Rosen & Barkin's 5-Minute Emergency Medicine Consult (55 page)

• Kinin-related etiologies:
  
  • HAE
    
  • Acquired angioedema:
    
    • Lymphoproliferative
      
    • Autoimmune
      
  • ACE inhibitor induced
    
• Mast cell–mediated etiologies:
  
  • Food allergies:
    
    • Additives
      
    • Nuts
      
    • Eggs/milk
      
    • Shellfish
      
    • Soy/wheat
      
  • Drug allergies:
    
    • Aspirin
      
    • NSAID
      
    • Antihypertensives
      
    • Narcotics
      
    • Oral contraceptives
      
  • Insect stings
    
  • Physically induced:
    
    • Cold/heat
      
    • Exercise/trauma/vibrations
      
    • Stress
      
    • UV light
      
• Hypereosinophilic syndromes such as Gleich syndrome
  
• Thyroid autoimmune disease
  
• Idiopathic recurrent AE
  

DIAGNOSIS

• A family history or history of recurrent episodes can be useful in the diagnosis. Use of culprit foodstuffs or medications, especially ACEIs should increase index of suspicion
  
• Abdominal pain associated with nausea, vomiting, and diarrhea
  
• Attacks of HAE are not associated with hives or itching
  
• Emotional stress or physical trauma can trigger attacks.
  

• The lesions of angioedema are large, swollen, and nonpitting wheals.
  
• The eyelids and lips are frequently involved.
  
• Involvement of the pharynx and larynx may cause airway obstruction.
  
• Lesions are often asymmetric and do not typically involve gravitationally dependent areas
  

• Diagnosis is made of clinical grounds based on the presentation of large nonpitting, nonpruritic wheals.
  
• A family history need not be present: 25% of HAE patients have a new mutation and may not have a positive family history.
  

• CBC with differential, ESR, ANA, rheumatoid factor, C4 and C3 levels.
  
• Skin biopsy if an urticarial lesion is accessible
  

Measurement of C1-INH levels (not routinely available in EDs):

• Patients affected with HAE type 1 have very low levels; carriers will have half-normal levels.
  
• C4 and C2 levels are low during attacks in both hereditary and acquired forms.
  

• Edema:
  
  • SVC syndrome
    
  • Right heart failure
    
  • Constrictive pericarditis
    
  • Renal failure
    
  • Nephrotic syndrome
    
• Allergic contact dermatitis
  
• Blepharochalasis
  
• Facial cellulitis
  
• Facial lymphedema
  
• Edema secondary to autoimmune disorders:
  
  • Dermatomyositis
    
  • Lupus
    
  • Polymyositis
    
  • Sjögren syndrome
    
• Hypothyroidism
  

Recurrent angioedema presenting around puberty should raise suspicion of HAE.

TREATMENT

• Establish IV access
  
• Early intubation may be necessary due to the rapid progression of laryngeal swelling.
  
• Administration of H1 blocker when available
  
• Epinephrine to be considered for laryngeal edema especially if itching or other signs of a mast cell etiology with histamine release is suspected.
  

• Active airway management and supportive measures are the primary goals of emergency treatment.
  
• Intubation may be necessary in severe cases:
  
  • Orotracheal intubation is the technique of choice but may be difficult because of laryngeal edema, spasm, or soft-tissue swelling.
    
  • Consider advanced airway adjuncts such as the gum elastic bougie to assist in securing endotracheal tube placement.
    
  • Blind nasotracheal intubation if soft tissue swelling prohibits an oral approach
    
  • Transtracheal jet insufflation or cricothyrotomy may be necessary to control the airway.
    
• Epinephrine, antihistamines, and steroids in obstructive airway swelling, although patient response can be variable.
  

• Acute angioedema with features of a type 1 hypersensitivity reaction:
  
  • Treat similarly to an allergic reaction with H1 and H2 blockers along with corticosteroids.
    
  • Epinephrine should be used in refractory cases where the benefits outweigh the risks.
    
