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1.
Vaccine ; 41(47): 6922-6929, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37891051

RESUMO

The global COVID-19 public health crisis has resulted in extraordinary collaboration to expeditiously develop vaccines and therapeutics. The safety of these biologics is closely monitored by the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). Novel products may have limited safety data, and although serious medical outcomes associated with vaccination are rare, knowledge of background incidence rates of medical conditions in the US population puts reported adverse events (AEs) in perspective for further study. Although relatively minor vaccination skin reactions are common, rare instances of severe delayed hypersensitivity reactions such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome may occur. To aid in the assessment of these events, we performed a literature search in PubMed and Web of Science on the background incidence of EM, SJS, SJS/TEN, and TEN in the US population and on published reports of these conditions occurring post-vaccination. The US background annual incidence rates per million individuals of all ages ranged from 5.3 to 63.0 for SJS, from 0.4 to 5.0 for TEN, and from 0.8 to 1.6 for SJS/TEN. Since these conditions may overlap, some studies reported rates for EM/SJS/TEN combined, however we did not find studies with exclusive EM incidence rates. The published literature, including studies of reports submitted to the FDA/CDC Vaccine Adverse Event Reporting System (VAERS), describes post-vaccination EM, SJS, SJS/TEN and/or TEN as rare occurrences. The vaccines most frequently associated with these conditions were measles, mumps, and rubella; diphtheria, tetanus, and pertussis; and varicella. The majority of VAERS reports of EM, SJS, SJS/TEN, or TEN occurred in children within 30 days of vaccination. This review summarizes background rates of these disorders in the general population and published AEs among vaccine recipients, to support safety surveillance of COVID-19 vaccines and other biologics.


Assuntos
Produtos Biológicos , Vacinas contra COVID-19 , Criança , Humanos , Produtos Biológicos/efeitos adversos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Eritema Multiforme/epidemiologia , Pele , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia
2.
Rev Alerg Mex ; 70(1): 38-42, 2023 May 24.
Artigo em Espanhol | MEDLINE | ID: mdl-37566754

RESUMO

BACKGROUND: Stevens-Johnson syndrome is a severe drug reaction. Sulfonamides have been associated with drug reactions, complications, sequelae, even death. CASE REPORT: A 40-year-old female patient with a medical history of endometriosis and recently diagnosed chronic inflammatory ulcerative colitis. She was treated at the Allergology service of the San Juan de Dios Hospital of the Costa Rican Social Security Fund, and after 20 days of treatment with sulfasalazine she had a severe drug reaction on the skin, compatible with Stevens-Johnson syndrome. The lymphocyte transformation test was positive, confirming sulfasalazine as the causative agent. CONCLUSION: The lymphocyte transformation test is a useful method that can confirm the causative agent and prevent important complications in the future.


ANTECEDENTES: El síndrome de Stevens-Johnson es una reacción medicamentosa severa. Las sulfamidas se han asociado con reacciones medicamentosas, complicaciones, secuelas, incluso la muerte. REPORTE DE CASO: Paciente femenina de 40 años, con antecedentes médicos de endometriosis y colitis ulcerativa crónica inflamatoria de reciente diagnóstico. Fue atendida en el servicio de Alergología del Hospital San Juan de Dios de la Caja Costarricense del Seguro Social, y luego de 20 días de tratamiento con sulfasalazina tuvo una reacción medicamentosa severa en la piel, compatible con síndrome de Stevens-Johnson. La prueba de transformación linfocitaria resultó positiva, con lo que se confirmó la sulfasalazina como el agente causal. CONCLUSIÓN: La prueba de transformación linfocitaria es un método útil que puede confirmar el agente causal y prevenir complicaciones importantes a futuro.


