Management of hereditary hemorrhagic telangiectasia-like symptoms induced by trastuzumab emtansine in a breast cancer patient: case report.

Trastuzumab emtansine (T-DM1) is a targeted therapy combining trastuzumab and emtansine for human epidermal growth factor receptor 2(HER2)-positive breast cancer, with common side effects including fatigue, nausea, pain, headache, low platelet count, and elevated liver enzymes. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by vascular malformations and telangiectasias in various organs. We present a case of a female patient with advanced breast cancer who developed HHT-like symptoms while on T-DM1 treatment. A 59-year-old woman treated with radiotherapy and T-DM1 every 21 days developed recurring nosebleeds and mucocutaneous and liver telangiectasias indistinguishable from HHT three months after receiving the first dose of T-DM1. Other organ vascular malformations were ruled out through screening protocols. The patient had no previous HHT symptoms or family history. Nasal care measures like lubrication and antifibrinolytics (tranexamic acid) were provided. In addition, propranolol was also prescribed due to its antiangiogenic and antitumoral properties, leading to significantly decreased epistaxis and telangiectasias. Microtubule disruptions caused by T-DM1, along with other angiogenic mechanisms may contribute to the development of telangiectasias resembling HHT. The use of propranolol, an initial approach for HHT, proved to be effective in this case. It is crucial for oncologists and HHT specialists to be aware of this rare adverse event associated with T-DM1 and to implement appropriate management strategies.

Prevalence of hereditary hemorrhagic telangiectasia in a medical care program organization in Buenos Aires, Argentina / Prevalencia de telangiectasia hemorrágica hereditaria en un sistema privado de salud de Buenos Aires, Argentina

Abstract Introduction : Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia that might affect 1/5000-10 000 individuals worldwide. It is a rare and underdiagnosed condition. Population-based epidemiological studies are crucial for comprehending and quantifying the impact of this disease. We aim to estimate the prevalence in a Prepaid Health Care System of Buenos Aires, Argentina. Methods : A descriptive cross-sectional study was de signed, which included all patients over 18 years of age affiliated with the Hospital Italiano Medical Care Program (IHMCP), a prepaid health maintenance organization (HMO) of Buenos Aires. For case inclusion, individuals were required to have a clinical diagnosis of HHT. Case detection included the search in our Institutional Registry. The prevalence was calculated by dividing the number of cases of HHT by the total number of all active affiliates at January 2023. Age and gender specific prevalence rates were estimated. Results : 48 cases were reported. The prevalence was 3.2 in 10 000 (IC 95% 2.4-4.2). Specific prevalence in women was 3.9 in 10 000 (IC 95% 2.8-5.5) and in men 2.1 in 10 000 (IC 95% 1.2-3.6). The average age was 54.8 (19), 35 patients were women (72.9%) with an aver age age of 55 (19.9), and 55 (17.2) for men. The most common referrals were physicians (60.4%) followed by family history (18.7%). The 48 patients corresponded to 39 families. Discussion : The prevalence identified in our study is higher than the one documented in other studies.

Resumen Introducción : La telangiectasia hemorrágica heredita ria (HHT) es una displasia vascular que puede afectar a 1 de 5000 a 10 000 personas en el mundo. Es una afección rara y subdiagnosticada. Los estudios epidemiológicos son fundamentales para comprender y cuantificar el im pacto de esta enfermedad. Nuestro objetivo fue estimar la prevalencia en un Sistema Prepago de Atención de la Salud, en Buenos Aires, Argentina. Métodos : Estudio descriptivo transversal en pacientes mayores de 18 años afiliados al Programa de Atención Médica del Hospital Italiano en Buenos Aires (Plan de Sa lud). Para la inclusión de casos, se requería el diagnóstico de HHT. La detección de casos incluyó su búsqueda en nuestro Registro Institucional. La prevalencia se calculó dividiendo el número de casos por el número total de afiliados activos en enero de 2023. Se estimaron tasas específicas por edad y género. Resultados : Se reportaron 48 casos. La prevalencia fue de 3.2 por 10 000 personas (IC 95% 2.4-4.2). La específica en mujeres fue de 3.9 (IC 95% 2.8-5.5) y en hombres de 2.1 por 10 000 (IC 95% 1.2-3.6). La edad promedio fue de 55 años (19), con 35 pacientes mujeres (72.9%) con una edad promedio de 55 años (19.9) y 55 (17.2) para hom bres. La derivación más común fue de médicos (60.4%), seguidas por antecedentes familiares (18.7%). Los 48 pacientes correspondían a 39 familias. Discusión : La prevalencia identificada en nuestro es tudio es más alta que la documentada en otros estudios.

