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.

Ischemic cholangitis: Lethal complication of Osler-Weber-Rendu disease.

Osler-Weber-Rendu disease (OWRD), also known as hereditary haemorrhagic telangiectasia (HHT), is an autosomal dominant genetic disorder characterised by arteriovenous malformations in several organs. Ischemic cholangitis is a rare life-threatening complication of OWRD, with only a few documented cases in the literature. A liver transplant is the main curative treatment. In this paper, we report a case of a 33-year-old woman with a history of recurrent epistaxis, admitted with abdominal pain and fever, physical examination found multiple cutaneous and mucosal telangiectasias and the biological workup showed cholestasis, abdominal imaging identified arterio-venous shunts and multiple cystic hepatic lesions, one of them seemed to communicate with an intrahepatic biliary duct, finally the diagnosis of ischemic cholangitis due to OWRD was retained and antibiotic treatment has been initiated. We review the various therapeutic options available to improve the management of this fatal complication.

Early Infantile Diagnosis of Hereditary Hemorrhagic Telangiectasia Complicated by Child Abuse.

We report a rare case of hereditary hemorrhagic telangiectasia (HHT) in a 4-month-old female infant with findings of child abuse. She presented with poor feeding, vomiting, and irritability after a short fall from the bed. Initial evaluation found subdural hematomas, persistent hypoxia, failure to thrive, a frenulum tear, facial lacerations, and bruising. The patient was admitted, and an extensive workup led to the diagnosis of brain and pulmonary arteriovenous malformations and finally the diagnosis of HHT. The subdural hematomas, cutaneous injuries, and oral injury were highly suspicious for child abuse and were reported to Child Protective Services and law enforcement for investigation simultaneous to the medical work-up. Her hospital course was complicated by progressive hypoxemia with radiographic evidence of several large pulmonary arteriovenous malformations, for which she underwent successful embolization. Her head injury was indeterminate for physical abuse in the setting of a medical condition predisposing to intracranial hemorrhage. A few weeks later, she was readmitted with repeat abusive injuries in the form of femur fractures. This case demonstrates the unique diagnostic dilemma when 2 diagnoses are occurring simultaneously-HHT and child abuse-and showcases the importance of a detailed family history, genetic testing, strong multidisciplinary collaboration with a holistic approach and medically informed Child Protective Services systems to ensure accurate diagnoses and safe disposition.

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.

[Sir William Osler: facets of personality].

William Osler is one of the most honored and influential physicians in the English medicine late 19th early 20th century, who has made a great contribution on development of medical science and it's teaching. The scope of his multifaceted personality goes far beyond the characteristics of an outstanding doctor and scientist. The historical essay presents various aspects of the Osler's personality, highlighting his uniqueness as a doctor, teacher and philosopher.

ACR Appropriateness Criteria® Pulmonary Arteriovenous Malformation (PAVM): 2023 Update.

Pulmonary arteriovenous malformations (PAVMs) occur in 30% to 50% of patients with hereditary hemorrhagic telangiectasia. Clinical presentations vary from asymptomatic disease to complications resulting from the right to left shunting of blood through the PAVM such as paradoxical stroke, brain abscesses, hypoxemia, and cardiac failure. Radiology plays an important role both in the diagnosis and treatment of PAVM. Based on different clinical scenarios, the appropriate imaging study has been reviewed and is presented in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Pulmonary arteriovenous malformation (PAVM): 2023 update

Pulmonary arteriovenous malformations (PAVMs) occur in 30% to 50% of patients with hereditary hemorrhagic telangiectasia. Clinical presentations vary from asymptomatic disease to complications resulting from the right to left shunting of blood through the PAVM such as paradoxical stroke, brain abscesses, hypoxemia, and cardiac failure. Radiology plays an important role both in the diagnosis and treatment of PAVM. Based on different clinical scenarios, the appropriate imaging study has been reviewed and is presented in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Spontaneous haemothorax caused by a ruptured pulmonary arterio-venous malformation: A manifestation of hereditary haemorrhagic telangiectasia in pregnancy.

