Transcript 2007_11_22-Burgess-Allergy-anaphylaxis

Gavin Burgess
EM Rounds
22 November 2007
Thanks Dr T
Vander Leek
Anna
Phil
Axis
Introduction
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“Anaphylaxis” coined in 1902 (Portier +
Richet)
Experimented with dogs and sea anemone
venom immunisations
Dogs unexpectedly died after previously
tolerated doses
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Lieberman in Allergy: Principles and Practice v.5,
1079-92
Definition?
Definition
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A Severe, potentially fatal, systemic
allergic reaction that occurs suddenly after
contact with an allergy-causing substance
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Sampson et al JACI 2006;117:391-7
Definition
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A severe allergic reaction to any stimulus,
having sudden onset, involving one or
more body systems with multiple
symptoms
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Canadian Anaphylaxis Guidelines www.allergysafecommunities.ca
Definition
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An acute, life-threatening reaction
mediated by IgE
IgE-mediated Type I hypersensitivity
Release of Mast cell and Basophil contents
What’s in the cells?
Biochemical Mediators
and Chemotactic Substances
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Degranulation of mast cells and basophils.
Preformed granule-associated
substances, e.g., histamine, tryptase,
chymase, heparin, histamine-releasing
factor, other cytokines.
Newly generated lipid-derived
mediators, e.g., prostaglandin D2,
leukotriene B4, PAF, LTC4, LTD4, and LTE4.
Biochemical Mediators
and Chemotactic Substances
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Eosinophils may play pro-inflammatory
role (release of cytotoxic granuleassociated proteins) or anti-inflammatory
role (e.g., metabolism of vasoactive
mediators)
Incidence
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Analysis of published studies of most
common causes
3.3 to 4 million Americans at risk.
1,433 to 1,503 at risk for fatal reaction.
Neugut, Ghatak, Miller Arch Int Med 2001
Incidence Based on
Epinephrine Rx for
Out-of-Hospital Use
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From Canada and Wales.
0.95% of population in Manitoba, Canada.
0.2 per 1000 in Wales.
Incidence increased in Wales between 1994 &
1999.
Simons, Peterson, Black JACI 2002
Rangaraj, Tuthill, Burr, Alfaham JACI 2002
Case 1
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6y at friend’s birthday party, ate peanutcontaining peanuts
Tingling around mouth, thick tongue, lip
swelling
In ED, urticaria, swollen lips and tongue,
flushing
Vitals: P120, RR 35-40, afebrile, BP 70/40
Signs of anaphylaxis….
Case 1
Signs of anaphylaxis
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Loss of consciousness
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“sense of impending doom”
Signs of anaphylaxis
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Cutaneous – urticaria, angioedema,
pruritis, erythema/flushing
Oral – tingling lips/tongue/palate, swollen
tongue/lips
Ocular – periocular oedema, erythema,
conjunctival injection, tearing
Signs of anaphylaxis
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Respiratory
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Upper airway – voice change, throat clearing,
airway obstruction (tongue, laryngeal or
oropharyngeal oedema), sneezing, nasal
pruritis, rhinorrhea, congestion
Lower airway - wheeze, cough, tight chest
Signs of anaphylaxis
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Gastrointestinal – nausea, vomiting,
cramps, diarrhea, urgency, incontinence
Genitourinary – uterine cramps, urgency,
incontinence
Cardiovascular – hypotension, arrhythmia,
shock, syncope, chest pain
Signs of anaphylaxis
Signs/symptoms
%
Urticaria and angiooedema
88
Dyspnoea, wheeze
47
Dizziness, syncope, hypotension
33
N,V+D, cramps
30
Flushing
46
Upper airway oedema
56
Headache
15
Rhinitis
16
Substernal pain
6
Itch without rash
4.5
Seizure
1.5
Lieberman in Allergy: Principles and practice v.5 1079-92
Case 2
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25y F, known ED, stands, has syncopal
event, diaphoresis, nausea
Looks pale, P110, BP (L) 110/70, BP (s)
90/50, RR18
Differential Diagnosis
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Anything can resemble anaphylaxis
Vasovagal, globus hystericus, status
asthmaticus, hereditary angioedema,
hypoglycaemia, FB aspiration, seizures,
etc.
Hypersensitivity
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Type I – immediate, preformed
Almost all <60min
 Can skin test, IgE-mediated ONLY
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Type II – cytotoxic, IgM, IgG on cell
surface
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<72hours
Hypersensitivity
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Type III – immune complex, serum
sickness, IgG
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1-3 week delay LN, arthritis
Type IV – T-cell mediated, NO antibodies
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>48 hours
Adverse reactions
Reactions
Unpredictable (20-30%)
Non immune mediated (15-20%)
Predictable(75-80%)
Immune mediated (5-10%)
Mixed
Adverse Reactions
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Mixed reactions
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Unpredictable, non immune mediated
“pseudo allergic”
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Erythema multiforme -> Stevens-Johnson, fixed
drug reaction
Red man, morphine, ACEI, G6PD
Predictable reactions
Causes
Causes
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Food
Vaccines
Medications
Blood products
Latex
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Drugs and biologicals
Exercise
Insect venom
Idiopathic
Significance
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Food allergy is now the most common
cause of anaphylaxis in the ED.
