A 62-year-old woman presents to the urgent care clinic with rapidly progressive swelling of the lips and tongue that began overnight. She denies urticaria, pruritus, or known allergen exposure. Three weeks ago, she was started on lisinopril (Zestril) 20 mg daily for newly diagnosed hypertension. Vital signs: BP 148/92, HR 96, RR 18, SpO2 97%. Voice is slightly muffled but she is protecting her airway. Which of the following is the MOST likely diagnosis?

Question

Accepted Answer

✅ A. ACE-inhibitor–induced angioedema
Lisinopril and other ACE inhibitors cause bradykinin-mediated angioedema in about 0.1–0.7% of users. Swelling characteristically involves the lips, tongue, and upper airway and is typically non-pruritic and non-urticarial (distinguishing it from histaminergic/allergic angioedema). It can appear within hours of the first dose OR weeks to years after initiation — the delayed timing in this case is classic and commonly missed. Management: immediately STOP lisinopril, protect the airway, and NEVER rechallenge with ANY ACE inhibitor. Cross-reactivity with ARBs exists but is low (<10%), so ARBs may be used cautiously if absolutely needed.

❌ B. Anaphylaxis to an unknown food or environmental allergen
Anaphylaxis is histamine-mediated and almost always accompanied by urticaria, pruritus, flushing, bronchospasm, or hypotension — all absent here. The painless, non-pruritic lip/tongue swelling plus recent ACEI start points strongly to bradykinin-mediated angioedema, which does not respond to epinephrine/antihistamines the way anaphylaxis does.

❌ C. Hereditary angioedema (C1 esterase inhibitor deficiency)
HAE typically presents earlier in life with recurrent episodes of facial, GI, and extremity swelling, often with a positive family history. A first-ever episode in a 62-year-old 3 weeks after starting an ACEI is overwhelmingly drug-induced.

❌ D. Contact dermatitis of the lips (cheilitis)
Contact dermatitis produces pruritic, erythematous, scaling or vesicular changes — not tense, non-pitting angioedema of the tongue. It also does not threaten the airway.

:::danger
ACEI angioedema can occur weeks to YEARS after the first dose. Stop the drug, protect the airway, and NEVER rechallenge any ACE inhibitor — document it as a class allergy.
:::

Lisinopril

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