Pulmonary arteriovenous malformations in Rendu-Osler-Weber syndrome.

Rendu-Osler-Weber syndrome, also known as hereditary hemorrhagic telangiectasia, is an autosomal dominant hereditary disorder. It is characterized by presence of multiple arteriovenous malformations (AVMs) and telangiectasias. This article reports two cases of patients with Rendu-Osler-Weber syndrome who had pulmonary AVMs and underwent successful endovascular treatment. A brief review of the literature shows that up to 50% of patients with the syndrome have pulmonary AVMs and there is usually a positive family history in these patients. These pulmonary AVMs are multiple in 30% of cases and are associated with the most severe disease complications. Most patients are asymptomatic, even in the presence of AVMs with right-left shunts. When these shunts exceed 25% of the total blood volume, dyspnea, cyanosis, digital clubbing, and extracardiac murmurs may occur. Endovascular treatment is safe and offers control of complications from hereditary hemorrhagic telangiectasia and is currently the treatment of choice for these lesions.

Prevalence of hereditary hemorrhagic telangiectasia in a medical care program organization in Buenos Aires, Argentina.

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia that might affect 1/5000-10 000 individuals worldwide. It is a rare and underdiagnosed condition. Population-based epidemiological studies are crucial for comprehending and quantifying the impact of this disease. We aim to estimate the prevalence in a Prepaid Health Care System of Buenos Aires, Argentina. METHODS: A descriptive cross-sectional study was designed, which included all patients over 18 years of age affiliated with the Hospital Italiano Medical Care Program (IHMCP), a prepaid health maintenance organization (HMO) of Buenos Aires. For case inclusion, individuals were required to have a clinical diagnosis of HHT. Case detection included the search in our Institutional Registry. The prevalence was calculated by dividing the number of cases of HHT by the total number of all active affiliates at January 2023. Age and gender specific prevalence rates were estimated. RESULTS: 48 cases were reported. The prevalence was 3.2 in 10 000 (IC 95% 2.4-4.2). Specific prevalence in women was 3.9 in 10 000 (IC 95% 2.8-5.5) and in men 2.1 in 10 000 (IC 95% 1.2-3.6). The average age was 54.8 (19), 35 patients were women (72.9%) with an average age of 55 (19.9), and 55 (17.2) for men. The most common referrals were physicians (60.4%) followed by family history (18.7%). The 48 patients corresponded to 39 families. DISCUSSION: The prevalence identified in our study is higher than the one documented in other studies.

Introducción: La telangiectasia hemorrágica hereditaria (HHT) es una displasia vascular que puede afectar a 1 de 5000 a 10 000 personas en el mundo. Es una afección rara y subdiagnosticada. Los estudios epidemiológicos son fundamentales para comprender y cuantificar el impacto de esta enfermedad. Nuestro objetivo fue estimar la prevalencia en un Sistema Prepago de Atención de la Salud, en Buenos Aires, Argentina. Métodos: Estudio descriptivo transversal en pacientes mayores de 18 años afiliados al Programa de Atención Médica del Hospital Italiano en Buenos Aires (Plan de Salud). Para la inclusión de casos, se requería el diagnóstico de HHT. La detección de casos incluyó su búsqueda en nuestro Registro Institucional. La prevalencia se calculó dividiendo el número de casos por el número total de afiliados activos en enero de 2023. Se estimaron tasas específicas por edad y género. Resultados: Se reportaron 48 casos. La prevalencia fue de 3.2 por 10 000 personas (IC 95% 2.4-4.2). La específica en mujeres fue de 3.9 (IC 95% 2.8-5.5) y en hombres de 2.1 por 10 000 (IC 95% 1.2-3.6). La edad promedio fue de 55 años (19), con 35 pacientes mujeres (72.9%) con una edad promedio de 55 años (19.9) y 55 (17.2) para hombres. La derivación más común fue de médicos (60.4%), seguidas por antecedentes familiares (18.7%). Los 48 pacientes correspondían a 39 familias. Discusión: La prevalencia identificada en nuestro estudio es más alta que la documentada en otros estudios.

