Allergy
Anaphylaxis
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Anaphylaxis
, Allergic Reaction
See Also
Urticaria
Angioedema
Epidemiology
Anaphylaxis
Anaphylaxis most commonly occurs in the home environment, the setting for 40-50% of cases
Incidence
: 2.1 cases per 1,000 person-years
Lifetime
Prevalence
: 0.05 to 2%
Mortality: 1%
Peak ages
Children 2-12 years old
Adults 50-69 years old
Risk Factors
Severe or Fatal Anaphylaxis
Comorbid
Asthma
Mild Asthma
confers a 2 fold risk of Anaphylaxis of any severity (and
Severe Asthma
a 3 fold risk)
Known
Food Allergy
,
Hymenoptera Sting
allergy or medication allergy
Mast Cell
Disorders
Underlying cardiovascular disease
Age >50 years old
Pathophysiology
Anaphylaxis Types
IgE Mediated Anaphylaxis (most cases)
Antibodies bind
Antigen
and activate
Mast Cell
s and
Basophil
s
Mast Cell
s and
Basophil
s release chemical mediators
Non-Immune Anaphylaxis (direct activation)
Direct
Mast Cell
or
Basophil
activation by receptor binding or complement
Precautions
Anaphylaxis is a life threatening condition that requires immediate
ABC Management
and
Epinephrine
injection IM
Biphasic reactions occur in up to 20% of cases
Second acute anaphylactic reaction despite no repeat exposure to the original allergen
Second reaction may be delayed up to 8 hours later (24-72 hour delay has been reported in atypical cases)
Lack of skin involvement (e.g. hives) results in misdiagnosis (esp. children)
Children may present without hives, but rather with gastrointestinal symptoms and respiratory symptoms
Cardiovascular compromise alone (e.g.
Hypotension
) without other system involvement may be due to Anaphylaxis
More common in drug-induced Anaphylaxis
See Criteria 3 under diagnosis below
Causes
Common
Idiopathic (10-20% of Anaphylaxis)
See
Urticaria
Consider
Mastocytosis
Hymenoptera Allergy
(15-25% of Anaphylaxis)
See
Insect
sting
Results in >50 fatal U.S. reactions per year
Occurs with
Insect Bite
s of bees, wasps, fire ants
Food Allergy
(32-37% of anaphylactic episodes, especially in children under age 4 years)
Cow's Milk (2-10%, esp. in infants)
Egg whites (1-4%)
Fish (10-15%)
Peanuts (2-13%)
Tree nuts (7-12%)
Sesame
Food additives
Shellfish
Medications (21-58% of cases, most common in age over 50-55 years)
Penicillin Allergy
(14% of Anaphylaxis, 75% of anaphylactic deaths)
NSAID
s (7-12% of Anaphylaxis case)
Aspirin
Radiographic
Intravenous Contrast
Material
Allopurinol
ACE Inhibitor
s (esp.
ACE inhibitor Induced Angioedema
)
Opioid
s
Interferon
Occupational Allergans
Allergic Contact Dermatitis
(e.g.
Latex Allergy
)
Chemical exposures (e.g. dyes, bleaches,
Insecticide
s)
Miscellaneous
Anaphylactoid Reaction to Radiocontrast
(1-5% of Anaphylaxis cases)
Animal dander
Infection with
Echinococcus
species (
Hydatid Disease
)
Physical reactions (e.g. cold, heat,
Sun Exposure
or
Exercise
, similar to physical
Urticaria
- rare Anaphylaxis)
Symptoms
Anaphylaxis symptom onset within 1-2 hours of allergan exposure
Food Allergy
reactions have onset within 30 minutes of exposure
Insect
reactions often start within minutes of exposure
Parenteral
medication reactions may start within minutes of exposure
Signs
Anaphylaxis typical presentation
