Guia prático de urticária aguda / Practical guide to acute urticaria

A urticária aguda é uma causa frequente de consulta com alergistas, caracterizada por urticas e/ou angioedema. Embora autolimitada e benigna, pode causar desconforto significativo e raramente representar uma doença sistêmica grave ou reação alérgica com risco de vida. Nesta revisão, elaborada pelo Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia, foram abordadas as principais questões referentes ao tema para auxiliar o médico especialista e generalista.

Acute urticaria is a frequent cause of consultations with allergists, being characterized by wheals and/or angioedema. Although self-limited and benign, it may cause significant discomfort and uncommonly represent a serious systemic disease or life-threatening allergic reaction. In this review prepared by the Urticaria Scientific Department of the Brazilian Association of Allergy and Immunology, the main questions about this topic are addressed to help specialists and general practitioners.

Mepolizumab in hypereosinophilic syndrome: a systematic review and meta-analysis

We aimed to evaluate the efficacy and safety of mepolizumab (MEP) in the management of hypereosinophilic syndrome (HES). A systematic search was performed, and articles published until March 2021 were analyzed. The primary efficacy results evaluated were hospitalization rate related to HES, morbidity (new or worsening), relapses/failure, treatment-related adverse effects, prednisone dosage ≤10 mg/day for ≥8 weeks, and eosinophil count <600/μL for ≥8 weeks. A meta-analysis was conducted, when appropriate. Three randomized controlled trials (RCTs), with a total of 255 patients, were included. The studies contemplated the use of MEP 300 mg/SC or 750 mg/IV. According to the evaluation of the proposed outcomes, when relapse rates/therapeutic failures were assessed, there was a 26% reduction with MEP 300 mg/SC (RD=-0.26; 95% CI: -0.44 to -0.08; p=0.04) and 48% reduction with MEP 750 mg/IV (RD=-0.48; 95% CI: -0.67, -0.30; p<0.00001). For the outcomes, prednisone dosage ≤10 mg/day for ≥8 weeks was 48% (RD=0.48; 95% CI: 0.35 to 0.62; p<0.00001), and the eosinophil count <600/μL for ≥8 weeks was 51% (RD=0.51; 95% CI: 0.38 to 0.63; p<0.00001), both showed a reduction with MEP 300 mg/IV and 750 mg/IV. No statistically significant differences in treatment-related adverse effects outcomes were observed for either dosage (RD=0.09; 95% CI: -0.05 to 0.24; p=0.20; RD=0.09; 95% CI: -0.11 to 0.29; p=0.39). Despite the positive effects observed for the studied outcomes, the exact significance remains unclear.

Síndrome hipereosinofílico con eritrodermia / Hypereosinophilic syndrome with erythrodermia

Varón de 77 años de edad, con antecedentes de insuficiencia cardiaca y fibrilación auricular recibiendo warfarina, hipotiroidismo, diabetes mellitus e hiperuricemia, con historia de un año de lesiones dérmicas eritematosas y descamativas en el tronco, pruriginosas y con moderada eosinofilia recurrente. Después de descartarse causas alérgicas, parasitarias, autoinmunes y neoplásicas, se hizo el diagnóstico de síndrome hipereosinofílico idiopático. Recibió tratamiento con prednisona e hidroxiurea, consiguiéndose una remisión completa de la eosinofilia y mejoría progresiva de las lesiones dérmicas. (AU)

A 77-year-old male, with a history of heart failure and atrial fibrillation receiving warfarin, hypothyroidism, diabetes mellitus and hyperuricaemia, with a one-year history of erythematous and desquamative skin lesions in the trunk, pruritic and moderate recurrent eosinophilia. After allergic, parasitic, autoimmune and neoplastic causes were ruled out, the diagnosis of idiopathic hypereosinophilic syndrome was done. He was treated with prednisone and hydroxyurea, resulting in complete remission of eosinophilia and progressive improvement of dermal lesions. (AU)

Hepatitis hipóxica en paciente con endomiocardiofibrosis / Hypoxic hepatitis in a patient with endomyocardial fibrosis

La endomiocardiofibrosis es una causa de miocardiopatía restrictiva frecuente en la región de África subsahariana, aunque poco frecuente en nuestra población. Posee estrecha relación con la presencia de hipereosinofilia en sangre y tiene alta morbimortalidad. La hepatitis hipóxica es una afección clínica con un patrón enzimático característico, muy prevalente en unidades de cuidados intensivos y elevada mortalidad. Se reconocen múltiples mecanismos fisiopatológicos, como la isquemia, la congestión venosa y la alteración en la utilización de oxígeno del hepatocito. Describimos el caso de u na paciente de 35 años, consumidora de cocaína, con diagnóstico de endomiocardiofibrosis secundario a síndrome hipereosinofílico idiopático que presentó shock cardiogénico y hepatitis hipóxica asociada. Evolucionó favorablemente con el tratamiento de sostén adecuado.

