Allergy to penicillin and betalactam antibiotics / Alergia a penicilina e antibióticos beta-lactâmicos

ABSTRACT Betalactams are the most frequent cause of hypersensitivity reactions to drugs mediated by a specific immune mechanism. Immediate reactions occur within 1 to 6 hours after betalactam administration, and are generally IgE-mediated. They clinically translate into urticaria, angioedema and anaphylaxis. Non-immediate or delayed reactions occur after 1 hour of administration. These are the most common reactions and are usually mediated by T cells. The most frequent type is the maculopapular or morbilliform exanthematous eruption. Most individuals who report allergies to penicillin and betalactams can tolerate this group of antibiotics. To make diagnosis, a detailed medical history is essential to verify whether it was an immediate or non-immediate reaction. Thereafter, in vivo and/or in vitro tests for investigation may be performed. The challenging test is considered the gold standard method for diagnosis of betalactam hypersensitivity. The first approach when suspecting a reaction to betalactam is to discontinue exposure to the drug, and the only specific treatment is desensitization, which has very precise indications. The misdiagnosis of penicillin allergy affects the health system, since the "penicillin allergy" label is associated with increased bacterial resistance, higher rate of therapeutic failure, prolonged hospitalizations, readmissions, and increased costs. Thus, it is essential to develop strategies to assist the prescription of antibiotics in patients identified with a label of "betalactam allergy" at hospitals, and to enhance education of patients and their caregivers, as well as of non-specialist physicians.

RESUMO Os beta-lactâmicos constituem a causa mais frequente de reações de hipersensibilidade a fármacos mediadas por mecanismo imunológico específico. As reações imediatas ocorrem em 1 até 6 horas após a administração do beta-lactâmico, sendo geralmente IgE-mediadas. Elas se traduzem clinicamente por urticária, angioedema e anafilaxia. As reações não imediatas ou tardias ocorrem após 1 hora da administração. São as reações mais comuns, sendo geralmente mediadas por células T. O tipo mais frequente é o exantema maculopapular ou morbiliforme. A maioria dos indivíduos que refere alergia aos beta-lactâmicos pode tolerar esse grupo de antibióticos. No diagnóstico, uma história clínica detalhada é fundamental para verificar se a reação foi do tipo imediato ou não imediato. A partir daí, podem ser realizados testes in vivo e/ou in vitro para investigação. O teste de provocação é considerado o método padrão-ouro no diagnóstico de hipersensibilidade aos beta-lactâmicos. A primeira conduta diante da suspeita de uma reação ao beta-lactâmico é suspender a exposição ao medicamento, e o único tratamento específico é a dessensibilização, que possui indicações bem precisas. O diagnóstico equivocado de alergia à penicilina afeta o sistema de saúde, pois o rótulo de "alergia à penicilina" está associado a aumento da resistência bacteriana, maior índice de falha terapêutica, hospitalizações prolongadas, readmissões e aumento dos custos. Assim, torna-se fundamental elaborar estratégias com o objetivo de auxiliar na prescrição de antibióticos em pacientes com rótulo de "alergia aos beta-lactâmicos" nos hospitais e melhorar a educação dos pacientes e seus responsáveis, além de médicos não especialistas.

Update on perioperative hypersensitivity reactions: joint document from the Brazilian Society of Anesthesiology (SBA) and Brazilian Association of Allergy and Immunology (ASBAI) - Part II: etiology and diagnosis / Atualização sobre reações de hipersensibilidade perioperatória: documento conjunto da Sociedade Brasileira de Anestesiologia (SBA) e Associação Brasileira de Alergia e Imunologia (ASBAI) - Parte II: etiologia e diagnóstico

Abstract This second joint document, written by experts from the Brazilian Association of Allergy and Immunology (ASBAI) and Brazilian Society of Anesthesiology (SBA) concerned with perioperative anaphylaxis, aims to review the pathophysiological reaction mechanisms, triggering agents (in adults and children), and the approach for diagnosis during and after an episode of anaphylaxis. As anaphylaxis assessment is extensive, the identification of medications, antiseptics and other substances used at each setting, the comprehensive data documentation, and the use of standardized nomenclature are key points for obtaining more consistent epidemiological information on perioperative anaphylaxis.

