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1.
Angiogenesis ; 24(2): 379-386, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33211216

RESUMO

The inhibiting effects of itraconazole, an antifungal drug on vascular endothelial growth factor (VEGF) have recently been discovered. By inhibiting VEGF, itraconazole has shown potential in clinical trials as anti-cancer treatment. In hereditary hemorrhagic telangiectasia (HHT) patients, VEGF levels are elevated and inhibition of VEGF can decrease bleeding. Itraconazole could potentially serve as anti-angiogenic therapy for HHT-related bleeding. We report a proof of concept study with HHT patients and severe epistaxis. Patients were treated with daily 200 mg orally administered itraconazole for sixteen weeks. Twenty-one HHT patients, 8 females (38%), 13 males (62%), median age of 59 years (interquartile range (IQR) 55-69) were enrolled. Of these patients, 13 (62%) were diagnosed with HHT type 1, seven (33%) with HHT type 2 and in one patient (5%), no pathognomonic HHT mutation was found. Four patients (19%) prematurely terminated the study (3 due to mild or moderate side-effects) resulting in 17 patients included in the analyses. The median epistaxis severity score significantly decreased during treatment from 6.0 (IQR 5.1-7.2) to 3.8 (IQR 3.1-5.2) (p = 0.006). The monthly epistaxis frequency decreased from 56 to 38 epistaxis episodes (p = 0.004) and the monthly duration from 407 to 278 minutes (p = 0.005). Hemoglobin levels did not significantly change. The quality of life showed a small but significant improvement. In conclusion, oral itraconazole significantly improved epistaxis in HHT patients. The potential benefit of itraconazole in HHT should be further investigated.


Assuntos
Epistaxe/tratamento farmacológico , Doenças Genéticas Inatas/tratamento farmacológico , Itraconazol/administração & dosagem , Qualidade de Vida , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Administração Oral , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito
2.
Angiogenesis ; 23(3): 271-274, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32112177

RESUMO

BACKGROUND: Local application of fluorouracil (Efudix, 5-FU) induces sclerosis in patients with sinonasal tumors and superficial basocellular skin carcinoma. As a 'back against the wall' treatment, we investigated the local effect of nasally applied 5-FU and whether this could decrease the burden of severe epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: HHT patients with severe and frequent epistaxis, subsequent anemia and a necessity for blood and/or iron infusions were treated with a nasal tampon with 5-FU. This tampon was placed unilaterally in the nasal cavity on the side of the most severe epistaxis and replaced once weekly during 4 weeks. Outcome measures were safety and side effects, the aspect of the nasal mucosa measured with the mucosal HHT score, the epistaxis severity score (ESS), hemoglobin and ferritin plasma levels, and quality of life assessment pre-treatment, one and three months post-treatment. RESULTS: Six HHT patients participated. During treatment and follow-up, the nasal mucosa turned more pale and sclerotic and the number of telangiectases diminished. The mucosal HHT score improved and the ESS declined (p = 0.01). The decline of ESS persisted up to 3 months post-5-FU treatment. Moreover, mean hemoglobin levels increased from 6.0 pre-5-FU to 6.8 after one month post-5-FU. CONCLUSION: Unilateral application of 5-FU on a nasal tampon diminished the severity and frequency of epistaxis in all HHT patients. This effect sustained up to three months post-treatment, despite the fact that the contralateral side remained untreated. Subsequently, hemoglobin levels increased. Intranasal 5-FU is a promising entity for further research on epistaxis treatment in HHT patients.


Assuntos
Epistaxe/tratamento farmacológico , Fluoruracila/administração & dosagem , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Administração Intranasal , Adulto , Idoso , Epistaxe/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Telangiectasia Hemorrágica Hereditária/metabolismo
3.
Rhinology ; 47(2): 166-71, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19593974

RESUMO

OBJECTIVES: To evaluate the results of embolization in patients with hereditary hemorrhagic telangiectasia (HHT) because of severe epistaxis. METHODS: All HHT patients who underwent an embolization (between 1992 and 2006) were asked to participate in this retrospective study. Twelve patients who had in total 19 embolization procedures were interviewed. A questionnaire was used assessing the frequency, severity, duration of epistaxis and their Impact on Lifestyle (IoL). Haemoglobin values were collected from the patients' records. Embolization of the pathologically enhancing lesions was performed using PVA particles. RESULTS: The direct effect of the embolization is very good in 95% of patients. The Impact factor (daily frequency x severity) of epistaxis improved in the first month (p = 0.000) and one year after embolization (p = 0.009). Eleven embolizations (61%) were still associated with significant improvement. There was a reduction in the duration of epistaxis by 16 minutes per day one month after embolization (p = 0.005). However, this reduction was not found one year after embolization. Mean haemoglobin rose significantly after 1 year by an average of 0.8 mmol/l (p = 0.045). Impact on Lifestyle improved in 68% of the procedures and was unchanged in 32%. CONCLUSION: Embolizations remain a therapeutic option in experienced hands. The indication should be made carefully, because of possible (major) complications.


Assuntos
Embolização Terapêutica/métodos , Epistaxe/etiologia , Epistaxe/terapia , Telangiectasia Hemorrágica Hereditária/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Inquéritos e Questionários , Resultado do Tratamento
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