Hereditary angioedema (HAE) presents with recurrent non-pruritic, non-pitting soft-tissue swelling without urticaria. The underlying defect responsible for bradykinin accumulation is:

• A Deficiency of C3 convertase regulatory protein leading to uncontrolled alternative pathway activation
• B Absence of terminal complement components C5–C9 impairing MAC formation
• C Deficiency of C1 esterase inhibitor (C1-INH) leading to uncontrolled activation of the contact (kallikrein-kinin) system and excess bradykinin generation ✓
• D Gain-of-function mutation in Factor XII causing constitutive fibrin polymerization

Explanation

C1 esterase inhibitor (C1-INH/SERPING1) is a serine protease inhibitor that normally down-regulates both the complement classical pathway (inhibiting C1r and C1s) and the contact activation pathway (inhibiting Factor XIIa and plasma kallikrein). In HAE (autosomal dominant), C1-INH deficiency allows unchecked kallikrein activity to cleave high-molecular-weight kininogen and generate excess bradykinin, a potent vasodilator that increases vascular permeability through B2 receptors on endothelium. The resulting angioedema is mast-cell independent and antihistamine-resistant; treatment targets bradykinin (icatibant) or kallikrein (lanadelumab).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.