Hypersensitivity Disorders
Allergic Emergencies
Jim Holliman, M.D., F.A.C.E.P.
Professor of Military and Emergency Medicine
Uniformed Services University of the Health Sciences
Clinical Professor of Emergency Medicine
George Washington University
Bethesda, Maryland, U.S.A.
Hypersensitivity Disorders & Allergic
Emergencies : Lecture Objectives
ƒ Describe & compare :
–Anaphylaxis & anaphylactoid reactions
–Angioneurotic edema
–Drug allergies
ƒ Describe emergent Rx & followup
outpatient Rx for anaphylactic & other
allergic reactions
Allergic Reactions
Definitions of Terms
ƒ Anaphylaxis (Greek = "backward protection")
–Rapid generalized immunologic reaction after
exposure to antigens in a sensitized person, with at
least 2 of :
ƒ resp. or airway compromise from swelling or
wheezing
ƒ hypotension or cardiovascular collapse
ƒ diffuse cutaneous findings (urticaria, angioedema,
+/- erythroderma)
Allergic Reactions
Definitions of Terms (cont.)
ƒ Anaphylactoid reaction :
–Syndrome presenting similar to anaphylaxis, expressed
by similar mediators, but not triggered by IgE & not
necessarily due to prior exposure to the inciting agent
ƒ Urticaria :
–Diffuse patchy erythematous pruritic rash with raised
borders
ƒ Angioedema :
–Non-pitting subcutaneous tissue swelling
–Often of the face, mouth, or peri-airway tissue
Pathophysiology of Allergic
Reactions
ƒ Mast cell
–Final common pathway of all allergic reactions
–Present in most tissues
–When activated, release (from cell granules) :
ƒ Histamine
ƒ Bradykinins
ƒ Prostaglandins
ƒ Leukotrienes
–Clinical effects are due to these above
mediators
Four Mechanisms that Lead to Mast
Cell Degranulation (Release of Mediators)
ƒ Immunoglobulin E (IgE) mediated
hypersensitivity
ƒ Complement cascade activation
ƒ Direct stimulation of mast cell by
anaphylactoid substances
ƒ Inhibition of arachidonic acid pathway
Sequence of Events in IgE Mediated
Hypersensitivity Reactions
ƒ 1. Initial exposure to allergen
ƒ 2. IgE antibody produced in reponse
to allergen
ƒ 3. Re-exposure of patient to same
allergen
ƒ 4. Preformed IgE cross links on mast
cell surface
ƒ 5. Mediators (esp. histamine) released
by mast cell
Histamine Receptors
ƒ 3 types with the following effects
when stimulated :
–H1 : brochoconstriction, vascular
permeability, smooth muscle contraction
–H2 : gastric acid secretion, cardiac
chronotropy & inotropy
–H3 : inhibition of histamine formation &
release
General Clinical Effects of
Release of Allergic Mediators
ƒ Mucocutaneous :
–pruritis, flushing, erythema, urticaria, angioedema
ƒ Respiratory :
–upper airway angioedema
–bronchoconstriction
–pulmonary hyperinflation +/- pulm. edema
ƒ Cardiovascular :
–vasodilatation, increased vascular permeability,
intravascular volume depletion, vasogenic shock,
myocardial contractile dysfunction
ƒ Gastrointestinal :
–cramping, vomiting, diarrhea
Causes of Anaphylactic and
Anaphylactoid Reactions
ƒ IgE mediated allergies :
–Beta lactams, hymenoptera stings, food, latex
ƒ Direct mast cell degranulation :
–Xray contrast media, opiates, mannitol,
neuromuscular blockers
ƒ Altering bradykinin metabolism :
–angiotensin converting enzyme (ACE) inhibitors
ƒ Affecting metabolism of arachidonic acid :
–aspirin, NSAID's
Considerations About Beta
Lactam Antibiotic Allergies
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Penicillin is most common cause
Incidence of hypersensitivity about 4 %
Anaphylaxis in 1 per 10,000 administrations
100 to 500 deaths per year in U.S.
Co-reactivity with cephalosporins < 5%
Can undergo desensitization process but risky
and many alternative antibiotics now available
ƒ Can occur from topical exposure (mother preparing
antibiotic suspension for child)
Considerations About Allergy
to Hymenoptera Stings
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Hymenoptera include bees, wasps, ants
Mostly cause local allergic reactions
10 % have regional swelling
1 % have anaphylaxis
–Causes 40 to 50 deaths per year in U.S.
