This 25-year-old African American female presents to the emergency department (ED) 2 hours after the onset of lip swelling that has progressed to difficulty in breathing. Her past medical history is unremarkable, with the exception of newly diagnosed hypertension. Last week, her primary care physician began a course of a new antihypertensive medication, lisinopril. She has had no previous history of tissue swelling and there is no family history of disorders characterized by tissue swelling. Her ED vital signs are heart rate 100 bpm, respiratory rate 22 breaths per minute, blood pressure 165/90 mm Hg, temperature 37°C, and SpO2 is 99% on 2 L·min−1 of oxygen by nasal prongs.
The patient is seated (Figure 26–1) with markedly edematous lips. She has a mufﬂed voice (“hot potato voice”) and is unable to swallow her own secretions. There is no stridor. The remainder of the physical examination is within normal limits.
DIAGNOSIS AND INVESTIGATIONS
What Is the Pathophysiology of Angioedema? Are There Different Etiologies?
Angioedema is deﬁned as the abrupt onset of transient, well-demarcated, non-pitting swelling of the skin, mucous membranes, and deep subcutaneous tissues, including the linings of the upper respiratory and gastrointestinal tracts.1-3 Angioedema develops because of a local increase in permeability of the submucosal or subcutaneous capillary vessels, causing local plasma extravasation into the interstitial space.1,3 This is exacerbated by the release of vasoactive substances such as histamines, prostaglandins, cytokines, and bradykinin.4
Angioedema can be divided into hereditary angioedema (HAE) and acquired angioedema. HAE is extremely rare, affecting in the range of 1:30,000 to 1 in 80,000 people.4,5 It develops due to a C1 esterase inhibitor deﬁciency, which is inherited in an autosomal dominant pattern with almost complete penetrance.5 This deﬁciency results in an abnormal increase in the activation of C1 and subsequent excessive formation of the enzyme kallikrein. The excess kallikrein transforms kininogen into kinins, including bradykinin. Bradykinin, the primary biologic mediator of angioedema,5 is highly vasoactive and produces the characteristic tissue swelling seen in angioedema.4 HAE is commonly precipitated by trauma and emotional stress. Frequently, the trauma is considered to be minor and can be as innocuous as prolonged sitting on a hard surface or clapping of the hands. Dental and surgical trauma are well-recognized precipitators of an acute attack.5
Patients with known HAE should have a predetermined comprehensive management plan that includes access to treatment in acute attacks and a prophylactic strategy, when indicated, such as prior to elective surgery. Bradykinin-mediated angioedema is not responsive to standard angioedema treatment modalities used for mast cell-mediated anaphylactic angioedema such as corticosteroids, antihistamines, and epinephrine and must be treated with C1 inhibitor ...