RESUMO
Os anticorpos monoclonais são uma nova classe de medicamentos que representa um marco na evolução da terapia de doenças alérgicas graves. Além de possibilitar uma terapia imunológica alvo específico, proporciona maior controle de sintomas, redução de exacerbações, melhoria da qualidade de vida e da segurança. A eficácia e a segurança dos anticorpos monoclonais no tratamento de doenças alérgicas estão bem documentadas nos estudos clínicos pivotais, de extensão e de vida real. No Brasil, estão licenciados atualmente pela Agência Nacional de Vigilância Sanitária (ANVISA) imunobiológicos para asma, dermatite atópica (DA), esofagite eosinofílica (EoE), granulomatose eosinofílica com poliangeíte (GEPA), rinossinusite crônica com pólipo nasal (RSCcPN), síndromes hipereosinofílicas (SHE) e urticária crônica espontânea (UCE). Com a incorporação do uso dessas novas terapias no dia a dia do médico alergologista e imunologista, naturalmente emergem aspectos práticos que exigem orientações práticas perante as evidências científicas mais atuais, a fim de se manter a boa prática médica, com uso criterioso e consciente pelo especialista capacitado. Assim, nesse guia prático, abordaremos os imunobiológicos aprovados até o momento para doenças alérgicas graves, com objetivo de auxiliar o especialista em Alergia e Imunologia na prescrição e manejo dessas medicações, incluindo indicações, contraindicações, monitoramento da eficácia e segurança, notificação de eventos adversos, bem como aspectos associados aos cuidados com vacinas, populações especiais, acesso, transporte, armazenamento e aplicação domiciliar.
Monoclonal antibodies are a new class of drugs that represent a milestone in the evolution of therapy for severe allergic diseases. In addition to allowing targeted immunologic therapy, they can improve symptom control, reduce exacerbations, and increase quality of life and safety. The efficacy and safety of monoclonal antibodies in the treatment of allergic diseases are well documented in pivotal, extension, and real-life clinical studies. In Brazil, immunobiologic agents are currently licensed by the National Health Surveillance Agency (ANVISA) for use in asthma, atopic dermatitis (AD), eosinophilic esophagitis (EoE), eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyps (CRSwNP), hypereosinophilic syndrome (HES), and chronic spontaneous urticaria (CSU). With the incorporation of these new therapies into the daily practice of the allergist and immunologist, practical aspects will naturally emerge and require practical guidelines in light of the most current scientific evidence in order to maintain good medical practice, with judicious and conscious use by a qualified specialist. Therefore, in this practical guide, we will address the immunobiologic agents currently approved for severe allergic diseases, aiming to assist allergy and immunology specialists in the prescription and practical management of these medications, including indications, contraindications, efficacy and safety monitoring, adverse event reporting, as well as health care factors associated with vaccination, special populations, access, transport, storage, and home use.
Assuntos
HumanosRESUMO
A utilização de agentes imunobiológicos em alergia e imunologia tem sido cada vez mais frequente nos últimos anos, emergindo como potencialmente eficazes para o tratamento de doenças alérgicas e de hipersensibilidade. O uso de imunobiológicos em doenças alérgicas está recomendado nas formas graves onde a eficácia, segurança e custo-efetividade estão comprovados. O objetivo deste artigo é sintetizar os efeitos adversos mais comuns ou significativos, incluindo as reações de hipersensibilidade aos principais anticorpos monoclonais aprovados para o tratamento de doenças alérgicas licenciados e comercializados no Brasil até o momento.
The use of immunobiological agents in allergy and immunology has increased in recent years, emerging as potentially effective strategies to treat allergic and hypersensitivity diseases. The use of immunobiological agents is recommended in the severe forms of allergic diseases, for which their efficacy, safety, and cost-effectiveness have been established. The purpose of this study was to summarize the most common or significant adverse effects, including hypersensitivity reactions to the main monoclonal antibodies approved for the treatment of allergic diseases that are currently licensed and marketed in Brazil.