Endomyocardial fibrosis is a restrictive cardiomyopathy with high morbidity and mortality rates, prevalent in the sub-Saharan Africa region but infrequent in our population. It has a close relation with blood hypereosinophilia. Hypoxic hepatitis is frequently observed in intensive care units and its diagnosis is clinical. It shows a typical enzyme pattern with high mortality too. There are multiple mechanisms responsible for this condition, such as ischemia, passive congestion and dysoxia. We described the case of a 35 year-old cocaine addict woman diagnosed with endomyocardial fibrosis and hypereosinophilic syndrome who developed cardiogenic shock with hypoxic hepatitis. The patient evolved favorably with the appropriate treatment.

Hypereosinophilic syndrome in an infant / Síndrome hipereosinofílico en un lactante

Abstract Background The hypereosinophilic syndrome (HES) is defined by an eosinophilic count > 1500 cell/mm3 and organ damage or dysfunction that can be easily mistaken for atopic dermatitis or pulmonary pathologies. Timely diagnosis and treatment can improve the prognosis and avoid heart and renal complications or lung fibrosis. Case report The case of an infant is reported with a 24-h evolution of cough and fever, personal history of atopic dermatitis, and a generalized dermatosis 2 months earlier. In the initial approach, respiratory disease was considered. However, blood count reported hypereosinophilia, which led to further studies and the diagnosis of the HES. Conclusions Although a rare pathology, it is important to consider the HES in children with common symptoms, and unusual evolution or poor treatment response and persistent hypereosinophilia.

Resumen Introducción El síndrome hipereosinofílico se define por la cuenta de eosinófilos > 1,500 células/mm3 con daño orgánico o disfunción, sin ninguna causa subyacente. Puede ser fácilmente confundido con una dermatitis atópica o con patologías pulmonares. El diagnóstico temprano y el tratamiento adecuado pueden mejorar el pronóstico y evitar complicaciones cardíacas y renales o el desarrollo de fibrosis pulmonar. Caso clínico Se reporta el caso de un lactante con tos y fiebre de 24 horas de evolución y una historia personal de dermatitis atópica, además de dermatosis generalizada dos meses antes. Inicialmente, se consideró como una enfermedad respiratoria; sin embargo, la cuenta de células sanguíneas reportó hipereosinofilia, lo cual condujo a estudios confirmatorios y al diagnóstico de síndrome hipereosinofílico. Conclusiones A pesar de ser una enfermedad rara, es de suma importancia considerar el síndrome hipereosinofílico en el diagnóstico diferencial en niños con una evolución atípica o con pobre respuesta al tratamiento, además de hipereosinofilia persistente.

Case for diagnosis. Erythroderma as manifestation of hypereosinophilic syndrome

Abstract: Hypereosinophilic syndrome is defined as persistent eosinophilia (>1500/µL for more than six months) associated with organ involvement, excluding secondary causes. It is a rare, potentially lethal disease that should be considered in cutaneous conditions associated with hypereosinophilia. We report a case of erythroderma as a manifestation of hypereosinophilic syndrome. A 36-year-old male with no comorbidities presented progressive erythroderma, pruritus, peripheral neuropathy, and eosinophilia in the previous seven months. No mutations were found in FIP1L1/PDGFRA. Patient experienced rapid remission in response to oral prednisone and hydroxyurea. Cutaneous manifestations may be the only evidence of hypereosinophilic syndrome. Genotyping excludes myeloproliferative disease, thereby orienting treatment and prognosis.

