Approach to Angioedema in the Emergency Department

Kyle McGivery, PGY1 FMEM, Dalhousie University

Reviewed by Dr Jo-Ann Talbot and Dr. David Lewis


Angioedema, the swelling of subcutaneous tissues, is a physical sign often attributed to allergic- or histamine-mediated processes and is treated accordingly. There are, however, alternative causes which must be considered when evaluating a patient in the Emergency Department. Most patient visits will involve allergic angioedema with or without evidence of urticaria or anaphylaxis. These presentations may require treatment with anti-histamines, corticosteroids, and epinephrine in addition to IV fluids and airway management for anaphylaxis or airway compromise. Bradykinin-mediated angioedema, however, is not associated with urticaria, does not respond to anti-histamines or corticosteroids, and is poorly responsive to epinephrine. Additionally, attacks may last 2-5 days whereas histamine-mediated angioedema typically resolves within 24-48 hours. With this in mind, developing a clinical approach to angioedema is necessary.


Figure 1. Elements of the history and physical examination that help to establish the working diagnosis. FFP = fresh-frozen plasma; f/u = follow-up; HAE = hereditary angioedema. (Moellman, J., 2014. Academic Emergency Medicine)


As suggested by the algorithm, any patient showing signs of anaphylaxis or airway compromise should be treated imminently. If signs of airway involvement are present (hoarseness, dyspnea, odynophagia) fiberoptic laryngoscopy may be indicated. Following assessment of ABC’s, differentiating histaminergic from non-histaminergic causes should direct subsequent management. In patients presenting with urticaria and/or a history of allergies, the typical histamine-targeted therapies are indicated. In those with known hereditary angioedema (HAE), therapy may include complement inhibitor concentrates (where available), fresh frozen plasma for severe cases, and supportive measures as necessary. This approach also applies to patients using ACE-Inhibitors in addition to discontinuing the inciting medication. For those with an unknown etiology, treating as a histamine-mediated process is safe and its response may provide diagnostic information. To help classify angioedema in the ED, providers should consider several historical features:


Historical Features of Patients Presenting with Different Causes of Angioedema

Characteristic HAE Acquired ACE inhibitor–induced Allergic Idiopathic
  • Female > > Male.

  • ACE = angiotensin-converting enzyme; HAE = hereditary angioedema.

  • For hereditary angioedema with normal complement with or without a genetic mutations.
  • Can have a rapid onset in less than 1 hour.
Age of onset 2–13 yr Adult Adult Any age Any age
Family history 75% No No History of atopy No
Ethnicity None None 80% African American None None
Sex-associated predilection Noa No No No No
Location of attacks Peripheral, abdominal, facial, laryngeal, genitourinary Peripheral, abdominal, facial, laryngeal, genitourinary Lips, tongue, facial Lips, tongue, laryngeal Lips, tongue, rarely laryngeal
Speed of attack onset Gradual over a few hoursb Gradual over a few hours Gradual over a few hours Immediate within 1 hour Variable
Duration of attacks 3–5 days without treatment 3–5 days without treatment 24–48 hours after drug discontinued Several hours without treatment Several hours without treatment
Recurrent nature of attacks Yes Yes with or without treatment No, if drug discontinued; attacks can persist for 4–6 weeks after drug discontinuation Yes only if reexposed to allergen avoided Yes with or without treatment
Associated with urticaria No No No Yes or no Typically no but possible
Presents with abdominal pain Yes Yes Usually not No No
Response to H1 antagonists and oral corticosteroids No No No Yes Variable
Response to epinephrine No No No Yes Variable

(Moellman, J., 2014. Academic Emergency Medicine)


Bottom line: Angioedema has a wide differential diagnosis that includes both histamine- and non histamine-mediated processes. Using both response to therapy and a detailed history/physical, they can be differentiated in the ED and treated accordingly. Despite the possibility of bradykinin-induced angioedema, however, usual therapies for presumed histamine-mediated angioedema should not be withheld in cases where etiology is unknown and intervention is necessary.



Moellman, J. J., Bernstein, J. A., & Lindsell, C. (2014). A CONSENSUS PARAMETER FOR THE EVALUATION AND MANAGEMENT OF ANGIOEDEMA IN THE EMERGENCY DEPARTMENT. Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine,21(4), 469–484. doi:10.1111/acem.12341

Lawrence, L. M. (2013). Angioedema: Etiology, Pathophysiology, Current and Emerging Therapies. Journal of Emergency Medicine, 45(5), 789-796.!/content/1-s2.0-S0736467913005878

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