Allergy

Anaphylaxis

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Anaphylaxis, Allergic Reaction

  • Epidemiology
  • Anaphylaxis
  1. Incidence: 50 cases per 100,000 person-years
  2. Lifetime Prevalence: 0.05 to 2%
  3. Mortality: 1%
  • Risk Factors
  • Anaphylaxis
  • Precautions
  1. Anaphylaxis is a life threatening condition that requires immediate ABC Management and Epinephrine injection IM
  2. Biphasic reactions occur in up to 20% of cases
    1. Second acute anaphylactic reaction despite no repeat exposure to the original allergen
    2. Second reaction may be delayed up to 8 hours later (24-72 hour delay has been reported in atypical cases)
  • Causes
  • Common
  1. Idiopathic
    1. See Urticaria
    2. Consider mastocytosis
  2. Hymenoptera Allergy (Bees, wasps, fire ants)
    1. See Insect sting
    2. Results in >50 fatal U.S. reactions per year
  3. Food Allergy (30% of anaphylactic episodes, especially in children under age 4 years)
    1. Cow's Milk
    2. Egg whites
    3. Fish
    4. Peanuts
    5. Tree nuts
    6. Sesame
    7. Food additives
    8. Shellfish
  4. Medications (most common in age over 55 years)
    1. Penicillin Allergy (75% of anaphylactic deaths)
    2. NSAIDs or Aspirin
    3. Radiographic Intravenous Contrast Material
    4. Allopurinol
    5. ACE Inhibitors
    6. Opioids
    7. Interferon
  5. Allergic Contact Dermatitis
    1. Latex Allergy
  6. Infection
    1. Echinococcus species (Hydatid Disease)
  7. Miscellaneous
    1. Animal dander
  • Signs
  • Anaphylaxis typical presentation
  1. Urticaria and Angioedema (90% of cases)
  2. Respiratory distress, especially upper airway obstruction (70% of cases)
    1. Lower airway obstruction may occur, especially in Asthma
  3. Cardiovascular collapse with Hypotension (45% of cases)
  4. Gastrointestinal symptoms such as Vomiting (45% of cases)
  5. Neurologic symptoms such as Headache or Dizziness (15% of cases)
  • Signs
  • Mild
  1. General
    1. Feeling impending doom
    2. Pruritus (uncommon without rash)
    3. Metallic Taste in mouth
  2. Naso-ocular
    1. Itchy nose or eyes
    2. Sneezing
    3. Clear, watery Eye Discharge or Nasal Discharge
  3. Skin (occurs)
    1. Urticaria: Hives
    2. Angioedema: Facial swelling and Lip swelling
  • Signs
  • Moderate
  1. Neurologic
    1. Dizziness
    2. Weakness
  2. Gastrointestinal
    1. Nausea, Vomiting
    2. Bloody Diarrhea
    3. Abdominal Pain
    4. Fecal urgency or Incontinence
  3. Genitourinary
    1. Uterine cramps
    2. Urinary urgency or Incontinence
  • Signs
  • Severe (Anaphylaxis)
  1. Airway Compromise
    1. Hoarseness or Dysphonia
    2. Stridor
    3. Inability to manage own secretions
    4. Airway posturing (sniffing position)
  2. Breathing Compromise
    1. Wheezing and bronchospasm
    2. Dyspnea
    3. Tachypnea
    4. Hypoxia
    5. Increased work of breathing
  3. Circulatory compromise
    1. Hypotension
    2. Tachycardia
    3. Hypoperfusion
    4. Syncope
  • Labs
  • Confirms diagnosis (do not rely on labs to make or treat acute episode)
  1. Serum histamine
    1. Requires special handling for accuracy
    2. Obtain first level within 1 hour of symptom onset
    3. Compare to baseline level
  2. Serum tryptase
    1. Levels rise 30 minutes after onset and peak at 1-2 hours
    2. Obtain level on presentation, in 1-2 hours and 24 hours after presentation
  • Differential Diagnosis
  • Diagnosis
  • Anaphylaxis
  1. High likelihood if ONE of the following three criteria present
  2. Criteria 1: Acute illness onset within minutes to hours AND
    1. Skin or mucosal effects (e.g. Hives, Pruritus, Flushing, swollen lips/Tongue/uvula) AND
