Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler Weber Rendu, is a genetically inherited condition. It is characterized by small blood vessel malformations, known as telangiectasias, affecting the skin and mucosal membranes. Nosebleeds, known as epistaxis, are the most common symptom, with recurrent bleeds affecting 50-80% of patients. Larger arteriovenous malformations can develop in internal organs and pose a risk for serious bleeding. Typically, HHT will present in puberty or early adulthood, and 90% of patients will have some symptoms by age 40. Congenital arteriovenous malformations, particularly in the lungs, will usually lead to a diagnosis within the first year of life. Major bleeding from the gastrointestinal tract becomes more likely with increased age, with the risk increasing after age 50.
HHT is passed as an autosomal dominant gene, meaning that each child of an affected individual has a 50% chance of inheriting the HHT gene. Three distinct genes have been identified and attributed to HHT types I, II, and III. This diverse genetic origin may help explain the clinical variance of those affected. Some individuals only experience infrequent epistaxis while others may suffer significant and progressive bleeding with the need for recurrent blood transfusions. The risk of developing serious internal arteriovenous malformations is also related to the gene involved. While the frequency of HHT was once estimated to be around 1:100,000, greater recognition of this order has shown a prevalence estimated at 1-2:10:000 in recent surveys. Males and females are equally affected and there is no known racial predilection.
Patients with HHT should undergo a thorough medical work-up which includes genetic testing and radiographic imaging to document telangiectasias and bleeding sites throughout the body. The physician and patient need to be aware that screening the lungs and brain is an important part of the initial medical evaluation. This helps detect abnormalities that can be treated in order to prevent later complications.
For many, epistaxis is a major problem that progresses with age. At this time, there is no way to predict who will suffer nosebleeds and no way to prevent their occurrence and progression; therefore, the medical and surgical management is directed at controlling the bleeding. With good management, epistaxis should be kept to a minimum. Blood count, commonly measured as hematocrit, should be maintained at a reasonable level, preferably at a hematocrit greater than 36% and hemoglobin greater than 12%; transfusions should not be required. There is no single best way to manage every patient with HHT, so one must explore and utilize the different techniques and approaches and tailor these for the individual.
The following are the therapies that are most commonly used at the UCSD Nasal Dysfunction Clinic:
1. One should maintain good nasal hygiene. This is done through pulsatile nasal irrigation with hypertonic saline. If pulsatile irrigation is not an option, laminar irrigation with any of the many available over-the-counter devices, such as the Netipot, is a second option.
2. Nasal moisture is important. Crusting can be managed with the application of Vaseline. A small amount of Vaseline is applied in each nostril. Then, a clean finger (not a Q-tip or any other device) is inserted into the nostril and twisted back and forth so that the Vaseline is spread over the septum and lateral nasal wall. This is generally performed twice daily, but in times of difficulty, it can be performed more frequently. Anticoagulants, such as aspirin, make management more difficult. For those with medical problems requiring blood thinners, management becomes even more difficult.
3. The nasal mucosa is a hormone-modulated tissue. Estrogens support the nasal mucosa and decrease bleeding. Estrogen is available as an ointment, and one of the early treatments is to apply a small amount of Estrace cream at least once daily. If beneficial, one can apply it twice daily.
4. As HHT epistaxis progresses, some form of cautery becomes necessary. At first, this can be managed with spot welding. The welding or coagulation can be performed with silver nitrate sticks, electric cautery, or even laser.
5. As the disease continues to progress and epistaxis becomes more frequent and more difficult to control, a more thorough cautery becomes necessary. Current treatment is to cauterize the entire nasal mucosa with a laser, preferably the KTP laser. This requires general anesthesia. The entire nasal mucosa is striped with the laser. At the completion of the laser therapy, typically involving 7000 or more Joules, the nose is sprayed with a fibrin sealant. This controls bleeding from the open wounds and nurtures healing of the lasered tissues. Packing is rarely required. The surgery is normally performed as an out-patient procedure, and patients are able to go home the same day. Nasal irrigation should be initiated 5-7 days following the surgery. Lasering controls epistaxis, but does not cure it. The laser treatment is normally repeated every 3-6 months. However, in some individuals, there may be times when it is repeated every 6 weeks. In the occasional patient, it may only be required annually.
