hereditary angioedema; hereditary angioneurotic edema (HANE, HAE)
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Pathology
- C1-esterase inhibitor deficiency
- activation of the complement cascade
- unchecked generation of plasma kallikrein
- cleavage of HMW kininogen -> excess bradykinin production
- excess bradykinin results in disabling & life-threatening edema
Genetics
- autosomal dominant
- 50% may present without family history, apparently a new mutation
- associated with defect in C1-esterase inhibitor (SERPING1)
Clinical manifestations
- onset in childhood
- recurrent angioedema without urticaria
- episodic local subcutaneous edema, & submucosal edema involving the upper respiratory & gastrointestinal tracts
- abdominal angioedema may present as severe abdominal pain
- lip swelling, tongue swelling unresponsive to epinephrine
- spontaneous resolution of episodes
Laboratory
- C1-esterase inhibitor assay (deficiency)
- complement C4 in serum is persistently diminished
- complement C2 in serum is diminished during acute attacks
- SERPING1 gene mutation
- see ARUP consult[1]
Management
*
- C1 inhibitor (Cinryze) infusions IV twice weekly
- subcutaneous C1 inhibitor twice weekly found to be effective[3]
- danazol
- lanadelumab twice monthly SQ
- on-demand therapy for acute attacks
- C1 inhibitor concentrate, icatibant (Firazyr), or ecallantide (Kalbitor)
* costs > US $300,000 annually[3]
More general terms
More specific terms
References
- ↑ 1.0 1.1 ARUP Consult: Hereditary Angioedema - C1-INH Deficiency The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/hereditary-angioedema
- ↑ Amrol DJ Novel Medication for Hereditary Angioedema NEJM Journal Watch. Feb 23, 2017 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
Banerji A, Busse P, Shennak M et al. Inhibiting plasma kallikrein for hereditary angioedema prophylaxis. N Engl J Med 2017 Feb 23; 376:717. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28225674 <Internet> http://www.nejm.org/doi/10.1056/NEJMoa1605767 - ↑ 3.0 3.1 3.2 Longhurst H, Cicardi M, Craig T et al. Prevention of hereditary angioedema attacks with a subcutaneous C1 inhibitor. N Engl J Med 2017 Mar 23; 376:1131 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28328347 <Internet> http://www.jwatch.org/na43697/2017/03/23/new-preventive-treatment-hereditary-angioedema
- ↑ Busse PJ, Christiansen SC Hereditary Angioedema N Engl J Med 2020; 382:1136-1148. March 19, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32187470 https://www.nejm.org/doi/full/10.1056/NEJMra1808012
- ↑ Longhurst H, Cicardi M. Hereditary angio-oedema. Lancet. 2012 Feb 4;379(9814):474-81. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22305226 Free article. Review.
- ↑ Barmettler S, Li Y, Banerji A. New and evolving therapies for hereditary angioedema. Allergy Asthma Proc. 2019 Jan 1;40(1):7-13. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30582490 Review.