Immunology · Year 2 · from Immunology
Case 2: Hereditary Angioedema
Patient Demographics
- Age: 28 years old
- Sex: Female
- Ethnicity: Hispanic
Chief Complaint
Recurrent episodes of facial swelling and abdominal pain
History of Present Illness
A 28-year-old woman presents to the emergency department with progressive swelling of her lips and face over the past 6 hours. She has experienced similar episodes multiple times since adolescence, often preceded by stress or minor trauma. She also reports frequent episodes of severe abdominal pain lasting 1-3 days, sometimes associated with vomiting. Notably, antihistamines and corticosteroids have never provided relief during these episodes. Her sister and father have similar symptoms.
Past Medical History
- Multiple ER visits for facial swelling (10+ episodes)
- One episode of laryngeal swelling requiring intubation at age 22
- Frequent unexplained abdominal pain episodes
Family History
- Father with similar recurrent swelling episodes
- Sister with recurrent abdominal pain and one episode of laryngeal edema
- Paternal grandmother died of "airway swelling"
Physical Examination
- General: Anxious-appearing woman with visible facial swelling
- Vital Signs: T 37.0C, HR 95, RR 18, BP 125/80, SpO2 98% on room air
- HEENT: Significant lip edema (especially upper lip), periorbital edema, no urticaria
- Oropharynx: Uvula edema, no stridor, able to handle secretions
- Skin: No hives or erythema
- Lungs: Clear
- Abdomen: Soft, mild diffuse tenderness
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| C4 level | 3 mg/dL | 14-40 mg/dL |
| C1 inhibitor level | 6 mg/dL | 21-39 mg/dL |
| C1 inhibitor function | 15% | 70-130% |
| C3 level | Normal | -- |
| Tryptase | Normal | -- |
Clinical Image
Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Angioedema2010.JPG). Licensed under CC BY-SA 3.0.
Diagnosis
Hereditary Angioedema Type 1 due to C1 inhibitor deficiency.
Discussion
Hereditary angioedema (HAE) results from deficiency or dysfunction of C1 inhibitor (C1-INH), a serine protease inhibitor that regulates the classical complement pathway (inhibiting C1r and C1s) and the contact activation system (inhibiting kallikrein and factor XIIa). When C1-INH is deficient, uncontrolled activation of the contact system leads to excessive bradykinin generation. Bradykinin is the primary mediator of angioedema in HAE, causing increased vascular permeability without mast cell activation - explaining why antihistamines and corticosteroids are ineffective.
Key features:
- Angioedema WITHOUT urticaria (distinguishing it from allergic angioedema)
- Recurrent abdominal attacks from bowel wall edema
- Risk of potentially fatal laryngeal edema
- Low C4 (even between attacks) is a sensitive screening test
- Autosomal dominant inheritance
Treatment
Acute attacks:
- C1 inhibitor concentrate (plasma-derived or recombinant)
- Icatibant (bradykinin B2 receptor antagonist)
- Ecallantide (kallikrein inhibitor)
- Fresh frozen plasma (if specific treatments unavailable)
Prophylaxis (for frequent attacks):
- Lanadelumab (anti-kallikrein monoclonal antibody)
- C1 inhibitor concentrate
- Berotralstat (oral kallikrein inhibitor)
- Attenuated androgens (danazol) - less commonly used due to side effects