Angioedema: Difference between revisions

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==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===
*'''Allergic angioedema:''' [[Allergic reaction|IgE–mediated type I]] [[Hypersensitivity Reaction|hypersensitivity reaction]]
*'''Hereditary angioedema:''' Congenital or acquired loss of C1 esterase inhibitor
*'''[[ACE inhibitor|ACE-I]] induced angioedema:''' ACEI adverse reaction from excessive bradykinin
*'''Idiopathic angioedema'''
 
[[File:Angioedema_post_lisinopril_use_2014-12-08_12-35.jpg|thumbnail|Angioedema]]
[[File:Angioedema2013.jpg|thumbnail|Angioedema of tongue]]
 
==Hereditary angioedema==
===Background===
===Background===
*Due to C1 esterase inhibitor deficiency
*Due to C1 esterase inhibitor deficiency
**Leads to unregulated activity of vasoactive mediators (bradykinin) associated with complement pathway
**Leads to unregulated activity of vasoactive mediators (bradykinin) associated with complement pathway
**Autosomal dominant
**Autosomal dominant
*Edema of face, extremities, bowel wall


===Diagnosis===
===Evaluation===
*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


===Treatment===
==ACE inhibitor-induced angioedema==
*Strongly consider definitive airway if voice change, hoarseness, stridor, dyspnea - arrange transfer to OR if not crashing
*Epinephrine can produce some improvement in early acute attacks associated with anaphylaxis, however, HAE is bradykinin mediated and the role of steroids and H1/H2 blockers is limited
*If available - C1 esterase inhibitors (Berinert 20u/kg IV), kallikrein/bradykinin inhibitors (ecallantide 30mg SQ), or bradykinin receptor antagonist (icantibant 30mg SQ)
*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===
===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  
*Physiology more closely related to bradykinin-mediated pathway than IgE-mediated pathway, therefore current treatments may be insufficient
 
===Treatment===
*Airway management as above, consider awake fiberoptic intubation
*Epinephrine 0.3mg IM q15-20min prn
*Consider glucagon 1-5mg IV if pt on B-blockers and not responding to epi
*Diphenhydramine 50mg IV OR cetirizine 10mg PO
*Methylprednisolone 125mg IV
*H2 blocker IV or PO


==Differential Diagnosis==
==Differential Diagnosis==
{{Template:Acute Allergic DDX}}
{{Template:Acute Allergic DDX}}
{{Template:Tongue DDX}}
 
==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<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 4-6 hrs obs if there is no airway edema and pt 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)
*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  
**Stage 1 - face/lip  
***48% outpatient, 52% floor, 0% ICU or advanced airway
***48% outpatient, 52% floor, 0% ICU or advanced airway
**Stage 2 - soft palate
**Stage 2 - soft palate
***60% outpt, 40% floor, 0 ICU or advanced airway
***60% outpatient, 40% floor, 0 ICU or advanced airway
**Stage 3 - tongue
**Stage 3 - tongue
***26% outpt, 67% ICU, 7% advanced airway
***26% outpatient, 67% ICU, 7% advanced airway
**Stage 4 - larynx
**Stage 4 - larynx
***100% ICU, 24% advanced airway
***100% ICU, 24% advanced airway
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*[[Tongue Diagnoses]]
*[[Tongue Diagnoses]]


==Source==
==References==
*Tintinalli
<references/>
*EB Medicine "Angioedema in the Emergency Department: An Evidence Based Review" Nov 2012
 
*Ishoo, et al, 1999, "Predicting Airway Risk in Angioedema: staging system based on presentation" in Otolaryngology - Head and Neck Surgery
[[Category:ENT]]
[[Category:ENT]]

Revision as of 17:38, 25 January 2019

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

Angioedema
Angioedema of tongue

Hereditary angioedema

Background

  • 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

Evaluation

  • 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

Background

  • 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

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[2]
    • 2 units
  • Consider definitive airway if voice change, hoarseness, stridor, dyspnea

Hereditary Angioedema

First-Line Therapies

  • C1 inhibitor (C1INH)[3]
    • 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[4], but consider:
  • Icatibant
    • 30mg SQ
    • Significantly decreases time to complete resolution (8 hrs vs 27.1 hrs)[5]
    • 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[6]
    • No benefit seen in mild-moderate cases in multi-center, double blind study[7]

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 (based on retrospective study)[8]
    • Stage 1 - face/lip
      • 48% outpatient, 52% floor, 0% ICU or advanced airway
    • Stage 2 - soft palate
      • 60% outpatient, 40% floor, 0 ICU or advanced airway
    • Stage 3 - tongue
      • 26% outpatient, 67% ICU, 7% advanced airway
    • Stage 4 - larynx
      • 100% ICU, 24% advanced airway

See Also

References

  1. Winters ME, et al. Emergency department management of patients with ACE-inhibitor angioedema. JEM. 2013; 45(5):775–780.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Ishoo E, et al. Predicting airway risk in angioedema: staging system based on presentation. Otolaryngol Head Neck Surg. 1999; 121(3):263-268.