Assuntos
Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , OmalizumabRESUMO
Os medicamentos imunobiológicos têm sido frequentemente utilizados no tratamento das doenças alérgicas e de natureza imunológica. Esses agentes regulam a resposta imunológica do tipo 2 nas doenças alérgicas ou atuam em diversas vias de ativação alteradas nos erros inatos da imunidade. Com o surgimento da pandemia COVID-19 um crescente número de pacientes em uso de imunobiológicos para essas condições deverão ser vacinados contra o vírus SARS-CoV-2. Dessa forma, existe a necessidade de avaliar a segurança e eficácia destas vacinas nos pacientes em uso de imunobiológicos para asma, dermatite atópica, rinossinusite crônica com pólipos nasais, urticária crônica e erros inatos da imunidade. Foi realizada uma busca de literatura recente relevante sobre imunobiológicos e vacinas COVID-19 no PubMed. Existe um consenso de manutenção desses agentes durante a pandemia COVID-19, embora nas doenças alérgicas os mesmos devam ser suspensos durante a infecção ativa. Por outro lado, dados disponíveis em relação à segurança e eficácia das vacinas contra a COVID-19 nesse grupo de pacientes são escassos. Existem relatos do uso de outras vacinas inativadas em associação com alguns imunobiológicos demonstrando serem eficazes e seguras. Portanto, considerando o risco potencial da infecção COVID-19, especialmente nos pacientes portadores de erros inatos da imunidade, recomendamos que as vacinas contra a COVID-19 sejam utilizadas nos pacientes em uso de imunobiológicos. Desta forma, existe uma necessidade de estudos que avaliem estas questões haja vista que a terapia com diversos imunobiológicos tem sido amplamente utilizada nos pacientes com doenças alérgicas e de natureza imunológica.
Immunobiological drugs have often been used to treat allergic and immunological diseases. These agents regulate the type 2 immune response in allergic diseases or act on different activation pathways altered in inborn errors of immunity. With the emergence of the COVID-19 pandemic, an increasing number of patients with these conditions using these agents should be vaccinated against the SARS-CoV-2 virus. Thus, there is a need to evaluate the safety and efficacy of these vaccines in patients using biologics for asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, chronic urticaria, and inborn errors of immunity. A search for relevant recent literature on biologics and COVID-19 vaccines was conducted on PubMed. There is a consensus on maintaining the use of these agents during the COVID-19 pandemic, although in allergic diseases they must be suspended during active infection. Conversely, the available data regarding the safety and efficacy of the COVID-19 vaccines are scarce. There are reports of the use of other inactivated vaccines with some biologics proving to be effective and safe. Therefore, considering the potential risk of COVID-19 infection, especially in patients with inborn errors of immunity, we recommend that COVID-19 vaccines should be used in patients using biologics. Thus, there is a need for studies to assess these issues, given that therapy with several biologics has been widely used in patients with allergic and immunological diseases.
