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Anaphylaxis
Objectives
Definitions
 Pathophysiology
 Etiologies
 Signs and Symptoms
 Differential Diagnosis
 Acute Management
 Referrals

Definitions

Anaphylaxis

Severe, systemic allergic reaction

Involves 2 or more systems:
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Skin, respiratory, cardiovascular, GI tract
Often life threatening
IgE mediated reaction
Anaphylactoid reaction (AKA Non-IgE Anaphylaxis)
Identical clinical syndrome
 NOT IgE mediated

Pathophysiology
First exposure to allergen
TH2 activation, IgE class switching
IgE production
IgE binding to mast cells
Repeat exposure to allergen
Activation of mast cells
Pathophysiology cont.
Anaphylaxis is an acute, lifethreatening systemic reaction
with varied mechanisms,
clinical presentations, and
severity that results from the
sudden systemic release of
mediators from mast cells and
basophils.
Pathophysiology cont.
Allergic Reaction: Time Course
Immediate
Late Phase
Histamine
Leukotrienes
Prostaglandins
Thromboxanes
Bradykinins
Cytokines
Time Course

Immediate
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Late phase
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Within seconds to minutes of exposure
Similar symptoms occur 1 to 8-12 hr after onset
Prolonged
Protracted sx up to 32 hours
 May not be affected by corticosteroids

Kemp SF. J Allergy Clin Immunol 2002;110:341-8.
Wade JP, et al. Proc Clin Biol Res 1989;297:175-82.
Brazil E, MacNamara AF. J Accid Emerg Med 1998;15:252-3.
Signs and Symptoms
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2 or more body systems involved
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Cutaneous (90%)
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Respiratory (40-60%)
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Pruritus, urticaria, angioedema, flushing
Upper airway edema → Stridor, angioedema
Lower airway edema → Dyspnea, wheezing
Rhinitis
Dizziness, syncope (30-35%)
The diagnosis and Management of Anaphylaxis:
An Updated Practice Parameter. J Allergy Clin Immunol 2010.
Signs and Symptoms cont.
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Cardiovascular (30-35%)
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Vasodilation → Relative hypovolemia
Increased capillary permeability →
intravascular volume loss
50% of intravascular fluid transfers
into extravascular space within 10
minutes
Hypotension
2005 AHA Guidelines for CPR and ECC.
The diagnosis and Management of Anaphylaxis:
An Updated Practice Parameter. J Allergy Clin Immunol 2005;115:S483-523.
Signs and Symptoms cont.

Gastrointestinal
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25-30%
Abdominal pain, emesis, diarrhea
Miscellaneous
Headache
5-8%
 Substernal pain
4-6%
 Seizure
1-2%
 Sense of “impending doom”
 Metallic taste

The diagnosis and Management of Anaphylaxis:
An Updated Practice Parameter. J Allergy Clin Immunol 2005;115:S483-523.
Etiologies
 Drugs
 Latex
 Stinging
insects
 Foods
 Exercise
 Seminal
Fluid
 Idiopathic
Risk Factors Related to Anaphylaxis
Prior hx of anaphylaxis
 Beta-blocker use
 Atopic background
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Latex
 Venom
 RCM - anaphylactoid
 Not risk factor for anaphylaxis to medications
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Penicillins and beta-lactam
family
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Penicillin is most commonly reported drug allergy
Up to 0.04% of PCN treated subjects
Anaphylaxis - 0.001% PCN treated pt
Cross-reactivity

Cephalosporins – Unknown but LOW
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Some Carbapenems are cross-reactive*
• Meropenum may be tolerated by some PCN allergic patients

Aztreonam does not cross-react with other beta-lactams except
ceftAzadime
Idsoe O, et al. Bull World Health Organ 1968;38:159-88.
Aspirin and NSAIDs
 Second
most common cause
 Anaphylactic reactions

Drug specific
 Aspirin
exacerbated respiratory disease
(AERD)