Endomiocardite de Loeffler ­ manifestação cardíaca da síndrome hipereosinofílica: relato de caso / Loeffler's endomyocarditis ­ cardiac manifestation of hypereosinophilic syndrome: case report'

Introdução: A síndrome hipereosinofílica é caracterizada por uma produção aumentada e contínua de eosinófilos e pode levar a lesões teciduais em múltiplos órgãos, como consequência da infiltração eosinofílica. Os pacientes apresentam eosinofilia absoluta no sangue periférico (> 1.500 eosinófilos/mm3) sem uma causa primária de eosinofilia. A manifestação cardíaca desta síndrome geralmente se apresenta como endomiocardite de Loeffler, que constitui uma miocardiopatia restritiva primária resultante da infiltração de eosinófilos no tecido cardíaco. Descrição do caso: Relatamos o caso raro de uma paciente de 64 anos com eosinofilia a esclarecer e comprometimento cardíaco, que teve o diagnóstico estabelecido a partir de exames de imagem. Comentários: Enfatizamos os aspectos clínicos e evolutivos, ressaltando as dificuldades diagnósticas e a importância da investigação de eosinofilias persistentes sem causa aparente, uma vez que o diagnóstico e tratamento precoce podem proporcionar melhores taxas de sobrevida e prognóstico nestes pacientes.

Introduction: The hypereosinophilic syndrome is characterized by an increased, continuous production of eosinophils, and it may lead to tissue damage in multiple organs as a consequence of eosinophilic infiltration. Patients with this syndrome present absolute eosinophil count > 1,500 eosinophils/mm3 in the peripheral blood without a primary cause for eosinophilia. The cardiac manifestation of this syndrome usually presents as Loeffler's endomyocarditis, a primary restrictive cardiomyopathy resulting from the infiltration of eosinophils into cardiac tissue. Case description: We report the rare case of a 64-year-old woman with eosinophilia and cardiac involvement, who had the diagnosis established based on imaging tests. Comments: We emphasize the clinical and evolutionary aspects of the condition, highlighting the diagnostic difficulties and the importance of investigating persistent eosinophilia without an apparent cause, as early diagnosis and treatment can provide better survival rates and improved prognosis in these patients.

Edema idiopático. Presentación de un caso y revisión de la literatura / Idiopathic edema. Case report and literature review

El edema idiopático es un diagnóstico de exclusión, caracterizado por la acumulación de líquido en tejido intersticial en mujeres premenopáusicas en ausencia de patología cardiaca, renal o hepática. Típicamente los laboratorios y estudios complementarios son normales. El tratamiento es la Espironolactona debido al Hiperaldosteronismo secundario concomitante. De no ser efectivo, puede ser añadido o cambiado a un diurético tiazídico a la menor dosis efectiva. Es frecuente la resistencia a este grupo farmacológico.

Idiopathic edema is a diagnosis of exclusion, characterized by the accumulation of fluid in interstitial tissue in premenopausal women in the absence of cardiac, renal or hepatic pathology. Typically laboratories and complementary studies are normal. Treatment is Spironolactone due to concomitant secondary hyperaldosteronism. If not effective, it can be added or changed to a thiazide diuretic at the lowest effective dose. Resistance to this pharmacological group is frequent.

Síndrome Hipereosinofílico con Angioedema Recurrente: reporte de un caso clínico / Recurrent Angioedema with hypereosinophilic syndrome: a case report

El Síndrome Hipereosinofílico (SHE) constituye un grupo heterogéneo de enfermedades, que se caracterizan por una marcada eosinofilia en sangre, mayor a 1500 cel/mm³ de más de seis meses de evolución, asociado a daño de múltiples órganos, por infiltración eosinofílica ó liberación de mediadores. La eosinofilia es un hallazgo común en la práctica clínica, pero cuando se encuentran valores elevados de eosinófilos constituye un desafío diagnóstico. Presentamos el caso clínico de una paciente con antecedente de angioedema facial recurrente que consultó por tos poco productiva, toracodinia y disnea. El laboratorio mostró insuficiencia respiratoria con eosinofilia severa. La radiografía de tórax confirmó infiltrados pulmonares y derrame pleural. La paciente fue sometida a varios estudios complementarios, que nos orientaron hacia el diagnóstico de Síndrome Hipereosinofílico Idiopático, debido a la ausencia de causas secundarias y al hallazgo de eosinófilos en varios tejidos como médula ósea, líquido pleural, y lavado broncoalveolar. Se observó buena respuesta al tratamiento con corticoides sistémicos, logrando remisión completa de la enfermedad.

