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1.
Gan To Kagaku Ryoho ; 48(1): 154-156, 2021 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-33468752

RESUMO

Case 1: A 51-year-old man with advanced gastric cancer and peritoneal metastasis was referred to our hospital. He received fourth-line chemotherapy with nivolumab, but it became PD. Next, he received S-1 plus docetaxel therapy as fifth- line therapy. After 2 courses of S-1 plus docetaxel, erythema and blisters appeared on his limbs, with erosions of the oral mucosa and penis. We diagnosed Stevens-Johnson syndrome(SJS)based on the clinical and pathological findings. He received steroid treatment, but the cutaneous symptoms persisted; therefore, it was impossible to continue the chemotherapy because of the SJS. Case 2: A 75-year-old woman with recurrence of peritoneally disseminated gastric cancer received third-line chemotherapy with nivolumab. After 1 course of nivolumab, erythema appeared on her body and limbs, with erosion of the lips and oral mucosa. We diagnosed SJS based on the clinical findings. She received steroid treatment, but the cutaneous symptoms persisted; therefore, it was impossible to continue chemotherapy because of the SJS. It should be noted that the onset of serious irAEs, such as SJS, might make continuous chemotherapy difficult.


Assuntos
Síndrome de Stevens-Johnson , Neoplasias Gástricas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Nivolumabe/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Neoplasias Gástricas/tratamento farmacológico
2.
J Med Case Rep ; 14(1): 210, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33138853

RESUMO

BACKGROUND: Since the World Health Organization declared a global pandemic due to the novel coronavirus disease2019, there have been targeted efforts to establish management modalities. Hydroxychloroquine has been suggested as a possible treatment; however, it is associated with multiple adverse reactions. We report a rare case of a patient with acute generalized exanthematous pustulosis with Stevens-Johnson syndrome due to hydroxychloroquine. Acute generalized exanthematous pustulosis is characterized by acute onset of a generalized rash that is pustular and erosive in nature, affecting limbs; trunk; face; and, less often, mucosal membranes. Although rare, it is important to be mindful of this side effect because the diagnosis is often delayed, and the disease has the potential to be life-threatening. CASE PRESENTATION: A 68-year-old American woman presented to our hospital with a painful, rapidly spreading rash. Its morphologic features included erythema multiforme-like lesions with extensive skin sloughing in various regions of the head, neck, and trunk and mucosal involvement. Her Nikolsky sign was negative, and she had no evidence of lesions on areas of skin trauma. Four weeks prior, she had been initiated on hydroxychloroquine for a presumed diagnosis of cutaneous sarcoidosis. Three punch biopsies of the head and neck area revealed subcorneal pustules consistent with acute generalized exanthematous pustulosis. Treatment began with high doses of methylprednisolone, leading to only minimal improvement of existing areas and ongoing spread to new areas. Treatment with intravenous immunoglobulin was initiated, at which point disease stability was achieved. The patient's rash ultimately resolved, as did her cutaneous pain and pruritus. CONCLUSIONS: Among many potential adverse reactions involving hydroxychloroquine, cutaneous side effects are varied and can lead to significant morbidity or even death. The drug is currently being investigated in a multitude of trials for coronavirus disease2019 treatment, prevention, and prophylaxis after exposure to severe acute respiratory syndrome coronavirus 2. Acute generalized exanthematous pustulosis is a rare side effect of hydroxychloroquine, and even fewer cases demonstrate histologic evidence of acute generalized exanthematous pustulosis while clinically presenting with Stevens-Johnson syndrome. Patients who develop Stevens-Johnson syndrome/toxic epidermal necrolysis require best supportive care with aggressive fluid and electrolyte replacement and prevention of further breakdown of the skin barrier. With the potential of widespread hydroxychloroquine use, it is important that providers be aware of its potential severe adverse drug reactions.


