Abstract
Current treatment of severe epistaxis in patients with hereditary hemorrhagic telangiectasia is not durable in reducing the frequency and severity of bleeds. Recent reports have demonstrated marked improvement of epistaxis with administration of either intravenous or topical bevacizumab. We present the long-term outcome of a patient who received repeated treatments of intravenous bevacizumab followed by maintenance intranasal bevacizumab. We demonstrate durable control of epistaxis with intranasal bevacizumab. This allows delivery of bevacizumab effectively, reduces cost, and obviates the risk of systemic adverse effects related to bevacizumab.
1
Introduction
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome , is an autosomal dominant inherited disease affecting approximately 1 in 5000. Spontaneous and recurrent epistaxis is the most common presenting symptom. Other manifestations include mucocutaneous telangiectases, visceral organ arteriovenous malformations, and affected first-degree relatives . Recurrent epistaxis can result in severe anemia requiring intravenous (IV) iron and blood transfusions. Management of severe HHT can be invasive, and its effects are not durable in reducing the frequency and severity of bleeds.
Elevated plasma levels of vascular endothelial growth factor (VEGF) play a key pathogenic role in HHT . Bevacizumab, an anti-VEGF monoclonal antibody, prevents the binding of VEGF to VEGF receptor on endothelial cells, thus blocking cellular proliferation and angiogenesis. As a result, bevacizumab has been used as a potential treatment of recurrent epistaxis . Previous studies have demonstrated marked improvement of epistaxis with administration of bevacizumab. We recently reported the efficacy of IV bevacizumab for long-term treatment of anemia and epistaxis in a separate patient with severe HHT .
Intranasal treatment with bevacizumab, by either submucosal injection or topical nasal spray, has recently been reported to be a safe alternative to IV treatment . We describe a patient initially treated with IV bevacizumab who subsequently demonstrated durable control of epistaxis with topical intranasal bevacizumab.
2
Case report
A 55-year-old woman with HHT, chronic epistaxis, and baseline hemoglobin level of 11 g/dL was treated for breast cancer with chemotherapy. In addition to chemotherapy-induced anemia, chemotherapy also resulted in increased epistaxis despite having a normal platelet count. She required multiple red blood cell transfusions during her chemotherapy course. Her epistaxis persisted after chemotherapy, causing her to be transfusion dependent.
Prior treatments for her HHT-related epistaxis included 2 decades of cauterization, initially with silver nitrate, then neodymium:yttrium-aluminum-garnet laser treatments, followed by potassium-titanyl-phosphate laser treatments. These treatment modalities became less effective the longer she dealt with the disease. Because of chemotherapy-induced anemia and increased epistaxis, a new treatment option was sought.
She received 4 infusions of IV bevacizumab delivered every 2 weeks (10 mg/kg for dose 1 and 2 and 5 mg/kg for doses 3 and 4). Within 1 month, her epistaxis frequency decreased and ceased altogether. She received 2 infusions of IV bevacizumab over the next 9 months whenever her epistaxis recurred. Intravenous bevacizumab therapy resulted in a steady rise in her hemoglobin to 13.6 g/dL. At that point, she began receiving topical intranasal bevacizumab therapy as maintenance treatment of epistaxis. Topical treatment seemed to control her epistaxis for at least 8 weeks at a time. She received 100 mg of scheduled intranasal bevacizumab every 8 to 9 weeks with doses instilled topically in a 4-mL spray with an atomizer. She only had 2 minor episodes of epistaxis throughout her maintenance therapy, which were easily controlled in clinic. Her hemoglobin levels were maintained, and she continues to receive topical therapy to date ( Fig. 1 ). She experienced no systemic adverse effects from intranasal bevacizumab.
2
Case report
A 55-year-old woman with HHT, chronic epistaxis, and baseline hemoglobin level of 11 g/dL was treated for breast cancer with chemotherapy. In addition to chemotherapy-induced anemia, chemotherapy also resulted in increased epistaxis despite having a normal platelet count. She required multiple red blood cell transfusions during her chemotherapy course. Her epistaxis persisted after chemotherapy, causing her to be transfusion dependent.
Prior treatments for her HHT-related epistaxis included 2 decades of cauterization, initially with silver nitrate, then neodymium:yttrium-aluminum-garnet laser treatments, followed by potassium-titanyl-phosphate laser treatments. These treatment modalities became less effective the longer she dealt with the disease. Because of chemotherapy-induced anemia and increased epistaxis, a new treatment option was sought.
She received 4 infusions of IV bevacizumab delivered every 2 weeks (10 mg/kg for dose 1 and 2 and 5 mg/kg for doses 3 and 4). Within 1 month, her epistaxis frequency decreased and ceased altogether. She received 2 infusions of IV bevacizumab over the next 9 months whenever her epistaxis recurred. Intravenous bevacizumab therapy resulted in a steady rise in her hemoglobin to 13.6 g/dL. At that point, she began receiving topical intranasal bevacizumab therapy as maintenance treatment of epistaxis. Topical treatment seemed to control her epistaxis for at least 8 weeks at a time. She received 100 mg of scheduled intranasal bevacizumab every 8 to 9 weeks with doses instilled topically in a 4-mL spray with an atomizer. She only had 2 minor episodes of epistaxis throughout her maintenance therapy, which were easily controlled in clinic. Her hemoglobin levels were maintained, and she continues to receive topical therapy to date ( Fig. 1 ). She experienced no systemic adverse effects from intranasal bevacizumab.