Assuntos
Colite Ulcerativa , Ativação Linfocitária , Síndrome de Stevens-Johnson , Sulfassalazina , Adulto , Feminino , Humanos , Ativação Linfocitária/efeitos dos fármacos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Sulfanilamida/efeitos adversos , Sulfassalazina/efeitos adversos , Sulfonamidas , Colite Ulcerativa/tratamento farmacológico
3.
JAMA Dermatol ; 159(8): 830-836, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37342052

RESUMO

Importance: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe hypersensitivity reaction. Identifying a culprit drug is critical for patient care, yet identification is based on clinical judgment. Data are limited on the accuracy in or approach to identifying a culprit drug. Objective: To evaluate patient allergy list outcomes, current approaches in identifying culprit drugs, and potential methods of improving culprit drug identification. Design, Setting, and Participants: This retrospective cohort study spanned 18 years (January 2000 to July 2018), was conducted at Brigham and Women's Hospital and Massachusetts General Hospital (Boston), and included patients with clinically and histologically confirmed cases of SJS/TEN overlap and TEN. Main Outcomes and Measures: This study descriptively analyzed potential culprits to SJS/TEN, patients' allergy lists, and currently used approaches that led to those lists. It then tested the theoretical contribution of incorporating various parameters to allergy list outcomes. Results: Of 48 patients (29 women [60.4%]; 4 Asian [8.3%], 6 Black [12.5%], 5 Hispanic [10.4%], and 25 White [52.1%] individuals; median age, 40 years [range, 1-82 years]), the mean (SD) number of drugs taken per patient at disease onset was 6.5 (4.7). Physicians labeled 17 patients as allergic to a single culprit drug. Comparatively, 104 drugs were added to allergy lists across all patients. Physicians' approaches relied largely on heuristic identification of high-notoriety drugs and the timing of drug exposure. Use of a vetted database for drug risk improved sensitivity. Algorithm for Drug Causality for Epidermal Necrolysis scoring was discordant in 28 cases, labeling an additional 9 drugs missed by physicians and clearing 43 drugs labeled as allergens by physicians. Human leukocyte antigen testing could have potentially affected 20 cases. Consideration of infection as a culprit was limited. Conclusions and Relevance: The results of this cohort study suggest that currently used approaches to identify culprit drugs in SJS/TEN are associated with overlabeling patients allergic to likely nonculprit drugs and less commonly missed possible culprit drugs. Incorporation of a systematized unbiased approach could potentially improve culprit drug identification, although ultimately a diagnostic test is necessary.


Assuntos
Síndrome de Stevens-Johnson , Adulto , Feminino , Humanos , Antígenos HLA , Estudos Retrospectivos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Masculino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
4.
Dermatol Clin ; 40(3): 265-277, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35750410

RESUMO

Postmarket surveillance is critical for the identification of rare safety risks, which are unlikely to be identified during clinical trials and the drug development program. Rare adverse drug reactions with the potential for serious outcomes, including fatalities, include the severe cutaneous adverse reactions of Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Dermatologists play an important role in the diagnosis of these serious drug reactions and contribute to drug safety by reporting cases of suspected cutaneous adverse drug reactions.


Assuntos
Produtos Biológicos , Dermatologia , Síndrome de Stevens-Johnson , Antibacterianos/efeitos adversos , Produtos Biológicos/efeitos adversos , Humanos , Pele , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia
5.
Curr Drug Saf ; 17(1): 40-46, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34126908

RESUMO

BACKGROUND AND OBJECTIVE: Identification of the offending drug is crucial and challenging in cases of severe cutaneous adverse drug reactions (CADR) like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Poor reproducibility and varying levels of agreement have been observed among different causality assessment tools (CATs) in assessing severe CADRs. This study was conducted to examine the agreement among four different CATs in assessing cases of drug-induced SJS, TEN and SJS/TEN overlap. METHODS: All cases of drug-induced SJS, TEN and SJS/TEN overlap, which were reported between January 2012 and January 2020, were identified from the ADR register at an ADR monitoring centre. Causality assessment was done in these reported cases using the following CATs: The World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale, Naranjo algorithm, Liverpool algorithm and Algorithm of drug causality for epidermal necrolysis (ALDEN). Weighted kappa (κw) test was used to evaluate the agreement among four CATs. RESULTS: A total of 30 cases of drug-induced SJS, TEN and SJS/TEN overlap were included in our analyses. The most common offending groups of drugs were anticonvulsants (46.7%), antimicrobials (40%) and nonsteroidal anti-inflammatory drugs (13.3%). Of the anticonvulsants, phenytoin (13.3%), carbamazepine (10%), and valproate (10%) were the commonly reported offending drugs. Poor agreement was observed among the four different causality assessment scales. CONCLUSION: Discrepancies were observed among four different CATs in assessing drug-induced SJS and TEN. A CAT, which is more specific to drug-induced SJS and TEN, simple, user-friendly with limited subjective interpretation, incorporating new immunological and pharmacogenetic markers, is necessary.