Un caso pediátrico de telangiectasia hemorrágica hereditaria (Síndrome de Rendu-Osler-Weber) con compromiso pulmonar / A pediatric case of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber Syndrome) with pulmonary involvement

La telangiectasia hemorrágica hereditaria (HHT), o síndrome de Rendu-Osler-Weber, se considera dentro del grupo de las enfermedades raras, pues afecta a 1 de cada 3.000 a 8.000 individuos. Tiene un patrón de herencia autosómica dominante y la mayor parte de los casos se debe a una alteración en la codificación de los genes endoglina (ENG) y activina receptor-like kinase 1 (ALK1), dando origen a los tipos 1 y 2, respectivamente. Esta alteración genética se traduce en una displasia del endotelio de la pared vascular debido a haploinsuficiencia para endoglina y se manifiesta clínicamente con epistaxis a repetición, telangiectasias mucocutáneas y malformaciones arteriovenosas (MAV) viscerales. A continuación, se presenta el caso clínico de una paciente pediátrica de 11 años de edad que se manifestó por disnea e hipoxemia severa debido a múltiples fístulas arteriovenosas pulmonares.

Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is considered among rare diseases, as it affects 1 in every 3,000 to 8,000 individuals. It follows an autosomal dominant inheritance pattern, and most cases are due to alterations in the coding of the endoglin (ENG) and activin receptor-like kinase 1 (ALK1) genes, leading to types 1 and 2, respectively. This genetic alteration results in vascular endothelial dysplasia due to haploinsufficiency for endoglin and clinically manifests with recurrent epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations (AVMs). Herein, we present the clinical case of an 11-year-old pediatric patient who exhibited severe dyspnea and hypoxemia due to multiple pulmonary arteriovenous fistulas.

Malformações arteriovenosas pulmonares na síndrome de Rendu-Osler-Weber / Pulmonary arteriovenous malformations in Rendu-Osler-Weber syndrome

Resumo A síndrome de Rendu-Osler-Weber, também conhecida como telangiectasia hemorrágica hereditária, é uma doença hereditária autossômica dominante. Ela é caracterizada pela presença de múltiplas malformações arteriovenosas e telangiectasias. Este artigo relata dois casos de pacientes com síndrome de Rendu-Osler-Weber que apresentaram malformações arteriovenosas pulmonares e foram submetidos a tratamento endovascular com sucesso. Uma breve revisão da literatura mostra que até 50% dos pacientes com a síndrome têm malformações arteriovenosas pulmonares e geralmente há um histórico familiar positivo nesses pacientes. Em 30% dos casos, elas são múltiplas e estão associadas a complicações mais graves da doença. A maioria dos pacientes é assintomática, mesmo na presença de malformações arteriovenosas com shunt direito-esquerdo. Quando esses shunts excedem 25% do volume total de sangue, podem surgir dispneia, cianose, baqueteamento digital e sopros extracardíacos. O tratamento endovascular oferece segurança e controle das complicações da telangiectasia hemorrágica hereditária, sendo atualmente o tratamento de escolha para essas lesões.

Abstract Rendu-Osler-Weber syndrome, also known as hereditary hemorrhagic telangiectasia, is an autosomal dominant hereditary disorder. It is characterized by presence of multiple arteriovenous malformations (AVMs) and telangiectasias. This article reports two cases of patients with Rendu-Osler-Weber syndrome who had pulmonary AVMs and underwent successful endovascular treatment. A brief review of the literature shows that up to 50% of patients with the syndrome have pulmonary AVMs and there is usually a positive family history in these patients. These pulmonary AVMs are multiple in 30% of cases and are associated with the most severe disease complications. Most patients are asymptomatic, even in the presence of AVMs with right-left shunts. When these shunts exceed 25% of the total blood volume, dyspnea, cyanosis, digital clubbing, and extracardiac murmurs may occur. Endovascular treatment is safe and offers control of complications from hereditary hemorrhagic telangiectasia and is currently the treatment of choice for these lesions.

Síndrome de Rendu-Osler-Weber com acometimento multissistêmico: um relato de caso e revisão de literatura frente à Terapia Antiangiogênica / Rendu-Osler-Weber syndrome with multisystem involvement: a case report and literature review regarding Antiangiogenic Therapy

A Telangiectasia Hemorrágica Hereditária ou Síndrome de Rendu-Osler-Weber é uma displasia fibrovascular sistêmica de herança autossômica dominante caracterizada por epistaxes de repetição, telangiectasias mucocutâneas e malformações arteriovenosas (MAVs) que frequentemente acometem as circulações pulmonar, hepática e cerebral. Tratamentos sistêmicos podem ser necessários para aqueles com sangramento refratário geralmente manifestados por necessidade de múltiplas transfusões sanguíneas e reposição de ferro. Com o avançar dos estudos, em 2020, houve a incorporação de terapias antiangiogênicas sistêmicas nos algoritmos para epistaxe, sangramentos de trato gastrointestinal e MAVs hepáticas graves. Neste estudo, trazemos o relato de uma paciente com a síndrome atendida no Hospital Municipal Moysés Deutsch localizado em São Paulo-SP no mês de maio de 2022. Além disso, faz-se uma revisão bibliográfica de sua etiopatogenia, manifestações clínicas e terapêutica com ênfase no que temos de mais novo em relação às terapias sistêmicas antiangiogênicas, ainda com necessidade de estudos controlados randomizados em busca de evidências mais consolidadas em relação à eficácia, perfis de segurança e eventos adversos.

