Angioedema

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
    • Isolated uvular angioedema, or Quincke's disease, is a relatively rare presentation of angioedema of the upper airway
Uvular Angioedema (Quincke's Disease)

Etiologies

  • Allergic angioedema: IgE–mediated type I hypersensitivity reaction
  • Hereditary angioedema: Congenital or acquired loss of C1 esterase inhibitor
    • 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
  • ACE-I induced angioedema: ACEI adverse reaction from excessive bradykinin
  • Idiopathic angioedema

Clinical Features

Angioedema of face.
Angioedema
Angioedema of tongue

Differential Diagnosis

Acute allergic reaction

Evaluation

Hereditary angioedema

  • 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[2]
  • 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

Management

General

  • 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 beta-blockers and not responding to Epinephrine
  • FFP for possible etiology related to bradykinin or C1-esterase deficiency[3]
    • 2 units
  • Consider definitive airway if voice change, hoarseness, stridor, dyspnea

Hereditary Angioedema

First-Line Therapies

  • C1 inhibitor (C1INH)[4]
    • 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

ACE-I Induced Angioedema

  • Typical anaphylaxis medications do not effect bradykinin levels[5], but consider:
  • Icatibant
    • 30mg SQ
    • Significantly decreases time to complete resolution (8 hrs vs 27.1 hrs)[6]
    • Note: control group did not receive FFP
  • Consider Ecallantide
    • 10mg SQ x 3 in different anatomical locations (30mg in total)
    • A 2015 trial showed a non-statistically significant trend towards increased rate of ED discharge[7]
    • No benefit seen in mild-moderate cases in multi-center, double blind study[8]

Disposition

  • Consider discharge after 4-6 hrs observation if there is no airway edema and patient improves or swelling remains isolated to face and lips only
  • 24 hrs obs if epinephrine given

Ishoo Staging^[9]

Stage Area Outpatient Floor ICU Advanced Airway
1 Face/lip 48% 52% 0% 0%
2 Soft palate 60% 40% 0% 0%
3 Tongue 26% 7% 67% 7%
4 Larynx 0% 0% 100% 24%

^Based on retrospective study

See Also

References

  1. https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic,-autoimmune,-and-other-hypersensitivity-disorders/angioedema?query=angioedema
  2. Winters ME, et al. Emergency department management of patients with ACE-inhibitor angioedema. JEM. 2013; 45(5):775–780.
  3. Moellman, J.J., Bernstein, J.A., Lindsell, C., Banerji, A., Busse, P.J., Camargo, C.A., Collins, S.P., Craig, T.J., Lumry, W.R., Nowak, R., Pines, J.M., Raja, A.S., Riedl, M., Ward, M.J., Zuraw, B.L., Diercks, D., Hiestand, B., Campbell, R.L., Schneider, S. and Sinert, R. (2014) ‘A consensus parameter for the evaluation and management of Angioedema in the emergency department’, Academic Emergency Medicine, 21(4), pp. 469–484.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Lewis, L.M., Graffeo, C., Crosley, P., Klausner, H.A., Clark, C.L., Frank, A., Miner, J., Iarrobino, R. and Chyung, Y. (2015) ‘Ecallantide for the acute treatment of angiotensin-converting enzyme Inhibitor–Induced Angioedema: A Multicenter, Randomized, controlled trial’, Annals of Emergency Medicine, 65(2), pp. 204–213.
  9. Ishoo E, et al. Predicting airway risk in angioedema: staging system based on presentation. Otolaryngol Head Neck Surg. 1999; 121(3):263-268.