Hypereosinophilic Syndrome (HES) is a heterogeneous group of diseases, which are characterized by a marked eosinophilia in blood, greater than 1500 cells / mm³ over six months duration, associated with damage to multiple organs, eosinophilic infiltration, or release mediators. Eosinophilia is a common finding in clinical practice, but when levels of eosinophils are elevated can be a diagnostic challenge. We report the case of a patient with a history of recurrent facial angioedema, she consulted for some productive cough, dyspnea and toracodinia. The laboratory showed severe respiratory failure with eosinophilia. Chest radiography confirmed pulmonary infiltrates and pleural effusion. The patient underwent several complementary studies that guided us to the diagnosis of Idiopathic Hypereosinophilic Syndrome due to absence of secondary causes and finding of eosinophils in various tissues such as bone marrow, pleural fluid, and bronchoalveolar lavage. Good response to treatment with systemic corticosteroids was observed, achieving complete remission of the disease.

Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) / Reação a drogas com eosinofilia e sintomas sistêmicos (síndrome DRESS)

SUMMARY Objective: To review the hypersensitivity reaction to drugs known as drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), based on a case report. We also intend to discuss the difficulty and importance of disease recognition, since none of the changes is pathognomonic of this disease and failure to identify it may have disastrous consequences for the patient. Method: To describe this case report, in addition to the information collected for clinical assessment, a literature review was performed in the PubMed and Bireme databases in order to retrieve the latest information published in literature on DRESS syndrome. Results: The case of a 20-year old patient is reported. After anamnesis, physical examination and laboratory tests a diagnosis of DRESS syndrome was performed, characterized by rash, hematologic alterations, lymphadenopathy and lesions in target organ. This is a rare syndrome, whose frequency varies according to the drug used and the immune status of the patient, being more often associated with the use of anticonvulsants. Conclusion: The approach and discussion of the topic are of paramount importance, in view of the potential lethality of this treatable syndrome. Recognizing the occurrence of DRESS syndrome and starting treatment as soon as possible is crucial to reduce the risk of mortality and improve prognosis.

RESUMO Objetivo: fazer uma revisão da reação de hipersensibilidade a drogas denominada reação a drogas com eosinofilia e sintomas sistêmicos (síndrome DRESS), com base em um relato de caso clínico. Pretende-se ainda discutir a dificuldade e importância de seu reconhecimento, uma vez que nenhuma alteração dessa doença é patognomônica e sua não identificação pode trazer consequências desastrosas para o paciente. Método: para descrever este relato, além das informações coletadas no caso clínico, uma revisão da literatura nas bases de dados PubMed e Bireme foi realizada com o intuito de rever as informações mais recentes publicadas na literatura acerca da síndrome DRESS. Resultados: relatou-se o caso de uma paciente de 20 anos de idade que, após anamnese, exame físico e exames laboratoriais, foi diagnosticada com síndrome DRESS, caracterizada por erupção cutânea, alterações hematológicas, linfonodomegalia e lesões em órgão-alvo. É uma síndrome rara, cuja frequência varia conforme a droga utilizada e o estado imunológico do indivíduo, sendo mais associada ao uso de anticonvulsivantes. Conclusão: a abordagem e discussão do tema são de extrema importância, tendo em vista o potencial de letalidade dessa síndrome, que possui tratamento. Reconhecer precocemente a DRESS e instituir terapêutica é fundamental para reduzir o risco de mortalidade e melhorar o prognóstico.

Doenças hepatobiliares eosinofílicas: relato de dois casos e revisão de literatura / Eosinophilic hepatobiliary diseases: a report of two cases and literature review

As doenças hepatobiliares eosinofílicas são patologias raras de origem e de fatores etiológicos ainda não esclarecidos, sendo muitas vezes relacionadas à gastroenterite eosinofílica ou síndrome hipereosinofílica. Caracterizam-se por infiltração de eosinófilos em tecidos hepatobiliares e podem estar associadas à eosinofilia periférica na ausência de outras causas de eosinofilia. A raridade e conhecimento incompleto dessas doenças refletem na dificuldade de diagnóstico e de escolha terapêutica. O diagnóstico é feito através da exclusão de outras causas de eosinofilia periférica, tais como parasitoses, reações medicamentosas e doenças malignas, e também por análise histopatológica do tecido infiltrado. A maioria dos casos é responsiva ao tratamento com corticosteroides. Descrevemos dois casos clínicos, um de colecistite eosinofílica e outro de hepatite eosinofílica, avaliando, segundo revisão de literatura, a possibilidade de uma gastroenterite eosinofílica ou de uma síndrome hipereosinofílica em ambos os casos.