Cirugía de Young para el tratamiento quirúrgico de la epistaxis en telangiectasia hemorrágica hereditaria: reporte de un caso y revisión de la literatura / Young's procedure for surgical treatment of epistaxis in hereditary hemorrhagic telangiectasia: A case report and literature review

La telangiectasia hemorrágica hereditaria (THH) es una displasia vascular multisistémica, de herencia autosómica dominante, caracterizada por el desarrollo de telangiectasias mucocutáneas y malformaciones arteriovenosas viscerales. El diagnóstico se realiza mediante los criterios de Curasao publicados en el año 2000 y su manejo requiere de un equipo multidisciplinario donde el rol del otorrinolaringólogo(a) es fundamental, puesto que la epistaxis se presenta en un 90%-95% de los pacientes siendo una de las primeras manifestaciones clínicas de la enfermedad y pudiendo amenazar la vida del paciente. En la literatura se describen múltiples alternativas de tratamiento médico y quirúrgico para la epistaxis, sin existir un tratamiento definitivo para la enfermedad. A continuación, presentaremos el caso de una paciente de 56 años con THH y epistaxis recurrentes severas que, tras no responder al tratamiento médico conservador y múltiples procedimientos quirúrgicos, se realizó el cierre nasal mediante el procedimiento de Young, constituyendo el primer caso reportado en nuestro país.

Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic vascular dysplasia, of autosomal dominant inheritance, characterized by the development of mucocutaneous telangiectasias and visceral arteriovenous malformations. The diagnosis is made using the Curafao criteria published in 2000 and its management requires a multidisciplinary team where the role of the ENTs is fundamental, since epistaxis occurs in 90%-95% of patients, being one of the first clinical manifestations of the disease and may threaten the life of the patient. Multiple medical and surgical treatment alternatives for epistaxis are described in the literature without a definitive treatment for the disease. Here, we present the case of a 56-year-old patient with severe recurrent HHT and epistaxis who, after not responding to the initial conservative and surgical treatments, a nasal closure was performed, using the Young's procedure, constituting the first case reported in our country.

Enfermedad de Rendu-Osler-Weber con presentación inusual / Rendu-Osler-Weber´s disease with unusual presentation

La enfermedad de Rendu-Osler-Weber, también conocido como telangiectasia hemorrágica hereditaria, es una enfermedad genética de herencia autosómica dominante con penetrancia incompleta. Afecta por igual a ambos sexos y los síntomas se inician habitualmente entre los 20 y 40 años, pero se considera que la enfermedad está infradiagnosticada. Típicamente las formas clínicas y el debut de esta enfermedad se asocian a los órganos y tejidos que se afectan con mayor frecuencia: telangiectasias en mucosas y en piel, epistaxis, sangramiento gastrointestinal, pulmonar e intracerebral. En contraste, el caso clínico que se presenta se caracteriza porque las primeras manifestaciones clínicas que motivaron la consulta médica fueron crisis de dolores e inflamación ósea en el miembro superior derecho, lo cual es inusual y se inscribe como un elemento de novedad en la enfermedad. Es el objetivo de esta publicación exponer un caso de telangiectasia hemorrágica hereditaria con una forma de presentación atípica en una adolescente. Al alta hospitalaria, la paciente estaba estable, sin complicaciones. Se recomendó seguimiento hospitalario fundamentalmente por la especialidad de Neumología, por ser los pulmones los órganos más afectados(AU)

Rendu-Osler-Weber´s disease, also known as hereditary hemorrhagic telangiectasia, is a genetic disease of autosomal dominant inheritance with incomplete penetrance. It affects both sexes equally and symptoms usually begin between the ages of 20 and 40, but it is considered that the disease is underdiagnosed. Typically, the clinical forms and the onset of this disease are associated with the organs and tissues that are most frequently affected: mucosal and skin telangiectasias, epistaxis, gastrointestinal, pulmonary and intracerebral bleeding. In contrast, the clinical case that is presented is characterized because the first clinical manifestations that motivated the medical consultation were crises of pain and bone inflammation in the right upper limb, which is unusual and is inscribed as an element of novelty in the disease. The objective of this publication is to present a case of hereditary hemorrhagic telangiectasia with an atypical presentation in a female teenager(AU)

A Novel Splicing Mutation in the ACVRL1/ALK1 Gene as a Cause of HHT2.

