A deficiency of C1 inhibitor primarily predisposes to which condition?

• A. Paroxysmal nocturnal hemoglobinuria
• B. Hemolytic uremic syndrome
• C. Increased bacterial infections
• D. Hereditary angioedema

Answer: (D)

C1 esterase inhibitor keeps the complement system and the kallikrein–kinin (contact) system in check. When this inhibitor is deficient, there is unregulated activation of these pathways, especially increased production of bradykinin. Bradykinin makes blood vessels leaky, causing episodes of deep, non-itchy swelling in the skin and mucosal tissues, which is the hallmark of hereditary angioedema. This swelling can affect the face, lips, tongue, or GI tract and is not driven by histamine, so antihistamines aren’t effective. Other conditions listed involve different disease mechanisms (such as hematologic or infectious processes) and are not primarily caused by C1-INH deficiency, which is why hereditary angioedema is the correct association.