Assuntos
Síndrome de Stevens-Johnson , Anti-Inflamatórios não Esteroides , Anticonvulsivantes/toxicidade , Humanos , Fenitoína , Reprodutibilidade dos Testes , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia
6.
JAMA Dermatol ; 157(10): 1182-1190, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34431984

RESUMO

IMPORTANCE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug reactions associated with a high rate of mortality and morbidity. There is no consensus on the treatment strategy. OBJECTIVE: To explore treatment approaches across Europe and outcomes associated with the SJS/TEN disease course, as well as risk factors and culprit drugs. DESIGN, SETTING, AND PARTICIPANTS: A retrospective pan-European multicenter cohort study including 13 referral centers belonging to the ToxiTEN ERN-skin subgroup was conducted. A total of 212 adults with SJS/TEN were included between January 1, 2015, and December 31, 2019, and data were collected from a follow-up period of 6 weeks. MAIN OUTCOMES AND MEASURES: Risk factors for severe acute-phase complications (acute kidney failure, septicemia, and need for mechanical ventilation) and mortality 6 weeks following admission were evaluated using a multivariable-adjusted logistic regression model. One tool used in evaluation of severity was the Score of Toxic Epidermal Necrolysis (SCORTEN), which ranges from 0 to 7, with 7 the highest level of severity. RESULTS: Of 212 patients (134 of 211 [63.7%] women; mean [SD] age, 51.0 [19.3] years), the mean (SD) body surface area detachment was 27% (32.8%). In 176 (83.0%) patients, a culprit drug was identified. Antibiotics (21.2%), followed by anticonvulsants (18.9%), nonsteroidal anti-inflammatory drugs (11.8%), allopurinol (11.3%), and sulfonamides (10.4%), were the most common suspected agents. Treatment approaches ranged from best supportive care only (38.2%) to systemic glucocorticoids (35.4%), intravenous immunoglobulins (23.6%), cyclosporine (10.4%), and antitumor necrosis factor agents (3.3%). Most patients (63.7%) developed severe acute-phase complications. The 6-week mortality rate was 20.8%. Maximal body surface area detachment (≥30%) was found to be independently associated with severe acute-phase complications (fully adjusted odds ratio [OR], 2.49; 95% CI, 1.21-5.12; P = .01) and SCORTEN greater than or equal to 2 was significantly associated with mortality (fully adjusted OR, 10.30; 95% CI, 3.82-27.78; P < .001). Cyclosporine was associated with a higher frequency of greater than or equal to 20% increase in body surface area detachment in the acute phase (adjusted OR, 3.44; 95% CI, 1.12-10.52; P = .03) and an increased risk of infections (adjusted OR, 7.16; 95% CI, 1.52-33.74; P = .01). Systemic glucocorticoids and intravenous immunoglobulins were associated with a decreased risk of infections (adjusted OR, 0.40; 95% CI, 0.18-0.88; P = .02). No significant difference in 6-week mortality was found between treatment groups. CONCLUSIONS AND RELEVANCE: This cohort study noted differences in treatment strategies for SJS/TEN in Europe; the findings suggest the need for prospective therapeutic studies to be conducted and registries to be developed.


Assuntos
Síndrome de Stevens-Johnson , Adulto , Estudos de Coortes , Ciclosporina/uso terapêutico , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia
8.
J Dermatol Sci ; 98(1): 2-12, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32192826

RESUMO

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.