Resumo Este segundo documento, escrito por especialistas da Associação Brasileira de Alergia e Imunologia (ASBAI) e da Sociedade Brasileira de Anestesiologia (SBA) interessados no tema anafilaxia perioperatória, tem por objetivo revisar os mecanismos fisiopatológicos, agentes desencadeantes (em adultos e crianças), assim como a abordagem diagnóstica durante e após o episódio. Por se tratar de uma avaliação abrangente, a identificação das medicações, antissépticos e outras substâncias usadas em cada região, registros detalhados, e nomenclatura padronizada são pontos fundamentais para a obtenção de dados epidemiológicos mais fidedignos sobre a anafilaxia perioperatória.

Update on perioperative hypersensitivity reactions: joint document of the Brazilian Society of Anesthesiology (SBA) and Brazilian Association of Allergy and Immunology (ASBAI) - Part I: post-crisis guidelines and treatment / Atualização sobre reações de hipersensibilidade perioperatória: documento conjunto da Sociedade Brasileira de Anestesiologia (SBA) e Associação Brasileira de Alergia e Imunologia (ASBAI) - Parte I: tratamento e orientação pós-crise

Abstract Experts from the Brazilian Association of Allergy and Immunology (ASBAI) and the Brazilian Society of Anesthesiology (SBA) interested in the issue of perioperative anaphylaxis, and aiming to strengthen the collaboration between the two societies, combined efforts to study the topic and to prepare a joint document to guide specialists in both areas. The purpose of the present series of two articles was to report the most recent evidence based on the collaborative assessment between both societies. This first article will consider the updated definitions, treatment and guidelines after a perioperative crisis. The following article will discuss the major etiologic agents, how to proceed with the investigation, and the appropriate tests.

Resumo Especialistas da Associação Brasileira de Alergia e Imunologia (ASBAI) e da Sociedade Brasileira de Anestesiologia (SBA) interessados no tema anafilaxia perioperatória reuniram-se com o objetivo de intensificar a colaboração entre as duas sociedades no estudo desse tema e elaborar um documento conjunto que possa guiar os especialistas de ambas as áreas. O objetivo desta série de dois artigos foi mostrar as evidências mais recentes alicerçadas na visão colaborativa entre as sociedades. Este primeiro artigo versará sobre as definições mais atuais, formas de tratamento e as orientações após a crise no perioperatório. No próximo artigo serão discutidos os principais agentes causais e a condução da investigação com testes apropriados.

Loss of tolerance 5 days after discontinuing sulphonamide introduced via desensitization in delayed reaction / Perda da tolerância 5 dias após suspensão de sulfonamida introduzida através de dessensibilização por reação tardia

ABSTRACT The fixed drug eruption is a non-immediate hypersensitivity reaction to drug, characterized by recurrent erythematous or violaceous, rounded, well-defined border plaques, which always appear in the same location every time the culprit drug is administered. The usual practice is to avoid the drug involved and to use a structurally different drug. However, there are situations in which there is no safe and effective therapy. In such situations, desensitization is the only option. We describe the case of a patient who presented fixed eruption due to sulfamethoxazole-trimethoprim, who underwent successful desensitization, but required a repeat procedure twice due to relapse after inadvertent full-dose reintroduction. In non-immediate hypersensitivity reaction to drug, the indication is controversial and there is no technical standardization. Furthermore, the time at which such tolerance is lost after discontinuing the drug involved is unknown. In severe non-immediate reactions of types II and III, desensitization is contraindicated. The patient underwent desensitisation to sulfamethoxazole-trimethoprim three times − the first with recurrence of lesions and the second and third without manifestations, all concluded successfully and with no premedication.

