Can hereditary angioedema cause sudden pharyngeal swelling?

Hereditary Angioedema and Pharyngeal Swelling

Yes, hereditary angioedema (HAE) can cause sudden pharyngeal swelling that can be life-threatening and potentially lead to asphyxiation. 1

Clinical Presentation of Pharyngeal/Laryngeal Involvement in HAE

HAE is characterized by recurrent episodes of non-pruritic, non-pitting angioedema that can affect various parts of the body. When it involves the oropharynx and larynx, it presents as:

• Sudden onset swelling of the pharynx, larynx, or both
• Progressive worsening over 24 hours before gradually resolving over the following 48-72 hours 1
• Potentially life-threatening airway compromise
• Historical mortality rate of approximately 30% from laryngeal angioedema 1, 2

While laryngeal attacks are less common than abdominal or peripheral attacks, more than 50% of HAE patients experience at least one laryngeal attack during their lifetime 3.

Epidemiology and Risk

• Laryngeal/pharyngeal attacks represent a smaller percentage of total HAE attacks compared to abdominal and peripheral attacks
• In clinical studies, approximately 16 out of 57 subjects (28%) experienced laryngeal attacks 4
• The median time to initial onset of symptom relief for laryngeal attacks was 0.25 hours and median time to complete resolution was 8.4 hours when treated with C1 inhibitor concentrate 4

Pathophysiology

HAE is caused by deficiency or dysfunction of C1 inhibitor protein, leading to:

• Inappropriate activation of multiple pathways including complement and contact systems 1
• Increased bradykinin production, which is the primary mediator of swelling 1
• Temporary localized increase in vascular permeability affecting the pharyngeal and laryngeal tissues 5

Types of HAE and Pharyngeal Involvement

Both major types of HAE can present with pharyngeal swelling:

• Type I HAE: Low C1INH antigenic and functional levels
• Type II HAE: Normal C1INH antigenic levels but decreased C1INH functional levels 1

HAE with normal C1INH can also present with pharyngeal swelling, though this is less common 1.

Management of Pharyngeal/Laryngeal HAE Attacks

When pharyngeal/laryngeal swelling occurs:

1. Immediate assessment for signs of airway compromise 2
2. Consider early elective intubation if signs of impending airway closure develop 2
3. Observe in a facility capable of emergency airway management 2
4. Administer HAE-specific medications immediately:
   • Plasma-derived C1 esterase inhibitor (20 IU/kg IV) 2, 4
   • Icatibant 30 mg subcutaneously 2
   • Fresh frozen plasma only if first-line treatments are unavailable 2

Important Considerations

• Standard angioedema treatments (epinephrine, corticosteroids, antihistamines) are not effective for HAE attacks 1
• Early treatment is crucial for pharyngeal attacks to prevent progression to complete airway obstruction
• All patients with HAE should have an established emergency plan for responding to laryngeal attacks 1
• Patients with known HAE should have immediate access to on-demand HAE-specific medications 1

Triggers for Pharyngeal Attacks

Common triggers that may precipitate pharyngeal swelling in HAE include:

• Trauma (including dental procedures)
• Stress
• Infection
• Hormonal changes (menstruation, oral contraceptives) 6
• ACE inhibitors (should be avoided in HAE patients) 2

HAE pharyngeal attacks are unpredictable and can occur without any identifiable trigger 1.