1. In all patients, always inquire about any allergy and clearly document it in the chart. Re-evaluate this periodically.
  2. Clarify the manifestations of a reaction in order to try to diagnose a true allergic reaction (e.g., do not misdiagnose viral rashes as antibiotic allergy, or medication intolerance as true allergy).
  3. In a patient reporting allergy (e.g., to food, to medications, environmental), ensure that the patient has the appropriate medication to control symptoms (e.g., antihistamines, bronchodilators, steroids, an EpiPen).
  4. Prescribe an EpiPen to every patient who has a history of, or is at risk for, anaphylaxis.
  5. Educate appropriate patients with allergy (e.g., to food, medications, insect stings) and their families about the symptoms of anaphylaxis and the self-administration of the EpiPen, and advise them to return for immediate reassessment and treatment if those symptoms develop or if the EpiPen has been used.
  6. Advise patients with any known drug allergy or previous major allergic reaction to get a MedicAlert bracelet.
  7. In a patient presenting with an anaphylactic reaction:
    1. Recognize the symptoms and signs.
    2. Treat immediately and aggressively.
    3. Prevent a delayed hypersensitivity reaction through observation and adequate treatment (e.g., with steroids).
  8. In patients with anaphylaxis of unclear etiology refer to an allergist for clarification of the cause.
  9. In the particular case of a child with an anaphylactic reaction to food:
    1. Prescribe an EpiPen for the house, car, school, and daycare.
    2. Advise the family to educate the child, teachers, and caretakers about signs and symptoms of anaphylaxis, and about when and how to use the EpiPen.
  10. In a patient with unexplained recurrent respiratory symptoms, include allergy (e.g., sick building syndrome, seasonal allergy) in the differential diagnosis.

Drug Reaction Classification

  • Type A - Adverse reaction
  • Type B - Hypersensitivity
    • Exaggerated sensitivity to known drug toxicity (eg. tinnitus with single dose of aspirin)
    • Idiosyncratic drug reaction (due to genetic differences, eg. hemolytic anemia in G6PD after primaquine)
    • Immunologic/Drug allergy
      • Type I - Immediate IgE (mast cells +/- basophils)
        • Within 30mins-1h
        • Urticarial rash, pruritus, flushing, angioedema, wheezing, GI symptoms, hypotension
        • Anaphylaxis is most severe type of presentation
      • Type II - Delayed antibody (IgG) mediated cell destruction
        • Usually 5-8d after exposure
        • Hemolytic anemia, thrombocytopenia, neutropenia
      • Type III - Delayed IgG:drug immune complex deposition and complex activation
        • Usually 1-2 weeks after exposure
        • May have low complement, high ESR
        • Serum sickness - fever, urticarial/purpuric rash, arthralgia, acute glomerulonephritis (eg. antitoxin)
        • Vasculitis - palpable purpura/petechiae, often lower extremities (eg. penicillins, cephalosporins, sulfonamides, phenytoin, allopurinol)
        • Arthus reaction - localized skin inflammation, necrosis (post-vaccine)
      • Type IV - Delayed T-cell mediated
        • >48h, usually days-weeks after exposure (but <24h upon re-exposure)
        • SJS/TEN - fever, painful diffuse erythema, bullae, oral/mucosal erosions, necrosis and skin sloughing/epidermal detachment (eg. allopurinol, lamotrigine, anticonvulsants, sulfonamides, COX2i NSAIDs, mycoplasma pneumoniae)
        • DRESS - fever, skin eruption, eosphinophilia (or atypical lymphocytosis), lymphadenopathy, organ involvement (anticonvulsants, sulfonamides)
        • Other: Contact dermatitis, maculopapular eruptions

Anaphylaxis Diagnosis

If one of the following

    1. Acute onset of illnesss (minutes to several hours) with involvement of skin, mucosal tissue or both (eg, generalized hives, pruritus or flushing, or swollen lips-tongue-uvula) and at least one of the following:
      • Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF or hypoxemia)
      • Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope or incontinence)
    2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):
      • Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush or swollen lips-tongue-uvula)
      • Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF or hypoxemia)
      • Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope or incontinence)
      • Persistent gastrointestinal symptoms (eg, crampy abdominal pain or vomiting)
    3. Reduced BP after exposure to a known allergen for that patient (minutes to hours)
      • Low BP for children defined as <70mmHg + [2 x age] up to 10yo