RESUMO A erupção fixa por drogas é uma reação de hipersensibilidade a medicamento não imediata, caracterizada por placas eritematosas ou violáceas, arredondadas, recorrentes, de bordas bem definidas e que aparecem sempre na mesma localização cada vez que o medicamento culpado é administrado. A prática habitual é evitar a droga envolvida e utilizar um medicamento estruturalmente diferente. Contudo, há situações em que não há terapêutica segura e eficaz. Em tais situações, a dessensibilização é a única opção. Descrevemos o caso de um paciente que apresentou erupção fixa por drogas por sulfametoxazol-trimetoprim, tendo sido submetido à dessensibilização com sucesso, mas necessitou repetição do procedimento duas vezes, por recidiva da reação após reintrodução inadvertida em dose plena. Em reação de hipersensibilidade a medicamento não imediata, a indicação é controversa e não há padronização técnica. Além disso, não se conhece o tempo durante o qual essa tolerância é perdida após a suspensão da droga envolvida. Nas reações não imediatas graves e dos tipos II e III, a dessensibilização está contraindicada. O paciente foi submetido a dessensibilização ao sulfametoxazol-trimetoprim por três vezes − a primeira com recorrência de lesões, e a segunda e terceira sem manifestações, sendo todas concluídas com sucesso e sem uso de pré-medicação.

Sensibilidad aumentada a lidocaína: estudio genético de un caso / Increased sensitivity to lidocaine: Genetic study of a case

Systemic toxicity by local anesthetics (LAs) is a severe and feared complication in anesthetic practice that generally results from the administration of an inappropriately high dose of LAs or an injection at an inappropriate place, either intravascular or a site with high absorption[1]. However, it is known that the susceptibility to these drugs may vary within the population, which may occur due to genetic changes in the LA binding site, located in the potential-dependent Na+ channels (Nav), thus increasing or decreasing its affinity and, therefore, its clinical consequences. We present a case of a 61 years-old female patient with a medical history of increased sensitivity to LAs. In this scenario, a genetic study was performed to exclude a Nav channel dysfunction.

La toxicidad sistémica por anestésicos locales (ALs) es una grave y temida complicación en la práctica anestésica que generalmente resulta de la administración de una dosis inapropiadamente alta de ALs o a una inyección en un lugar inadecuado, llámese intravascular o un sitio al alta absorción[1]. A pesar de lo anterior, es conocido que la susceptibilidad al efecto de estos fármacos puede variar dentro de la población, lo cual puede ocurrir debido a cambios genéticos en el sitio de unión de los AL, localizado en los canales de Na+ dependientes de potencial (Nav), incrementando o disminuyendo así su afinidad y, por ende, sus consecuencias clínicas. Presentamos el caso de una paciente de 61 años con historia de sensibilidad aumentada a Als. En este escenario, se le ofreció un estudio genético para excluir una disfunción específica a nivel de canal Nav

Low frequency of hypersensitivity reactions to abacavir in HIV infected patients in a referral center in Bahia, Brazil

Abstract Abacavir can cause a multi-systemic hypersensitivity reaction (HSR) in 5-8% of the patients, which is related to HLA-B*57-01 allele. In Brazil, the HLA-B*57-01 screening test became available only in March 2018, several years after abacavir was in use. In this retrospective study we reviewed medical charts of all patients receiving an abacavir-containing regimen to evaluate the frequency of HSR in patients followed at a referral center in Salvador, Brazil. A total of 192 patients who received abacavir were identified, most male (67.1%), black or racially mixed (77.8%), and having diagnosis of a previous AIDS defining conditions (83.7%). Only one patient developed HSR (incidence: 0.52%). The main reasons for abacavir-containing antiretroviral therapy discontinuation were virological failure (28%), adverse effects to other components of the regimen (25%), and simplification of therapy (16%). The low incidence of HSR to abacavir does not support the use of HLA-B*57-01 screening test, in Salvador, Brazil.

Sensibilización a los alérgenos de las penicilinas en pacientes que padecen enfermedades alérgicas / Sensitization to penicillin allergens in patients suffering from allergic diseases

