Angioedema: Difference between revisions
 
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==Background==
==Background==
[[File:Gray1014.png|thumb|Anatomy of the posterior pharynx.]]
*Angioedema is paroxysmal, nondemarcated swelling of dermal or submucosal layers of skin or mucosa
*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
**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
[[File:Nejmicm020617 f1.jpg|thumb|Uvular Angioedema (Quincke's Disease)]]


===Etiologies===
===Etiologies===
*'''Allergic angioedema:''' [[Allergic reaction|IgE–mediated type I]] [[Hypersensitivity Reaction|hypersensitivity reaction]]  
*'''Histamine-mediated'''
*'''Hereditary angioedema:''' Congenital or acquired loss of C1 esterase inhibitor
**Allergic angioedema: [[Allergic reaction|IgE–mediated type I]] [[Hypersensitivity Reaction|hypersensitivity reaction]]  
*'''[[ACE-I ]]induced angioedema:''' ACEI adverse reaction from excessive bradykinin
*'''Bradykinin-mediated'''
*'''Idiopathic angioedema'''
**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
**[[ACE inhibitor|ACE-I]]-induced angioedema: ACE-I adverse reaction from excessive bradykinin
*'''Idiopathic'''


==Clinical Features==
[[File:Angioedema2010.jpg|thumb|Angioedema of face.]]
[[File:Angioedema_post_lisinopril_use_2014-12-08_12-35.jpg|thumbnail|Angioedema]]
[[File:Angioedema_post_lisinopril_use_2014-12-08_12-35.jpg|thumbnail|Angioedema]]
[[File:Angioedema2013.jpg|thumbnail|Angioedema of tongue]]
[[File:Angioedema2013.jpg|thumbnail|Angioedema of tongue]]
*Non-pitting edema that most often affects face, lips, and/or tongue
*May also involve<ref>https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic,-autoimmune,-and-other-hypersensitivity-disorders/angioedema?query=angioedema</ref>:
**Upper airway --> [[respiratory distress]], [[stridor]]
**Skin --> urticaria suggests histamine-mediated
**Face, hands, genitals
**Intestines --> [[nausea/vomiting]], [[abdominal pain]], [[diarrhea]], SBO-like presentation


==Hereditary angioedema==
==Differential Diagnosis==
===Background===
{{Template:Acute Allergic DDX}}
*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


===Diagnosis===
==Evaluation==
===Hereditary angioedema===
*Suspect in patients with history of recurrent peripheral angioedema and abdominal pain
*Suspect in patients with history of recurrent peripheral angioedema and abdominal pain
**75% experience onset of symptoms before age 15yr
**75% experience onset of symptoms before age 15yr
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*Decreased levels of C1 and C4 esterase inhibitors confirms diagnosis
*Decreased levels of C1 and C4 esterase inhibitors confirms diagnosis


==ACE inhibitor-induced angioedema==
===ACE inhibitor-induced angioedema===
===Background===
*Incidence is highest within the first month; however, may occur at anytime
*Incidence is highest within the first month; however, may occur at anytime
*40% present months to years after initial dose<ref>Winters ME, et al. Emergency department management of patients with ACE-inhibitor angioedema. JEM. 2013; 45(5):775–780.</ref>
*40% present months to years after initial dose<ref>Winters ME, et al. Emergency department management of patients with ACE-inhibitor angioedema. JEM. 2013; 45(5):775–780.</ref>
*Incidence is 0.1-2.2% (more common in blacks)
*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
*Physiology more closely related to bradykinin-mediated pathway than IgE-mediated pathway, therefore current treatments may be insufficient
==Differential Diagnosis==
{{Template:Acute Allergic DDX}}


==Management==
==Management==
===General===
===General===
*Consider [[Epinephrine]] 0.3mg IM if there is any concern this could be allergic in nature
*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 [[Glucagon]] 1-5mg IV if patient is on beta-blockers and not responding to Epinephrine
*Consider [[Tranexamic acid]] (1 g IV, over 10 min) for bradykinin-mediated angioedema <ref>[https://emcrit.org/ibcc/angioedema/#algorithms IBCC Angioedema Chapter Algorithm]</ref><ref>C Beauchene et al. Tranexamic Acid as First-Line Emergency Treatment for Episodes of Bradykinin-Mediated Angioedema Induced by ACE Inhibitors. Rev Med Interne. 2018 Oct;39(10):772-776.</ref>
*[[FFP]] for possible etiology related to bradykinin or C1-esterase deficiency<ref>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.</ref>
**2 units
*Consider definitive airway if voice change, hoarseness, stridor, dyspnea
*Consider definitive airway if voice change, hoarseness, stridor, dyspnea
**Prepare for a [[difficult airway]] which can include need for fiberoptics, ENT/anesthesia assistance, [[surgical airway]], or transfer to the OR  
**Prepare for a [[difficult airway]] which can include need for [[Awake intubation|fiberoptics]], ENT/anesthesia assistance, [[surgical airway]], or transfer to the OR


===Hereditary Angioedema===
===Hereditary Angioedema===
====First-Line Therapies====
====First-Line Therapies====
*C1 inhibitor (C1INH)<ref>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.</ref>
*[[C1 inhibitor]] (C1INH)<ref>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.</ref>
**1000 units if ≤50kg
**1000 units if ≤50kg
**1500 units if >50-75kg
**1500 units if >50-75kg
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*[[Icatibant]]
*[[Icatibant]]
**30mg SQ
**30mg SQ
====First-Line Therapies====
*[[FFP]]
**2 units


