Causes of Telangiectasia
Telangiectasias develop through two primary mechanisms: genetic mutations affecting vascular signaling pathways (most notably in Hereditary Hemorrhagic Telangiectasia) or secondary to tissue injury and vasoactive substance release in acquired forms.
Hereditary/Genetic Causes
Hereditary Hemorrhagic Telangiectasia (HHT)
- Loss-of-function mutations in the BMP9-10/ENG/ALK1/SMAD4 signaling pathway cause HHT, an autosomal dominant disorder affecting approximately 1 in 5,000 individuals 1, 2
- ENG (endoglin) mutations on chromosome 9 cause HHT type 1, accounting for approximately 54% of HHT families 3
- ACVRL1 (activin receptor-like kinase 1) mutations on chromosome 12 cause HHT type 2, accounting for approximately 43% of HHT families 3, 4
- SMAD4 mutations cause juvenile polyposis-HHT overlap syndrome, occurring in 1-2% of HHT cases 3, 5
- These genetic mutations disrupt vascular quiescence, leading to abnormal blood vessel formation with enlarged vessels and thin walls prone to rupture 3, 1
Pathophysiology of HHT-Related Telangiectasias
- The fundamental pathology involves direct artery-to-vein connections that bypass normal capillaries, creating arteriovenous malformations throughout the body 3
- Telangiectasias develop in characteristic locations including lips, oral cavity, fingers, nose, and can occur on any mucosal surface including gastrointestinal and uterine endometrium 3
- These vascular lesions have age-related expression, with epistaxis typically starting at mean age 11 years and telangiectasias becoming more prominent with age 3
Acquired/Secondary Causes
Tissue Injury and Environmental Factors
- Telangiectasias occur through release or activation of vasoactive substances under multiple conditions including sun damage, post-radiation therapy, and prolonged topical steroid application 6, 7
- Chronic sun exposure damages dermal blood vessels, leading to persistent dilation and telangiectasia formation 6
- Radiation therapy causes endothelial damage and subsequent abnormal vessel formation in the treatment field 6
- Long-term topical corticosteroid use thins the skin and weakens vessel walls, making superficial vessels more visible and prone to dilation 6
Underlying Medical Conditions
- Secondary telangiectasias can arise from underlying systemic conditions, though the specific mechanisms vary by disease 6
- Localized telangiectasia may represent a marker of internal or cutaneous malignancy, including mycosis fungoides 6
Clinical Distinction Between Primary and Secondary
Primary Telangiectasias
- Occur spontaneously without preceding injury or underlying condition 6
- In HHT, multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose) are a major diagnostic criterion requiring 3 of 4 Curaçao criteria for definite diagnosis 3, 2
Secondary Telangiectasias
- Develop after identifiable skin injury or in association with systemic disease 6
- Location combined with careful history and examination helps elucidate the correct diagnosis 6
Critical Diagnostic Considerations
- For patients with multiple telangiectasias, apply the Curaçao criteria to evaluate for HHT: spontaneous/recurrent epistaxis, multiple telangiectasias at characteristic sites, visceral arteriovenous malformations, and first-degree relative with HHT 3, 5
- Genetic testing for ENG, ACVRL1, and SMAD4 mutations identifies causative mutations in 97% of patients with definite clinical HHT diagnosis 3, 5
- A diagnosis of malignancy-associated telangiectasia is one of exclusion requiring thorough evaluation before confirmation 6