In a patient with hereditary angioedema (C1 inhibitor deficiency), repeated episodes of subcutaneous and mucosal swelling occur without urticaria. The mediator primarily responsible for the angioedema attacks is:

• A Histamine from mast cell degranulation
• B Bradykinin accumulation due to unregulated plasma kallikrein activity ✓
• C Leukotriene C4 from mast cells and eosinophils
• D C3a and C5a anaphylatoxins

Explanation

C1 inhibitor (C1-INH) normally regulates both the complement (C1r, C1s) and contact activation (plasma kallikrein, Factor XII) systems. In hereditary angioedema (autosomal dominant C1-INH deficiency/dysfunction), uncontrolled plasma kallikrein generates excessive bradykinin, which binds B2 receptors on endothelial cells, causing vasodilation and increased permeability — producing non-pitting, non-urticarial angioedema that can be life-threatening when laryngeal. Antihistamines and corticosteroids are ineffective (not histamine-mediated); treatment is with C1-INH concentrate, icatibant (B2 receptor antagonist), or kallikrein inhibitor (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.