Difference between revisions of "Angioedema"

(Created page with "==Background== *Angioedema is paroxysmal, nondemarcated swelling of dermal or submucosal layers of skin or mucosa **Swelling is asymmetric, nonpitting, and nonpruritic *4 etiolog...")
 
(Management)
 
(69 intermediate revisions by 16 users not shown)
Line 1: Line 1:
 
==Background==
 
==Background==
 
*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
+
**Swelling is asymmetric, nonpitting, and nonpruritic, however can be associated with allergic features depending on cause
*4 etiologies:
+
**Isolated uvular angioedema, or Quincke's disease, is a relatively rare presentation of angioedema of the upper airway
**1. Congenital or acquired loss of C1 esterase inhibitor
+
[[File:Nejmicm020617 f1.jpg|thumb|Uvular Angioedema (Quincke's Disease)]]
**2. IgE–mediated type I allergic reaction
 
**3. ACEI adverse reaction
 
**4. Idiopathic
 
  
==Hereditary Angioedema==
+
===Etiologies===
===Background===
+
*'''Allergic angioedema:''' [[Allergic reaction|IgE–mediated type I]] [[Hypersensitivity Reaction|hypersensitivity reaction]]
*Due to C1 esterase inhibitor deficiency
+
*'''Hereditary angioedema:''' Congenital or acquired loss of C1 esterase inhibitor
**Leads to unregulated activity of vasoactive mediators associated with complement pathway
+
**Due to C1 esterase inhibitor deficiency
 +
**Leads to unregulated activity of vasoactive mediators (bradykinin) associated with complement pathway
 
**Autosomal dominant
 
**Autosomal dominant
 +
**Edema of face, extremities, bowel wall
 +
*'''[[ACE inhibitor|ACE-I]] induced angioedema:''' ACEI adverse reaction from excessive bradykinin
 +
*'''Idiopathic angioedema'''
  
===Diagnosis===
+
==Clinical Features==
 +
[[File:Angioedema2010.jpg|thumb|Angioedema of face.]]
 +
[[File:Angioedema_post_lisinopril_use_2014-12-08_12-35.jpg|thumbnail|Angioedema]]
 +
[[File:Angioedema2013.jpg|thumbnail|Angioedema of tongue]]
 +
*Angioedema
 +
*Swelling most often includes 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]]
 +
**Face, hands, genitals
 +
**Intestines--> [[nausea/vomiting]], [[abdominal pain]], [[diarrhea]], SBO-like presentation
 +
 
 +
==Differential Diagnosis==
 +
{{Template:Acute Allergic DDX}}
 +
 
 +
==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
 +
*C4 level screens for HAE (suspect if low)
 
*Decreased levels of C1 and C4 esterase inhibitors confirms diagnosis
 
*Decreased levels of C1 and C4 esterase inhibitors confirms diagnosis
  
===Treatment===
+
===ACE inhibitor-induced angioedema===
*Epinephrine IM can produce some improvement in early acute attacks
 
*C1 esterase inhibitor (if available)
 
*FFP
 
**Replaces the missing inhibitor protein
 
**Not recommended in life-threatening laryngeal edema (some pts may become more edematous)
 
***Instead, pt should undergo fiberoptic intubation w/ preparation for surgical airway
 
 
 
==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>
 
*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
  
===Treatment===
+
==Management==
*Epinephrine 0.3mg IM q15-20min prn
+
===General===
*Diphenhydramine 50mg IV OR cetirizine 10mg PO
+
*Consider [[Epinephrine]] 0.3mg IM if there is any concern this could be allergic in nature
*Methylprednisolone 125mg IV
+
*Consider [[Glucagon]] 1-5mg IV if patient is on beta-blockers and not responding to Epinephrine
*Awake fiberoptic intubation
+
*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
 +
**Prepare for a [[difficult airway]] which can include need for fiberoptics, ENT/anesthesia assistance, [[surgical airway]], or transfer to the OR
 +
 
 +
===Hereditary Angioedema===
 +
====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>
 +
**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<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
 +
**[[Diphenhydramine]] 50mg IV
 +
**[[Methylprednisolone]] 125mg IV
 +
*[[Icatibant]]
 +
**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>
 +
**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<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 obs it pt improves and there is no airway edema
+
*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^<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>===
 +
{| {{table}}
 +
| align="center" style="background:#f0f0f0;"|'''Stage'''
 +
| align="center" style="background:#f0f0f0;"|'''Area'''
 +
| align="center" style="background:#f0f0f0;"|'''Outpatient'''
 +
| 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%
 +
|}
 +
^Based on retrospective study
 +
 
 +
==See Also==
 +
*[[Anaphylaxis]]
 +
*[[Tongue Diagnoses]]
  
==Source==
+
==References==
Tintinalli
+
<references/>
  
 
[[Category:ENT]]
 
[[Category:ENT]]

Latest revision as of 13:35, 16 August 2020

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
  • 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 effect bradykinin levels[7], but consider:
  • Icatibant
    • 30mg SQ
    • Significantly decreases time to complete resolution (8 hrs vs 27.1 hrs)[8]
    • 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[9]
    • No benefit seen in mild-moderate cases in multi-center, double blind study[10]

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^[11]

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. 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. 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.
  9. 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.
  10. 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.
  11. Ishoo E, et al. Predicting airway risk in angioedema: staging system based on presentation. Otolaryngol Head Neck Surg. 1999; 121(3):263-268.