Oral itraconazole for epistaxis in hereditary hemorrhagic telangiectasia: a proof of concept study.

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.

Intranasal Efudix reduces epistaxis in hereditary hemorrhagic telangiectasia.

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.

The effect of N-acetylcysteine on epistaxis and quality of life in patients with HHT: a pilot study.

BACKGROUND: Free O2- radicals may cause precapillary sphincter abnormalities, resulting in epistaxis in hemizygous knockout mice for Endoglin. The objective of this study was to test if antioxidants, like N-acetylcysteine (NAC), are have a role in the treatment of epistaxis in hereditary hemorrhagic telangiectasia (HHT). METHODS: Forty-three patients participated in this study taking NAC 600 mg t.i.d for 12 weeks. Patients registered frequency, severity and duration of epistaxis and private and work-related quality of life (QOL), using a diary for two 6 weeks periods. The first period was prior to starting treatment and the second started after 6 weeks using NAC. RESULTS: There was a decrease infrequency (p < 0.01) and severity (p < 0.01) of epistaxis during the day. The improvement was most remarkable in male patients and patients with an ENDOGLIN mutation. In women and patients with an ALK-1 mutation, only a trend for improvement was found. Nocturnal epistaxis did not improve. The effect of epistaxis on the ability to work (p = 0.02) was reduced. CONCLUSION: This pilot study was conducted to investigate whether animal experiments can be translated to humans with HHT regarding epistaxis. The positive results with NAC are promising and justify a randomised clinical trial.

Percutaneous embolization on hereditary hemorrhagic telangiectasia patients with severe epistaxis.

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.

Epistaxis in hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is characterized by easily bleeding telangiectases of the skin and mucosa. Epistaxis is the most common symptom of HHT. Larger arteriovenous malformations (AVM) occur in the lungs (in up to 33% of the patients), brain (in up to 11% of patients), and liver. These may cause severe complications which can be prevented by early therapy. To gain insight in the characteristics of epistaxis in HHT, 171 persons were investigated, who either had HHT or participated in a screening programme for relatives of HHT patients. Of these, 58 persons had HHT. Epistaxis without signs of HHT was present in 12 persons, whereas 10% of HHT patients did not have epistaxis. Seventeen HHT patients with epistaxis had visited an otorhinolaryngologist before, without a correct diagnosis of HHT being made. Telangiectases were most common on lips, tongue, the nasal septum, and the turbinates. In view of the prevalence of visceral AVM and the associated complications, HHT patients presenting to an otorhinolaryngologist should be encouraged to engage in a screening programme for these AVM.

Anatomical aspects of sinus floor elevations.

Inadequate bone height in the lateral part of the maxilla forms a contra-indication for implant surgery. This condition can be treated with an internal augmentation of the maxillary sinus floor. This sinus floor elevation, formerly called sinus lifting, consists of a surgical procedure in which a top hinge door in the lateral maxillary sinus wall is prepared and internally rotated to a horizontal position. The new elevated sinus floor, together with the inner maxillary mucosa, will create a space that can be filled with graft material. Sinus lift procedures depend greatly on fragile structures and anatomical variations. The variety of anatomical modalities in shape of the inner aspect of the maxillary sinus defines the surgical approach. Conditions such as sinus floor convolutions, sinus septum, transient mucosa swelling and narrow sinus may form a (usually relative) contra-indication for sinus floor elevation. Absolute contra-indications are maxillary sinus diseases (tumors) and destructive former sinus surgery (like the Caldwell-Luc operation). The lateral sinus wall is usually a thin bone plate, which is easily penetrated with rotating or sharp instruments. The fragile Schneiderian membrane plays an important role for the containment of the bonegraft. The surgical procedure of preparing the trap door and luxating it, together with the preparation of the sinus mucosa, may cause a mucosa tear. Usually, when these perforations are not too large, they will fold together when turning the trap door inward and upward, or they can be glued with a fibrin sealant, or they can be covered with a resorbable membrane. If the perforation is too large, a cortico-spongious block graft can be considered. However, in most cases the sinus floor elevation will be deleted. Perforations may also occur due to irregularities in the sinus floor or even due to immediate contact of sinus mucosa with oral mucosa. Obstruction of the antro-nasal foramen is, due to its high location, not a likely complication, nor is the occurrence of severe haemorrhages since the trap door is in the periphery of the supplying vessels. Apart from these two aspects, a number of anatomical considerations are described in connection with sinus floor elevation.

Bilateral sequential facial palsy during chickenpox.

UNLABELLED: Facial palsy is a rare neurological complication of chickenpox. A 5-year-old girl exhibited a right facial palsy followed by the appearance of the characteristic chicken pox exanthem. Subsequently she suffered a left facial palsy. In this patient both pathophysiological mechanisms responsible and their relation to the phase of infection are illustrated. CONCLUSION: Facial palsy as a complication of chickenpox can result from pre-eruptive haematogenous or neurogenous spread of varicella-zoster virus.