A 22-year-old man has repeated episodes of tense, non-pitting swelling of the lips and hands without any accompanying urticaria or pruritus. One episode required intubation for laryngeal edema. Serum drawn during an attack shows a markedly reduced C4 level with normal C3. What is the underlying defect?

• A Deficiency of C1 esterase inhibitor with uncontrolled bradykinin generation ✓
• B Deficiency of the terminal complement components C5 to C9
• C IgE-mediated mast cell degranulation from food allergen exposure
• D Mutation in the NLRP3 gene causing excessive IL-1beta release

Explanation

Hereditary angioedema is an autosomal dominant deficiency of C1 inhibitor, permitting unregulated classical pathway activation and excess bradykinin formation; bradykinin increases vascular permeability and produces the edema. Low C4 with normal C3 during attacks is the screening abnormality. Lack of urticaria excludes allergic angioedema (option C), and terminal complement deficiency presents with recurrent Neisseria infections, not angioedema.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.