• | GI symptoms common = crampy abdominal pain |
• | drug induced = ACE inhibitors (captopril) |
• | Facial edema with eosinophilia |
• | Melkersson-Rosenthal syndrome/granulomatous cheilitis |
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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) |
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C4 level
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C1-INH level
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C1q level
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type I HAE
|
low
|
low
|
normal
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type II HAE
|
low
|
normal
|
normal
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acquired angioedema
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low
|
low
|
low
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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) |
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