Revision as of 00:16, 14 July 2016 by ClaireLewis (talk | contribs) (Background)


  • Angioedema is paroxysmal, nondemarcated swelling of dermal or submucosal layers of skin or mucosa
    • Swelling is asymmetric, nonpitting, and nonpruritic, however can be associated with allergic features depending on cause


Angioedema of tongue

Hereditary angioedema


  • Due to C1 esterase inhibitor deficiency
    • Leads to unregulated activity of vasoactive mediators (bradykinin) associated with complement pathway
    • Autosomal dominant
  • Edema of face, extremities, bowel wall


  • Suspect in patients with history of recurrent peripheral angioedema and abdominal pain
    • 75% experience onset of symptoms before age 15yr
  • C4 level screens for HAE (suspect if low)
  • Decreased levels of C1 and C4 esterase inhibitors confirms diagnosis

ACE inhibitor-induced angioedema


  • Incidence is highest within the first month; however, may occur at anytime
  • 40% present months to years after initial dose[1]
  • Incidence is 0.1-2.2% (more common in blacks)
  • Physiology more closely related to bradykinin-mediated pathway than IgE-mediated pathway, therefore current treatments may be insufficient

Differential Diagnosis

Acute allergic reaction



  • Consider Epinephrine 0.3mg IM if there is any concern this could be allergic in nature
  • Consider Glucagon 1-5mg IV if patient is on B-blockers and not responding to Epinephrine
  • Consider definitive airway if voice change, hoarseness, stridor, dyspnea

Hereditary Angioedema

First-Line Therapies

  • C1 inhibitor (C1INH)[2]
    • 1000 units if ≤50kg
    • 1500 units if >50-75kg
    • 2000 units if >75-100kg
    • 2500 units if >100kg
  • Ecallantide
    • 10mg SQ x 3 in different anatomical locations (30mg in total)
  • Icatibant
    • 30mg SQ

First-Line Therapies

ACE-I Induced Angioedema

Typical anaphylaxis medications do not effect bradykinin levels[3], but consider:


  • Consider discharge after 4-6 hrs obs if there is no airway edema and patient improves
  • 24 hrs obs if epi given
  • Ishoo Staging (based on retrospective study)[6]
    • Stage 1 - face/lip
      • 48% outpatient, 52% floor, 0% ICU or advanced airway
    • Stage 2 - soft palate
      • 60% outpt, 40% floor, 0 ICU or advanced airway
    • Stage 3 - tongue
      • 26% outpt, 67% ICU, 7% advanced airway
    • Stage 4 - larynx
      • 100% ICU, 24% advanced airway

See Also


  1. Winters ME, et al. Emergency department management of patients with ACE-inhibitor angioedema. JEM. 2013; 45(5):775–780.
  2. Craig TJ, Levy RJ, Wasserman RL, et al. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009; 124(4):801.
  3. Bas M, Greve J, Stelter K, et al. Therapeutic efficacy of icatibant in angioedema induced by angiotensin-converting enzyme inhibitors: a case series. Ann Emerg Med. 2010; 56(3):278-282.
  4. Baş M, Greve J, Stelter K, et al. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015; 372(5):418-25.
  5. Bernstein JA, Moellman JJ, Collins SP, et al. Effectiveness of ecallantide in treating angiotensin-converting enzyme inhibitor-induced angioedema in the emergency department. Ann Allergy Asthma Immunol. 2015; 114(3):245.
  6. Ishoo E, et al. Predicting airway risk in angioedema: staging system based on presentation. Otolaryngol Head Neck Surg. 1999; 121(3):263-268.