Conditions That Cause Pulmonary Arteriovenous Malformations
Hereditary hemorrhagic telangiectasia (HHT) accounts for 70-90% of all pulmonary arteriovenous malformations, making it the overwhelmingly dominant cause, while other etiologies are rare and primarily include acquired conditions related to hepatic disease, trauma, and post-surgical states. 1, 2, 3
Primary Etiology: Hereditary Hemorrhagic Telangiectasia
HHT represents the principal cause of PAVMs and should be systematically evaluated in all patients with PAVMs. 4, 1, 2
HHT Genetic Subtypes
HHT Type 1 results from ENG gene mutations on chromosome 9 and characteristically presents with cerebral and pulmonary AVMs 2, 5, 6
HHT Type 2 results from ACVRL1/ALK1 gene mutations and typically presents with pulmonary hypertension and hepatic AVMs 2, 5
SMAD4 mutations occur in 1-2% of HHT patients and associate with juvenile polyposis syndrome 2
Clinical Recognition of HHT
When evaluating patients with PAVMs, actively screen for the following HHT features:
Recurrent epistaxis - particularly when associated with anemia or requiring repeated evaluation 1, 5, 7
Mucocutaneous telangiectasias - visible vascular lesions on skin and mucous membranes 1
Family history of HHT - autosomal dominant inheritance with age-related penetrance 1, 7
Visceral involvement - hepatic, cerebral, or gastrointestinal AVMs 1
Secondary and Acquired Causes
While the evidence base focuses predominantly on HHT-related PAVMs, other etiologies exist but are substantially less common:
Post-Surgical States
- Glenn shunts or Fontan circulation can lead to development of venous collateral channels or arteriovenous malformations in the right lung, potentially requiring conversion to modified Fontan procedure 1
Hepatic Disease
- Hepatic cirrhosis and portal hypertension can be associated with pulmonary vascular abnormalities, though this relationship is less well-characterized in the guideline literature 8
Trauma
- Thoracic trauma can rarely result in acquired PAVMs, as suggested by case reports of hemothorax presentations 9
Critical Clinical Pitfall
The most important pitfall is failing to obtain a complete past medical and family history in young patients with recurrent epistaxis, which delays HHT diagnosis and prevents appropriate family screening. 7 This oversight has cascading consequences:
Family members miss opportunities for screening and early detection 7, 6
Patients remain unaware of complication risks including stroke (3.2-55%), brain abscess (0-25%), and pregnancy-related hemorrhage (1 in 100 women) 4, 1, 2
Prophylactic measures such as antibiotic coverage before dental procedures are not implemented 7
Diagnostic Approach When Etiology Is Uncertain
When PAVMs are discovered incidentally or in patients without obvious HHT features:
Perform transthoracic contrast echocardiography as the initial screening test with 98-99% sensitivity for detecting intrapulmonary shunts 4, 3
Obtain CT chest with IV contrast to accurately detect number, size, location, and distribution of PAVMs 4, 1
Systematically evaluate for HHT clinical criteria even in the absence of family history, as this represents a new diagnosis in many cases 7, 6
Consider genetic testing for at-risk family members as a cost-effective screening measure 8
Age-Related Considerations
PAVM diagnosis in HHT patients shows a linear distribution between ages 20-75 years, with mean age at diagnosis of 43 years 6
The diagnosis of both PAVM and HHT was made simultaneously at the time of cerebral abscess presentation in 54% of cases, highlighting the importance of maintaining diagnostic suspicion 6