Assuntos
Humanos , Asma , Terapêutica , Dermatite Atópica , Omalizumab , Urticária Crônica , Vacinas contra COVID-19 , SARS-CoV-2 , COVID-19 , Vacina BNT162 , Vacina de mRNA-1273 contra 2019-nCoV , ChAdOx1 nCoV-19 , Anticorpos Monoclonais , Produtos Biológicos , Preparações Farmacêuticas , Eficácia , Infecções por Coronavirus , PubMed , Doenças do Sistema ImunitárioRESUMO
Objetivo: Avaliar a hipersensibilidade a medicamentos em pacientes com o diagnóstico de doenças autoimunes. Métodos: Estudo clínico, analítico, do tipo caso-controle. Foram selecionadas 35 mulheres com doenças autoimunes e 35 sem esse diagnóstico que participaram do protocolo de pesquisa sobre antecedentes de hipersensibilidade a drogas. Resultados: As pacientes apresentavam idade variando de 16 a 66 anos, com a mediana semelhante nos dois grupos. A doença autoimune mais prevalente foi o lupus eritematoso sistêmico, 24/35 (68,5%). A proporção de hipersensibilidade a medicamentos, nas pacientes com doenças autoimunes, foi de 14/35 (40%), e apenas 2/35 (5,7%) no grupo controle (p = 0,0029). As reações de hipersensibilidade do tipo tardia foram as mais frequentes, e na maioria dos casos precederam o diagnóstico de doença autoimune em um total de cinco pacientes, sendo que destas cinco, duas apresentaram síndrome de Stevens Johnson, duas exantema maculopapular, e uma eritema fixo pigmentar. O grupo de drogas mais envolvido foi os anti-inflamatórios não esteroides, seguidos pelos anticonvulsivantes. Conclusão: Hipersensibilidade a medicamentos foi mais frequente em pacientes portadoras de doenças autoimunes, e pode preceder o diagnóstico, especialmente se for do tipo tardia. Estudos adicionais multicêntricos para verificar uma eventual associação de hipersensibilidade a medicamentos e doenças autoimunes são necessários.
Objective: To evaluate drug hypersensitivity in patients with autoimmune diseases. Methods: In this clinical, analytical, casecontrol study, we selected 35 women with autoimmune diseases and 35 women without this diagnosis to participate in this research protocol on history of drug hypersensitivity. Results: Patients' age ranged from 16 to 66 years with similar median in both groups. The most prevalent autoimmune disease was systemic lupus erythematosus, in 24/35 (68.5%) patients. The proportion of drug hypersensitivity was 14/35 (40%) in the autoimmune disease group and only 2/35 (5.7%) in the control group (p = 0.0029). Delayed hypersensitivity reactions were most frequent and preceded the diagnosis of autoimmune disease in five patients, including two with Stevens-Johnson syndrome, two with maculopapular rash and one with fixed pigmented erythema. The most frequently involved group of drugs was nonsteroidal anti-inflammatory drugs, followed by anticonvulsants. Conclusion: Drug hypersensitivity was more common in patients with autoimmune diseases and may precede the diagnosis, especially in delayed-type. Additional multicenter studies are required to evaluate a possible association of drug hypersensitivity to autoimmune diseases.
Assuntos
Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Doenças Autoimunes , Hipersensibilidade a Drogas , Lúpus Eritematoso Sistêmico , Pacientes , Preparações Farmacêuticas , Anti-Inflamatórios não Esteroides , Grupos Controle , Síndrome de Stevens-Johnson , Diagnóstico , Eritema , Doença de Hashimoto , Exantema , Hipersensibilidade TardiaRESUMO
INTRODUCTION: In Brazil, glomerulopathies are the third leading cause of chronic renal disease, accounting for 11% of dialysis patients. Studies on the prevalence of this disease in Northeastern Brazil are scarce. OBJECTIVE: The aim was to describe the findings of biopsies and to conduct a comparative analysis on the clinical laboratory presentation of primary glomerulopathies (PG) and secondary glomerulopathies (SG). METHODS: This was a retrospective study conducted at two public teaching hospitals in the state of Pernambuco, Northeastern Brazil. RESULTS: A total of 1151 biopsies performed between 1998 and 2016 were analyzed. The sample consisted of 670 biopsies of native kidneys, after excluding extra glomerular diseases and unsuitable material. PG were more frequent than SG (58% vs. 42%). There was a prevalence among PG of focal segmental glomerulosclerosis (43%). Membranoproliferative glomerulonephritis and collapsing glomerulopathy, accounted for 9% and 3% of the PG, respectively. For SG, the main etiologies were lupus nephritis (67%) and infections (10%). Female sex, hematuria and an elevated level of creatinine were related to a greater chance of SG, at multivariate analysis. An increase of proteinuria reduced this chance. Nephrotic syndrome was more common among the PG, while urinary abnormalities and nephritic syndrome prevailed in patients with SG. CONCLUSION: This is the first registry of glomerulopathies in Northeastern Brazil. It also presents a comparative analysis of the main clinical laboratory abnormalities of PG and SG, and includes the current classifications of glomerular diseases.
