Death from angioedema occurs from airway obstruction and that’s why the most important resource for the emergency treatment of Angioedema is the IBCC Chapter Angioedema, August 1, 2019 by Dr. Josh Farkas. I reviewed the chapter today as well as what follows below.
Today I reviewed hereditary angioedema after reading the NY Times article, Her Stomach Hurt Unbearably. Her Doctors Were Baffled, of December 28, 2020.
A 45 year old woman began experiencing excruciating abdominal pain that was finally diagnosed as Hereditary Angioedema, Type 3*.
*See Hereditary angioedema type III (estrogen-dependent) report of three cases and literature review [PubMed Abstract]. An Bras Dermatol. 2013 Jul-Aug; 88(4): 578–584.
In this article, three cases of hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor) are reported. The HAE was initially described in women of the same family in association with high-leveled estrogenic conditions such as the use of oral contraceptives and pregnancy. There is no change in the C1 inhibitor as happens in other types of hereditary angioedema, and mutations are observed in the encoding gene of the XII factor of coagulation in several patients. The current diagnosis is mainly clinical and treatment consists in the suspension of the triggering factors and control of acute symptoms. A brief review of physiopathology, clinical features, genetic alterations and treatment are also presented.
Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of swelling of the skin and / or mucous, which can also affect the gastrointestinal tract and upper airways in a severe way. 1The crisis does not respond to antihistamines, corticosteroids or adrenaline and usually disappear spontaneously within 12-72 hours. There is a mutation in the gene that encodes the C1 inhibitor of the complement factor (INHC1), inducing a reduction in its synthesis (type I HAE) or the formation of a dysfunctional protein (type II HAE). In 2000, a new subtype of HAE was described, which is clinically indistinguishable from the others, predominantly in women, in which the INHC1 is normal. 2The new disorder was called hereditary angioedema type III, estrogen-dependent hereditary angioedema or hereditary angioedema with normal C1 activity (type III HAE). There is a verifiable association with this type of hereditary angioedema and situations where increased levels of estrogen occur such as the use of oral contraceptives and pregnancy, which are recognised crises factors.2-4The objective of this article is to describe the clinical and laboratory findings of three cases of this new type of HAE as well as briefly reviewing existing literature on the physiopathology, clinical features, genetic alterations, diagnosis and treatment.
Hereditary angioedema (HAE) is an autosomal dominant disease caused by low levels of the plasma protein C1 inhibitor (C1-INH).
Deficiencies in C1-INH allow unchecked activation of the classic complement pathway and other biochemical systems including the bradykinin system. Patients can present with any combination of painless, nonpruritic, nonpitting swelling of the skin (cutaneous angioedema); severe abdominal pain; or acute airway obstruction.
There are 3 types of HAE. Type I HAE is defined by low plasma levels of a normal C1-INH protein reflecting an abnormality of one of the gene alleles of the protein. Type II HAE is characterized by the presence of normal or elevated levels of a dysfunctional C1-INH. Again, one of the two gene alleles is abnormal but here the allele leads to the release of a non-functional protein. HAE with normal C1 inhibitor was identified as an estrogen-dependent inherited form of angioedema occurring mainly in women with normal functional and quantitative levels of C1-INH. There is still no clear understanding of its pathophysiologic mechanism
Prior to the development of effective therapy, the mortality rate from HAE was 20-30%. Although preventable and treatable, the complications of this disease do not respond well to the usual therapies for angioedema; therefore, establishment of the correct diagnosis is critical. The most reliable and cost-effective screening test for HAE is a serum C4 level (see Workup).Treatment of HAE consists of prophylaxis, management of acute attacks, and prophylactic therapy in situations where attacks may occur. In HAE types I and II, the treatment of choice in acute attacks consists of replacement with commercially available C1 inhibitor (C1-INH) concentrates  , a kallikrein inhibitor or a bradykinin receptor type 2 antagonist. If there is no specific treatment available, fresh-frozen plasma has been used, but the physician should understand that, because the plasma may supply the substrate for bradykinin generation, attacks can at times worsen before they improve.
At the time of this report there is no consensus on best therapy for HAE with normal C1 inhibitor (See Treatment.)