  • For abdominal attacks consider the addition of parenteral pain relief, antiemetics, and IV fluid replacement.
    
• HAE and acquired angioedema:
  
  • C1-INH
    
  • Fresh frozen plasma (FFP) may be used as an alternative to C1-INH.
    
  • The kallikrein inhibitor ecallantide (Kalbitor) was approved in 2009 for the treatment of acute attacks of HAE.
    
  • Tranexamic acid (Cyklokapron), an antifibrinolytic agent, is not as effective for acute attacks and is used primarily in prevention.
    

General principles of pharmacologic treatment are based on suspected underlying cause:

• Suspected HAE:
  
  • C1-INH
    
    • Ecallantide
      
    • Icatibant
      
• Non-HAE:
  
  • H1 blockers
    
  • H2 blockers
    
  • Corticosteroids
    
• C1 esterase inhibitor replacement proteins (C1INHRP):
  
  • In the US currently only plasma-derived products:
    
    • Cinryze: 20 U/kg U slow IV infusion
      
    • Berinert: 20 U/kg IV slow IV infusion with additional doses if no improvement in 2 h, sooner if worsening or if laryngeal symptoms
      
    • In the EU recombinant C1INHRP is also available (at this time not yet approved by US FDA)
      
    • Ruconest (not yet FDA approved) 50 U/kg, generally does not require repeat dosing
      
  • Cimetidine: 300 mg IV
    
  • Danazol: 400–600 mg PO up to 1 g/d.
    Contraindicated in children and pregnancy
    .
    
  • Diphenhydramine: Adult: 50 mg IV; peds: 1–2 mg/kg slow IVP
    
  • Ecallantide (kallikrein inhibitor available US only): 30 mg SC given as 3 separate injections (about 1 mL each anatomically distant from AE affected area)
    
  • Epinephrine: 0.3–0.5 mg (use 1:1,000 dilution for SC route, and 1:10,000 for IV route); peds: 0.01 mg/kg SC/IV
    
  • Racemic epinephrine: 2.25% solution (0.5 mL placed in a nebulizer in 2.5 mL of NS)
    
  • FFP (if C1-INH is unavailable): Adult: 2 U
    
  • Hydrocortisone: Adult: 500 mg IV; peds: 4–8 mg/kg/dose IV.
    
  • Icatibant (bradykinin B2 receptor antagonist): 30 mg SC once
    
  • Methylprednisolone: Adult: 125 mg IV; peds: 1–2 mg/kg IV
    
  • Prednisone: Adult: 60 mg PO; peds: 1 mg/kg PO
    
  • Ranitidine: Adult: 50 mg IV
    
  • Stanozolol: 2 mg PO up to 16 mg/d:
    
    • Discontinued in the US
      
    • Contraindicated in children and in pregnancy
      
  • Tranexamic acid: 1 g PO q3–4h for up to 48 h if necessary
    

Safety and efficacy of newer HAE treatment agents (such as C1-INH Cinryze and Berinert) have not been established in children as of this writing. Dosing for adolescents is suggested to be weight based at 20 U/kg.

FOLLOW-UP

• Patients with systemic symptoms that do not resolve completely will need to be hospitalized for observation.
  
• A monitored bed is recommended for those with airway involvement.
  

• Patients presenting with minor symptoms of angioedema without progression after 4–6 hr of observation may be safely discharged home on a short course of steroids and antihistamines.
  
• Patients should be provided with an EpiPen and instructions on its use.
  

Patients should be evaluated by an allergist/immunologist after the initial presentation, especially if there is a family history of angioedema, or if the angioedema is accompanied by abdominal pain, or triggered by trauma.

Patients without systemic symptoms who are stable for discharge should been seen in outpatient follow-up in a few days.

• Early measures should be employed to maintain the patient’s airway.
  
• Consider use of newer agents in HAE patients (e.g., C1-INH and Kallikrein inhibition).
  

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