Assuntos
Necessidades e Demandas de Serviços de Saúde/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Síndrome de Stevens-Johnson/terapia , Congressos como Assunto , Carga Global da Doença , Saúde Global , Humanos , Cooperação Internacional , Farmacogenética/organização & administração , Sistema de Registros/estatística & dados numéricos , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia , Pesquisa Translacional Biomédica/organização & administração
10.
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
11.
Australas Psychiatry ; 26(6): 640-642, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29480028

RESUMO

OBJECTIVES:: To detail some serious lamotrigine side effects and their management, and raise awareness about the possible lack of quality control of some brands of lamotrigine. METHODS:: A literature review is provided and some personal observations added. RESULTS:: While most psychiatrists are aware of the risks of Stevens-Johnson syndrome (SJS), awareness of two other serious side effects - toxic epidermal necrosis (TEN) and drug-related eosinophilia and systemic symptoms (DRESS) - is seemingly lower. Awareness that failure to respond to lamotrigine and that the prevalence of serious side effects may reflect poor quality control of some preparations is also less well recognized. CONCLUSIONS:: While lamotrigine may be retrialled at a lower dose escalation rate following some skin reactions, it should not be recommenced following a SJS, TEN or DRESS reaction. Prescribers should be aware of quality control concerns about some available brands of lamotrigine.


Assuntos
Antipsicóticos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Prescrições de Medicamentos/normas , Eosinofilia/induzido quimicamente , Lamotrigina/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Controle de Medicamentos e Entorpecentes , Humanos , Controle de Qualidade
13.
J Clin Lab Anal ; 32(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28440597

RESUMO

BACKGROUND: Due to the significant risk of developing Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the use of carbamazepine is not recommended in patients carrying the human leukocyte antigen B (HLA-B) *15:02 allele. In an effort to guarantee reliable community-based HLA-B*15:02 testing throughout China, a HLA-B*15:02 genotyping external quality assessment (EQA) program was set up. METHODS: In 2016, 10 genomic DNA samples with known HLA-B*15:02 allele status were sent to 37 laboratories from 16 provinces with a request for routine HLA-B*15:02 screening. The samples were validated using Sanger sequencing by a reference laboratory. Both genotyping results and clinical written reports were evaluated. RESULTS: Thirty-six of the participating laboratories correctly identified the HLA-B*15:02 allele status for all EQA samples. However, one lab failed to identify any positive challenges. The overall analytical sensitivity was 97.3% (180/185 challenges; 95% confidence interval: 93.8%-99.1%) and the analytic specificity was 100% (185/185; 95% confidence interval: 98.0%-100%). A review of the written reports showed that the clinical reporting for HLA-B*15:02 detection should be improved. Some essential information was missing, most notably laboratory information/contact, therapeutic recommendations, and methodology. CONCLUSION: External quality assessment is valuable in assessing and improving the quality of laboratory testing of HLA-B*15:02 allele.


Assuntos
Carbamazepina/efeitos adversos , Antígeno HLA-B15/genética , Síndrome de Stevens-Johnson , Carbamazepina/uso terapêutico , Contraindicações de Medicamentos , Epilepsia/tratamento farmacológico , Predisposição Genética para Doença/genética , Humanos , Fatores de Risco , Sensibilidade e Especificidade , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/genética
14.
HLA ; 90(6): 335-342, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28884973

RESUMO

HLA-A*31:01 and HLA-B*15:02 have been widely reported to confer genetic susceptibility to carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCARs). Accordingly, the screening for these alleles has been highly recommended to prevent SCAR prior to introducing CBZ therapy. Although a number of methods are available for screening of HLA-A*31:01 or HLA-B*15:02 alleles separately, developing an assay that can detect both these alleles would be more clinically practical, cost-effective and less time-consuming. Therefore, in this study, a multiplex polymerase chain reaction (PCR) using TaqMan Probe was designed and validated to be able to detect HLA-A*31:01 and HLA-B*15:02. In comparison with Luminex-SSO/SBT/SSB, the multiplex PCR assay for detection of HLA-A*31:01 and HLA-B*15:02 had a perfect agreement in the validation group of 125 samples. The method was able to detect the target genes at the DNA concentration of 0.037 ng/µL. The unit cost of this assay is less than $5 USD with total time of 110 minutes.