Urticaria
and
Angioedema
(90% of cases)
Respiratory distress, especially upper airway obstruction (70% of cases)
Lower airway obstruction may occur, especially in
Asthma
Cardiovascular collapse with
Hypotension
(45% of cases)
Gastrointestinal symptoms such as
Vomiting
(45% of cases)
Neurologic symptoms such as
Headache
or
Dizziness
(15% of cases)
Signs
Mild
Gene
ral
Feeling impending doom
Pruritus
(uncommon without rash)
Metallic Taste
in mouth
Naso-ocular
Itch
y nose or eyes
Sneezing
Clear, watery
Eye Discharge
or
Nasal Discharge
Skin (occurs)
Urticaria
:
Hives
Angioedema
: Facial swelling and Lip swelling
Signs
Moderate
Neurologic
Dizziness
Weakness
Gastrointestinal
Nausea
,
Vomiting
Bloody
Diarrhea
Abdominal Pain
Fecal urgency or
Incontinence
Genitourinary
Uterine cramps
Urinary urgency or
Incontinence
Signs
Severe (Anaphylaxis)
Airway Compromise
Hoarseness
or
Dysphonia
Stridor
Inability to manage own secretions
Airway posturing (sniffing position)
Breathing Compromise
Wheezing
and bronchospasm
Dyspnea
Tachypnea
Hypoxia
Increased work of breathing
Circulatory compromise
Hypotension
Tachycardia
Hypoperfusion
Syncope
Labs
Confirms diagnosis (do not rely on labs to make or treat acute episode)
Serum tryptase
Marker of
Mast Cell
degranulation
Levels rise 30 minutes after onset and peak at 1-2 hours of Anaphylaxis
Consider in cases in which Anaphylaxis diagnosis is unclear
Obtain level on presentation, in 1-2 hours and 24 hours after presentation
Serum tryptase is often normal in food-related reactions
Serum
Histamine
Requires special handling for accuracy
Obtain first level within 1 hour of symptom onset
Compare to baseline level
Differential Diagnosis
Allergic Reaction without Anaphylaxis
More mild, self limited symptoms with only one organ system involved
Two or more involved systems or isolated cardiovascular compromise is consistent with Anaphylaxis
Flushing
See
Flushing
Carcinoid Syndrome
Medulla
ry
Carcinoid
of the
Thyroid
Vasomotor Symptoms of Menopause
Red Man Syndrome
(
Vancomycin
)
Respiratory compromise (e.g.
Wheezing
,
Stridor
)
See
Wheezing
Foreign Body Aspiration
Acute
Asthma Exacerbation
COPD
Exacerbation
Vocal Cord Dysfunction
Following Eating
Foreign Body Aspiration
Scombroid Fish Poisoning
Sulfite Intake
Monosodium
Glutamate
Other form of shock
See
Shock
Hypovolemic Shock
or
Hemorrhagic Shock
Cardiogenic Shock
Neurogenic Shock
Septic Shock
Other causes
Angioedema
Panic Attack
Systemic Mastocytosis
Leukemia
Diagnosis
Anaphylaxis
High likelihood if ONE of the following three criteria present
Criteria 1: Acute illness onset within minutes to hours AND
Skin or mucosal effects (e.g.
Hives
,
Pruritus
,
Flushing
, swollen lips/
Tongue
/uvula) AND
Respiratory distress (e.g.
Dyspnea
, bronchospasm) or cardiovascular collapse (e.g.
Hypotension
,
Syncope
)
Criteria 2: Acute illness onset within minutes to hours after likely allergen exposure AND a least TWO of the following
Skin or mucosal effects (e.g.
Hives
,
Pruritus
,
Flushing
, swollen lips/
Tongue
/uvula)
Hives
may be absent (esp. in children) who may have cardiopulmonary and gastrointestinal symptoms
Respiratory distress (e.g.
Dyspnea
, bronchospasm)
Cardiovascular collapse (e.g.