Assuntos
Pustulose Exantematosa Aguda Generalizada , Infecções por Coronavirus/epidemiologia , Hidroxicloroquina , Imunoglobulinas Intravenosas/administração & dosagem , Metilprednisolona/administração & dosagem , Pneumonia Viral/epidemiologia , Sarcoidose/tratamento farmacológico , Síndrome de Stevens-Johnson , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/fisiopatologia , Pustulose Exantematosa Aguda Generalizada/terapia , Idoso , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Biópsia/métodos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Fatores Imunológicos , Pandemias , Pele/patologia , Dermatopatias/tratamento farmacológico , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/fisiopatologia , Síndrome de Stevens-Johnson/terapia , Resultado do Tratamento
3.
Asian Cardiovasc Thorac Ann ; 28(9): 601-603, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32787441

RESUMO

Stevens-Johnson syndrome and toxic epidermal necrolysis are rare diseases that cause acute destruction of the epithelium of the skin and mucous membranes, almost always attributable to drugs. However, warfarin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis is extremely rare. We report the case of 71-year-old woman who died due to destructive erosion all over her skin and mucous membranes. She had received a mitral valve prosthesis, and warfarin was prescribed for antithrombotic therapy. A lymphocyte transformation test for drug hypersensitivity and the clinical history confirmed this phenomenon as warfarin-induced toxic epidermal necrolysis.


Assuntos
Anticoagulantes/efeitos adversos , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Síndrome de Stevens-Johnson/etiologia , Varfarina/efeitos adversos , Idoso , Evolução Fatal , Feminino , Humanos , Síndrome de Stevens-Johnson/diagnóstico
5.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32595945

RESUMO

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases characterized by detachment of the epidermis and mucous membrane. SJS/TEN are considered to be on the same spectrum of diseases with different severities. They are classified by the percentage of skin detachment area. SJS/TEN can also cause several complications in the liver, kidneys, and respiratory tract. The pathogenesis of SJS/TEN is still unclear. Although it is difficult to diagnose early stage SJS/TEN, biomarkers for diagnosis or severity prediction have not been well established. Furthermore, optimal therapeutic options for SJS/TEN are still controversial. Several drugs, such as carbamazepine and allopurinol, are reported to have a strong relationship with a specific human leukocyte antigen (HLA) type. This relationship differs between different ethnicities. Recently, the usefulness of HLA screening before administering specific drugs to decrease the incidence of SJS/TEN has been investigated. Skin detachment in SJS/TEN skin lesions is caused by extensive epidermal cell death, which has been considered to be apoptosis via the Fas-FasL pathway or perforin/granzyme pathway. We reported that necroptosis, i.e. programmed necrosis, also contributes to epidermal cell death. Annexin A1, released from monocytes, and its interaction with the formyl peptide receptor 1 induce necroptosis. Several diagnostic or prognostic biomarkers for SJS/TEN have been reported, such as CCL-27, IL-15, galectin-7, and RIP3. Supportive care is recommended for the treatment of SJS/TEN. However, optimal therapeutic options such as systemic corticosteroids, intravenous immunoglobulin, cyclosporine, and TNF-α antagonists are still controversial. Recently, the beneficial effects of cyclosporine and TNF-α antagonists have been explored. In this review, we discuss recent advances in the pathophysiology and management of SJS/TEN.


Assuntos
Síndrome de Stevens-Johnson , Apoptose , Epiderme , Humanos , Necrose , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia
7.
Sci Rep ; 10(1): 4353, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152391

