Effect of Topical Intranasal Therapy on Epistaxis Frequency in Patients With Hereditary Hemorrhagic Telangiectasia

Whitehead, Kevin J.; Sautter, Nathan B.; McWilliams, J.; Chakinala, Murali M.; Merlo, Christian A.; Johnson, Maribeth H.; James, Melissa K.; Everett, Eric; Clancy, Marianne; Faughnan, Marie E.; Oh, S. Paul; Olitsky, Scott E.; Pyeritz, Reed E.; Gossage, James R.

doi:10.1001/jama.2016.11724

Cited by 87 publications

(136 citation statements)

References 24 publications

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“…These observations are in line with several early-phase clinical trials supporting that bevacizumab treatments—using topical, submucosal, or i.v. infusion routes—were effective at reducing epistaxis in HHT patients484950, but see also refs 51 and 52.…”

Section: Discussionmentioning

confidence: 99%

A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10

Ruíz

Zhao

Chandakkar

et al. 2016

Sci Rep

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Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening genetic vascular disorder caused by loss-of-function mutations in the genes encoding activin receptor-like kinase 1 (ALK1), endoglin, Smad4, and bone morphogenetic protein 9 (BMP9). Injections of mouse neonates with BMP9/10 blocking antibodies lead to HHT-like vascular defects in the postnatal retinal angiogenesis model. Mothers and their newborns share the same immunity through the transfer of maternal antibodies during lactation. Here, we investigated whether the transmammary delivery route could improve the ease and consistency of administering anti-BMP9/10 antibodies in the postnatal retinal angiogenesis model. We found that anti-BMP9/10 antibodies, when intraperitoneally injected into lactating dams, are efficiently transferred into the blood circulation of lactationally-exposed neonatal pups. Strikingly, pups receiving anti-BMP9/10 antibodies via lactation displayed consistent and robust vascular pathology in the retina, which included hypervascularization and defects in arteriovenous specification, as well as the presence of multiple and massive arteriovenous malformations. Furthermore, RNA-Seq analyses of neonatal retinas identified an increase in the key pro-angiogenic factor, angiopoietin-2, as the most significant change in gene expression triggered by the transmammary delivery of anti-BMP9/10 antibodies. Transmammary-delivered BMP9/10 immunoblocking in the mouse neonatal retina is therefore a practical, noninvasive, reliable, and robust model of HHT vascular pathology.

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Section: Discussionmentioning

confidence: 99%

A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10

Ruíz

Zhao

Chandakkar

et al. 2016

Sci Rep

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“…Affected patients develop cutaneous, mucosal, or visceral telangiectasias and sometimes aneurysms, that may be associated with severe bleeding, for example nose bleed or intracranial hemorrhage [26].…”

Section: Resultsmentioning

confidence: 99%

Interdisciplinary Management of Head and Neck Vascular Anomalies: Clinical Presentation, Diagnostic Findings and Minimalinvasive Therapies

Sadick

Wohlgemuth

Huelse

et al. 2017

European Journal of Radiology Open

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ObjectivesVascular anomalies are included in the 30 000 rare diseases worldwide affecting less than 5/10 000 people. Depending on their morphology and biological properties, they can cause varied disorders with organ involvement. Almost 60% of vascular anomalies have a predilection for the head and neck region in children. Clinical and scientific effort to establish interdisciplinary management concepts for vascular anomalies is increasing worldwide.MethodsEspecially in the head and neck region, clinical impairment and organ dysfunction is associated with cosmetic issues that may represent a physical and psychological issue for the patient. Correct diagnosis, based on clinical presentation and symptoms, is a prerequisite for appropriate therapy, ranging from conservative management to a spectrum of minimally invasive treatment options. We searched PubMed for German and English language published data until December 2016 with focus on clinical studies, review articles and case reports on vascular anomalies with a focus on the head and neck region.ResultsThe last ISSVA update in 2014 has contributed to a better understanding of vascular anomalies, classifying them in vascular tumors and vascular malformations. The predominant representatives of vascular tumors are congenital and infantile hemangiomas. Infantile hemangiomas have the ability of spontaneous regression in more than 80%. Patients with symptomatic growing hemangiomas with ulcerations, bleeding complications and restriction of hearing, swallowing disorder, impairment of vision, or cosmetic dysfigurement require treatment. Therapies include oral propanolol, transcatheter embolization and surgery. Vascular malformations tend to progress with patientś age and are subdivided in slow flow and fast flow lesions. Symptomatic slow flow lesions, e.g. venous and lymphatic malformations, benefit from percutaneous sclerotherapy. Fast flow lesions, as arteriovenous malformations, are rare but undoubtedly therapeutically the most challenging vascular anomaly. Depending on location and size, they may require multiple transcatheter embolization procedures for successful occlusion of the AVM.ConclusionsThis review provides knowledge on the current ISSVA classification of vascular anomalies, their clinical presentation, diagnostic evaluation and minimally invasive therapy options to encourage the establishment of a comprehensive interdisciplinary management for head and neck vascular anomalies.

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“…Dupuis-Girod et al 12 compared a placebo group and three groups receiving different doses of bevacizumab (25, 50 or 75 mg per treatment) administered as a nasal spray (three sprays 14 days apart for a total treatment duration of 4 weeks), resulting in total doses of 75 mg, 150 mg and 225 mg in the bevacizumab treatment groups. In the other clinical trials,13 patients received twice-daily nose sprays for 12 weeks with either bevacizumab 1% (4 mg/day), estriol 0.1% (0.4 mg/day), tranexamic acid 10% (40 mg/day) or placebo (0.9% saline). No statistical difference was observed in mean duration of epistaxis after treatment in the placebo group compared with the other groups, regardless of dose group.…”

Section: Discussionmentioning

confidence: 99%

Intranasal bevacizumab treatment on epistaxis in hereditary haemorrhagic telangiectasia: a case report

et al. 2017

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Hereditary haemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a rare, vascular, autosomal dominant disorder. The purpose of this paper is to describe the efficacy and safety of treatment with intranasal bevacizumab in HHT.A 42-year-old woman with HHT presented with frequent episodes of epistaxis. Iron studies showed anaemia of iron deficiency from chronic blood loss. Because of the frequent epistaxis (Epistaxis Severity Score (ESS) 6.76) and varying haemoglobin levels (Hb range: 7.7–9.9g/dL) her doctors sought treatment with intranasal bevacizumab. This treatment was prescribed at the hospital pharmacy department in a laminar flow hood. 2.5 mL (25 mg) were placed in a nasal spray bottle. The recommended dosage was twice a day for two consecutive months. Nasal treatment seemed to control her epistaxis, and no adverse effects were reported. She only had a few further minor episodes of epistaxis, which were easily controlled (ESS 3.44). The haemoglobin levels evreached normal levels (Hb range: 12.8–14.1g/dL).

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Effect of Topical Intranasal Therapy on Epistaxis Frequency in Patients With Hereditary Hemorrhagic Telangiectasia

Cited by 87 publications

References 24 publications

A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10

A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10

Interdisciplinary Management of Head and Neck Vascular Anomalies: Clinical Presentation, Diagnostic Findings and Minimalinvasive Therapies

Intranasal bevacizumab treatment on epistaxis in hereditary haemorrhagic telangiectasia: a case report

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