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare disorder of vascular development. Common manifestations include epistaxis, telangiectasias and arteriovenous malformations in multiple organs. Different deletions or nonsense mutations have been described in the ENG (HHT1) or ACVRL1/ALK1 (HHT2) genes, all affecting endothelial homeostasis. A novel mutation in ACVRL1/ALK1 has been identified in a Peruvian family with a clinical history compatible to HHT. Subsequently, 23 DNA samples from oral exchanges (buccal swaps) of the immediate family members were analyzed together with their clinical histories. A routine cDNA PCR followed by comparative DNA sequencing between the founder and another healthy family member showed the presence of the aforementioned specific mutation. The single mutation detected (c.525 + 1G > T) affects the consensus splice junction immediately after exon 4, provokes anomalous splicing and leads to the inclusion of intron IV between exons 4 and 5 in the ACVRL1/ALK1 mRNA and, therefore, to ALK1 haploinsufficiency. Complete sequencing determined that 10 of the 25 family members analyzed were affected by the same mutation. Notably, the approach described in this report could be used as a diagnostic technique, easily incorporated in clinical practice in developing countries and easily extrapolated to other patients carrying such a mutation.

Telangiectasia hemorrágica hereditaria durante el embarazo: Reporte de caso / Hereditary hemorrhagic telangiectasia during pregnancy: Case report

Resumen ANTECEDENTES: La telangiectasia hemorrágica hereditaria, o síndrome de Rendu-Osler-Weber, es una enfermedad vascular, hereditaria y autosómica caracterizada por telangiectasias mucocutáneas y malformaciones arteriovenosas en el pulmón, el cerebro e hígado. La prevalencia estimada es de 1.5 a 2 personas afectadas por cada 10,000 habitantes. El 90% de los casos se debe a una mutación en el gen endoglina y en el de la cinasa 1 similar al receptor de activina (ACVRL1). En la mujer embarazada, la telangiectasia hemorrágica hereditaria es de alto riesgo, sobre todo durante el segundo y tercer trimestre. OBJETIVO: Reportar un caso de telangiectasia hemorrágica hereditaria y exponer las complicaciones que pueden registrarse durante el embarazo. CASO CLÍNICO: Paciente de 23 años, con antecedente heredofamiliar de madre con diagnóstico de telangiectasia hemorrágica hereditaria (síndrome de Osler-Weber-Rendu) que falleció a los 38 años. Antecedente personal patológico de telangiectasia hemorrágica hereditaria, con diagnóstico a los 12 años luego de múltiples episodios de epistaxis. Recibió tratamiento con transfusiones sanguíneas en múltiples ocasiones y 200 mg de sulfato ferroso cada 24 horas. CONCLUSIÓN: La telangiectasia hemorrágica hereditaria condiciona, en la mujer embarazada, la aparición de complicaciones que pueden poner en riesgo la vida de la madre y el feto. Las mujeres con antecedente conocido deben valorarse antes de la concepción con el propósito de conocer el estado de la enfermedad.

Abstract BACKGROUND: Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber syndrome, is an autosomal inherited vascular disease characterized by mucocutaneous telangiectasias and arteriovenous malformations in the lung, brain and liver. The estimated prevalence is 1.5 to 2 affected persons per 10,000 population. Ninety percent of cases are due to a mutation in the endoglin gene and in the activin receptor-like kinase 1 gene (ACVRL1). In pregnant women, hereditary hemorrhagic telangiectasia is high risk, especially during the second and third trimester. OBJECTIVE: To report a case of hereditary hemorrhagic telangiectasia and to expose the complications that can occur during pregnancy. CLINICAL CASE: 23-year-old patient, with hereditary family history of mother diagnosed with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) who died at 38 years of age. Personal pathological history of hereditary hemorrhagic telangiectasia, diagnosed at the age of 12 years after multiple episodes of epistaxis. She was treated with multiple blood transfusions and 200 mg of ferrous sulfate every 24 hours. CONCLUSION: Hereditary hemorrhagic telangiectasia conditions, in pregnant women, the appearance of complications that can put the life of the mother and fetus at risk. Women with a known history should be evaluated before conception in order to know the status of the disease.

