What are the pathologic causes of recurrent epistaxis?

Pathologic Causes of Recurrent Epistaxis

The most important pathologic cause of recurrent nosebleeds to identify is hereditary hemorrhagic telangiectasia (HHT), which affects 1 in 5,000 people and presents with spontaneous recurrent epistaxis in over 90% of adults, often starting in childhood. 1

Primary Vascular Disorders

Hereditary Hemorrhagic Telangiectasia (HHT)

• HHT is an autosomal dominant disorder caused by mutations in ENG, ACVRL1, or SMAD4 genes, leading to abnormal blood vessel formation with fragile telangiectasias throughout the nasal mucosa and other organs. 1, 2
• Diagnosis requires 3 of 4 Curaçao criteria: spontaneous recurrent epistaxis, multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose), visceral arteriovenous malformations (pulmonary, hepatic, cerebral, gastrointestinal), or first-degree relative with HHT. 1, 3
• Look specifically for visible telangiectasias on the nasal mucosa, oral mucosa, conjunctiva, tongue, lips, and fingertips during physical examination—these punctate red lesions are pathognomonic. 2, 4
• Epistaxis in HHT typically begins around age 11 years and progressively worsens, occurring multiple times per week and lasting hours per episode. 1, 3

Other Vascular Malformations

• Nasal hemangiomas present as visible mass lesions causing unilateral obstruction with associated facial pain, though they are uncommon causes of epistaxis. 5
• Isolated angiodysplasias can occur without systemic disease, particularly in elderly patients. 6

Hematologic Disorders

Coagulation Defects

• Von Willebrand disease and hemophilia cause recurrent epistaxis through impaired hemostasis, requiring documentation of personal or family history of bleeding disorders. 7, 8
• Thrombocytopenia from any cause (bone marrow disorders, immune destruction, medication-induced) predisposes to mucosal bleeding. 7
• Malignant hematologic disorders including leukemia and lymphoma can present with epistaxis as an early manifestation. 7

Medication-Related Coagulopathy

• Anticoagulants (warfarin, direct oral anticoagulants) and antiplatelet agents (aspirin, clopidogrel) cause persistent epistaxis by preventing normal clot formation. 7, 5
• 15% of patients presenting with epistaxis are on long-term anticoagulation therapy. 7, 5

Systemic Diseases

Hepatic and Renal Disease

• Liver disease causes coagulopathy through reduced synthesis of clotting factors and thrombocytopenia from portal hypertension. 7
• Chronic kidney disease impairs platelet function through uremic toxins, leading to mucosal bleeding. 7

Hypertension

• While causality remains controversial, hypertension is present in 24-64% of patients with epistaxis and is independently associated with more severe bleeding requiring emergency intervention. 7, 5
• Posterior epistaxis (5-10% of cases) is more common in older hypertensive patients and more difficult to control. 5

Neoplastic Causes

Intranasal Tumors

• Suspect malignancy when unilateral epistaxis is accompanied by nasal obstruction, facial pain, or visual changes—these red flags mandate nasal endoscopy. 7
• Nasopharyngeal carcinoma, inverted papilloma, and squamous cell carcinoma can present with recurrent unilateral bleeding. 7
• Juvenile nasopharyngeal angiofibroma occurs in adolescent males and causes severe recurrent epistaxis. 8

Inflammatory and Infectious Causes

Chronic Rhinosinusitis

• Localized infection and inflammation cause mucosal friability and bleeding, typically affecting one side of the nasal cavity. 7
• Granulomatosis with polyangiitis (Wegener's) causes destructive nasal inflammation with crusting and recurrent bleeding. 8

Intranasal Drug Use

• Cocaine and other illicit drugs cause direct mucosal injury, vasoconstriction followed by rebound vasodilation, and septal perforation. 7
• Chronic topical decongestant overuse (rhinitis medicamentosa) leads to mucosal atrophy and bleeding. 7

Critical Diagnostic Approach

Initial Evaluation

• Perform anterior rhinoscopy after removing blood clots to identify telangiectasias, masses, septal perforations, or localized bleeding sites. 7
• Use nasal endoscopy for persistent or recurrent unilateral epistaxis to thoroughly examine posterior nasal cavity and nasopharynx. 7

Laboratory Assessment

• Obtain complete blood count to assess for anemia severity and thrombocytopenia. 3, 2
• Check INR if patient is on warfarin, as supratherapeutic levels require specialty consultation or reversal agents. 7
• Consider coagulation studies (PT, PTT, von Willebrand panel) when bleeding disorder is suspected based on history. 7

Genetic Testing

• Order genetic testing for ENG, ACVRL1, and SMAD4 mutations when HHT is suspected clinically, particularly for asymptomatic family members of known HHT patients. 3
• Genetic testing identifies causative mutations in 97% of patients meeting definite Curaçao criteria. 3

Common Pitfalls to Avoid

• Do not dismiss recurrent bilateral epistaxis in young patients as "just nosebleeds"—actively look for telangiectasias and family history suggesting HHT. 1
• Do not perform liver biopsy in patients with proven or suspected HHT due to catastrophic hemorrhage risk from hepatic arteriovenous malformations. 3
• Do not overlook SMAD4 mutations, which cause combined HHT and juvenile polyposis syndrome with 73% prevalence of gastric polyposis and high gastric cancer risk. 3
• Do not aggressively lower blood pressure acutely during active epistaxis, as excessive reduction causes renal, cerebral, or coronary ischemia in elderly patients with chronic hypertension. 7, 5