A 40-year-old man with spells of generalized weakness and paresthesias
MANIFESTATIONS OF HEREDITARY HEMORRHAGIC TELANGIECTASIA
2. Which is the most common clinical manifestation of HHT?
- Epistaxis
- Mucocutaneous telangiectases
- Hematochezia
- Dyspnea
Epistaxis is the most common presentation, occurring in more than 90% of patients.9 Many patients experience only mild occasional nosebleeds that are not frequent or severe enough to cause anemia or to lead to medical treatment or consultation. Others, however, have heavy, frequent bleeding that requires invasive interventions.10
Mucocutaneous telangiectases are the second most common clinical manifestation, documented in about 75% of patients. They are cosmetically unpleasant but rarely bleed. They occur most commonly on the face, lips, tongue, and fingertips, and they increase in size and number with age.11
Gastrointestinal bleeding, sometimes manifesting as hematochezia, occurs in one-third of people with HHT. It most commonly presents with iron-deficiency anemia in patients over age 40.12
Dyspnea. Pulmonary AVMs occur in 30% to 50% of affected people, but interestingly, most patients with pulmonary AVMs have no respiratory symptoms, including dyspnea.
In pulmonary AVMs, abnormal vessels replace normal capillary beds, creating a capillary-free communication between the pulmonary and systemic circulations. This abnormal connection prevents blood from the pulmonary arterial system from being oxygenated, resulting in hypoxemia and secondary polycythemia, as in our patient. One-third of patients have evidence of right-to-left shunting, such as the clubbing in our patient.9,13
Other, less common complications of HHT include seizures or hemorrhage from cerebral AVMs and stroke and brain abscesses from paradoxical embolization due to the loss of the capillary filter in the pulmonary vascular bed. Hepatic involvement may result in portal hypertension and hepatic encephalopathy.14
Back to our patient
As mentioned above, during one of the patient’s spells of paresthesia and weakness, we noted his oxygen saturation by oximetry was 85%. At that time, his arterial Po2 was also low at 50 mm Hg (normal 70–100). With oxygen supplementation, his spell completely resolved and his Po2 improved to 80 mm Hg. Though the shunt fraction of his pulmonary AVM was never measured, it was likely less than 30% of the cardiac output, as his hypoxemia improved with oxygen supplementation alone.15 When he was taken off oxygen supplementation, his spells recurred, but with oxygen support he remained clinically stable.
MANAGEMENT
3. Which is the next logical step in our patient’s management?
- Consult a surgeon for lobectomy
- Consult an interventional radiologist for embolization therapy
- Transfer to the intensive care unit for elective intubation
- Observe with close follow-up
Untreated pulmonary AVMs enlarge at an estimated rate of 0.3 mm/year. The estimated death rate is up to 15.8% per year, with most deaths resulting from stroke, cerebral abscess, hemoptysis, and hemothorax.16–18 Common indications for treatment are progressively enlarging lesions, symptomatic hypoxemia, and paradoxical embolization.19 Pulmonary AVMs in which the feeding artery is 3 mm or more in diameter require treatment.
Embolization therapy, in which the AVM is occluded angiographically, is considered a first-line treatment for pulmonary AVM, with a procedural success rate (defined as involution of the AVM) of 97%.20 Embolization therapy allows patients to avoid major surgery, with its potential complications, and it has a shorter recovery time.
Surgical procedures such as excision, vascular ligation, or lobectomy can be considered if the lesion cannot be treated by embolization or if the patient has an anaphylactic allergy to contrast dyes.
This patient had no clinical signs of impending respiratory failure requiring elective intubation.
Since he was experiencing symptoms, there is no role for observation in this case.
Back to our patient
An interventional radiologist was consulted, and the patient underwent bilateral pulmonary artery angiography with successful coil embolization of his large left-upper-lobe AVM. He was weaned off oxygen and had no further spells of generalized weakness and paresthesias.
Given his father’s history of recurrent epistaxis and oral telangiectases, the patient asks about the risk of his children acquiring this disease.
GENETICS OF HEREDITARY HEMORRHAGIC TELANGIECTASIA
4. Which of the following is the inheritance pattern for HHT?
- Autosomal dominant
- Autosomal recessive
- Maternal inheritance
- X-linked recessive
The inheritance pattern is autosomal dominant with variable expression and penetrance. At least four different mutations have been identified in genes on chromosomes 9 and 12 that result in abnormal vascular malformations.21–24 The other modes of inheritance have not been described in HHT.
