Periodic Severe Angioedema without Exogenous Hormone Exposure

Abstract

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 or corticosteroid. 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.

In Silico Analysis and In-depth Assessment of a Female Patient with a Missense Mutation in the F12 Gene Associated with Hereditary Angioedema Symptoms: A Case Study

“…This pattern aligns with prior studies, which have demonstrated that HAE III type primarily develops in females, with initial symptoms typically emerging during adolescence [56]. One compelling link to this phenomenon is that mutations of the F12 gene can be associated with increased sensitivity of the F12 protein to estrogen-like elements, leading to elevated bradykinin production and the development of soft tissue edema [57,58]. The underlying reason of this phenomenon can be that estrogens can interact with most stages of the complex bradykinin cascade, and the hormonal in uence can be mediated either through classical nuclear-genomic actions or non-genomic effects at the membrane level or by affecting various kinases in the cytoplasm [59].…”