RESUMO

Stevens - Johnson syndrome (SJS) has manifestation through the exfoliation of epidermis and mucosal tissue. Ocular surface is usually affected in acute and chronic stage. The patients are usually suffered from chronic ocular sequelae including symblepharon, limbal stem cell deficiency, etc. Furthermore, ocular microbiome may also be altered in SJS. This is prospective, age and sex matched analytical study which including 20 chronic SJS patients and 20 healthy subjects for specimen collection from inferior conjunctiva for microbiome analysis by conventional cultures and Next-Generation Sequencing (NGS) methods. Significant higher proportion of positive-cultured specimen was demonstrated in SJS group (SJS group 60%, healthy 10%, p-value = 0.001). In addition, NGS which providing high-throughput sequencing has demonstrated the greater diversity of microbial species. The higher proportion of pathogenic microorganisms including Pseudomonas spp., Staphylococcus spp., Streptococcus spp., Acinetobacter spp. was shown in SJS group. Ocular surface in SJS is usually occupied by more diverse microorganisms with increased proportion of pathogenic species. This condition may affect chronic inflammation and opportunistic infections in SJS group. In order to prevent and treat infection in these patients, appropriate antibiotics based on bacterial examination should be considered as the first-line treatment in the SJS patients.


Assuntos
Oftalmopatias/complicações , Microbiota , Síndrome de Stevens-Johnson/complicações , Adulto , Idoso , Anti-Infecciosos/farmacologia , Biodiversidade , Estudos de Casos e Controles , Túnica Conjuntiva/microbiologia , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Adulto Jovem
8.
Dermatol Online J ; 26(1)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32155033

RESUMO

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening, cutaneous reactions often associated with culprit drugs. A growing body of knowledge has deepened our understanding of the pathophysiology and clarified mechanisms such as drug-specific cytotoxicity mediated by T-cells, genetic linkage with HLA and non-HLA genes, TCR restriction, and cytotoxicity mechanisms. Physicians should broadly consider the etiology of SJS/TEN in order to better understand treatment strategies as well as identify which patients may be at risk for developing this condition. Mechanisms for how radiotherapy and rare malignancies may contribute to the development of TEN and SJS have been proposed.


Assuntos
Lipossarcoma/radioterapia , Radioterapia/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação , Pele/patologia , Síndrome de Stevens-Johnson/patologia
9.
Clin Dermatol ; 38(1): 94-104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32197753

RESUMO

Immune checkpoint inhibitors (ICPi) have emerged as a new frontier of cancer therapy. Although monoclonal antibodies to cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have revolutionized oncologic management, these agents may result in a spectrum of immune-related adverse events (irAE) of which dermatologic toxicities are among the most frequent. Prompt recognition and management of irAE is essential for dermatologists caring for the expanding population of cancer patients exposed to these drugs. Cutaneous toxicities range from mild cases to severe and life-threatening presentations that may cause significant morbidity and mortality. This review provides an overview of severe cutaneous adverse reactions (SCARs) that may develop during ICPi therapy, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). In addition, immunobullous disorders, erythroderma, neutrophilic dermatoses, and cutaneous eruptions associated with systemic manifestations are discussed.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Erupção por Droga/etiologia , Erupção por Droga/patologia , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/patologia , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Humanos , Receptor de Morte Celular Programada 1 , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/patologia
10.
Acta Derm Venereol ; 100(5): adv00057, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32039459

RESUMO

Bullous drug eruptions are infrequent, but because they pose a challenge both to affected patients and to treating physicians they are considered to be the most severe cutaneous adverse reactions (SCAR). It is important to recognize these conditions and to differentiate them from other clinical entities involving blister formation. There may be early signs and symptoms that indicate a severe bullous drug eruption even before blisters and erosions of the skin and mucous membranes become obvious. Once the diagnosis is suspected, appropriate diagnostic procedures and adequate management must be initiated. The latter includes identification of the potentially inducing drug, although it should be taken into account that not all cases of bullous eruptions are drug-induced. In cases with drug causality the potentially culprit agent must be withdrawn, while in cases with other aetiology the underlying condition, e.g. an infection, must be treated appropriately. In addition to best supportive care, immunomodulating therapy may be considered.


