Periodic Severe Angioedema without Exogenous Hormone Exposure
Hereditary angioedema (HAE) is characterized by recurrent attacks of skin and mucosal swelling in any part of the body including the digestive and respiratory tract which generally improve spontaneously within 12-72 hours. The underlying mechanism in HAE is related to bradykinin dysregulation which causes these attacks not to respond to common treatment strategies including epinephrine/corticosteroid or adrenaline. There are several types of HAE with different etiology but with the same clinical picture. Type 1 is due to the deficiency of C1 Inhibitor (C1-INH) protein and type 2 is related to dysfunctional C1-INH protein. The third type of HAE which comprises the minority of cases is associated with the normal amount and function of C1-INH protein. The presented case in this report was a 15-years old girl with a history of spontaneous angioedema attacks from the age of 14. The frequency of attacks was initially every two months but consequently increased to every two weeks after using some hormonal medications for ovarian cyst. Each episode has lasted around 10 days without any symptoms in between. Complement studies including C4, C1q, and C1-INH protein, both quantitative and qualitative, were reported as normal. A genetic assessment revealed a mutation in the exon 9 on the gene related to factor XII, hence the diagnosis of HAE type 3 was confirmed. This was a rare type of angioedema with normal amount and function of C1-INH protein which is predominantly seen in women during periods of imbalanced estrogen increments like pregnancy, lactation, and menopause, and hence it is responsive to hormonal manipulation strategies such as the use of progesterone containing medications.
2. Serrano C, Guilarte M, Tella R, et al. Oestrogen-dependent hereditary angio-oedema with normal C1 inhibitor: description of six new cases and review of pathogenic mechanisms and treatment. Allergy. 2008;63(6):735-741.
3. Cugno M, Zanichelli A, Foieni F, Caccia S, Cicardi M. C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends Mol Med. 2009;15(2):69-78.
4. Kaplan AP, Joseph K. Pathogenesis of Hereditary Angioedema: The Role of the Bradykinin-Forming Cascade. Immunol Allergy Clin North Am. 2017;37(3):513-25
5. Bork K, Barnstedt SE, Koch P, Traupe H. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet. 2000;356(9225):213-17.
6. Bork K, Gül D, Dewald G. Hereditary angio-oedema with normal C1 inhibitor in a family with affected women and men. Br J Dermatol. 2006;154(3):542-5.
7. Binkley KE. Factor XII mutations, estrogen-dependent inherited angioedema, and related conditions. Allergy, Asthma & Clinical Immunology. 2010;6(1):16.
8. Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun. 2006;343(4):1286-9.
9. Bork K, Wulff K, Meinke P, Wagner N, Hardt J, Witzke G. A novel mutation in the coagulation factor 12 gene in subjects with hereditary angioedema and normal C1-inhibitor. Clin Immunol. 2011;141(1):31-5.
10. Kiss N, Barabás E, Várnai K, et al. Novel duplication in the F12 gene in a patient with recurrent angioedema. Clin Immunol. 2013;149(1):142-5.
11. McKibbin L, Barber C, Kalicinsky C, Warrington R. Review of the Manitoba cohort of patients with hereditary angioedema with normal C1 inhibitor. Allergy Asthma Clin Immunol. 2019;15:66.
12. Cicardi M, Aberer W, Banerji A, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy. 2014;69(5):602-16.
13. Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-36.
14. Depetri F, Tedeschi A, Cugno M. Angioedema and emergency medicine: From pathophysiology to diagnosis and treatment. Eur J Intern Med. 2019; 59:8-13.
15. Bork K, Gül D, Hardt J, Dewald G. Hereditary angioedema with normal C1 inhibitor: clinical symptoms and course. Am J Med. 2007;120(11):987-92.
16. Bork K. Hereditary angioedema with normal C1 inhibitor. Immunol Allergy Clin North Am. 2013;33(4):457-70.
17. Bork K, Wulff K, Hardt J, Witzke G, Lohse P. Characterization of a partial exon 9/intron 9 deletion in the coagulation factor XII gene (F12) detected in two Turkish families with hereditary angioedema and normal C1 inhibitor. Haemophilia. 2014;20(5): e372-e375.
18. Björkqvist J, de Maat S, Lewandrowski U, et al. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III. J Clin Invest. 2015;125(8):3132-46.
19. Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun. 2006;343(4):1286-9.
20. Gompels MM, Lock RJ, Abinun M, et al. C1 inhibitor deficiency: consensus document [published correction appears in Clin Exp Immunol. 2005 Jul;141(1):189-90]. Clin Exp Immunol. 2005;139(3):379-94.
21. Katelaris C, Smith W, Wong M, Jordan A. Position paper on hereditary angioedema (HAE). Australas Soc Clin Immunol Allergy. 2017:1-44.
22. Bork K, Gül D, Hardt J, Dewald G. Hereditary angioedema with normal C1 inhibitor: clinical symptoms and course. Am J Med. 2007;120(11):987-92.
23. Serrano C, Guilarte M, Tella R, et al. Oestrogen-dependent hereditary angio-oedema with normal C1 inhibitor: description of six new cases and review of pathogenic mechanisms and treatment. Allergy. 2008;63(6):735-41.
|Issue||Vol 20 No 1 (2021)|
|Bradykinin Complement C1 inhibitor protein Factor XII Hereditary angioedema|
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