Assuntos
Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/genética , Antígenos HLA-A/genética , Antígeno HLA-B15/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Síndrome de Stevens-Johnson/genética , Alelos , Sequência de Bases , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/imunologia , Expressão Gênica , Predisposição Genética para Doença , Antígenos HLA-A/imunologia , Antígeno HLA-B15/imunologia , Humanos , Limite de Detecção , Reação em Cadeia da Polimerase Multiplex/economia , Reprodutibilidade dos Testes , Alinhamento de Sequência , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/imunologia
16.
Clin Exp Allergy ; 43(9): 1027-37, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23957338

RESUMO

BACKGROUND: Patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are often exposed simultaneously to a few potentially culprit drugs. However, both the standard lymphocyte transformation tests (LTT) with proliferation as the assay end-point as well as skin tests, if done, are often negative. OBJECTIVE: As provocation tests are considered too dangerous, there is an urgent need to identify the relevant drug in SJS/TEN and to improve sensitivity of tests able to identify the causative drug. METHODS: Fifteen patients with SJS/TEN with the ALDEN score ≥ 6 and 18 drug-exposed controls were included. Peripheral blood mononuclear cells (PBMC) were isolated and cultured under defined conditions with drugs. LTT was compared to the following end-points: cytokine levels in cell culture supernatant, number of granzyme B secreting cells by ELISpot and intracellular staining for granulysin and IFNγ in CD3(+) CD4(+), CD3(+) CD8(+) and NKp46(+) cells. To further enhance sensitivity, the effect of IL-7/IL-15 pre-incubation of PBMC was evaluated. RESULTS: Lymphocyte transformation tests was positive in only 4/15 patients (sensitivity 27%, CI: 8-55%). Similarly, with granzyme B-ELISpot culprit drugs were positive in 5/15 patients (sensitivity 33%, CI: 12-62%). The expression of granulysin was significantly induced in NKp46(+) and CD3(+) CD4(+) cells (sensitivity 40%, CI: 16-68% and 53%, CI: 27-79% respectively). Cytokine production could be demonstrated in 38%, CI: 14-68% and 43%, CI: 18-71% of patients for IL-2 and IL-5, respectively, and in 55%, CI: 23-83% for IFNγ. Pre-incubation with IL-7/IL-15 enhanced drug-specific response only in a few patients. Specificities of tested assays were in the range of 95 (CI: 80-99%)-100% (CI: 90-100%). CONCLUSIONS AND CLINICAL RELEVANCE: Granulysin expression in CD3(+) CD4(+) , Granzyme B-ELISpot and IFNγ production considered together provided a sensitivity of 80% (CI: 52-96%) and specificity of 95% (80-99%). Thus, this study demonstrated that combining different assays may be a feasible approach to identify the causative drug of SJS/TEN reactions; however, confirmation on another group of patients is necessary.


Assuntos
Ativação Linfocitária/imunologia , Linfócitos/imunologia , Síndrome de Stevens-Johnson/etiologia , Adulto , Idoso , Antígenos de Diferenciação de Linfócitos T/biossíntese , Citocinas/metabolismo , Citocinas/farmacologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Feminino , Granzimas/metabolismo , Humanos , Interleucina-15/farmacologia , Interleucina-7/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Curva ROC , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/imunologia , Adulto Jovem
18.
Prescrire Int ; 21(130): 220-3, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23016261

RESUMO

Amalyste is a French patient-advocacy group for victims of two very serious adverse drug reactions: Lyell and Stevens-Johnson syndromes. The aims of this organisation are to represent the interests of patients who have experienced these syndromes; to better inform the public about these syndromes; to provide analyses of drug-related risks; and to demand collective compensation for victims of serious adverse drug reactions. The following text is our translation of an Amalyste position statement on drug-related risks. It provides valuable food for thought, both for healthcare professionals and for drug regulatory agencies, and has the potential to improve practice (a).