Class specific (Due to inhibition of COX-1 and
shunting to AA metabolites to produce
increased amounts of Leukotrienes)
Latex
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Prevalence < 1% general population
High risk populations
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Health care workers (5-15%)
Pts with spina bifida (24-60%)
Workers with occupational latex exposure
Most important factor is degree of exposure
Up to 17% cases of intraoperative anaphylaxis
No commercially avail skin test reagents in US
Diagnosis: Hx + IgE Latex
Alenius H, et al. J Lab Clin Med 1994;123:712-20.
Poley G, Slater J. J Allergy Clin Immunol 2000;105:1054-62.
Stinging Insects
40-50 reported deaths per year in US
 3% of adults, up to1% of children
 Bees, yellow jackets, hornets, wasps
 Fire ants
 25-70% chance of systemic rxn if re-stung
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Maintenance Venom IT reduces this risk to 1-2% if re-stung.
Natural History: Systemic reaction
Golden et.al. JACI 2000;105:385-90
Foods
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Food is the most common cause of anaphylaxis
in the outpatient setting, and food allergens account for 30% of fatal
cases of anaphylaxis.
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Most common offenders:
- peanuts, tree nuts, fish, shellfish, cow’s milk, soy, and egg (Sesame Seeds)
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Common themes associated with fatal food
anaphylaxis include the following:
•
•
•
•
Reactions commonly involve peanuts and tree nuts
Victims are typically teenagers and young adults;
Patients have a previous history of food allergy and asthma
Failure to administer epinephrine promptly
Oral Allergy Syndrome
(Food-Pollen Allergy)
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Seen in patients with seasonal allergic rhinitis
Itching and swelling in mouth and oropharynx
Associated with ingestion of fresh fruits, vegetables,
or nuts
Basically the immune system mistakenly confused
certain epitopes on the fruit for a tree, grass or weed
pollen (aeroallergens).
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Birch - apples, pears, hazelnut, carrot, potato, kiwi
Ragweed – melons, banana
Mugwort – celery, carrot, fennel, parsley
Tolerate cooked or processed fruits, vegetables
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Cooking denatures the 3-D shape of the proteins such that
they no longer resemble to aeroallergen.
Exercise Induced Anaphylaxis
Associated factors: foods and meds
 Within 2-4 hours after ingestion
 Eating the same foods without exercising does
not cause symptoms
 Exercise changes absorption of antigen
 Implicated foods: celery, shrimp, apples, and
wheat
 Avoidance of exercise 4-6 hr after eating
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Seminal Fluid Induced Anaphylaxis
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Coital anaphylaxis caused by human seminal fluid has
been shown to be a result of IgE-mediated
sensitization to seminal plasma proteins.
Prostate-specific antigen (PSA) has been
demonstrated to be a relevant allergen in some
cases.
It is essential to exclude other underlying causes
such as allergens in natural rubber latex condoms or
in drugs or foods passively transferred via seminal
plasma.
Patients with seminal plasma allergy may be able to
conceive without undergoing desensitization, by
artificial insemination with washed spermatozoa.
Idiopathic Anaphylaxis
The symptoms of idiopathic anaphylaxis are
identical to those of episodes related to known
causes.
 Patients with idiopathic anaphylaxis should
receive an intensive evaluation, including a
meticulous history to rule out a definite cause of
the events.
 specific laboratory studies to exclude systemic
disorders such as indolent systemic mastocytosis
are often utilized.
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Differential Diagnosis
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Scombroid poisoning
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Rxn within 30 min of eating spoiled fish
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Tuna, mackerel, mahi-mahi
Urticaria, nausea, vomiting, diarrhea, headache
Histidine → Histamine
Angioedema
Asthma exacerbation
Psychiatric conditions – panic attacks, conversion d/o
Vocal cord dysfunction
Vasovagal reactions
Flushing syndromes
Systemic mastocytosis
Cardiogenic shock
Other cardiovascular or respiratory events
What is Red Man
Syndrome?
A.
B.
C.
Anaphylactic reaction
Anaphylactoid reaction
Neither
Red Man Syndrome
Associated with rapid infusion of vancomycin
 Flushing, tingling, pruritus, erythema,
maculopapular rash, hypotension
 Onset 15-45 min after start of infusion
 Resolves 10-60 min after d/c infusion
 Tx: Pretreat pt with antihistamines prior to
infusion, infuse dose over 2 hr
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Susla G, et al. Critical Care Medicine. 2nd Ed., 2002, 335.
Anaphylactoid Reactions
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Nonspecific mast cell
release
May occur with first
exposure
Opioids
Anesthetics
Vancomycin
ASA, NSAIDs
Radiocontrast media
Individuals with a hx of anaphylactoid reactions are at increased risk of having another
with future exposures. i.e. Pre-treatment protocols for RCM etc….
Anaphylactic Reaction
in the operating room
Incidence is 1 in 4000 to 1 in 25,000 anesthetic
procedures.
 Mortality as high as 5%
 NMBA are the most common cause during
anesthesia. Succinylcholine is the most common
offender.
 Latex(23%) and Antibiotics (15%)
 Less common: Local anesthetics, Opioid
analgesics (anaphylactoid)
 Presents as CV collapse, airway obstruction,
flushing, and/or edema