Avastin is a medicine developed to stop new blood vessel growth in patients with certain types of cancer. It has been used in a "off-label" fashion by ophthalmologists to treat abnormal vessel growth in the retina. An HHT patient of mine who worked for an ophthalmologist recommended I try this and so I have on several patients over the past year. In some the result has been impressive, and they have had no recurrence of their HHT epistaxis. In others, the bleeding has been markedly diminished. There have been no complications. The current practice is to inject 100mg into the nasal mucosa at the completion of each KTP laser treatment. This is an off-label use. Systemic (intravenous) has been reported to cause complications with the gastrointestinal tract with wound healing and with bleeding. This, however, is with multiple doses. To date, I have seen no complications in our nasal-mucosal injections.
6. Patients with a deviated or crooked nasal septum may require septoplasty; this has benefit for breathing but is also required so the surgeon can gain easy access to the nasal cavity for repeat laser procedures. The septoplasty must be performed conservatively. It is important to preserve as much nasal septal cartilage as possible. One of the troublesome complications of epistaxis and repeat cautery is a nasal septal perforation. This occurs when the mucosa is cauterized on both sides. If the cautery and injury are full thickness, a hole may develop in the septum. This hole is called a septal perforation; while it is not impossible to manage, it increases crusting, nasal discomfort, and bleeding. Nasal septal perforations are typically managed with twice daily hypertonic saline nasal irrigation. If epistaxis remains problematic in spite of repeat KTP laser treatment, alternate surgical approaches may be considered.
7. An arteriogram is often recommended to identify the arteries most responsible for the bleeding.
8. Interventional radiologists like to treat the offending vessels in the nose with embolization. We have not found this terribly useful, for patients invariably develop collateral circulation. Nonetheless, a large offending vessel can be identified and either embolized or surgically clipped.
9. Septodermoplasty is recommended by some; this is an operation in which the offending nasal mucosa is scraped away, and a skin graft, often taken from the leg or buttock, is applied to the nasal cavity. The treatment has variable success, but the telangiectasias invariably return. It is a bloody procedure and requires 7-10 days of nasal packing. Septodermoplasty is therefore not recommended or performed at the UCSD Nasal Dysfunction clinic.
10. If or when the epistaxis progresses and can no longer be controlled with repeat laser therapies, the next and final treatment is to block or obstruct nasal airflow. The nasal mucosa is responsible for filtering, humidifying, and warming inspired air. It is therefore a very vasoactive mucosa. By obstructing airflow, the work of the nose is reduced, and the recurrent bleeding is generally controlled. The current procedure used to obstruct nasal airflow is called the Young procedure. In this operation, the tissues of the anterior nose are dissected and sewn together so that the nose becomes permanently blocked. This renders an individual an obligate mouth-breather. It also reduces or completely interferes with olfaction (smelling). While at first glance this procedure seems rather radical, the patients are individuals who spend most of their lives with their nose packed; therefore, they have already lost the ability to breathe and smell normally. For many, it seems like a major step. However, patients who have undergone the Young procedure no longer suffer nosebleeds and find their lives generally improved. An alternate and temporizing approach is to obstruct the nose, either with cotton saturated in a bacitracin ointment or with a specially designed silicone obturator. If the nose is indeed obstructed 100% of the time, either therapy can be effective. However, in the long term, it is better to permanently obstruct the nose with the Young procedure. The operation is reversible, meaning that the nose can be re-opened. I have yet to meet a patient who has requested reopening a closed nose.
At the time of this writing, I am unaware of other approaches to better manage epistaxis. The only therapy that is just beginning to be explored is an injection of a medicine called Avastin into the nasal cavity. This is a medicine that inhibits blood vessel growth. It theoretically should retard the development of new telangiectasias. It has been reported to cause septal perforation. It is worth considering, but at this time, it is an off-label use of Avastin and an experimental treatment.
In summary, epistaxis is a major problem for patients with HHT. Its severity is variable and progresses with age. Other than treatment through the Young procedure, epistaxis cannot be cured; however, the recurrent epistaxis can be controlled with good nasal hygiene and repeat nasal surgeries.
“The disorder occurs because an abnormal dominant gene is present meaning half the offspring will inherit the genetic material and thus have HHT; over the past 7 years, there have been 2 genes found to be responsible for 70% of the cases and breakthroughs are expected soon in identifying another suspected 2 genes accounting for another 25-30%. The 2 known genes are on chromosomes 9 and 12; the endoglin gene is associated with the 9 chromosome and Alk-1 gene associated with chromosome 12. The expression or findings (called phenotype) in any one family can be quite variable from rarely no symptoms to multiple malformations of vessels particularly in the lungs and brain leading to numerous complications.” -Frank Miller, MD