What is the treatment for hereditary hemorrhagic telangiectasia (HHT) epistaxis?

Treatment of Hereditary Hemorrhagic Telangiectasia Epistaxis

Begin with moisturizing topical therapies (saline gels, humidification), then escalate to oral tranexamic acid for mild bleeding, followed by local ablative procedures or systemic bevacizumab for refractory cases, reserving highly invasive surgical interventions only as a last resort due to their temporary effectiveness. 1

Stepwise Treatment Algorithm

First-Line: Conservative Management

• Nasal moisturization is the foundation of epistaxis prevention through air humidification and topical application of saline solution or gels to reduce cracking and bleeding of fragile telangiectasias. 1
• This approach alone is inadequate for many patients but should always be initiated first. 1

Second-Line: Oral Tranexamic Acid

• For epistaxis not responding to moisturizing therapies alone, oral tranexamic acid is now recommended as standard treatment. 1
• Randomized controlled trials demonstrated a 17.3% reduction in epistaxis duration per month in 118 patients and a 54% reduction in composite epistaxis endpoints (duration and intensity) in 22 patients. 1
• No increase in thrombotic complications was observed in these trials. 1
• Hemoglobin improvement was not significant, though patients were not severely anemic at baseline. 1

Third-Line: Local Ablative Therapies

For moderate bleeding unresponsive to tranexamic acid, local ablative procedures are recommended before systemic antiangiogenics: 1

• Laser treatment (argon, Nd:YAG, KTP/532, diode—avoid CO2) has stronger evidence. 1, 2
• Electrosurgery has stronger supporting evidence. 1
• Sclerotherapy and radiofrequency ablation have less robust evidence. 1

Critical caveat: Invasive procedures initially improve epistaxis frequency and intensity, but benefits often diminish within 1-9 months postoperatively, with hemorrhagic symptoms recurring at similar or worsened levels. 3 These procedures risk causing anatomical-functional changes in the rhino-sinus area that complicate future management. 3

Fourth-Line: Systemic Bevacizumab

For severe epistaxis failing moisturizing therapies, oral tranexamic acid, and/or local ablative therapies, systemic bevacizumab (not topical or intranasal) is now recommended. 1, 4

Evidence Supporting Bevacizumab:

• The InHIBIT-Bleed study (238 patients with moderate-to-severe HHT bleeding) demonstrated mean epistaxis severity score (ESS) improvement from 6.81 to 3.44—a 50% relative reduction. 1
• 85% of patients achieved epistaxis control in smaller studies. 1
• Substantial improvements in hemoglobin, iron infusion needs, and red cell transfusion requirements were observed. 1
• Safety profile was favorable with only 2% venous thromboembolism rate and no fatal adverse events. 1
• Topical nasal bevacizumab and intranasal bevacizumab injections did NOT show significant benefit—only systemic administration is effective. 1

Alternative Systemic Agent: Thalidomide

• Thalidomide downregulates VEGF levels and improves vascular wall integrity, with effectiveness documented in 67 patients across small studies. 1
• However, persistent peripheral neuropathy as an adverse event has limited enthusiasm for long-term use. 1
• Should be reserved only for refractory cases after multiple other interventions have failed. 5
• Contraindications include recent thrombosis, atrial fibrillation, and known thrombophilia. 5

Last Resort: Nasal Cavity Closure

• Closure of the nasal cavities is the only method that successfully and permanently solves severe refractory epistaxis in HHT. 2
• Reserved for patients with severe disease requiring multiple blood transfusions who have failed all other interventions. 6, 2
• Patients with mild-to-moderate disease (requiring one or no blood transfusions) do well with sequential laser therapy with or without septodermoplasty or hormone therapy and should NOT undergo nasal closure. 6

Treatments to Avoid

Nasal packing and electrocauterization should be avoided as they cause further trauma to blood vessels. 2

Pathophysiologic Rationale

The treatment escalation is based on understanding that increased VEGF drives telangiectasia formation in HHT, and normalization of VEGF suppresses these anomalous vascular structures. 1 This explains why systemic antiangiogenic therapy targeting VEGF (bevacizumab) is more effective than local destructive procedures that don't address the underlying pathophysiology. 1

Quality of Life Considerations

Epistaxis in HHT can last hours per day and causes significant psychosocial morbidity, social isolation, and difficulties with employment, travel, and routine daily activities. 1 Treatment decisions should prioritize reducing bleeding burden to improve these quality-of-life outcomes, not just hemoglobin levels. 1