We report our experience of managing a massive haemothorax caused by a ruptured, previously unknown, pulmonary arteriovenous malformation (pAVM) at 34 + 5 weeks of gestation, which proved to be a manifestation of hereditary haemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome. The patient underwent an emergency caesarean section under general anaesthesia after placement of a chest tube and gave birth to a healthy infant. A postoperative thoracic computed tomography angiography highlighted the presence of the large pAVM. Transcatheter embolization was performed right after the delivery. Subsequent patient's anamnesis, family history and genetic analysis finally revealed the presence of the syndrome. The aim of our report is to create awareness of this serious condition with potential life-threatening complications, especially in pregnancy. Simple criteria have been published and allow to easily consider HHT and the presence of potential AVM during anamnesis, ideally even before pregnancy.

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.

Prenatal diagnosis of pulmonary arteriovenous malformations with a postnatal diagnosis of Osler-Weber-Rendu syndrome.

Hereditary Hemorrhagic Telangiectasia (HHT), commonly known as Osler-Weber-Rendu disease, is an autosomal dominant multisystemic vascular disease associated with approximately 70% of cases of pulmonary arteriovenous malformations (PAVMs). Prenatal cases of PAVMs typically present with pulmonary vein dilatation on ultrasonography. This study presents a prenatal diagnosis of PAVMs with enlarged right pulmonary vein, cardiomegaly, cystic-appearing areas in the right lung and subsequent confirmation of Osler-Weber-Rendu syndrome using autopsy and whole exom sequencing.

Conservative management by embolization of a ruptured renal arterio-venous malformation (AVM) in Hereditary Hemorrhagic Telangiectasia (HHT).

BACKGROUND: Renal arteriovenous malformation (AVM) in Hereditary Hemorrhagic Telangiectasia (HHT) is uncommon and only few cases have been described, mainly with surgical management because of uncontrolled hematuria. CASE PRESENTATION: We managed a 70-year-old patient with HHT who presented with hematuria and left flank pain. Computed Tomography and ultrasound showed left renal AVM of 18 mm with clotting in the urinary tract. An external ureteral catheter was placed during 3 days to allow rinsing and facilitate elimination of clots. Given the patient's hemodynamic stability, a non-surgical management was chosen. Treatment of the AVM was performed by trans-arterial embolization using micro-coils and ethylene-vinyl alcohol copolymer. CONCLUSIONS: Our case study shows a conservative management by embolization of ruptured left renal AVM revealed by hematuria in a 70-year-old patient with HHT.

A Case of an Splenic Artery Aneurysm and Focal Nodular Hyperplasia Associated with an Abdominal Vascular Abnormality of Hereditary Hemorrhagic Telangiectasia.

In October 2021, a 51-year-old woman developed a skin rash. Abdominal computed tomography revealed a large splenic artery aneurysm and an intrahepatic portovenous shunt. As her splenic artery aneurysm was at risk of rupture, she was referred to the Kindai University Hospital and underwent coiling surgery. In October 2023, approximately two years after she had been initially referred, contrast-enhanced ultrasound revealed findings suggestive of focal nodular hyperplasia. No reports have confirmed the occurrence of liver masses in patients with hereditary hemorrhagic telangiectasia, which is considered to be an interesting finding when investigating the mechanism of tumor development.

Elevated FVIII levels in hereditary hemorrhagic telangiectasia: Implications for clinical management.

Objectives: The objective of this study was twofold: to determine the prevalence of arterial and venous thromboembolic events in the Norwegian Hereditary Hemorrhagic Telangiectasia (HHT) population, and to explore potential factors linked to such events, with particular emphasis on FVIII. Methods: Patients with an HHT diagnosis attending the Otorhinolaryngology Department at Oslo University Hospital-Rikshospitalet were included consecutively between April 2021 and November 2022. We recorded the participants' medical history with an emphasis on thromboembolic events. Measurements of blood constituents, including FVIII, FIX, vWF, hemoglobin, iron, ferritin, and CRP were performed. Results: One hundred and thirty-four patients were included in the study. The total prevalence of thromboembolic events among the participants was 23.1%. FVIII levels were high (>150 IU/dL) in the majority of HHT patients (n = 84) (68.3%) and were significantly associated with thromboembolic events (p < .001), as was age. Of the patients with high FVIII levels, 28 (33%) had experienced a thromboembolic event. Furthermore, FVIII levels were measured consecutively in 51 patients and were found to fluctuate above or below 150 IU/dL in 25% of these cases. Conclusion: Thromboembolic events are highly prevalent in the Norwegian HHT population and are significantly associated with FVIII levels. FVIII levels can fluctuate, and measurements should be repeated in HHT patients to assess the risk of thromboembolic events. Level of Evidence: 4.