Sangramento gastrointestinal em paciente portador de síndrome de Rendu-Osler-Weber: relato de caso / Gastrointestinal bleeding in a patient with Osler-Weber-Rendu syndrome: a case report / Sangrado gastrointestinal en paciente con síndrome de Rendu-Osler-Weber: reporte de caso

A síndrome de Rendu-Osler-Weber, ou telangiectasia hemorrágica hereditária (THH), é uma doença autossômica dominante de penetrância variável que altera a camada muscular e elástica da parede dos vasos sanguíneos, causando neles grande fragilidade e dilatação e tornando-os suscetíveis a sangramentos secundários, a traumatismos e malformações arteriovenosas (MAV) ­ sendo elas as mais comuns no cérebro, nos pulmões e no trato gastrointestinal e hepático. Este relato de caso tem como objetivo realizar uma revisão sobre essa síndrome, bem como a respeito da melhor terapia e do melhor manejo para sangramentos gastrointestinais por angiectasias. Trata-se de uma paciente de 62 anos de idade, com episódio de hematêmese e melena recorrentes, que foi admitida instável hemodinamicamente e com queda importante dos níveis de hemoglobina, necessitando de múltiplas transfusões sanguíneas. Após entrevista clínica, que chamou a atenção para o histórico familiar de quadros similares, epistaxes recorrentes associados ao exame físico e angiectasias gástricas à endoscopia digestiva alta, foi atribuído o diagnóstico de síndrome de Rendu-Osler-Weber. Angiectasias foram erradicadas com terapia endoscópica usando plasma de argônio. A THH é uma doença subdiagnosticada que merece atenção especial por conta do seu risco de causar hemorragias graves com expressão fenotípica mais aflorada com o avançar da idade. Por seu cunho hereditário, faz-se necessário um acompanhamento médico linear com a família para evitar complicações secundárias da doença, bem como para o manejo adequado de suas apresentações.

Osler-Weber-Rendu syndrome or hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that changes the muscular and elastic layer of the blood vessel wall, making them fragile and more susceptible to bleeding secondary to trauma and arteriovenous malformations (AVM) ­ a condition that commonly affects the brain, lungs, gastrointestinal tract, and liver. This study aims to perform a literature review on this syndrome, as well as on the best treatment and management for gastrointestinal bleeding from angioctasia. To this end, it reports the case of a 62-year-old female patient with recurrent episodes of hematemesis and melena, who was admitted to hospital with hemodynamic instability and low hemoglobin levels, requiring multiple blood transfusions. After clinical interview, which indicated family history of recurrent epistaxis, physical examination, and upper digestive endoscopy showing gastric angiectasias, the patient was diagnosed with Osler-Weber-Rendu syndrome. Angiectasias were treated with endoscopic argon plasma. Considering the risk of severe hemorrhages and its more pronounced phenotypic expression with advancing age, HHT is an underdiagnosed disease that deserves special attention. Due to its hereditary nature, a linear medical follow-up with the family is necessary to avoid secondary complications of the disease, as well as the proper management of its presentations.

El síndrome de Rendu-Osler-Weber o telangiectasia hemorrágica hereditaria (THH) es una enfermedad autosómica dominante de penetrancia variable, que modifica la capa muscular y elástica de la pared de los vasos sanguíneos, provocando una gran fragilidad y dilatación de estas, haciéndolas susceptibles a hemorragias secundarias a trauma y malformaciones arteriovenosas (MAV), que son las más comunes en el cerebro, pulmones, tracto gastrointestinal e hígado. Este estudio tiene como objetivo realizar una revisión de este síndrome, así como la mejor terapia y manejo del sangrado gastrointestinal por angioctasia en esta patología. Se trata de un paciente de 62 años, con episodio de hematemesis recurrente y melena, que ingresa hemodinámicamente inestable y con descenso significativo de los niveles de hemoglobina, requiriendo múltiples transfusiones sanguíneas. Tras entrevista clínica, destacando los antecedentes familiares de patologías similares, epistaxis recurrente, exploración física y angiectasias gástricas a endoscopia digestiva alta, se asignó el diagnóstico de síndrome de Rendu-Osler-Weber. Las angiectasias se erradicaron con terapia endoscópica con plasma de argón. La HHT es una enfermedad infradiagnosticada que merece una atención especial por su riesgo de hemorragias severas, con una expresión fenotípica más pronunciada con el avance de la edad. Además de su carácter hereditario, es necesario un seguimiento médico lineal con la familia para evitar complicaciones secundarias de la enfermedad, así como el adecuado manejo de sus presentaciones.

