Angioedema Basics

Angioedema (AE)




Figure 1: There are two main pathways which lead to angioedema: the mast-cell mediated pathway and the bradykinin-mediated pathway.. The bradykinin-mediated pathway is subdivided into ACE-inhibitor induced, hereditary angioedema and idiopathic angioedema. 



Mast Cell-Mediated:

●   Often associated with urticaria/pruritus and other stigmata of allergic reactions and anaphylaxis

●   Begins within minutes of exposure to antigen, builds over minutes to hours, resolves within 24-48 hrs

●.  Treatment: Anti-histamines, glucocorticoids, epinephrine (if severe)



●   Often affects: lips, tongue, mouth, larynx, pharynx and subglottic tissues

●   Associated with abdominal pain, nausea, vomiting, diarrhea

●   Develops over 24-36 hrs, resolves over 2-4 days


  1. ACE-Inhibitor Induced (ACEi)

●   Can happen even after months/years of taking medication

●   Degradation of bradykinin is inhibited → increased levels of bradykinin


  1. Hereditary Angioedema (HA)

●   Due to C1 Esterase Inhibitor Deficiency → Increased generation of bradykinin

●   Autosomal dominant

●   Can also be acquired, typically associated with autoimmune disease


  1. Idiopathic

●   Etiologies of unknown mechanism

●   Infection (mostly children) - URI, UTI, strep pharyngitis

●   Thrombolytics - streptokinase, alteplase (likely bradykinin)

●   DPP-4 inhibitors (-gliptans)

●   Calcium channel blockers 

●   Other drugs: sirolimus, everolimus, amiodarone, metoprolol, risperidone, paroxetine, etanercept, biologics, inhaled cocaine 


Final common pathway:

●   Inflammatory markers → increased vascular permeability → loss of vascular integrity → extravasation of fluid to interstitium→ self limited, localized swelling of skin or mucosal tissues

●   Fluid collects asymmetrically - face, larynx, bowel wall



Priority is airway management

●   Edema can be progressive resulting in airway occlusion

●   Awake intubation preferred (in stable situation) due to anticipated difficult airway

●   If edema is mild, can consider observation for airway monitoring

          - Can consider medications listed below

          - Can consider NPL to evaluate for posterior edema


  1. Fresh Frozen Plasma (FFP)

●   Source of kininase II (ACE) and other enzymes which degrade bradykinin

●   Symptoms improved roughly 2 hrs faster for both HA and ACEi-AE

●   Theoretically may worsen attack since new bradykinin can be formed (contains other substrates like prekallikrein)

●   Relatively inexpensive


  1. Plasma-derived C1 Esterase-Inhibitor

●   Decreases the excessive production of bradykinin

●   Symptoms improved roughly 2 hrs faster for ACEi-AE, HA and idiopathic AE

●   Expensive 


  1. Icatibant

●   Selective bradykinin-receptor 2 antagonist

●   Symptoms improved roughly 2 hrs faster for ACEi-AE, HA and idiopathic AE

●   Expensive

●   Patients with known HA will often have this med stocked at their local hospital


  1. Ecallantide

●   Recombinant protein, directly inhibits kallikrein

●   Symptoms improved roughly 75 min faster for HA and idiopathic AE

●   5% hypersensitivity reactions

●   No significant improvement in ACEi-AE

●   Expensive 


  1. Tranexamic Acid (TXA)

●   Very limited data 

●   Some retrospective studies showed improvement in symptoms with ACEi AE, HA and idiopathic AE

●   TXA inhibits plasminogen→ decreased production of bradykinin

●   Inexpensive 




1. Beauchene, C et al. Tranexamic acid as first-line emergency treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors. La Revue de Médecine Interne. 2018; 39(10):772-776.

2. Bernstein, J et al. Angioedema in the emergency department: a practical guide to differential diagnosis and management. Int J Emerg Med. 2017; 10: 15.

3. Du‐Thanh, A et al. Efficacy of tranexamic acid in sporadic idiopathic bradykinin angioedema. Allergy. 2010;65(6):793-795

4. Van Den Elzen, M et al. Efficacy of treatment of non-hereditary angioedema. Clinical Reviews in Allergy and Immunology. 2018; 54(3): 412-431. 

5. Zeerleder, S et al. Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment.Annals of Medicine. 2016;48:4.

6. Zuraw BL, Busse PJ, White M, Jacobs J, Lumry W, Baker J, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema.N Engl J Med. 2010;363:513–22.