Nejm 2008;359:1027

Cause:Genetic, autosomal dominant, or rarely acquired, C’1a esterase inhibitor deficiency (Ann IM 2000;132:144)

Pathophys:C'1a esterase inhibitor inactivates clotting factors XII and XI; the latter build up and release kallikreins/kinins causing pain, shock, etc (Nejm 1983;308:1050)

Most Western races

Sx:Onset not until age 20-50 yr; frequently precipitated by trauma, psychologic stress, or pharyngitis; abdominal pain often leads to surgery

Si:Edema of skin, upper gi and respiratory tracts, recurrent, acute, nonpitting, nonpruritic, circumscribed, transient, involves localized areas

Laryngeal edema causing asphyxia (26% patients die this way)

r/o:

• ACE inhibitor drug reaction angioedema (Jama 1997;278:232; Ann IM 1992;117:234)
• Much more common benign, ACQUIRED ANGIOEDEMA = 90% of pts with above sx; rx with prednisone 60 mg qd × 1 wk, then qod and decrease to 5-10 mg qod; plus hydroxyzine 25 mg tid helps decrease frequency and severity (Ann IM 1991;114:133); or, if no response, then, tranexamic acid (E-aminocaproic acid-like drug) up to 1 gm po tid (Am J Med 1999;106:650)
• "Pseudo-angioedema" associated with lymphoma and colon Ca
• Uvular edema of Franklin's disease (Waldenström's Macroglobulinemia)

Lab:Immunol:Screen for C₄, if decreased look for serum ₂-globulin inhibitor of C'1a (present in 90%, 10% have inactive, nonfunctioning C'1a esterase inhibitor)