Cauterización transoral de la arteria maxilar interna en la fosa infratemporal: informe de un caso / Transoral cauterization of the internal maxillary artery in the infratemporal fossa: case report

Se describe el caso clínico de una paciente de 84 años que tuvo epistaxis recidivante por padecer enfermedad de Rendu-Osler-Weber. Tuvo antecedentes de diversos tratamientos quirúrgicos que incluyeron el cierre de la fosa nasal izquierda (operación de Young). Por la persistencia de epistaxis izquierda se indicó una angiografía y embolización. Esta última no se hizo porque se diagnosticaron anastomosis entre el sistema carotídeo externo y el interno. Se realizó un abordaje intraoral paramaxilar asistido con endoscopios para cauterizar la arteria maxilar interna en la fosa infratemporal y un abordaje externo para cauterizar la arteria etmoidal anterior solucionando la epistaxis. (AU)

The clinical case of an 84-year-old patient who had recurrent epistaxis due to Rendu-Osler- Weber disease is described. She had a history of various surgical treatments including closure of the left nostril (Young's operation).Due to the persistence of left epistaxis, angiography and embolization were indicated. The latter was not done because anastomosis between the external and internal carotid system was diagnosed. An intraoral paramaxillary approach assisted with endoscopes was performed to cauterize the internal maxillary artery in the infratemporal fossa and an external approach to cauterize the anterior ethmoidal artery solving the epistaxis. (AU)

Rupture of suppurated liver hematoma into the anterior abdominal wall in a patient with Rendu-Osler-Weber syndrome.

We report a case of ruptured liver hematoma as a result of suppurated arteriovenous malformation (AVM) in a patient with Rendu-Osler-Weber (ROW) syndrome. The patient presented with unexplained fever and upper right abdominal pain associated with microcytic anemia. A computed tomography scan revealed increasing subcapsular liver hematoma and features of liver abscess. Intraoperatively, a left liver hematoma mixed with pus was found that was attached to the anterior abdominal wall. Surgery included left lateral bisegmentectomy, while pathohistological analysis showed AVM and genetic tests confirmed ROW. This is the first such life-threatening surgical case of ROW complication reported in the scientific literature.

Reportamos el caso de una paciente con síndrome de Rendu-Osler-Weber y rotura de un hematoma hepático supurado como resultado de una malformación arteriovenosa. La paciente presentó fiebre inexplicable y dolor abdominal superior derecho asociado con anemia microcítica. La tomografía computarizada reveló un aumento del hematoma hepático subcapsular y las características del absceso hepático. Durante la cirugía se encontró un hematoma hepático izquierdo mezclado con pus que estaba unido a la pared abdominal anterior. La intervención incluyó bisegmentectomía lateral izquierda. El análisis histopatológico mostró malformación arteriovenosa y las pruebas genéticas confirmaron el síndrome de Rendu-Osler-Weber. Este es el primer caso quirúrgico potencialmente mortal de complicación de síndrome de Rendu-Osler-Weber reportado en la literatura científica.

Síndrome de Osler-Weber-Rendu: presentación de un caso clínico y revisión de la literatura / Osler-Weber-Rendu syndrome: a case report and literature review

El síndrome de Osler-Weber-Rendu, también conocido como telangiectasia hemorrágica hereditaria, es una enfermedad de herencia autosómica dominante de baja prevalencia, que se caracteriza por unas paredes delgadas de los vasos sanguíneos que conducen a malformaciones arteriovenosas, principalmente en cerebro, pulmón e hígado, pero que pueden potencialmente afectar cualquier otro órgano. La principal manifestación clínica son las epistaxis recurrentes; sin embargo, también pueden aparecer otras manifestaciones como hemoptisis o sangrado gastrointestinal, y telangiectasias mucocutáneas, entre otras. Su expresión clínica varía de un paciente a otro y el diagnóstico usualmente se basa en los criterios de Curazao. Se describe el caso de una paciente con historia de 12 años de epistaxis recurrente, a quien se le diagnosticó síndrome de Osler-Weber-Rendu hace dos años. Fue referida al servicio de Hepatología por presentar compromiso hepático, además de malformaciones arteriovenosas cerebrales y pulmonares. El manejo óptimo de la telangiectasia hemorrágica en esta paciente por parte de los diferentes especialistas, apoyado en los estudios de imagenología, ha permitido que la paciente tenga una buena calidad de vida hasta el momento. Se presenta el caso de esta paciente de 46 años y se realiza una revisión corta de la literatura.

Osler-Weber-Rendu syndrome, also known as hereditary hemorrhagic telangiectasia, is an autosomal dominant low-prevalence disease, characterized by thin blood vessel walls, leading to arteriovenous malformations, mainly in the brain, lung and liver, but can potentially affect any other organ. The main clinical manifestation is recurrent epistaxis; however, other manifestations may also appear, such as hemoptysis or gastrointestinal bleeding, and mucocutaneous telangiectasias, among others. Its clinical expression varies from patient to patient and the diagnosis is usually based on Curacao criteria. We present the case of a patient with a 12-year history of recurrent epistaxis, who was diagnosed with Osler-Weber-Rendu syndrome two years ago. She was referred to the Hepatology service due to liver findings, in addition to brain and pulmonary arteriovenous malformations. The optimal management of hemorrhagic telangiectasia in this patient by the different specialists, supported by imaging studies, has allowed the patient to have a good quality of life. The case of this 46-year-old patient is presented, and a brief literature review is also provided.