ƒ Content of venom variable so re-sting may not
cause same reaction as before
ƒ F/U with allergist for desensitization Rx always
recommended for systemic reaction
Treatment of Allergic Reactions
from Hymenoptera Stings
ƒ If local reaction only :
–Ice pack, pain med, diphenhydramine PO
–Watch at least 30 minutes to be sure systemic
reaction does not occur
ƒ If systemic reaction :
–O2, epi, IV fluid bolus, IV diphenhydramine, IV
steroids, observe at least 4 hours
ƒ For both types :
–Check sting site & remove stinger if imbedded (scrape, don't
squeeze), update tetanus, consider antibiotic if ? cellulitis
Considerations About Allergic
Reactions to Foods
ƒ Most commonly due to :
–legume vegetables (peanuts, soybeans, peas, beans)
–crustaceans
–mollusks
–cow's milk
–eggs (may also react to MMR vaccine)
–nitrites or sulfite preservatives in foods
ƒ Must differentiate seafood allergy from
scombroid poisoning (due to ingestion of spoiled fish
containing histamine)
Considerations About Latex
Allergy
ƒ An increasingly recognized recent
problem
ƒ Can result in fatal anaphylaxis
ƒ High incidence in pts. with spina bifida
& congenital urologic problems
ƒ Be careful to select non-latex gloves &
catheters for pts. with this allergy
Allergic Reactions to
Radiocontrast Media
ƒ Occur in 1 % of cases
ƒ 10 % of occurences are severe
ƒ About 500 ( ? ) fatal reactions in U.S.
annually
ƒ Risk factors :
–prior reaction (30 % recurrence rate)
–advanced age
–renal or hepatic dysfunction
–asthma
Allergic Reactions to
Radiocontrast Agents (cont.)
ƒ High osmolarity agents (Hypaque, Renografin,
Conray)
–Tri-iodinated, ionic
ƒ Low osmolarity agents :
–non-ionic dimers
–produce less histamine release & less vascular
endothelial irritation
–Much more expensive (5 X)
–Recent reports show reduction in complications of contrast
studies using these agents, but reactions still occur in 30%
Allergic Reaction Prophylaxis
for Radiocontrast Agent Use
ƒ Pretreatment reduces recurrent allergic
reaction rate to 1%
ƒ One suggested regimen :
–Hydrocortisone 200 mg IV just prior to & 4 hours
after contrast, & cimetidine 300 mg IV &
diphenhydramine 50 mg IV just prior to contrast
–Should have epi & resus. equipment available
ƒ Pre-Rx indicated for pt. requiring a contrast
study with prior Hx of reaction or renal
dysfunction
Angioedema Due to ACE
Inhibitors
ƒ Occurs in 0.2 % of pts. on ACE inhibitors
ƒ Can occur even after prolonged use of ACE
inhibitors without a prior reaction
ƒ Predeliction for head & neck angioedema so
airway compromise possible
ƒ Rx by stopping the ACE inhibitor, epi,
steroids, diphenhydramine, +/- airway
management
Severe angioedema
Same patient on
prior slide after
treatment
Spectrum of Presentations of
Allergic Reactions
ƒ Time to onset, intensity, & duration of
reaction vary, depending on :
–degree of sensitivity of pt.
–route of exposure
–amount ("dose") of antigen
ƒ Rarely pts. may have "biphasic"
reaction with reexacerbation of Sx 4 to
8 hours after the initial reaction
Clinical Manifestations of
Systemic Allergic Reactions
ƒ Diffuse pruritis, urticaria, angioedema,
erythroderma
ƒ Anxiety, dizziness, sense of doom,
altered mental status
ƒ Dyspnea, stridor, wheezing
ƒ Dysphagia, dysarthria, drooling
ƒ Vomiting, diarrhea, abd. cramps
ƒ Urinary incontinence
ƒ Hypotension +/- bradycardia
Differential Dx of Severe
Allergic Reaction
ƒ Sudden loss of consciousness :
–vasovagal syncope, seizures, dysrhythmias, CVA
ƒ Acute respiratory distress :
–status asthmaticus, upper airway infection, foreign
body aspiration, pulm. embolus
ƒ Cardiovascular collapse :
–intraabdominal bleed, acute MI
ƒ Systemic disorders :
–mastocytosis, hereditary angioedema (C1 esterase deficiency
syndrome) , carcinoid syndrome, scromboid poisoning, MSG
syndrome
E.D. Management of Systemic
Allergic Reactions
ƒ Since may progress rapidly & unpredictably, all pts. with
possible systemic reaction should be rapidly triaged to
acute care room & continuously monitored
ƒ Suggested initial sequence :
–O2 / airway management
–SQ or IM epi (0.01 mg/kg or max. 0.3 mg in adults)
–IV placement ; IV fluid bolus (NS) if hypotensive
–IV diphenhydramine & IV steroids
–Beta 2 aerosol if wheezing
–Secondary meds ; consider repeat epi doses
