Editing Angioedema (section)

==Diagnosis==
The diagnosis is made on the clinical picture. Routine blood tests ([[complete blood count]], [[electrolyte]]s, [[kidney function]], [[liver enzyme]]s) are typically performed. [[Tryptase|Mast cell tryptase]] levels may be elevated if the attack was due to an acute allergic (anaphylactic) reaction. When the patient has been stabilized, particular investigations may clarify the exact cause; [[complement system|complement]] levels, especially depletion of complement factors 2 and 4, may indicate deficiency of ''[[C1-inhibitor]]''. HAE type III is a diagnosis of exclusion consisting of observed angioedema along with normal C1 levels and function.{{citation needed|date=November 2023}}

The hereditary form (HAE) often goes undetected for a long time, as its symptoms resemble those of more common disorders, such as allergy or intestinal colic. An important clue is the failure of hereditary angioedema to respond to [[antihistamines]] or [[glucocorticoid|steroids]], a characteristic that distinguishes it from allergic reactions. It is particularly difficult to diagnose HAE in patients whose episodes are confined to the gastrointestinal tract. Besides a family history of the disease, only a laboratory analysis can provide final confirmation. In this analysis, it is usually a reduced complement factor C4, rather than the C1-INH deficiency itself, that is detected. The former is used during the reaction cascade in the complement system of immune defense, which is permanently overactive due to the lack of regulation by C1-INH.

Angioedema is classified as either hereditary or acquired.

===Acquired angioedema===
Acquired angioedema (AAE) can be immunologic, nonimmunologic, or idiopathic.<ref name=Axelrod2011>{{cite journal|last=Axelrod|first=S|author2=Davis-Lorton, M|title=Urticaria and angioedema|journal=The Mount Sinai Journal of Medicine, New York|year=2011|volume=78|issue=5|pages=784–802|pmid=21913206|doi=10.1002/msj.20288}}</ref> It is usually caused by [[allergy]] and occurs together with other allergic symptoms and [[urticaria]]. It can also occur as a side effect to certain medications, particularly [[ACE inhibitor]]s. It is characterized by repetitive episodes of swelling, frequently of the face, lips, tongue, limbs, and genitals. Edema of the gastrointestinal mucosa typically leads to severe abdominal pain; in the upper respiratory tract, it can be life-threatening.<ref>{{cite web|last1=Moon |first1=Amanda T.|last2=Heymann |first2=Warren R.|title=Acquired Angioedema|url=http://emedicine.medscape.com/article/1048887-overview|website=MedScape|access-date=1 October 2015|url-status=live|archive-url=https://web.archive.org/web/20150905111954/http://emedicine.medscape.com/article/1048887-overview|archive-date=5 September 2015}}</ref>

===Hereditary angioedema===
[[Hereditary angioedema]] (HAE) exists in three forms, all of which are caused by a genetic mutation inherited in an [[Dominance (genetics)|autosomal dominant]] form. They are distinguished by the underlying genetic abnormality. Types I and II are caused by mutations in the ''SERPING1'' gene, which result in either diminished levels of the [[C1-inhibitor]] protein (type I HAE) or dysfunctional forms of the same protein (type II HAE). Type III HAE has been linked with mutations in the ''F12'' gene, which encodes the coagulation protein [[factor XII]]. All forms of HAE lead to abnormal activation of the [[complement system]], and all forms can cause swelling elsewhere in the body, such as the [[digestive tract]]. If HAE involves the [[larynx]], it can cause life-threatening [[asphyxiation]].<ref>{{cite journal |author=Zuraw B.L. |title=Clinical practice. Hereditary angioedema |journal=N. Engl. J. Med. |volume=359 |issue=10 |pages=1027–36 |date=September 2008 |pmid=18768946 |doi=10.1056/NEJMcp0803977}}</ref> The pathogenesis of this disorder is suspected to be related to unopposed activation of the contact pathway by the initial generation of kallikrein and/or clotting factor XII by damaged endothelial cells. The end product of this cascade, bradykinin, is produced in large amounts and is believed to be the predominant mediator leading to increased vascular permeability and vasodilation that induces typical angioedema "attacks".<ref>{{cite web|last=Loew|first=Burr|title=A 68-Year-Old Woman With Recurrent Abdominal Pain, Nausea, and Vomiting|url=http://www.medscape.org/viewarticle/743937_2|publisher=MedScape|access-date=19 October 2012|url-status=live|archive-url=https://web.archive.org/web/20121022004946/http://www.medscape.org/viewarticle/743937_2|archive-date=22 October 2012}}</ref>