  • Anaphylaxis symptoms
    • General/CNS - Lethargy, somnolence, altered LOC, syncope
    • Upper airway - Hoarseness, stridor, oropharyngeal/laryngeal/uvular edema, lip/tongue swelling, obstruction
    • Lower airway - Cough, dyspnea, tachypnea
    • Skin - Flushing, erythema, pruritus, urticaria, angioedema, maculopapular rash
    • CVS - Tachycardia, hypotension, arrhythmia, acute coronary syndrome
    • GI - N/V/D, abdominal pain
  • Trigger
    • Food (peanuts, tree nuts, fish, milk, eggs, shellfish [shrimp, lobster, crab, scallops, oysters])
    • Hymenoptera (bee/wasp) stings
    • Medications
  • Previous allergies and allergical reaction

Physical Examination

  • ABC, Vitals (Hypotension, tachycardia)
  • CVS
  • Resp
  • Abdominal exam
  • Skin


  • Respiratory
    • Asthma
    • Foreign body aspiration
  • Cardiovascular
    • Pulmonary embolism
    • Acute coronary syndrome
  • Shock
  • Mast cell disorder

Management of Anaphylaxis

  • ABC, vitals, monitors, IV x2, oxygen
    • Airway (intubation if impending airway obstruction)
  • Epinephrine 0.5mg IM mid-antero-lateral thigh q5mins x3 doses (Caution if bolus via IV)
    • 0.01mg/kg (0.01mL/kg of 1:1000 = 1mg/1mL) in children up to 0.3mg (eg. 30kg child should receive 0.3mg IM)
    • Infusion of epinephrine 0.1mcg/kg/min IV titrate to vitals (usually need 5-15mcg/min)
    • If on beta-blockers and poor response to epinephrine, consider glucagon 1-5mg IV over 5 minutes
  • Aggressive fluid resuscitation
    • Lie down, elevate legs
    • >1-2L (20mL/kg) NS IV bolus, repeat PRN
  • Salbutamol for bronchospasm 2.5-5mg in 3mL saline via nebulizer (or 5-10 puffs MDI with spacer), repeat PRN
  • Adjunctive
    • Antihistamine
      • H1 antagonist, eg. Diphenhydramine (1mg/kg/dose) 25-50mg PO/IM/IV q4-6h PRN
      • H2 antagonist, eg. Ranitidine 150mg IV, Famotidine 20mg IV
    • Glucocorticoids (Note: no evidence in decreasing return ER visits or biphasic reactions)
      • Methylprednisolone 1-2mg/kg/d (max 125mg IV)
      • Prednisone 1mg/kg PO (max 50mg PO)
  • Observation period for biphasic reactions (incidence of 20%, can occur up to 6 days)
    • Although most guidelines suggest 4, 6 or 24h of observation there is no data to suggest this improves outcomes
      • Consider discharge in patients with prompt and complete symptom resolution
      • Consider observation if
        • Risk factors (Previous biphasic, asthma)
        • Severe features (Refractory hypotension, laryngeal edema, and respiratory compromise)
        • Delayed or suboptimal treatment
  • If not improved with anti-histamine treatment consider bradykinin-mediated angioedema
    • Treat with Tranexamic acid 1g IV, Fresh frozen plasma (2 units), C1-inhibitor concentrate


  • Serum tryptase levels taken 15-180mins after symptom onset may support diagnosis
    • Compare to baseline tryptase improves accuracy
  • If no cause identified, rule out mast cell disorder


  • Education to patient, friends/family
    • Risk of biphasic reaction
    • Avoidance of triggers
    • Anaphylaxis emergency plan (self-administered epinephrine, call 9-1-1)
      • Printed and explain information about signs/symptoms of anaphylaxis and treatment
      • Teaching and practice on how to administer the self-injectable epinephrine
  • Prescribe minimum two epinephrine auto-injector to be carried on patient at all times
    • EpiPenJR or TwinjectJR <25kg
    • EpiPen or Twinject>25kg
  • MedicAlert bracelet
  • Allergy referral if needed to clarify trigger