    2. Respiratory distress (e.g. Dyspnea, bronchospasm) or cardiovascular collapse (e.g. Hypotension, Syncope)
  3. Criteria 2: Acute illness onset within minutes to hours after likely allergen exposure AND a least TWO of the following
    1. Skin or mucosal effects (e.g. Hives, Pruritus, Flushing, swollen lips/Tongue/uvula)
    2. Respiratory distress (e.g. Dyspnea, bronchospasm)
    3. Cardiovascular collapse (e.g. Hypotension, Syncope)
    4. Gastrointestinal symptoms persist (e.g. abdominal cramping, Vomiting)
  4. Criteria 3: Hypotension within minutes to hours after likely allergen exposure
    1. Systolic Blood Pressure with 30% decrease from baseline or <90 mmHg (adults)
    2. See Hypotension
    3. See Pediatric Vital Signs for age specific cut-offs for low Blood Pressure
  5. Summary
    1. Anaphylaxis is present if allergen exposure and Hypotension or two compromised organ systems
  6. References
    1. Sampson (2006) Ann Emerg Med 47(4): 373-80 [PubMed]
  • Management
  • Emergency Department
  1. General Measures
    1. ABC Management
    2. Supplemental Oxygen
  2. Anaphylaxis with Airway Compromise
    1. Epinephrine is the mainstay of Anaphylaxis management and must not be delayed
      1. Administer within 5 minutes of presentation
        1. Surviving severe Anaphylaxis cases share rapid Epinephrine delivery in common
        2. Sampson (1992) N Engl J Med 327(6): 380-84 [PubMed]
      2. Narrow window of opportunity with Epinephrine
        1. Prior to complete airway obstruction and cardiovascular collapse
      3. EpinephrineVasoconstricts, bronchodilates and decreases airway edema
      4. Epinephrine IM is safe even in older patients and should not be withheld when Anaphylaxis criteria are met
        1. Kawano (2017) Resuscitation 112:53-8 +PMID:28069483 [PubMed]
    2. Epinephrine (1:1000 concentration = 1 mg/ml)
      1. Intramuscular dosing preferred over subcutaneous (due to more reliable and faster rise in blood levels)
        1. Typically injected in lateral thigh
      2. Repeat every 5 to 15 minutes prn up to 3 doses
      3. Cardiac monitoring required for repeat dosing
      4. Epinephrine via vial
        1. Adult: 0.5 mg (0.5 ml) of 1:1000 Epinephrine IM
        2. Child: 0.01 mg/kg (0.01 ml/kg) IM up to 0.3 mg (0.3 ml)
      5. Epinephrine Autoinjector (preferred if available, as reduces errors and speeds delivery)
        1. Adult and children over 30 kg or 66 pounds: 0.3 mg autoinjector
        2. Children under 30 kg or 66 pounds: 0.15 autoinjector
    3. Dirty Epinephrine Drip
      1. See Dirty Epinephrine Drip
    4. Unresponsive to Epinephrine
      1. Glucagon 3.5 to 5 mg IV if patient uses Beta-Blockers
        1. May repeat if no Blood Pressure response within 10 minutes
      2. Norepinephrine may also be considered
  3. Hypotension (due to vasodilitation and third spacing)
    1. Fluid Resuscitation with isotonic saline (NS, LR)
      1. Adult: 2 Liters Normal Saline
      2. Child: 10-20 ml/kg per bolus until Hypotension improves
      3. Large volumes may be required
    2. Pressors (e.g. Norepinephrine, Dopamine) may be required
    3. Consider Epinephrine by continuous IV infusion
  4. Respiratory distress
    1. Nebulized Beta adrenergic agonist (e.g. Albuterol)
      1. Consider for signs of lower airway obstruction
    2. Consider Endotracheal Intubation
  5. Urticaria, Pruritus or Flushing
    1. General: H1 Antagonists
      1. Not a first-line agent in Anaphylaxis management
      2. Use only as an adjunct to Epinephrine and ABC Management
      3. Effects are delayed 1-2 hours from delivery
      4. Does not reverse upper airway obstruction or improve Hypotension
