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AND THE ANSWERS ARE . . .

  1. HAE is characterized by decreased serum levels of C1q, C3 and C4 components of complement.
    False
  2. Bradykinin is a major mediator of the angioedema in HAE.
    True
  3. All symptomatic HAE patients have decreased serum levels of the C1 inhibitor (C1 INH) as determined by immunoassay.
    False
  4. The clinical improvement during treatment of HAE with altered androgens (e.g. danazol) requires a normalization in serum levels of the C1 inhibitor (C 1 INH).
    False
  5. An acquired variant of hereditary angioedema is associated with increased serum levels of anti-C1 INH antibodies.
    True

Discussion
HAE of the congenital type is due in about 85% of cases to an absolute deficiency of the C1 INH. However, in about 15% of cases there are normal serum levels of C1 INH, as detected by usual immunoassays (1). However, this C1 INH is dysfunctional. Therefore, if HAE is strongly suspected based on clinical grounds, a C1 INH functional assay should be requested if the serum C1 INH levels are normal. When C1 INH levels are deficient or the C1 INH molecule is dysfunctional in congenital HAE, the C4 levels are markedly decreased when patients are symptomatic. However, the serum C1q and C3 levels are typically normal. Although the decreased C4 complement levels indicate increased complement activation in HAE, there is strong evidence that the angioedema in HAE is due to increased bradykinin formation (1,2). The latter likely results from increased activation of the kallikrein-kinin pathway (C1 INH inhibits several stages of this pathway). Treatment with altered androgens (e.g. danazol, stanazolol ) in sufficient dosage does result in increased serum C1 INH levels. However, it is a common clinical experience that control of angioedema in HAE can often be achieved with doses of these androgenic agents too low to induce a normalization of the serum C1 INH levels.

Acquired angioedema (AA) variants of HAE are due to either: 1) immune reaction associated with certain lymphoproliferative disorders and malignancies that consume the C1 INH as a result of increased complement activity or 2) an anti-C1 INH antibody. Unlike the congenital type of HAE, the AA variants are usually characterized by decreased serum C1q as well as decreased C4 levels in the serum.

References

1. Arch Int Med 2001;161:2417-29
2. N. Eng J. Med 2002;347: 621-622
3. Medicine (Baltimore). 2003;82:274-81

 



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