Assuntos
Glomerulonefrite , Adolescente , Adulto , Biópsia , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Glomerulonefrite/diagnóstico , Glomerulonefrite/epidemiologia , Humanos , Lactente , Rim/patologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Adulto JovemRESUMO
Abstract Introduction: In Brazil, glomerulopathies are the third leading cause of chronic renal disease, accounting for 11% of dialysis patients. Studies on the prevalence of this disease in Northeastern Brazil are scarce. Objective: The aim was to describe the findings of biopsies and to conduct a comparative analysis on the clinical laboratory presentation of primary glomerulopathies (PG) and secondary glomerulopathies (SG). Methods: This was a retrospective study conducted at two public teaching hospitals in the state of Pernambuco, Northeastern Brazil. Results: A total of 1151 biopsies performed between 1998 and 2016 were analyzed. The sample consisted of 670 biopsies of native kidneys, after excluding extra glomerular diseases and unsuitable material. PG were more frequent than SG (58% vs. 42%). There was a prevalence among PG of focal segmental glomerulosclerosis (43%). Membranoproliferative glomerulonephritis and collapsing glomerulopathy, accounted for 9% and 3% of the PG, respectively. For SG, the main etiologies were lupus nephritis (67%) and infections (10%). Female sex, hematuria and an elevated level of creatinine were related to a greater chance of SG, at multivariate analysis. An increase of proteinuria reduced this chance. Nephrotic syndrome was more common among the PG, while urinary abnormalities and nephritic syndrome prevailed in patients with SG. Conclusion: This is the first registry of glomerulopathies in Northeastern Brazil. It also presents a comparative analysis of the main clinical laboratory abnormalities of PG and SG, and includes the current classifications of glomerular diseases.
Resumo Introdução: No Brasil, glomerulopatias são a terceira causa de doença renal crônica terminal, responsáveis por 11% dos pacientes em diálise. Entretanto, estudos sobre a prevalência desta patologia no nordeste do Brasil são escassos. Objetivo: O objetivo foi descrever os achados das biópsias e analisar comparativamente a apresentação clínico laboratorial entre as glomerulopatias primárias (GP) e as glomerulopatias secundárias (GS). Métodos: Estudo retrospectivo, realizado em dois hospitais públicos de ensino do estado de Pernambuco, nordeste do Brasil. Resultados: Foram avaliadas 1.151 biópsias, de 1998 a 2016. A amostra foi composta por 670 biópsias de rins nativos, após exclusão de patologias extra glomerulares e materiais inadequados. GP foram mais frequentes do que GS (58% × 42%). Dentre as GP, houve predomínio de glomeruloesclerose segmentar e focal (GESF). Glomerulonefrite membranoproliferativa e glomerulopatia colapsante foram responsáveis por 9% e 3% das GP, respectivamente. Das GS, as etiologias principais foram nefrite lúpica (67%) e infecciosas (10%). Sexo feminino, hematúria e nível elevado de creatinina estiveram relacionadas a uma maior chance de GS na análise multivariada. Síndrome nefrótica foi mais comum dentre as GP, já anormalidades urinárias e síndrome nefrítica prevaleceram nos pacientes com GS. Conclusões: Este é o primeiro registro de glomerulopatias do nordeste do Brasil. Demonstrou-se também uma análise comparativa das principais alterações clínico laboratoriais das GP e GS, com classificações atualizadas das doenças glomerulares.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Glomerulonefrite/diagnóstico , Glomerulonefrite/epidemiologia , Biópsia , Brasil/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Rim/patologiaRESUMO