Radiocontrast Media
Overall frequency of adverse rxn 5-8%
 Life threatening rxn < 0.1%
 Prevalence greatest in 20-50 yo
 16-44% risk if hx of previous reaction
 Risk reduced to 1% if lower osmolarity agent
and pretreatment used
 No reliable data showing a link between RCM
and Iodine or shellfish.
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RCM Pretreatment Regimen
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Prednisone 50 mg po
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Diphenhydramine 50 mg po or IM
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13, 7, and 1 hr prior to RCM administration
1 hr prior
If emergency procedure
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Hydrocortisone 200 mg IV every 4 hr
Diphenhydramine 50 IM 1 hr prior
LOW OSMOLARITY CONTRAST IS BEST (and more
expensive – so you will need to beg for this)
Acute Management of
Anaphylactic Reaction
Epinephrine
Epinephrine
Epinephrine
Epinephrine
Epinephrine
Epinephrine
Epinephrine
Epinephrine
Epinephrine
Epinephrine
Acute Management
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Epinephrine
IM injection in thigh (vastus lateralis)
 All patients with S/S of systemic reaction
 0.3 – 0.5 mg (1:1000), repeat every 5 min, as
necessary
There is no contraindication to the use of
epinephrine in a life threatening situation
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
2005 AHA Guidelines for CPR and ECC.
Epinephrine
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Alpha-adrenergic effects
Vasoconstriction
 Increase coronary and cerebral perfusion pressure
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Beta-adrenergic effects
May increase myocardial work
 Reduce subendocardial perfusion
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Epipen in the Thigh!
Acute Management cont.
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Antihistamines
Second line treatment after administration of epi
 H1 antagonists
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H2 antagonists
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Diphenhydramine 25 to 50 mg slow IV or IM
Ranitidine 1 mg/kg IV, cimetidine 4 mg/kg IV
Inhaled beta-adrenergic agents
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Albuterol 2.5 – 5 mg in 3 ml saline
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Bronchospasm refractory to epi
Ipratropium use if patient on beta-blocker
2005 AHA Guidelines for CPR and ECC.
Acute Management cont.
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Corticosteroids
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High dose IV
corticosteroids
Methylprednisolone 1-2
mg/kg/d divided q6h
Effects delayed at least 46 hours
X
Acute Management cont.
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Aggressive fluid
resuscitation
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Isotonic crystalloid
1-2L, possibly 4L may be
needed
Oxygen
Monitors
Removal of venom sac
Patients on Beta-Blockers
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More likely to experience more severe
anaphylactic reactions.
 Epinephrine may be ineffective
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Unopposed alpha-adrenergic effects
Reflex vagotonic effects
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Profound hypotension, bradycardia,
bronchospasm
 Consider glucagon
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Activating adenyl cyclase directly and bypassing
beta-adrenergic receptor
Potential Therapies
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Glucagon
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Vasopressin
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Nonadrenergic peripheral vasoconstrictor
May benefit severely hypotensive pts
Dopamine
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If patient on beta-blocker
1 - 5 mg IV every 5 minutes
Side effects – nausea, vomiting, hyperglycemia
Stimulates alpha and beta adrenergic receptors
Atropine
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Reverses cholinergic-mediated decrease in HR, BP
Relative or severe bradycardia
Airway Obstruction
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Early elective intubation
recommended
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Hoarseness, lingual
edema, stridor,
oropharyngeal swelling
Pts can deteriorate
within ½ to 3 hours
2005 AHA Guidelines for CPR and ECC.
Cardiac Arrest
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Cardiopulmonary resuscitation
Aggressive volume expansion
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2 large bore IVs with pressure bags
4-8 L of isotonic crystalloid
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High dose epinephrine IV
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1-3 mg IV (3 min), 3-5 mg IV (3 min), 4-10ug/min infusion
Antihistamine IV
Corticosteroids
ACLS algorithms
2005 AHA Guidelines for CPR and ECC.
IV Epinephrine
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Risk for potentially lethal arrhythmias
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Not the preferred method.
Administer epinephrine IV only
During cardiac arrest (ACLS protocols)
 Profoundly hypotensive subjects unresponsive to
volume replacement and several IM injections
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Labs in Acute Setting
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Serum tryptase level
Peak 60-90 min after onset of sx
 Persist for 6 hrs
 Ideal measurement time 1-2 hr after onset
 Serum tryptase level may be normal in the setting of
food allergy induced anaphylaxis
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Plasma histamine level
Increase within 5-10 min after onset
 Persist 30-60 min
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Observation
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Biphasic reaction in up to 20% pts
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Symptoms recur within 1-8 hours
Observe until asymptomatic ≥ 4 hours
 Longer observation if severe reaction
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Discharge
EpiPen
 Corticosteroids
 Antihistamines
 Beta-agonist
 Buddy care
 Allergy consult
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Allergy Evaluation
Detailed allergy history
 Labs and allergy testing
 Avoidance measures
 Therapeutic options
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Graded dose challenge
 Drug desensitization
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Medical warning tags/ Red Dog Tags
Testing for Specific IgE