The eosinophilic hepatobiliary diseases are rare pathologies of origin and etiologic factors not yet clarified, being many times related to eosinophilic gastroenteritis or hipereosinophilic syndrome. They are characterized by an infiltration of eosinophils in hepatobiliary tissues and can be associated to peripheral eosinophilia, in the absence of other eosinophilia causes. The rareness and incomplete knowledge about these diseases reflect on the difficulty of diagnosis and choice of treatment. The diagnosis is made through exclusion of other causes of peripheral eosinofilia, such as parasitosis, drug reactions and malignant diseases, and also through histopathological analysis of the infiltrated tissue. Most cases respond to treatment with corticosteroids. We reported two cases, one of eosinophilic colecistitis and other of eosinophilic hepatitis, evaluating, according to literature review, the possibility of eosinophilic gastroenteritis or hipereosinophilic syndrome in both cases.

Gastroenteropatía eosinofílica: Reporte de un caso y revisión de la literatura / Case Report of Eosinophilic Gastroenteropathy and a Literature Review

Introducción: la gastroenteropatía eosinofílica es una enfermedad rara caracterizada por infiltración de eosinófilos en una o más capas a diferentes niveles del tracto grastrointestinal, siendo común en estómago y duodeno. Aunque en la mayoría de los casos se presenta con dolor abdominal, también puede aparecer vómito, diarrea, ascitis y pérdida de peso. Reporte de caso: hombre de 41 años con cuadro clínico de 9 meses de evolución de dolor abdominal súbito e intermitente, de predominio en mesogastrio irradiado a región lumbar, manejado con antiespasmódicos sin mejoría. Antecedentes de: infarto agudo de miocardio 2 años atrás con arterias coronarias sanas según angiografía, nefrectomía derecha hace 11 años por hidronefrosis, diagnóstico y tratamiento desde hace 3 años de anemia microcítica hipocrómica con hipereosinofilia, apendicitis aguda hace 7 meses con hallazgos en la patología de infiltrados eosinofílicos, y una biopsia de médula ósea que reveló eosinofilia. Al examen físico: signos vitales normales, ruidos intestinales aumentados en intensidad y frecuencia (40/min) y mesogastrio doloroso a la palpación; sin masas ni visceromegalias. Sus laboratorios revelaron anemia y eosinofilia de 16%. Las imágenes diagnósticas reportaron una esofagogastroileítis, con evidencia microscópica de infiltración eosinofila en todas las muestras, por lo cual se diagnosticó gastroenteropatía eosinofílica iniciando manejo con dieta hipoalergénica y prednisona. Discusión: hasta 25% de los pacientes con síndrome hipereosinofílico puede tener infiltración gastrointestinal, por lo que la gastroenteropatía eosinofílica debe sospecharse en todo paciente con dolor abdominal y eosinofilia periférica, no obstante, esta última no siempre está presente, siendo necesario un diagnóstico histopatológico.

Introduction: Eosinophilic gastroenteropathy is a rare disease characterized by infiltration of eosinophils into one or more layers in different parts of the gastrointestinal tract especially the stomach and the duodenum. Although in most cases it presents with abdominal pain, vomiting, diarrhea, ascites and weight loss may also appear. Case report: The patient was a 41 year old man with a clinical picture of 9 months of sudden, intermittent abdominal pain (predominantly mesogastric pain which radiated to the lumbar region). He had been treated with antispasmodics but had not improved. Eleven years earlier he had had a right nephrectomy because of hydronephrosis. Three years earlier he had been diagnosed and treated for hypochromic microcytic anemia with hypereosinophilia. Two years earlier he had had an acute myocardial infarct, although angiography showed healthy coronary arteries. Seven months earlier he developed acute appendicitis. The pathology report at that time showed eosinophilic infiltrates, and a bone marrow biopsy revealed eosinophilia. Physical examination showed normal vital signs, but his bowel sounds were more intense and frequent (40/min) than normal, and he suffered mesogastric pain on palpation. There were no masses or organomegaly. Laboratory tests revealed anemia and 16% eosinophilia. Diagnostic images showed esophageal and gastric ileitis with microscopic evidence of eosinophil infiltration in all samples. Eosinophilic gastroenteropathy was diagnosed, and the patient was started on a hypoallergenic diet and treated with prednisone. Up to 25% of patients with hypereosinophilic syndrome may have gastrointestinal infiltration. Eosinophilic gastroenteropathy should be suspected in any patient with abdominal pain and peripheral eosinophilia. However, peripheral eosinophilia is not always present, and histopathological diagnosis is necessary.