Assuntos
Erupção por Droga/etiologia , Imunomodulação , Dermatopatias Vesiculobolhosas/induzido quimicamente , Biópsia por Agulha , Erupção por Droga/epidemiologia , Erupção por Droga/imunologia , Feminino , Alemanha , Humanos , Imuno-Histoquímica , Incidência , Masculino , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Dermatopatias Vesiculobolhosas/epidemiologia , Dermatopatias Vesiculobolhosas/patologia , Dermatopatias Vesiculobolhosas/terapia , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/patologia , Síndrome de Stevens-Johnson/terapia , Resultado do Tratamento
11.
Dermatol Ther ; 33(1): e13174, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31750971

RESUMO

Combination therapy in the treatment of metastatic melanoma has been associated with more durable response rate compared to monotherapy. However, previous studies have shown that combined target therapy commonly causes a wide spectrum of adverse events. These adverse reactions are usually manageable, however, it is always necessary to compare drug efficacy with its potential adverse effects. Toxic epidermal necrolysis represents severe mucocutaneous reaction, usually triggered by medications and characterized by extensive necrosis and detachment of the epidermis. Here we present a first case of toxic epidermal necrolysis induced by combined target therapy (vemurafenib plus cobimetinib). The case was observed in a young patient with BRAF mutant melanoma who was started on first-line metastatic immunotherapy with pembrolisumab.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Melanoma/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Azetidinas/administração & dosagem , Humanos , Masculino , Melanoma/genética , Piperidinas/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/genética , Vemurafenib/administração & dosagem
12.
J Dermatolog Treat ; 31(1): 61-65, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30095319

RESUMO

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare drug-related life-threatening acute conditions. Infection is a major cause of morbidity and mortality in these patients. The aim of this study was to analyze the infective characteristics and antimicrobial strategies in patients with SJS and TEN.Methods: A total of 125 patients who were diagnosed with SJS/TEN in West China Hospital from 2010 to 2017 were retrospectively analyzed.Results: There were 75 patients with coinfections (75/125, 60%), of whom 44 had SJS (44/90, 48.9%) and 31 had TEN (31/35, 88.6%). The most common infections were skin infections and pulmonary infections. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were the most frequently identified pathogenic organisms. The most common antibiotics used in patients with infections were vancomycin, carbapenems, quinolones, macrolides, and lincomycin.Conclusions: Antimicrobial therapy should be administered promptly if there are clinical signs of an infection. Empiric antibiotic selection is based on knowledge of the local microbiota, the different infected sites, the pathogens involved, and the severity of disease.


Assuntos
Antibacterianos/efeitos adversos , Síndrome de Stevens-Johnson/diagnóstico , Adulto , Idoso , Antibacterianos/uso terapêutico , China , Escherichia coli/isolamento & purificação , Feminino , Humanos , Pneumopatias/diagnóstico , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia , Staphylococcus aureus/isolamento & purificação , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/microbiologia
13.
Int J Dermatol ; 59(2): 191-196, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31173347

RESUMO

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions characterized by epidermal necrosis, mostly caused by drugs. Despite the rarity of these conditions, morbidity and mortality are high (even in previously healthy patients), and they may be associated with permanent sequelae. METHODS: A retrospective study conducted at a quaternary hospital in Brazil in a period of 10 years. RESULTS: The sample was composed by 41 patients with SJS, SJS/TEN, and TEN confirmed by skin biopsy. Antibiotics and anticonvulsants were the most frequently implied drug classes, and phenytoin was the most important individual culprit drug. In this study, 12.2% of the patients had sequelae, being ophthalmological lesions the most common and one case of a newly described hearing loss. The mortality rate was 16.7% in patients with TEN. CONCLUSIONS: This study describes the largest Latin American case series of SJS and TEN with the diagnosis proven by skin biopsy and adds important data regarding the profile of the disease in Brazil. It also describes a novel sequelae of hearing loss.