William Osler and Harvey Williams Cushing: Friendship Around Neurosurgery.

William Osler was a mentor for the younger William Harvey Cushing and they intermingled careers and friendship for the rest of their lives. They shared a common interest in the anatomy and pathology of neurological disorders, and in the history of medicine. Their behavior was, however, sharply different: Osler was the revered physician, full of wisdom and good humor, and Cushing, the prestigious surgeon, in a perennial and successful struggle to improve neurosurgery and himself. Both became medical icons, one beloved, and the other admired, each praised at their death centennial and 150 birth anniversary, respectively.

Dosis atípica de bevacizumab en un paciente con síndrome de Osler-Weber-Rendu / Atypical dose of bevacizumab in a patient with Osler-Weber Rendu syndrome

Resumen El síndrome de Osler-Weber-Rendu es una enfermedad de transmisión autosómica dominante. Si bien el síntoma más común es la epistaxis, existen muchas alteraciones viscerales que deben considerarse al momento del estudio. Los anti-VEFG son un pilar en el tratamiento, aunque no existe consenso acerca de la dosis a administrar. Comunicamos el caso de un paciente con síndrome de Osler-Weber-Rendu atendido en el servicio de Medicina Interna del Hospital Regional de Puebla, al que se prescribió una dosis atípica de bevacizumab con buena respuesta terapéutica.

Abstract Osler-Weber-Rendu syndrome is an autosomical dominant condition. Although epistaxis is the most frequent symptom, many other visceral implications have to be considered while the workup takes place. While Anti-VEGF are the cornerstone of the treatment, there is no consensus regarding the specific dose to be administered. We communicate de case of a patient with Osler-Weber-Rendu syndrome attended at our Hospital in which we prescribed an atypical dose of bevacizumab with good outcome.

El legado de Sir William Osler a la Universidad Médica cubana / The legacy of Sir William Osler to the Cuban Medical University

William Osler es recordado como uno de los más grandes y respetados médicos de la historia. La autora describe aspectos esenciales de su vida, su obra y su filosofía. El objetivo de este artículo es destacar el aporte que hizo a la educación médica y el énfasis en la educación en el trabajo, pilares que forman parte indispensables en el sistema de educación médica cubana (AU).

William Osler is remembered as one of the biggest and more estimated physicians of the history. The author describes main aspects of his life, work and philosophy. The aim of this article is highlighting his contribution he made to medical education with emphasis in the education at work, mainstays and essential part of the Cuban medical education system (AU).

Telangiectasia hemorrágica hereditaria: a propósito de un caso clínico / Hereditary hemorrhagic telangiectasia: on the subject of a clinical case

La epistaxis, es un síntoma frecuente en la consulta de otorrinolaringología. Dentro de las causas posibles encontramos la telangiectasia hemorrágica hereditaria (síndrome de Rendu Osler Weber), que corresponde a un desorden autosómico dominante caracterizado por sangrados nasales y gastrointestinales asociados a malformaciones arteriovenosas sistémicas. Su manifestación más frecuente es la epistaxis, presentándose más frecuentemente en personas mayores de 40 años, sin predilección por género. Se presenta el caso de un paciente de sexo masculino de 46 años quien consulta por epistaxis a repetición y severa. Durante la hospitalización se efectúa el tratamiento convencional de la epistaxis, diagnóstico retroactivo del síndrome de Rendu Osler Weber y manejo multidisciplinario de la patología. Se realiza revisión de la literatura y discusión del manejo del paciente que cursa con esta enfermedad.

Epistaxis is a common symptom in the otorhinolaryngology consultation. Among the possible causes are hereditary hemorrhagic telangiectasia (Rendu Osler Weber syndrome), which corresponds to an autosomal dominant disorder characterized by nasal and gastrointestinal bleeding associated with systemic arteriovenous malformations. Its most frequent manifestation is epistaxis, presenting more frequently in people over 40 years of age, without gender preference. We present the case of a male patient of 46 years old who consults for recurrence and severe epistaxis. During hospitalization, conventional treatment of epistaxis, retroactive diagnosis of Rendu Osler Weber syndrome and multidisciplinary management of pathology are performed. We review the literature and discuss the management of patients with this disease.