Hypotension
,
Syncope
)
Gastrointestinal symptoms persist (e.g. abdominal cramping,
Vomiting
)
Criteria 3:
Hypotension
within minutes to hours after likely allergen exposure
Systolic
Blood Pressure
with 30% decrease from baseline (children) or <90 mmHg (adults)
See
Hypotension
See
Pediatric Vital Signs
for age specific cut-offs for low
Blood Pressure
More common in drug-induced Anaphylaxis (in which cardiovascular compromise is only system involved)
Summary
Anaphylaxis is present if allergen exposure and
Hypotension
or two compromised organ systems
References
Sampson (2006) Ann Emerg Med 47(4): 373-80 [PubMed]
Management
Emergency Department
Gene
ral Measures
ABC Management
Supplemental Oxygen
Anaphylaxis (All patients)
Epinephrine
is the mainstay of Anaphylaxis management and must not be delayed
Administer within 5 minutes of presentation
Surviving severe Anaphylaxis cases share rapid
Epinephrine
delivery in common
Sampson (1992) N Engl J Med 327(6): 380-84 [PubMed]
Narrow window of opportunity with
Epinephrine
Prior to complete airway obstruction and cardiovascular collapse
Epinephrine
Vasocon
stricts (raises
Blood Pressure
), bronchodilates and decreases airway edema
Epinephrine
also stabilizes
Mast Cell
s and
Basophil
s
Epinephrine
IM is safe even in older patients and should not be withheld when Anaphylaxis criteria are met
Epinephrine
has no absolute contraindications
Kawano (2017) Resuscitation 112:53-8 +PMID:28069483 [PubMed]
Epinephrine
(1:1000 concentration = 1 mg/ml)
Intramuscular dosing preferred over subcutaneous (due to more reliable and faster rise in blood levels)
Typically injected in the anterolateral thigh
Repeat every 5 to 15 minutes prn up to 3 doses
Cardiac monitoring required for repeat dosing
Epinephrine
via vial
Adult: 0.5 mg (0.5 ml) of 1:1000
Epinephrine
IM
Child: 0.01 mg/kg (0.01 ml/kg) IM up to 0.3 mg (0.3 ml)
Epinephrine Autoinjector
(preferred if available, as reduces errors and speeds delivery)
Adult and children over 30 kg or 66 pounds: 0.3 mg autoinjector
Children under 30 kg or 66 pounds: 0.15 autoinjector
Dirty Epinephrine Drip
See
Dirty Epinephrine Drip
Unresponsive to
Epinephrine
Glucagon
(esp. if patient uses
Beta-Blocker
s)
Dose: 3.5 to 5 mg IV in adults (20 to 30 mcg/kg up to 1 mg in children) over 5 minutes
May repeat if no
Blood Pressure
response within 10 minutes
Norepinephrine
may also be considered
Hypotension
(due to vasodilitation and third spacing)
Fluid
Resuscitation
with
Isotonic Saline
(NS, LR)
Adult: 1-2 Liters
Normal Saline
Child: 10-20 ml/kg per bolus until
Hypotension
improves
Large volumes may be required
Pressors (e.g.
Norepinephrine
,
Dopamine
) may be required
Consider
Epinephrine
by continuous IV infusion
Respiratory distress
Nebulized
Beta Adrenergic Agonist
(e.g.
Albuterol
)
Consider for signs of lower airway obstruction
Consider
Endotracheal Intubation
Urticaria
,
Pruritus
or
Flushing
Gene
ral: H1
Antagonist
s
Not a first-line agent in Anaphylaxis management
Use only as an adjunct to
Epinephrine
and
ABC Management
Effects are delayed 1-2 hours from delivery
Does not reverse upper airway obstruction or improve
Hypotension
Diphenhydramine
(
Benadryl
) every 6 hours prn
Adult: 25-50 mg IM, IV, or PO
Child: 1.25 mg/kg IM, IV or PO
Corticosteroid
s for severe or persistent symptoms not resolved in 30 min
Background
Not a first-line agent in Anaphylaxis management
Use only as an adjunct to
Epinephrine
and
ABC Management
Effects are delayed 6 hours from delivery
Studies proving benefit are lacking
Consider for prevention of biphasic reaction, protracted reaction or in comorbid
Asthma
with
Wheezing
Does not prevent Anaphylaxis relapse
Grunau (2015) Ann Emerg Med 66(4): 381-9 +PMID:25820033 [PubMed]
Preparations
Hydrocortisone
5 mg/kg IV
Methylprednisolone
(
Solu-Medrol
) every 6 hours
Adult: 60-125 mg IV/IM
Child: 0.5-1 mg/kg IV/IM
Predisone 60 mg orally in adults (or Methyprednisolone 1-2 mg/kg orally in children)
Dexamethasone
(
Decadron
) 10 mg IV or Orally
Disposition
Observation of moderate to severe reactions for 4 to 6 hours (or 6 to 10 hours per some guidelines)
Minimum observation time is 2-3 hours (long enough to witness waning of first
Epinephrine
dose)
Prolonged reaction or multiple
Epinephrine
doses may require 12-24 hour observation
Delayed, biphasic reactions are uncommon
Biphasic anaphylactic reactions were originally thought to occur several hours later in up to 20% of cases
More recent data suggests biphasic reactions in 0.4% of cases
Returning to the Emergency Department (bounce-back) for non-Anaphylaxis is common
Rash or other allergic, non-anaphylactic symptoms prompts return in up to 6% of patients in first week
References
Grunau (2014) Ann Emerg Med 63(6):736-44 +PMID:24239340 [PubMed]
Discharge medications
See Below
Hospitalization Indications
Severe initial Anaphylaxis presentation
Cyanosis
Altered Mental Status
Severe
Hypotension
Wide
Pulse Pressure
Drug-Induced Anaphylaxis in children
Multiple
Epinephrine
doses needed
Prior serious, protracted Anaphylaxis or bipashic reaction
Risk factors for severe or fatal Anaphylaxis (see above)
Continued
Vasopressor
(e.g.