Los antibióticos ß-lactámicos son los más utilizados, dada su eficacia para patógenos bacterianos comunes y su precio relativamente bajo. Para evaluar la sensibilización a los alérgenos mayores y menores de la penicilina en pacientes que padecen enfermedades alérgicas, se realizó un estudio observacional analítico de casos y controles, en el universo de 458 individuos derivados al Servicio de Alergia Previsora (Camagüey, Cuba), desde enero del 2010 hasta noviembre del 2016. Se seleccionó una muestra de 178 niños y adultos con el diagnóstico de asma, rinitis y urticaria de las edades 6 a 60 años. Los que tenían antecedentes, no confirmados, de alergia a penicilinas se consideraron casos (n=60) y los que no tenían el antecedente controles (n=118). Toda la muestra tenía pruebas de Prick positivas a uno o más de los ácaros domésticos Dermatophagoides pteronysinus, Dermatophagoides siboney y Blomia tropicalis, así como a algún alimento. Un grupo de ellos también resultaron positivos a PPL y MD. Se distribuyeron los pacientes en sensibilizados o no con los alérgenos PPL y MD. La prevalencia general de alergia a las penicilinas fue de 24,15 por ciento (15,7 por ciento en los casos y 8,9 por ciento en los controles). La prueba DAP® - Penicilinas mostró mayor número de positivos en los casos que en los controles (p=0,037, OR=5,21). Del total de alérgicos a las penicilinas, el mayor número de pacientes correspondieron al sexo femenino (p=0,031). El test cutáneo con alérgenos PPL y MD puede confirmar el diagnóstico de alergia a penicilinas en pacientes atópicos(AU)

ß-lactam antibiotics are the most widely used, given their efficacy for common bacterial pathogens and their relatively low price. To evaluate sensitization to major and minor allergens of penicillin in patients suffering from allergic diseases, an observational, analytical study of cases and controls was carried out in the universe of 458 individuals referred to the Previsora Allergy Service (Camagüey, Cuba) from January 2010 to November 2016. A sample of 178 children and adults aged 6 to 60 years diagnosed with asthma, rhinitis and urticarial was selected. Those who had a medical history, not confirmed, of allergy to penicillins were considered cases (n=60) and those who did not have the antecedent were the controls (n=118). All the sample had positive Prick tests to one or more of the house mites Dermatophagoides pteronysinus, Dermatophagoides siboney and Blomia tropicalis, as well as against some foods. Some individuals were also positive for PPL and MD. Patients were distributed in sensitized or not with the allergens PPL and MD. The general prevalence of allergy to penicillins was 24.15 percent (15.7 percent in cases and 8.9 percent in controls). The DAP® - Penicillins test showed a greater number of positives in cases than in controls (p=0.037; OR=5.21). The largest number of patients allergic to penicillins corresponded to the female sex (p=0.031). The skin test with allergens PPL and MD can confirm the diagnosis of allergy to penicillins in atopic patients(AU)

Desensibilización a levotiroxina: caso clínico / Successful oral desensitization to levothyroxine: report of one case

We report a 39-year-old female who underwent a total thyroidectomy as treatment for a thyroid papillary cancer. She suffered several episodes of mild angioedema in lips and tongue, after using different commercial Levothyroxine formulations, with and without excipients. Given the need to use this drug, the patient was admitted in our hospital and we proceeded to desensitize her with oral Levothyroxine. The patient fasted throughout the whole procedure, was properly monitored and had an adequate peripheral venous access. On the first day of the procedure, a 15-step protocol was performed, first administering placebo and then, compounded formulations of Levothyroxine starting from 0.01 ug, followed by doubling doses every 15 minutes until the cumulative dose of 111.95 ug was completed, corresponding to the daily dose of Levothyroxine her endocrinologist prescribed (112 ug). The patient was monitored at baseline, between each dose and up to 3 hours after the procedure was completed. There were no incidents such as urticaria, angioedema, or others. On the second day, the patient received a single-full dose of 112 ug on an empty stomach. The medication was successfully tolerated and she was discharged. Thereafter, she tolerates daily Levothyroxine.

Perianesthetic refractory anaphylactic shock with cefuroxime in a patient with history of penicillin allergy on multiple antihypertensive medications / Choque anafilático refratário perianestésico com cefuroxima em paciente com história de alergia à penicilina recebendo vários medicamentos anti-hipertensivos

Abstract We report a case of perianesthetic refractory anaphylactic shock with cefuroxime in a patient with history of penicillin allergy on regular therapy with atenolol, losartan, prazosin and nicardipine. Severe anaphylactic shock was only transiently responsive to 10 mL of (1:10,000) epinephrine and needed norepinephrine and dopamine infusion. Supportive therapy with vasopressors and inotropes along with mechanical ventilation for the next 24 hours resulted in complete recovery. She was successfully operated upon 2 weeks later with the same anesthetic drugs but intravenous ciprofloxacin as the alternative antibiotic for perioperative prophylaxis.