BACKGROUND: The ankle-brachial index (ABI) is a simple, non-invasive, and inexpensive method used in the diagnosis of peripheral arterial disease (PAD) and can identify individuals at risk for cardiovascular disease in other arteries of the body, especially the coronary and carotid arteries. The primary objective of this study was to assess whether patients with an ABI < 0.9 have more severe coronary artery disease detected on coronary angiography compared to patients with a normal ABI. METHODS: This is a prospective, analytical, cross-sectional study that was performed from July 1, 2013 to June 31, 2014 that recruited 163 patients (101 men (62%) and 62 women (38%)) according to the inclusion and exclusion criteria. All patients underwent coronary angiography, and then ABI measurements were performed. Pearson's Chi-square and Student's t-tests were used to compare variables between groups. The Poisson regression model was used to evaluate whether ABI was an independent predictor of stenoses > 50%. RESULTS: The prevalence of ABI < 0.9 was 9.8%. Patients with an ABI < 0.9 had a higher prevalence of stenoses ≥ 50% in the left anterior descendant (LAD) (68.7% vs. 36%, P = 0.02) and left main (8.7% vs. 0.6%, P < 0.001) than those with a normal ABI. On multivariate Poisson regression, an ABI < 0.9 was an independent predictor of stenosis ≥ 50% in the LAD (odds ratio (OR): 2.05 (1.39 - 3.04), P < 0.001). CONCLUSIONS: Patients with an ABI < 0.9 had a higher prevalence of stenoses ≥ 50% in the LAD and left main than those with a normal ABI. An abnormal ABI was an independent predictor of lesions ≥ 50% in LAD.
RESUMO
Brain metastases occur in up to 10-30% of patients with cancer. Metastatic lesions are usually diagnosed as multiple mass lesions at the junction of the grey and white matter with associated perilesional vasogenic oedema. Cysticercosis is an endemic disease in underdeveloped countries of Africa, Central and South America and is the most common parasitic infection of the central nervous system. The classical radiological finding of neurocysticercosis is cystic lesions showing the scolex in the brain parenchyma. We report a case of metastatic adenocarcinoma of the lung presenting with cystic brain lesions mimicking neurocysticercosis.
Assuntos
Adenocarcinoma/patologia , Neoplasias Encefálicas/secundário , Encéfalo/patologia , Cistos/diagnóstico , Neoplasias Pulmonares/patologia , Neurocisticercose/diagnóstico , Adenocarcinoma de Pulmão , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
JUSTIFICATIVA E OBJETIVOS: A hipertensão arterial sistêmica (HAS) é um problema de saúde pública tanto em países desenvolvidos quanto em desenvolvimento. Adesão a fármacos prescritos representa importante fator de bom prognóstico para os pacientes. O objetivo deste estudo foi avaliar as taxas de adesão a fármacos anti-hipertensivos de pacientes hipertensos. MÉTODOS:Estudo de mundo real, multicêntrico, transversal, prospectivo e analítico, que recrutou 850 pacientes hipertensos (média de idade de 62 ± 11 anos, 225 homens e 625 mulheres) no período de agosto de 2010 a julho de 2012. Foram avaliadas as características clínicas, sociais, econômicas e culturais dos pacientes.A adesão aos fármacos anti-hipertensivos foi avaliada através do questionário de Morisky-Green. Foi realizada estatística descrita das prevalências das características analisadas. RESULTADOS:As principais características clínicas, sociais, econômicas e culturais dos pacientes foram dislipidemia (DLP) 319 pacientes (37%), diabetes mellitus (DM) 213 (25%), tabagismo 204 (24%), doença arterial periférica 159 (19%), acidente vascular encefálico (AVE) prévio 69 (8%), doença renal crônica 37 (4%),analfabetismo 303 (35%), doença arterial coronariana (DAC) 85 (10%). Antecedentes familiares: HAS 142 (17%), DAC 96(11,2%), AVE 94 (11%), DM 90 (10%), DLP 77 (9%) e doença renal crônica 27 (3%). A taxa de adesão a fármacos anti-hipertensivos foi de 40%. CONCLUSÃO: A taxa de adesão aos anti-hipertensivos foi baixa, refletindo que menos da metade dos pacientes tomavam adequadamente os fármacos. Portanto a sua adesão representou importante fator do tratamento de hipertensos que necessita ser melhorado.