Allergen-specific IgE
 In vivo testing
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Prick and ID skin tests
• Venom
• Foods
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In vitro testing
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RAST
• Latex
• Venom
• Foods
Clinical Scenario
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25 yo AD male OIF air evac’ed from Iraq after
IED explosion
ICU for Acinetobacter sepsis
Childhood hx rash with amoxicillin
ICU team initially starts imipenem
ID recommends Unasyn (amp/sulbactam)
PCN Cross Reactivity
Carbapenems are cross-reactive
 Ampicillin is a beta-lactam antibiotic
 Patient requires drug desensitization
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Drug Desensitization
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Conversion from highly sensitive state to a
tolerant state
Mast cells unresponsive to specific drug
 Temporary, lasting as long as therapy is
uninterrupted
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Administration of gradually increasing doses of
drug over several hours or days
 Sensitivity returns within 48 hr of d/c drug
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Fatalities
Usually result from delayed administration of
epinephrine
 Severe respiratory complications
 Severe cardiovascular complications
 There is no absolute contraindication to
epinephrine administration in anaphylaxis

Long Term Management
Avoidance measures
 Pharmacologic prophylaxis to prevent
recurrent anaphylactoid rxn
 Allergen immunotherapy

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Venom – 90-98% effective
Patient education
 MedicAlert ID, red dog tags
 Medical record documentation

What test should you order to help
confirm a diagnosis of anaphylaxis?
A. C-reactive protein
 B. Leukotriene D4
 C. Serum Tryptase
 D. Plasma Histamine

Where does the autoinjector go?
A. Left Ventricle
 B. Deltoid
 C. Gluteus Maximus
 D. Vastus Lateralis

True or False

Patients with a history of seafood allergy are
by definition allergy to contrast dye (because
of the iodine)
When to refer to A/I ?
Evaluation and diagnosis, as well as long-term
management, can be complex. The
allergist/immunologist has the training and
expertise to obtain a detailed allergy history;
coordinate laboratory and allergy testing; evaluate
the benefits and risks of therapeutic options; and
counsel the patient on avoidance measures.
 For these reasons, patients with a history of
anaphylaxis should be considered for referral to
an allergy/immunology specialist.

Link for current anaphylaxis guidelines

http://www.allergyparameters.org/file_depot/0-10000000/30000-40000/30326/folder/73825/2010Anaphylaxis.pdf