| • | GI symptoms common = crampy abdominal pain |  
 | • | drug induced = ACE inhibitors (captopril) |  
   
  
| • | Facial edema with eosinophilia |  
 | • | Melkersson-Rosenthal syndrome/granulomatous cheilitis |  
  | 
 
 
 
  
Hereditary Angioedema (HAE) 
| • | painless, nonpruritic swelling of the skin |  
 | • | due to mutation in the C1 inhibitor gene |  
 | • | best screening test = C4 levels |  
 | • | decreased even between attacks in both type I and type II HAE |  
 | • | almost undetectable during attacks |  
 | • | if normal level during attacks, then not HAE |  
 | • | type I (85%) = low enzyme level– low C4, low C1-INH levels (30% below normal values) |  
 | • | type II  (15%) = dysfunctional enzyme  – low C4, normal C1-INH level (check functional assay) |  
   
treatment: 
| • | acute attack – C1-INH concentrate (if available);  or fresh frozen plasma |  
 | • | (epinephrine, corticosteroids, antihistamines are not effective) |  
 | • | long-term prophylaxis – first line = danazol or stanozolol (stimulates synthesis of C1 esterase inhibitor) |  
 | • | danazol dose = 20-30 mg/kg/day (max = 800mg/day);  may be used in children |  
 | • | avoid ACE inhibitors and estrogens |  
   
Acquired Angioedema 
| • | type I – associated with B-cell lymphoproliferative disorder |  
 | • | type II – autoantibody against C1-INH |  
 | • | type I pathogenesis – increased catabolism of C1-INH (an interaction between the idiotypes of monoclonal immunoglobulins and anti-idiotypic antibodies can result in consumption of c1q and C1-INH) |  
 | • | serum protein electrophoresis and immunopherisis |  
 | • | CT scan abdomen, pelvis, chest |  
 | • | peripheral blood lymphocyte immunophenotyping |  
   
treatment: 
| • | acute – glucocorticoids +/- epinephrine |  
 | • | chronic – androgens (e.g. danazol) |  
   
ddx vs. HAE: 
| • | present after 4th decade (vs. 2nd decade) |  
   
  
 
 | 
C4 level 
 | 
C1-INH level 
 | 
C1q level 
 | 
 
type I HAE 
 | 
low 
 | 
low 
 | 
normal 
 | 
 
type II HAE 
 | 
low 
 | 
normal 
 | 
normal 
 | 
 
acquired angioedema 
 | 
low 
 | 
low 
 | 
low 
 | 
 
 
 
  
  
ACE Inhibtor-induced Angioedema 
| • | ACE inhibitors are most common cause of angioedema severe enough to require hospitalization |  
 | • | usually within first week of therapy |  
 | • | angiotensin II-receptor blockers also reported |  
 | • | pathogenesis – not completely known |  
 | • | ACE = kininase II, therefore ACE inhibitor à locally increased bradykinin levels due to decreased bradykinin metabolism (proposed mechanism) |  
  
 |