersensitivity reaction to antibiotics was suspected, and a diagnosis of TEN was made. The patient was managed with withdrawal of the suspected causative agent, and the oral lesions were treated with low-level laser therapy (LLLT) and oral hygiene. This case highlights that TEN requires interdisciplinary intervention with dental assistance and follow-up to improve symptoms, nutrition, systemic condition, and quality of life.


Assuntos
Antibacterianos/efeitos adversos , Terapia com Luz de Baixa Intensidade/métodos , Doenças da Boca/radioterapia , Síndrome de Stevens-Johnson/radioterapia , Criança , Feminino , Humanos , Doenças da Boca/etiologia , Pele/patologia , Síndrome de Stevens-Johnson/diagnóstico
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