Hereditary angioedema

Rare autosomal dominant disorder causing deficiency or dysfunction of C1 esterase inhibitor; leads to recurrent episodes of bradykinin-mediated angioedema without urticaria.

• Attacks can be life-threatening (airway obstruction risk); must recognize HAE to give specific therapy (C1-INH, etc.) rather than ineffective epinephrine/steroids.

• Recurrent episodes of nonpitting edema (face, lips, tongue, extremities, GI tract) without urticaria or pruritus.
• Often triggered by minor trauma (e.g., dental work), stress, or high estrogen (OCPs, pregnancy); attacks typically last 2–5 days.
• Labs: ↓ C4 (usually low even between attacks); ↓ C1-INH antigen level (Type I) or function (Type II); normal C1-INH studies in Type III.

1. Ensure airway protection first if laryngeal edema (early intubation or cricothyrotomy).
2. Acute attack: treat promptly with C1-INH concentrate or bradykinin-targeted therapy (e.g., icatibant or ecallantide); consider FFP if specific meds unavailable.
3. Long-term prophylaxis: if attacks are frequent/severe, use lanadelumab (anti-kallikrein mAb), attenuated androgens (e.g., danazol), or regular C1-INH infusions; antifibrinolytics (e.g., tranexamic acid) are less effective alternatives.
4. Short-term prophylaxis: before procedures (especially dental), give C1-INH prior or a high-dose androgen starting ~5 days before (avoid androgens in pregnancy).
5. Differentiate from allergic angioedema: HAE has no urticaria and does not respond to epinephrine (requires C1-INH or bradykinin antagonist).

1. Acute attacks – secure airway as needed; give C1-INH concentrate or bradykinin-targeted therapy (icatibant or ecallantide). (FFP can be used if specific therapies unavailable.)
2. Chronic prophylaxis – e.g., lanadelumab injections q2–4 weeks, daily attenuated androgens (danazol), or tranexamic acid to reduce attack frequency.
3. Pre-procedure prophylaxis – short course of high-dose androgen starting 5 days prior, or give C1-INH before high-risk procedures (especially dental work).

• HAE has no hives — angioedema with urticaria is likely allergic (histamine-mediated).
• Epinephrine & antihistamines don't work for HAE (bradykinin-mediated) — use C1-INH or icatibant instead.
• Family history can be absent (≈25% are new mutations), so consider HAE even without known affected relatives.

• Laryngeal swelling (hoarseness, stridor) — risk of asphyxiation; intubate immediately.
• Severe abdominal attack + normal imaging — consider HAE (to avoid unnecessary surgery).

1. Recurrent angioedema without urticaria → check C4 level and C1-INH antigen/function.
2. If ↓ C4 with low C1-INH level or function → HAE Type I/II confirmed. Normal C1-INH but high suspicion → consider HAE with normal C1-INH (Type III, often F12 gene mutation).
3. Acute management: secure airway, then treat with C1-INH or bradykinin antagonist (do NOT rely on epinephrine/steroids).
4. Prophylaxis: start long-term therapy if frequent attacks; give short-term prophylaxis before known triggers (e.g., dental procedures).

• Young patient with recurrent face/lip swelling without urticaria, often after dental work or stress → hereditary angioedema.
• Severe abdominal pain with vomiting and normal endoscopy (mimicking an acute abdomen) → think HAE (intestinal angioedema).