Leucemia eosinofílica crónica con respuesta hematológica sostenida tras tratamiento con bajas dosis de imatinib / Sustained hematologic response in chronic eosinophilic leukemia with low dose imatinib. Report of one case

We report a 58 year-old-man without comorbid conditions, with a history of two months of weight loss, malaise and headache. His initial laboratory analysis showed leukocytosis of 16,100/mL with 65% eosinophils and an absolute eosinophil count of 10,465/mL. Both bone marrow biopsy and aspirate showed infiltration by mature appearing eosinophils. Treatment was started with hydroxyurea, associated with prednisone without satisfactory decrease in the eosinophil count. Polymerase chain reaction showed the presence of the gene fusion product FIP1L1/PDGFRA. Imatinib therapy was initiated, resulting in a rapid and progressive reduction in the absolute eosinophil count, with normalization at the second week of treatment. The incidence of the myeloproliferative variant causing hypereosinophilic syndrome is rare. However, the dramatic response to imatinib emphasizes the need to study the presence of the fusion product FIP1L1/PDGFRA in all patients with eosinophilia of unknown etiology.

Síndrome hipereosinofílico y síndrome de Churg-Strauss ¿Espectro de una misma enfermedad? Nuevos conceptos / Hypereosinophilic syndrome and Churg-Strauss syndrome Spectrum of the same disease? New concepts

Propósito de la revisión: revisar la literatura actual sobre el síndrome hipereosinofílico y establecercuáles son las diferencias y semejanzas con el síndrome de Churg-Strauss. Fuente de datos: revisión estructurada de la literatura médica, en las bases de datos Pubmed, Medline y Cochrane. Selección de estudios: se limitó la búsqueda a los artículos de revisión, guías de manejo y meta-análisis, sin límites en idioma ni fecha de publicación, utilizando los términos MESH: hypereosinophilic síndrome, eosinophilic, Churg-Strauss sindrome. Se acoplaron a términos como: update, review, associations. Extracción de datos: se hizo la lectura del resumen de 232 trabajos de los cuales se seleccionaron 111 que eran representativos para el tema de esta revisión, después de una clasificación y ordenamiento, se procedió a la redacción del texto. Conclusiones: el síndrome hipereosinofílico comprende un grupo heterogéneo de enfermedades con presentaciones clínicas muy variadas, para algunos autores el síndrome de Churg-Strauss o más recientemente conocido como granulomatosis eosinofílica con poliangiítis hace parte de este gran síndrome pero para otros, deben considerarse como entidades aparte. (Acta Med Colomb 2014; 39: 174-184).

Purpose of review: to review the current literature on the hypereosinophilic syndrome and establish which are the differences and similarities with Churg-Strauss syndrome. Source of data: structured review of the medical literature in databases Pubmed, Medline and Cochrane. Study selection: the search was limited to review articles, management guidelines and meta-analysis with no limits on language or publication date, using the MESH terms: hypereosinophilic syndrome, eosinophilic, Churg-Strauss syndrome. These were coupled to terms like:update, review, association. Data extraction: reading of the summary of 232 studies was made. Of these, 111 that were representative for the subject of this review, were selected, and after an ordered classification system, the wording was performed. Conclusions: The hypereosinophilic syndrome comprises a heterogeneous group of diseases with varied clinical presentations; for some authors, Churg-Strauss, more recently known as eosinophilic granulomatosis with polyangiitis, is part of this great syndrome, but for others these should be considered as separate entities. (Acta Med Colomb 2014; 39: 174-184).