Epinephrine
infusion) or airway compromise (
Advanced Airway
)
Refractory course (consider higher level of care)
Management
Home
See prevention recommendations below
Epinephrine Autoinjector
(
EpiPen
,
Twinject
,
Adrenaclick
)
Administer at onset of anxaphylaxis symptoms and present immediately for medical care or call 911
Prescribe to all patients with Anaphylaxis history
Less than 50% of children with Anaphylaxis receive
Epinephrine
before emergency department arrival
Robinson (2017) Ann Allergy Asthma Immunol 19(2):164-9 +PMID:28711194 [PubMed]
Prednisone
Corticosteroid
s most effective if started early
Administer within 1-2 hours if possible, but effect delayed for 6 hours after dose
Prednisone
1-2 mg/kg/day up to 40-60 mg/day for 3 days
Antihistamine
s (H1 Blockers)
Cetirizine
(
Zyrtec
)
Adults
Start at 10 mg orally once to twice daily and may advance up to 20 mg orally twice daily
May use
Diphenhydramine
for breakthrough
Pruritus
(esp at night)
Children 6 months to 2 years: 2.5 mg orally daily
Children 2-5 years old: 2.5 to 5 mg orally daily
Children >5 years old: 5 to 10 mg orally daily
Diphenhydramine
(
Benadryl
)
Liquid has better absorption than tablets
Adult: 25-50 mg orally every 6 hours for 3 days
Child: 5 mg/kg/day orally divided every 6 hours (or 1.25 mg/kg per dose)
H2 Blocker
Background
May improve
Urticaria
beyond H1 Blocker alone, but evidence is weak
Fedorowicz (2012) Cochrane Database Syst Rev (3):CD008596 [PubMed]
Famotidine
(
Pepcid
) for 3 days
Cimetidine
(
Tagamet
) for 3 days
Ranitidine
(
Zantac
)
Dose: 1-2 mg/kg/dose up to 150 mg twice daily for 2-3 days
Prognosis
Hospitalization: 5% of Anaphylaxis presentations
Anaphylaxis-related deaths
U.S. overall: 186 to 225 per year
U.S. Hospital or Emergency Department presentations: 0.3% fatality rate
Prevention
Medical Alert Bracelet should be worn
Strict avoidance of allergen
Anaphylaxis action plan
https://www.healthychildren.org/SiteCollectionDocuments/AAP_Allergy_and_Anaphylaxis_Emergency_Plan.pdf
Share with school and childcare
Includes patient identification including photo of patient, and emergency contact information
Includes list of allergans (including food allergans)
Includes symptoms and signs of Anaphylaxis
Includes key management including ephinephrine autoinjector
Epinephrine Autoinjector
, home injectable devices (
EpiPen
,
Twinject
,
Adrenaclick
)
Keep one in place where most of time spent
Bring an injector when traveling or at work (have available at all times)
Consider allergist referral
Consider
Skin Testing
and
Desensitization
therapy
Indicated if re-exposure is likely or unavoidable
Clinic office administration of medications and injections
Should include a policy to observe patient after injection for 20-30 minutes
References
(2020) Presc Lett 27(6): 35
Arnold (2011) Am Fam Physician 84(10): 1111-8 [PubMed]
Ben-Shoshan (2011) Allergy 66(1): 1-14 [PubMed]
Ellis (2003) CMAJ 169(4):307-11 [PubMed]
Pflipsen (2020) Am Fam Physician 102(6):355-62 [PubMed]
Sampson (2003) Pediatrics 111:1601-8 [PubMed]
Tang (2003) Am Fam Physician 68:1325-40 [PubMed]
Worth (2010) Expert Rev Clin Immunol 6(1): 89-100 [PubMed]
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