===ACE-I Induced Angioedema===
===ACE-I Induced Angioedema===
Typical anaphylaxis medications do not effect bradykinin levels<ref>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.</ref>, but consider:
*Typical anaphylaxis medications do not affect bradykinin levels<ref>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.</ref>, but consider:
**[[Epinephrine]] 0.3mg IM
**[[Epinephrine]] 0.3mg IM
**[[Diphenhydramine]] 50mg IV
**[[Diphenhydramine]] 50mg IV
**[[Methylprednisolone]] 125mg IV
**[[Methylprednisolone]] 125mg IV
*Consider [[Tranexamic acid]] (1 g IV, over 10 min) for bradykinin-mediated angioedema <ref>[https://emcrit.org/ibcc/angioedema/#algorithms IBCC Angioedema Chapter Algorithm]</ref><ref>C Beauchene et al. Tranexamic Acid as First-Line Emergency Treatment for Episodes of Bradykinin-Mediated Angioedema Induced by ACE Inhibitors. Rev Med Interne. 2018 Oct;39(10):772-776.</ref>
*[[Icatibant]]
*[[Icatibant]]
**30mg SQ
**30mg SQ
**Significantly decreases time to complete resolution (8 hrs vs 27.1 hrs)<ref>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.</ref>
**Significantly decreases time to complete resolution (8 hrs vs 27.1 hrs)<ref>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.</ref>
**Note: control group did not receive FFP
*Consider [[Ecallantide]]
*Consider [[Ecallantide]]
**10mg SQ x 3 in different anatomical locations (30mg in total)
**10mg SQ x 3 in different anatomical locations (30mg in total)
**A 2015 trial showed a non-statistically significant trend towards benefit<ref>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.</ref>
**A 2015 trial showed a non-statistically significant trend towards increased rate of ED discharge<ref>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.</ref>
**No benefit seen in mild-moderate cases in multi-center, double blind study<ref>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.</ref>


==Disposition==
==Disposition==
*Consider discharge after 4-6 hrs obs if there is no airway edema and patient improves
*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 epi given
*24 hrs obs if epinephrine given
*Ishoo Staging (based on retrospective study)<ref>Ishoo E, et al. Predicting airway risk in angioedema: staging system based on presentation. Otolaryngol Head Neck Surg. 1999; 121(3):263-268.</ref>
 
**Stage 1 - face/lip  
===Ishoo Staging===
***48% outpatient, 52% floor, 0% ICU or advanced airway
Ishoo Staging may predict severity of disease to help stratify disposition. It is based on retrospective study<ref>Ishoo E, et al. Predicting airway risk in angioedema: staging system based on presentation. Otolaryngol Head Neck Surg. 1999; 121(3):263-268.</ref>
**Stage 2 - soft palate
 
***60% outpt, 40% floor, 0 ICU or advanced airway
{| {{table}}
**Stage 3 - tongue
| align="center" style="background:#f0f0f0;"|'''Stage'''
***26% outpt, 67% ICU, 7% advanced airway
| align="center" style="background:#f0f0f0;"|'''Area'''
**Stage 4 - larynx
| align="center" style="background:#f0f0f0;"|'''Outpatient'''
***100% ICU, 24% advanced airway
| align="center" style="background:#f0f0f0;"|'''Floor'''
| align="center" style="background:#f0f0f0;"|'''ICU'''
| align="center" style="background:#f0f0f0;"|'''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%
|}


==See Also==
==See Also==
*[[Anaphylaxis]]
*[[Anaphylaxis]]
*[[Tongue Diagnoses]]
*[[Tongue Diagnoses]]
{{Related Difficult Airway Pages}}


==References==
==References==

Latest revision as of 21:27, 11 March 2022

Background

Anatomy of the posterior pharynx.
  • 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

  • Histamine-mediated
  • Bradykinin-mediated
    • 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
    • ACE-I-induced angioedema: ACE-I adverse reaction from excessive bradykinin
  • Idiopathic

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
  • Consider Tranexamic acid (1 g IV, over 10 min) for bradykinin-mediated angioedema [3][4]
  • FFP for possible etiology related to bradykinin or C1-esterase deficiency[5]
    • 2 units
  • Consider definitive airway if voice change, hoarseness, stridor, dyspnea

Hereditary Angioedema

First-Line Therapies

  • C1 inhibitor (C1INH)[6]
    • 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 affect bradykinin levels[7], but consider:
  • Consider Tranexamic acid (1 g IV, over 10 min) for bradykinin-mediated angioedema [8][9]
  • Icatibant
    • 30mg SQ
    • Significantly decreases time to complete resolution (8 hrs vs 27.1 hrs)[10]
    • 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[11]
    • No benefit seen in mild-moderate cases in multi-center, double blind study[12]

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

Ishoo Staging may predict severity of disease to help stratify disposition. It is based on retrospective study[13]

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%

See Also

Airway Pages

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. ↑ IBCC Angioedema Chapter Algorithm
  4. ↑ C Beauchene et al. Tranexamic Acid as First-Line Emergency Treatment for Episodes of Bradykinin-Mediated Angioedema Induced by ACE Inhibitors. Rev Med Interne. 2018 Oct;39(10):772-776.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ IBCC Angioedema Chapter Algorithm
  9. ↑ C Beauchene et al. Tranexamic Acid as First-Line Emergency Treatment for Episodes of Bradykinin-Mediated Angioedema Induced by ACE Inhibitors. Rev Med Interne. 2018 Oct;39(10):772-776.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Ishoo E, et al. Predicting airway risk in angioedema: staging system based on presentation. Otolaryngol Head Neck Surg. 1999; 121(3):263-268.
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