Assuntos
Compensação e Reparação , Organizações sem Fins Lucrativos , Defesa do Paciente , Segurança do Paciente , Síndrome de Stevens-Johnson/terapia , Compensação e Reparação/legislação & jurisprudência , Aprovação de Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , França , Regulamentação Governamental , Política de Saúde , Humanos , Organizações sem Fins Lucrativos/economia , Organizações sem Fins Lucrativos/legislação & jurisprudência , Defesa do Paciente/economia , Defesa do Paciente/legislação & jurisprudência , Segurança do Paciente/economia , Segurança do Paciente/legislação & jurisprudência , Medição de Risco , Fatores de Risco , Síndrome de Stevens-Johnson/induzido quimicamente , Síndrome de Stevens-Johnson/etiologia
19.
Pharmacogenomics ; 12(12): 1741-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22118056

RESUMO

Use of pharmacogenetics to inform treatment decisions remains a priority for clinicians, patients and public health agencies. We previously developed a framework for systematically assessing whether pharmacogenetic test information would likely bring value to clinical decision-making and enjoy practical uptake. We applied this tool to allopurinol to determine potential usefulness of HLA genetic information in assessing risk for allopurinol-induced severe cutaneous adverse reactions. We quantified allopurinol use data and the magnitude of adverse event signals using US FDA databases, reviewed reported cases of allopurinol-associated severe cutaneous adverse reactions to assess whether clinical subtypes of patients could be identified, performed pooled analyses of associations between HLA variation and allopurinol-induced severe cutaneous adverse reactions and described considerations in clinical implementation of allopurinol pharmacogenetics.


Assuntos
Alopurinol/efeitos adversos , Testes Genéticos/métodos , Variação Genética , Supressores da Gota/efeitos adversos , Antígenos HLA/genética , Dermatopatias/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopurinol/uso terapêutico , Criança , Eritema Multiforme/induzido quimicamente , Eritema Multiforme/genética , Feminino , Estudos de Associação Genética , Gota/tratamento farmacológico , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Farmacogenética , Medição de Risco , Dermatopatias/induzido quimicamente , Síndrome de Stevens-Johnson/induzido quimicamente , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/genética
20.
Dermatol Ther ; 22(5): 441-51, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19845721

RESUMO

Clinical risk management concedes that risk is inherent to all health-care processes. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially life-threatening reactions to medications. Risk management should be considered prior to starting, during, and after therapy. Prior to starting therapy, risks that need to be assessed include any specific patient groups that may be at greater risk for the development of SJS/TEN. Gene testing is in place for Chinese and Thai patients who are going to be exposed to carbamazepine. During therapy, it is important to recognize SJS/TEN as a possible adverse drug reaction. Diagnostic criteria have changed, and more data exist on drugs with an increased risk. Although there is no standardized treatment for all patients with SJS/TEN, options that have been used include cyclosporine, corticosteroids, and intravenous immunoglobulin. Standards of care are usually defined locally, but new treatments, such as amniotic membrane support for ocular damage, may need to be considered. Good communication skills are needed to allow practitioners to show empathy and to provide disclosure. Risk management after a reaction includes skills in acknowledging bad outcomes or error; freedom to say "sorry" as defined by "apology laws," and knowing the rights provided by "Quality Assurance Conferences," where the information discussed is protected. In other words, the patient is best supported after an event like SJS/TEN if the practitioner is knowledgeable about optimal care standards and their legal rights and obligations.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Síndrome de Stevens-Johnson/prevenção & controle , Comunicação , Humanos , Qualidade da Assistência à Saúde , Medição de Risco/métodos , Fatores de Risco , Gestão de Riscos/métodos , Síndrome de Stevens-Johnson/induzido quimicamente , Síndrome de Stevens-Johnson/etiologia
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