Assuntos
Antibacterianos/efeitos adversos , Anticonvulsivantes/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Feminino , Perda Auditiva/etiologia , Hospitais , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Stevens-Johnson/complicações , Síndrome de Stevens-Johnson/mortalidade , Síndrome de Stevens-Johnson/terapia , Triquíase/etiologia , Estreitamento Uretral/etiologia , Adulto Jovem
14.
Yakugaku Zasshi ; 139(12): 1557-1562, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31787645

RESUMO

Severe cutaneous adverse reactions (SCARs) are important in postmarketing drug safety because SCAR patients were highest in the adverse drug reaction relief system of Japan. The SCAR symptoms of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) include high fever, severe mucosal impairment, and epidermal necrosis-induced erosions and blisters. Approximately 600 cases of SJS and 300 cases of TEN are reported annually in Japan. Many suspected drugs such as acetaminophen, lamotrigine, allopurinol, and carbamazepine have been reported. Over the last 15 years, an association between human leukocyte antigen and SJS/TEN onset has been reported with several drugs. Pathophysiological examinations in those reports revealed marked CD8-positive T cell infiltration into epidermal lesions, and the presence of cytotoxic granulysin, soluble Fas ligand, and tumor necrosis factor (TNF)-α in blister fluid. Therefore, SJS and TEN are immunological disorders that lead to epidermal necrosis and are consequently treated with the systemic administration of corticosteroids and with high-dose intravenous immunoglobulin therapy and plasma exchange in severe cases. Additionally, because the epidermal necrosis has characteristics similar to those of organ rejection after transplantation, the administration of cyclosporine, an immunosuppressant that inhibits helper T cell activation, has been attempted. Further, the administration of the TNF-α inhibitor etanercept has also been reported. This review summarizes current knowledge on the mechanisms of onset of SJS/TEN and their treatments.


Assuntos
Acetaminofen/efeitos adversos , Alopurinol/efeitos adversos , Carbamazepina/efeitos adversos , Lamotrigina/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Corticosteroides/uso terapêutico , Antígenos de Diferenciação de Linfócitos T , Linfócitos T CD8-Positivos/imunologia , Ciclosporina/uso terapêutico , Epiderme/imunologia , Etanercepte/uso terapêutico , Proteína Ligante Fas , Antígenos HLA , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Japão/epidemiologia , Troca Plasmática , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/terapia , Fator de Necrose Tumoral alfa
15.
Seizure ; 72: 61-70, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31708349

RESUMO

Adverse cutaneous reactions caused by mostly aromatic antiepileptic drugs (AED) affect 50.000 people a year in the United Kingdom (UK; incidence 75.7/100.000). Optimal management of these cases is often difficult, as the patient may report symptoms to a general practitioner, attend Accident & Emergency or inform a specialist over the telephone or via email. When clinical assessment is limited it is thought safest to withdraw offending medication and inform the patient of a new drug allergy. This may unjustifiably restrict future treatment choices, and increase cost. Most frequent offenders are aromatic AEDs: carbamazepine, oxcarbazepine, eslicarbazepine, phenytoin, lamotrigine, phenobarbitone, primidone (recently licensed lacosamide associated with lower risk) and the sulpha-derivative zonisamide. Our study provides a summary of severe delayed allergic reactions and offers a pragmatic management pathway for patients suffering a suspected drug-induced rash. We include UK pretreatment screening guidelines, step by step clinical assessment of rash and associated symptoms aiding early identification of patients at risk of developing severe allergic reactions. At the same time our manuscript reviews published data informing best choice and titration of alternative medication when allergy confirmed. Finally we summarize current knowledge on genetic predisposition and other personalized risks of AED allergies identifying gaps in our current understanding.