The Mayo, Cushing, and Osler Influence on A. L. Rhoton: A Historical Vignette of the Interconnectedness Between Highly Influential Neurosurgery Leaders over 100 Years.

The careers of the Mayo brothers, Harvey Cushing, and Sir William Osler greatly shaped medical and surgical practice in the late 19th century and early 20th century and created a legacy to influence decades of physicians to follow. Additionally, these individuals were instrumental in the founding of neurosurgery as a distinct surgical specialty. Alongside these great men, Dr. Albert L. Rhoton Jr., revolutionized neurosurgical practice through his study of neuroanatomy and development of microsurgical technique in the second half of the 20th century. This review of the interactions and relationships between the Mayo brothers, Cushing, and Osler and their influences on Rhoton highlights the 100-year-long interconnectedness shared between these giants in the history of neurosurgery.

John Alexander Mullin (1835-1899): The Canadian Physician who first described Osler's Nodes.

Sir William Osler (1849-1919), who became Regius Professor of Medicine at Oxford in 1905, first drew attention in 1909 to the painful nodes in subacute bacterial endocarditis, which now carry his eponym, and he published an account in the Quarterly Journal of Medicine, which he helped establish. Attention is drawn to the often overlooked fact that it was a Dr John Alexander Mullin (1835-1899) of Hamilton, Ontario, Canada, who first drew the attention of Sir William Oster to their occurrence. Confusion arose over the relationship between Osler's nodes and the skin lesions described by Theodore Caldwell Janeway (1872-1917), which are generally non-tender and found in acute bacterial endocarditis. The evidence is that there is essentially no difference since their pathogenesis and histological findings are identical.

[Brain abscess as a complication of pulmonary manifestation of HHT]. / Hirnabszess als Komplikation bei pulmonaler Manifestation einer HHT.

A 43-year-old female patient with a brain abscess and a complicated clinical course was diagnosed with hereditary haemorrhagic telangiectasia (HHT) at the Martin Zeitz Centre for Rare Diseases in Hamburg, Germany. The brain abscess was caused by pulmonary arteriovenous malformations (AVM), a typical finding in HHT. Patients with cryptogenic brain abscess should be screened for pulmonary AVM and HHT. This case report illustrates the importance of patient history and interdisciplinary exchange in patients with a broad clinical spectrum as well as interdisciplinary treatment in the case of complications of rare diseases.

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.

Concept of Osler’s patient view and doctor-patient narrative community in narrative medicine / 中国医学伦理学

In the context of modern medicine， it’s difficult for doctors lacking narrative thinking to get into the hearts of patients and offer high-quality medical service. Precise classification terms and decontextualized abstract language have become communication barriers between doctors and patients， creating an atmosphere of unusual indifference and fear during the medical process. William Osler， the father of modern medicine， emphasized that doctors should respect the individuality of patients， and advocated that doctors should use life-oriented language to provide humanistic care to patients. This echoes the concept of the “doctor-patient narrative community” in the construction of the Chinese narrative medicine system. As a brand new clinical humanistic practice path， narrative medicine focuses on the keyword “narrative” and revolves around the theme of “inter-subjective relationship” in the medical context， advocates that doctors switch flexibly in the two references of science and life， achieve visual fusion with patients and their families， pay attention to patients’ life experiences， and establish narrative connections with them. On this basis， it can achieve two-way narrative interaction， build a harmonious doctor-patient narrative community， and thus enhance the patient’s medical experience.