    2. Diphenhydramine (Benadryl) every 6 hours prn
      1. Adult: 25-50 mg IM, IV, or PO
      2. Child: 1.25 mg/kg IM, IV or PO
  6. Corticosteroids for severe or persistent symptoms not resolved in 30 min
    1. Background
      1. Not a first-line agent in Anaphylaxis management
      2. Use only as an adjunct to Epinephrine and ABC Management
      3. Effects are delayed 6 hours from delivery
      4. Studies proving benefit are lacking
      5. Consider for prevention of biphasic reaction, protracted reaction or in comorbid Asthma with Wheezing
      6. Does not prevent Anaphylaxis relapse
        1. Grunau (2015) Ann Emerg Med 66(4): 381-9 +PMID:25820033 [PubMed]
    2. Preparations
      1. Hydrocortisone 5 mg/kg IV
      2. Methylprednisolone (Solu-Medrol) every 6 hours
        1. Adult: 60-125 mg IV/IM
        2. Child: 0.5-1 mg/kg IV/IM
      3. Predisone 60 mg orally in adults (or Methyprednisolone 1-2 mg/kg orally in children)
      4. Dexamethasone (Decadron) 10 mg IV or Orally
  7. Disposition
    1. Observation of moderate to severe reactions for 4 to 6 hours (or 6 to 10 hours per some guidelines)
      1. Minimum observation time is 3 hours (long enough to witness waning of first Epinephrine dose)
      2. Prolonged reaction or multiple Epinephrine doses may require 12-24 hour observation
    2. Delayed, biphasic reactions are uncommon
      1. Biphasic anaphylactic reactions were originally thought to occur several hours later in up to 20% of cases
      2. More recent data suggests biphasic reactions in 0.4% of cases
      3. Returning to the Emergency Department (bounce-back) for non-Anaphylaxis is common
        1. Rash or other allergic, non-anaphylactic symptoms prompts return in up to 6% of patients in first week
      4. References
        1. Grunau (2014) Ann Emerg Med 63(6):736-44 +PMID:24239340 [PubMed]
    3. Discharge medications
      1. See prevention recommendations below
      2. Epinephrine Autoinjector (e.g. epi-pen) prescription
      3. Corticosteroid: Prednisone 1-2 mg/kg/day up to 20-40 mg/day for 2-3 days
      4. H1 Blocker: Diphenhydramine (Benadryl) 1.25 mg/kg up to 25-50 mg/dose every 6 hours for 2-3 days
      5. H2 Blocker: Ranitidine (Zantac) 1-2 mg/kg/dose up to 150 mg twice daily for 2-3 days
        1. May improve Urticaria beyond H1 Blocker alone, but evidence is weak
        2. Fedorowicz (2012) Cochrane Database Syst Rev (3):CD008596 [PubMed]
  • Management
  • Home
  1. Epinephrine Autoinjector (EpiPen, Twinject, Adrenaclick)
    1. Administer at onset of anxaphylaxis symptoms and present immediately for medical care or call 911
  2. Diphenhydramine (Benadryl)
    1. Liquid has better absorption than tablets
    2. Adult: 25-50 mg orally every 6 hours for 3 days
    3. Child: 5 mg/kg/day orally divided every 6 hours (or 1.25 mg/kg per dose)
  3. Prednisone
    1. Corticosteroids most effective if started early
      1. Administer within 1-2 hours if possible
    2. Adult: 60 mg PO qd x3 days
    3. Child: 0.5-1 mg/kg/dose PO qd x3 days
  4. H2 Blocker
    1. Ranitidine (Zantac), Famotidine (Pepcid) or Cimetidine (Tagamet) for 3 days
  • Prevention
  1. Medical Alert Bracelet should be worn
  2. Strict avoidance of allergen
  3. Epinephrine Autoinjector, home injectable devices (EpiPen, Twinject, Adrenaclick)
    1. Keep one in place where most of time spent
    2. Bring an injector when traveling
  4. Consider allergist referral
  5. Consider Skin Testing and Desensitization therapy
    1. Indicated if re-exposure is likely or unavoidable
  6. Clinic office administration of medications and injections
    1. Should include a policy to observe patient after injection for 20-30 minutes