Resumo Relatamos um caso de choque anafilático refratário no período perianestésico com cefuroxima em paciente com história de alergia à penicilina em terapia regular com atenolol, losartan, prazosina e nicardipine. O choque anafilático grave foi apenas transitoriamente responsivo a 10 mL de epinefrina (1:10000) e precisou de infusão de norepinefrina e dopamina. A terapia de apoio com vasopressores e inotrópicos, juntamente com ventilação mecânica por 24 horas, resultou em recuperação completa. A paciente foi operada com sucesso duas semanas mais tarde, com os mesmos agentes anestésicos, mas com ciprofloxacina intravenosa como antibiótico opcional para a profilaxia perioperatória.

Clozapine-induced hypersensitivity myocarditis presenting as sudden cardiac death

Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia. The autopsy revealed hypersensitivity myocarditis, which usually occurs in the first 4 weeks after the initiation of clozapine. A 4-week monitoring protocol, including laboratory assessment of troponin and C-reactive protein, may assist in the early diagnosis of this potentially fatal condition.

Cardiac complications in a metamizole-induced type I Kounis syndrome / Complicações cardíacas em síndrome de Kounis tipo I induzida por metamizol

ABSTRACT Kounis syndrome is defined as the coincidental occurrence of allergic reaction and acute coronary syndrome secondary to vasospasm. Anti-inflammatory drugs are included as one of the multiple causes. Current data available about this syndrome come from case reports. We present the case of a patient who suffered Kounis syndrome with cardiogenic shock and asystole after intravenous infusion of Metamizole, and in which no lesions were observed in coronariography.

RESUMO A síndrome de Kounis é definida como a ocorrência concomitante de reação alérgica e síndrome coronariana aguda secundária ao vasoespasmo. Os medicamentos anti-inflamatórios estão incluídos como uma das múltiplas causas. Os dados atuais disponíveis sobre essa síndrome são provenientes de relatos de caso. Relatamos o caso de um paciente que apresentou síndrome de Kounis com choque cardiogênico e assistolia após infusão intravenosa de metamizol e no qual não foram observadas lesões na coronariografia.

Perioperative anaphylaxis / Anafilaxia perioperatória / Anafilaxia perioperatoria

Anaphylaxis remains one of the potential causes of perioperative death, being generally unanticipated and quickly progress to a life threatening situation. A narrative review of perioperative anaphylaxis is performed.

A anafilaxia continua sendo uma das causas potenciais de morte perioperatória, pois geralmente não é prevista e evolui rapidamente para uma situação ameaçadora da vida. Uma revisão da anafilaxia perioperatória é feita.

La anafilaxia sigue siendo una de las causas potenciales de muerte perioperatoria por ser generalmente no anticipada, y progresar rápidamente a una situación amenazante de la vida. Se realiza una revisión de la anafilaxia perioperatoria.

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Type 1 Ig-E mediated allergy to human insulin, insulin analogues and beta-lactam antibiotics / Hipersensibilidade imediata a insulina humana, análogos de insulina e a antibióticos beta-lactâmicos

Insulin, a crucial therapeutic agent for diabetes mellitus, has been rarely associated with hypersensitivity events. We present a 69-year-old type-2 diabetic patient with urticariform lesions on the sites of subcutaneous injection of insulin. The patient denied any known allergies, except for an unspecific cutaneous reaction after intramuscular penicillin administration in childhood. Prick tests revealed positive reactions to all tested human insulins and insulin analogues. Serum IgE levels were above normal range and RAST tests were positive for human, bovine and porcine insulins, as well as beta-lactams. Type 1 IgEmediated allergy to insulin analogues demands a prompt diagnosis and represents a significant therapeutic challenge in diabetic patients.