BACKGROUND AND OBJECTIVES: Systemic hypertension (SH) is a public health problem both in developed and developing countries. Adherence to antihypertensive drugs representsan important factor for good patients' prognosis. We aimed to evaluate the rate of adherence to antihypertensive drugs among hypertensive patients. METHODS: This is a multicenter, cross-sectional, prospective, analytical, real world registry, which enrolled 850 hypertensive patients (mean age 62 ± 11 years, 225 men and 650 women) between August 2010 and July 2012. Clinical, social, cultural and economic characteristics were evaluated. The adherence to antihypertensive drugs was assessed by Morisky-Green questionnaire. Descriptive statistical analysis was performed. RESULTS: The main clinical, social, cultural and economic characteristics were: dyslipidemia (DLP), 319 patients (37%); diabetes mellitus (DM), 213 (25%); smoking,204 (24%); peripheral artery disease, 159 (19%); prior stroke, 69 (8%); chronic renal disease (CRD), 37 (4%); illiteracy, 303 (35%); coronary artery disease (CAD), 85 (10%). Family history: systemic hypertension, 142 (17%); CAD, 96 (11.2%); stroke, 94 (11%); DM, 90 (10%); DLP, 77 (9%); and CRD, 27 (3%). The rate of adherence to antihypertensive drugs was of 40%. CONCLUSION:The rate of adherence to antihypertensive drugs was low, showing that less than 50% of the patients were taking their medicines according to recommendations. Therefore, adherence to antihypertensive drugs represents an important point of treatment that should be improved.
Assuntos
Humanos , Masculino , Feminino , Idoso , Pressão Arterial , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Blattella germanica and Periplaneta americana are the most common domestic species of cockroaches, found all over the world under favorable conditions. Allergen sensitivity can be detected through in vivo tests, such as skin prick tests (SPT) for immediate hypersensitivity and in vitro techniques, represented mainly by the sIgE determination. Nevertheless, there is no gold standard for the detection of hypersensitivity to cockroaches. This study aims to evaluate the agreement between skin prick test to different cockroach allergenic extracts with serum specific IgE determination in the diagnosis of cockroach allergy in asthmatic and non-asthmatic children. METHODS: A case-control study involving 74 asthmatic and 42 non-asthmatic children aged between 6 and 14 years was conducted in Recife, Brazil. All individuals were submitted to a skin prick test (SPT) with Dermatophagoides pteronyssinus, D. farinae, Blomia tropicalis (IPI-ASAC) and three different commercial cockroach extracts (Greer, Hollister-Stier, and IPI-ASAC Brasil) of B. germanica and P. americana, and to the quantification of total serum IgE and specific serum IgE to B. germanica and P. americana. RESULTS: The mean diameter of induced papule was considerably greater among the asthmatic patients when compared to non-asthmatic controls, regardless of the species or type of cockroach extract. The correlations between the various types of utilized extracts for the two species studied were not sufficiently strong. Hollister-Stier extract was the most sensible extract among asthmatics in this study for both B. germanica (54.1% [N = 40]) and P. americana (59.5% [N = 44]). A satisfactory correlation was found between the serum levels of specific IgE and total IgE for both species of cockroaches. The correlation of specific IgE serum level from each species with its respective SPT was not considered satisfactory. CONCLUSIONS: The weak correlation between the different extracts clearly indicates a need for standardization of the extracts for SPT for cockroach allergy diagnosis. According to this study, only a patient with high specific IgE serum levels and a positive SPT to a cockroach species should be truly classified as hypersensitive to B. germanica and/or P. americana.