Mesilato de imatinibe para o tratamento da síndrome hipereosinfílica / Imatinib mesylate for the treatment of hypereosinflic syndrome

CONTEXTO: A Síndrome Hipereosinofílica (SHE) é um grupo heterogêneo de doenças raras, definida por uma variedade de manifestações clínicas, como: presença persistente de eosinofilia no sangue periférico (≥1,5x109/L) por pelo menos 6 meses; ausência de uma causa secundária; e evidência de lesão em órgão alvo induzidas pela liberação de citocinas e fatores humorais dos grânulos eosinofílicos. A mutação genética mais encontrada é a fusão FIP1L1/PDGFRα. A taxa de incidência da SHE é de aproximadamente 0,035 por 100.000 pessoas-ano, já a incidência da fusão FIP1L1/ PDGFRα é em torno de 10-20% entre pacientes com hipereosinofilia idiopática. TRATAMENTO: O tratamento da SHE tenta limitar as lesões de órgãos controlando a contagem de eosinófilos e inclui prednisona, hidroxiuréia, interferon alfa e quimioterapia citotóxica. Na maioria dos casos, contudo, a doença é fatal. A TECNOLOGIA: O mesilato de imatinibe é um inibidor seletivo das proteínas tirosina quinase, incluindo o receptor alfa do fator de crescimento derivado de plaqueta (PDGFRα). O medicamento liga-se competitivamente ao receptor dependente de ATP e inibe a fosforilação da tirosina quinase. EVIDÊNCIAS CIENTÍFICAS: A evidência atualmente disponível sobre eficácia e segurança do mesilato de imatinibe para tratamento da SHE é baseada em um estudo experimental Fase II, duas séries de casos e um relato de casos. O estudo Fase II, com o melhor nível de evidência, foi realizado com 16 pacientes com a mutação FIP1L1/PDGFRα, com dose inicial diária de 100mg. Ao final do estudo, houve resposta hematológica completa em 100% dos casos em um tempo mediano de 0,8 meses (0,2-3,3) e resposta molecular completa em 75% dos pacientes (n=12) em 6 meses. O estudo demonstrou toxicidade hematológica em 31% dos pacientes e ocorreu durante as primeiras 4-6 semanas. CONSIDERAÇÕES FINAIS: A evidência atualmente disponível sobre eficácia e segurança do Mesilato de Imatinibe para tratamento da Sindrome Hipereosinofílica com a mutação FIP1L1/PDGFRα é baseada em estudos com baixa qualidade metodológica. Apesar disso, o benefício clínico demonstrado é aceitável, além do fato de ser uma doença rara, sem protocolo clínico estabelecido no SUS. O impacto orçamentário é relativamente baixo, tendo em vista o pequeno número de pacientes que possuem a doença. DELIBERAÇÃO FINAL: PORTARIA Nº 39, de 6 de outubro de 2014 - Torna pública a decisão de incorporar o mesilato de imatinibe para o tratamento da síndrome hipereosinfílica no Sistema Único de Saúde - SUS.

Hypoxia/reoxygenation-induced myocardial lesions in newborn piglets are related to interindividual variability and not to oxygen concentration

OBJECTIVE: Evaluation of myocardial histological changes in an experimental animal model of neonatal hypoxiareoxygenation. METHODS: Normocapnic hypoxia was induced in 40 male Landrace/Large White piglets. Reoxygenation was initiated when the animals developed bradycardia (HR <60 beats/min) or severe hypotension (MAP <15 mmHg). The animals were divided into four groups based on the oxygen (O2) concentration used for reoxygenation; groups 1, 2, 3, and 4 received 18%, 21%, 40%, and 100% O2, respectively. The animals were further classified into five groups based on the time required for reoxygenation: A: fast recovery (<15 min); B: medium recovery (15-45 min); C: slow recovery (45-90 min); D: very slow recovery (>90 min), and E: nine deceased piglets. RESULTS: Histology revealed changes in all heart specimens. Interstitial edema, a wavy arrangement, hypereosinophilia and coagulative necrosis of cardiomyocytes were observed frequently. No differences in the incidence of changes were observed among groups 1-4, whereas marked differences regarding the frequency and the degree of changes were found among groups A-E. Coagulative necrosis was correlated with increased recovery time: this condition was detected post-asphyxia in 14%, 57%, and 100% of piglets with fast, medium, and slow or very slow recovery rates, respectively. CONCLUSIONS: The significant myocardial histological changes observed suggest that this experimental model might be a reliable model for investigating human neonatal cardiac hypoxia-related injury. No correlation was observed between the severity of histological changes and the fiO2 used during reoxygenation. Severe myocardial changes correlated strictly with recovery time, suggesting an unreported individual susceptibility of myocardiocytes to hypoxia, possibly leading to death after the typical time-sequence of events.