A insulina é um agente indispensável para o controlo da diabetes mellitus. Os efeitos adversos da sua administração, em particular fenómenos de hipersensibilidade, são raros. Apresentamos um doente de 69 anos, diabético do tipo 2, com episódios recorrentes de lesões urticariformes nos locais de administração subcutânea de insulina. Negava alergias medicamentosas, à excepção de reacção não especificada na infância após penicilina intramuscular. Foram realizados testes cutâneos por puntura (prick tests) com diversos tipos de insulina humana e análogos, todos com reacções positivas, associando elevação dos níveis de IgE sérica e provas RAST positivas para as insulinas humana, bovina e porcina e para os antibióticos beta-lactâmicos. A alergia a análogos de insulina exige um diagnóstico precoce, originando um desafio terapêutico importante no doente diabético.

DRESS: clinicopathological features of 10 cases from an University Hospital in São Paulo / DRESS: características clinicopatológicas em 10 casos de Hospital Universitário em São Paulo

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms is a severe form of drug-induced reaction with multiorgan involvement. OBJECTIVES: The aim of this study is to evaluate the epidemiological, clinical and pathological features and prognosis of this drug reaction among patients seen at a dermatology service. METHOD: Retrospective review of medical records of ten patients diagnosed with drug reaction with eosinophilia and systemic symptoms at the Federal University of São Paulo, from august 2008 to may 2011. RESULTS: Phenytoin was the leading cause of drug reaction with eosinophilia and systemic symptoms in our cases, followed by allopurinol. Abnormal liver function tests were observed in 7 patients and renal function impairment in 2 patients. In all cases, patients were hospitalized and the culprit drug was withdrawn. The main treatment was systemic corticosteroid. Drug reaction with eosinophilia and systemic symptoms resulted in death in 2 cases. The causes of death were septic shock and hepatic failure. CONCLUSION: Our mortality rate of 20%, supports that drug reaction with eosinophilia and systemic symptoms is a severe form of drug-induced reaction and must be recognized by all dermatologists.

FUNDAMENTOS: A reação a droga com eosinofilia e sintomas sistêmicos é uma reação medicamentosa severa com envolvimento de múltiplos órgãos. OBJETIVO: Avaliar as características epidemiológicas, clínicas, histológicas e o prognóstico dessa reação medicamentosa entre os pacientes atendidos pelo serviço da dermatologia. MÉTODOS: Levantamento retrospectivo dos prontuários de dez pacientes diagnosticados com reação a droga com eosinofilia e sintomas sistêmicos pelo serviço de dermatologia da Universidade Federal de São Paulo, entre agosto de 2008 e maio de 2011. RESULTADOS: A fenitoína foi a principal causa de reação a droga com eosinofilia e sintomas sistêmicos entre os pacientes, seguida pelo alopurinol. A alteração das enzimas hepáticas foi observada em sete pacientes e diminuição da função renal em dois casos. Todos os pacientes estavam hospitalizados e o medicamento implicado foi suspenso. O principal tratamento foi corticóide sistêmico. Dois pacientes faleceram devido à síndrome reação a droga com eosinofilia e sintomas sistêmicos. A causa da morte foi choque séptico e falência hepática. CONCLUSÃO: A mortalidade de 20% entre os pacientes do estudo confirma que essa reação induzida por droga é grave e deve ser reconhecida por todos os dermatologistas.

Methylparaben concentration in commercial Brazilian local anesthetics solutions

OBJECTIVE: To detect the presence and concentration of methylparaben in cartridges of commercial Brazilian local anesthetics. MATERIAL AND METHODS: Twelve commercial brands (4 in glass and 8 in plastic cartridges) of local anesthetic solutions for use in dentistry were purchased from the Brazilian market and analyzed. Different lots of the commercial brands were obtained in different Brazilian cities (Piracicaba, Campinas and São Paulo). Separation was performed using high performance liquid chromatography (HPLC) with UV-Vis detector. The mobile phase used was acetonitrile:water (75:25 - v/v), pH 4.5, adjusted with acetic acid at a flow rate of 1.0 ml.min-1. RESULTS: When detected in the solutions, the methylparaben concentration ranged from 0.01% (m/v) to 0.16% (m/v). One glass and all plastic cartridges presented methylparaben. CONCLUSION: 1. Methylparaben concentration varied among solutions from different manufacturers, and it was not indicated in the drug package inserts; 2. Since the presence of methylparaben in dental anesthetics is not regulated by the Brazilian National Health Surveillance Agency (ANVISA) and this substance could cause allergic reactions, it is important to alert dentists about its possible presence.

Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) / Drug-induced Hypersensitivity Syndrome (DIHS): a review of current concepts / Reação a drogas com eosinofilia e sintomas sistêmicos (DRESS) / Síndrome da hipersensibilidade induzida por droga (DIHS): revisão dos conceitos atuais

The Drug Reaction with Eosinophilia and Systemic Symptoms syndrome, also known as Drug Induced Hypersensitivity Syndrome presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, causing damage to several systems, especially to the kidneys, heart, lungs, and pancreas. Recognition of this syndrome is of paramount importance, since the mortality rate is about 10% to 20%, and a specific therapy may be necessary. The pathogenesis is related to specific drugs, especially the aromatic anticonvulsants, altered immune response, sequential reactivation of herpes virus and association with HLA alleles. Early recognition of the syndrome and withdrawal of the offending drug are the most important and essential steps in the treatment of affected patients. Corticosteroids are the basis of the treatment of the syndrome, which may be associated with intravenous immunoglobulin and, in selected cases, Ganciclovir. The article reviews the current concepts involving this important manifestation of adverse drug reaction.

A síndrome Reação a Drogas com Eosinofilia e Sintomas Sistêmicos, também conhecida como Síndrome da Hipersensibilidade Induzida por Droga apresenta-se clinicamente como uma erupção cutâneomucosa extensa tipo exantemática, associada a febre, linfadenopatia, hepatite, anormalidades hematológicas com eosinofilia e linfócitos atípicos, e pode envolver outros órgãos, produzindo insuficiência renal, infiltrado eosinofílico cardíaco e pulmonar, além de pancreatite. O reconhecimento desta síndrome é de suma importância, uma vez que, a taxa de mortalidade é de cerca de 10% a 20% e uma terapia específica pode ser necessária. Sua etiopatogenia está relacionada a drogas específicas, principalmente os anticonvulsivantes aromáticos, alterações imunes, reativação sequencial de herpesvirus e associação com alelos do HLA. O pronto reconhecimento da síndrome e a retirada da droga desencadeante são os passos mais importantes e essenciais no tratamento dos doentes acometidos. Os corticosteróides são as medicações de escolha para o tratamento da síndrome, podendo ser associados imunoglobulina intravenosa e em, alguns casos selecionados, Ganciclovir. O artigo traz uma revisão dos conceitos atuais que envolvem essa importante manifestação de reação adversa a drogas.

Penfigoide ampollar por fármacos: entidad subdiagnosticada? / Drug-Induced Bullous Pemphigoid: an Underdiagnosaed Entity?

El penfigoide ampollar (PA) es una enfermedad infrecuente, de curso crónico y benigno, que aparece en personas de edad avanzada y se caracteriza por la presencia de ampollas subepidérmicas.En términos generales, el diagnóstico de las enfermedades ampollares se basa en las manifestaciones clínicas, los hallazgos histopatológicos y la inmunofluorescencia directa. Si bien la ausencia de alguno de estos métodos puede dificultar el mismo, una adecuada correlación clínico-patológica permite, en la mayoría de los casos, arribar al diagnóstico y realizar el tratamiento apropiado. El PA puede ser causado por fármacos y produce cuadros clínicos similares al PA idiopático. A continuación se presentan dos casos con diagnóstico de penfigoide ampollar por fármacos.

Bullous Pemphigoid is a chronic, infrequent benign disease of the elderly, characterized by the presenceof subepidermal bullae. Diagnosis is based on clinical, histopathological and direct immunofluorescencefindings. Though the absence of any of them hampers the diagnosis, a correct clinico-pathologic correlation is necessary to make the appropriate treatment. Drug induced-BullousPemphigoid presents with identical clinical features as those of the Idiopathic Bullous Pemphigoid.We present two patients with drug-induced Bullous Pemphigoid.