Assuntos
Assistência Ambulatorial/métodos , Anticonvulsivantes/efeitos adversos , Gerenciamento Clínico , Epilepsia/tratamento farmacológico , Síndrome de Stevens-Johnson/terapia , Adulto , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Epilepsia/diagnóstico , Humanos , Fatores de Risco , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia
16.
Sci Rep ; 9(1): 16240, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700100

RESUMO

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening acute inflammatory vesiculobullous reactions of the skin and mucous membranes. These severe cutaneous drug reactions are known to be caused by inciting drugs and infectious agents. Previously, we have reported the association of HLA-A*02:06 and HLA-B*44:03 with cold medicine (CM)-related SJS/TEN with severe ocular complications (SOCs) in the Japanese population. However, the conventional HLA typing method (PCR-SSOP) sometimes has ambiguity in the final HLA allele determination. In this study, we performed HLA-disease association studies in CM-SJS/TEN with SOCs at 3- or 4-field level. 120 CM-SJS/TEN patients with SOCs and 817 Japanese healthy controls are HLA genotyped using the high-resolution next-generation sequencing (NGS)-based HLA typing of HLA class I genes, including HLA-A, HLA-B, and HLA-C. Among the alleles of HLA class I genes, HLA-A*02:06:01 was strongly associated with susceptibility to CM-SJS/TEN (p = 1.15 × 10-18, odds ratio = 5.46). Four other alleles (HLA-A*24:02:01, HLA-B*52:01:01, HLA-B*46:01:01, and HLA-C*12:02:02) also demonstrated significant associations. HLA haplotype analyses indicated that HLA-A*02:06:01 is primarily associated with susceptibility to CM-SJS/TEN with SOCs. Notably, there were no specific disease-causing rare variants among the high-risk HLA alleles. This study highlights the importance of higher resolution HLA typing in the study of disease susceptibility, which may help to elucidate the pathogenesis of CM-SJS/TEN with SOCs.


Assuntos
Alelos , Olho/patologia , Predisposição Genética para Doença/genética , Antígeno HLA-A2/genética , Teste de Histocompatibilidade , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/genética , Adulto , Resfriado Comum/tratamento farmacológico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
17.
BMJ Case Rep ; 12(11)2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31678920

RESUMO

We present the case of a 33-year-old woman with no significant past medical history who was admitted to an outside hospital for the abrupt onset of fevers, malaise and a diffuse mucocutaneous rash. Her constellation of symptoms and presentation were most consistent with a diagnosis of Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome secondary to ibuprofen exposure. Her rash continued to worsen and she was transferred to our medical intensive care unit (ICU), where broad-spectrum antibiotics were discontinued and she was treated with supportive care as well as 'low-dose' intravenous hydrocortisone, ascorbic acid (vitamin C) and thiamine (HAT therapy). After starting this therapy, the patient demonstrated a dramatic response with rapid improvement of her cutaneous and mucosal lesions. She was tolerating a diet provided by the hospital on day 4 and was discharged from the ICU a few days later.


Assuntos
Corticosteroides/administração & dosagem , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Síndrome de Stevens-Johnson/tratamento farmacológico , Tiamina/administração & dosagem , Complexo Vitamínico B/administração & dosagem , Administração Intravenosa , Adulto , Quimioterapia Combinada , Feminino , Humanos , Ibuprofeno/efeitos adversos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia
18.
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
19.
Pediatr Dermatol ; 36(6): 929-931, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31576583

RESUMO

We present two pediatric cases of recurrent mucositis associated with influenza B infection, both in patients with prior episodes of Stevens-Johnson syndrome (SJS) due to Mycoplasma. Influenza B is an uncommon cause of both rash and mucosistis and SJS.


Assuntos
Exantema/virologia , Influenza Humana/diagnóstico , Mucosite/virologia , Pneumonia por Mycoplasma/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Adolescente , Conjuntivite Viral/virologia , Feminino , Humanos , Imunoglobulina M/sangue , Vírus da Influenza B/isolamento & purificação , Masculino , Mycoplasma pneumoniae/imunologia
20.
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 , Alquinos , Benzoxazinas/uso terapêutico , Ciclopropanos , Feminino , Humanos , Síndrome de Stevens-Johnson/diagnóstico
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