–Remove source of reaction if possible
– Give IV fresh frozen plasma if hereditary angioedema from C1
esterase deficiency
Airway Management Considerations
for Severe Allergic Reactions
ƒ Swelling impinging the airway may progress
rapidly so earlier intubation more likely
successful than later
ƒ Consider sedation without paralysis if anticipated
difficulty
ƒ Start with ETT size one size smaller than usual
ƒ Have surgical airway equipment at bedside
ƒ Place nasal airway early even if ETT not initially
required
ƒ Consider use of inhaled racemic epi
The Key Med in Rx of Allergic
Reactions : Epinephrine (epi)
ƒ Is the most important & effective Rx
med
ƒ Alpha agonist effects :
–Vasoconstriction, decreased vascular
permeability, resolution of angioedema
ƒ Beta agonist effects :
–Bronchodilatation, cardiac inotropy, mast
cell membrane stabilization
Potential Complications of Use of Epi
for Allergic Reactions
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Hypertension (may cause CNS bleed)
Increased myocardial O2 consumption
Coronary vasoconstriction
Tachycardia / dysrhythmias
In pts. who have HBP, CAD, CVA, or pregnancy,
should consider need for epi carefully & may
need to decrease dose; should still be given
though to these pts. if reaction is severe
Epi Doses for Allergic
Reactions
ƒ Give IM or SQ if unable to start IV line quickly
ƒ Give IV if markedly hypotensive
ƒ IM or SQ dose : 0.01 mg/kg
–0.01 ml/kg of 1:1000 ; max. dose 0.3 mg
ƒ IV dose : 0.1 mg (max.)
–1 cc of 1:10,000
ƒ Repeat as needed
ƒ Can also give via MDI (10 to 20 puffs)
Antihistamine Med Rx for
Allergic Reactions
ƒ Act by competitively inhibiting H1 & H2 receptors
ƒ Diphenhydramine is best single agent against
pruritis, but combo Rx (with H2 blocker) is superior
ƒ Give PO for mild & local reactions
ƒ Give IM only if airway compromise & unable to start
IV
ƒ Give IV for severe reactions
ƒ Usually give 50 mg diphenhydramine, & 300 mg
cimetidine or 50 mg ranitidine
Steroid Rx for Allergic
Reactions
ƒ Have antiinflammatory effects, stabilize mast cell
membranes, & may blunt the biphasic response
ƒ Indicated in almost all pts. with systemic reactions
ƒ Usually 100 mg hydrocortisone or equivalent is
sufficient
ƒ May need 1 to 2 days follow-on oral use (prednisone
40 mg/day) depending on source of reaction
ƒ Give PO if airway & BP not cpmpromised, otherwise
give IV
Use of Glucagon for Allergic
Reactions
ƒ 1 mg IV dose (repeated as needed)
may be useful for cases refractory to
initial Rx with epi & IV fluid & H1/H2
blockers & steroids
ƒ Also useful in pts. on beta blockers, &
as "back-up" med to lower dose epi in
pts. with CAD or HBP
ƒ Can cause emesis as side effect
Disposition Decisions for Patients
with Allergic Reactions
ƒ Mild local reactions should be observed for 30
minutes ; then sent home on PO diphenhydramine if
no Sx progression
ƒ Systemic reactions that respond to initial Rx should
be observed 2 to 4 hours for recurrence
ƒ Those manifesting airway compromise or
hypotension (even if they respond to Rx) probably
should be admitted overnight
ƒ Pts. on beta blockers, elderly, asthmatics, or with
other comorbid diseases should often be admitted
Discharge Medications for
Patients with Allergic Reactions
ƒ Most should receive :
–Diphenhydramine 25 to 50 mg PO QID X 2 days
–Cimetidine 300 mg PO QID X 2 days
–Prednisone 40 to 50 mg PO (1 to 2 mg/kg) QD X 2
days
–Consider susphrine (epi tannate in oil) 0.005 cc/kg
(max. 0.3 cc) SQ prior to D/C
–Consider epi self-injection kit (Epi-Pen or Ana-Kit)
–Consider standby albuterol MDI
–Consider non-sedating antihistamine
Other Discharge Considerations for
Patients with Systemic Allergic Reactions
ƒ Education about preventive or
avoidance measures
ƒ Get Medic-Alert bracelet or necklace
ƒ Consider epi self-injection kit
ƒ Standby oral diphenhydramine
ƒ Discontinue beta blockers if possible
ƒ Referral to allergist for desensitization
Hypersensitivity Disorders &
Allergic Reactions : Summary
ƒ Evaluate all pts. with allergic reactions
emergently
ƒ Assess airway & hemodynamics first
ƒ Epi is mainstay of Rx
ƒ Consider use of adjunctive meds
ƒ Observe to determine if relapse or
need for admission
ƒ Discharged pts. should be instructed
carefully about F/U & prevention