>1/3 of presentations
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Sampson HA. Pediatrics 2003;111:1601-8
Risk Factors
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Risk Factors
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Injected material vs ingested material
Atopy
Asthma (even if well controlled)
Failure to identify proper trigger
Previous reactions to trigger
Less risk at extremes of age
Risk Factors
Factor
Poor
Good
Dose
Large
Small
Onset of symptoms
Early
Late
Initiation of treatment
Late
Early
Route of exposure (drugs, not
food)
Β-blocker use
IV
Oral*
Yes
No
Presence of underlying disease
Yes
No
Risk Factors for severe anaphylaxis
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Prev anaphylaxis
Asthma
Failure to identify
trigger
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Teens
Β-blockers/ ACEI
Failure to
administer
epinephrine
immediately
Case 1 cont.
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Symptoms worsening. Wheezing,
lethargic.
Sats 89%, prolonged expiration phase,
Little air movement on auscultation
Management?
Management
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Failure to administer epinephrine early is
the single most important risk factor
for fatal or near fatal reactions
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Bock, SA J. Allergy Clin Immunol 2001;107:191-3
Management
I. Immediate Intervention
a) Assessment of airway, breathing,
circulation, and mentation.
b) Administer EPI, 1:1000 dilution, 0.3 0.5 ml (0.01 mg/kg in children, max
0.3 mg dosage) IM, to control SX and
BP. Repeat, as necessary.
Kemp and Lockey JACI 2002
Simons et al JACI 1998
Simons, Gu, Simons JACI 2001
Management
c) IM into the anterolateral thigh
produces higher & more rapid peak
plasma level versus SQ & IM in arm.
With moderate, severe, or progressive
ANA, EPI IM into anterolateral thigh.
Alternatively, an EPI autoinjector given
through clothing in same manner.
Repeat, as necessary
Epinephrine route of administration
Simons JACI 1998;101:33-7
Simons JACI 2001;108:871-3
Management
d) Aqueous EPI 1:1000, 0.1- 0.3ml in
10ml NS (1:100,000 to 1:33,000
dilution), IV over several minutes prn.
e) For potentially moribund subjects,
tubercular syringe, EPI 1:1000, 0.1 ml,
insert into vein (IV), aspirate 0.9 ml of
blood (1:10,000 dilution). Give as
necessary for response
Management
II.
General measures
a) Place in recumbent position and
elevate lower extremities. Up to
35% of intravascular fluid may be
lost in 10 min! Pressors may fail
to work
b) Maintain airway (endotracheal
tube or cricothyrotomy).
Management
c) O2, 6 - 8 liters/minute.
d) NS, IV. If severe hypotension, give
volume expanders (colloid
solution) – 35% of blood volume
can be lost in 20 min.
e) Venous tourniquet above reaction
site. ? if decreases
absorption of allergen.
Management
III. Specific Measures that Depend on
Clinical Scenario
a) Aqueous EPI 1:1,000, ½ dose (0.10.2 mg) at reaction site.
Management
b) Diphenhydramine, 50 mg or more in
divided doses orally or IV, maximum
daily dose 200 mg (5 mg/kg) for
children and 400 mg for adults.
c) Ranitidine, 50 mg in adults and 12.5 50 mg (1 mg/kg) in children, dilute in
D5W, total 20 ml, inject IV, over 5
minutes. (Cimetidine 4 mg/kg OK for
adults, not established for pediatrics).
Management
d) Bronchospasm, nebulized salbutamol
e) Aminophylline, 5mg/kg over 30 min IV
may be helpful. Adjust dose based on
age, medications, disease, current use.
f) Refractory hypotension, give
dopamine, 400 mg in 500 ml G/W IV 2
- 20 μg/kg/min more or less.
Management
g) Glucagon, 1- 5 mg (20 - 30 μg/kg
[max 1 mg] in children), administered
IV over 5 minutes followed with IV
infusion 5-15 μg/min.
h) Methylprednisolone, 1- 2 mg/kg per
24 hr; prevents prolonged reactions
and relapses- no studies, though
i) Cetirizine
Management
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Biphasic response in some individuals,
unpredictable
Recommended observation for 4h
Epipens
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0.15mg or 0.3mg doses available
Adult 0.3mg
Paeds
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0.15mg (10-25kg)
0.3mg (>25kg)
Epipens
Simons JACI 2000;105:1025-30
Case 3
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70y obese hypertensive, started on ACEI
(captopril).
Prev. ETT, thyroid surgery
To ED with swollen face and lips. No
largyneal involvement
Upper Airway Oedema
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Life-threatening oedema
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Hereditary angioedema
Aquired oedema
ACEI induced oedema
Angioedema
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First described by Quincke in 1882
Well-demarcated non-pitting oedema
Caused by same pathological factors that
cause urticaria
Reaction occurs deeper in dermis and
subcutaneous tissues
Face, tongue, lips, eyelids most commonly
affected
May cause life-threatening respiratory
distress if larynx involved
Angioedema
Hereditary
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Type 1: C1 esterase inhibitor deficiency
Type 2: functional abnormality of C1
esterase inhibitor
Angioedema
Acquired
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Idiopathic
IgE-mediated
Non-IgE-mediated
Systemic disease
Physical causes
Other
Angioedema
IgE-mediated
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Drugs
Foods
Stings
Infections (eg viral, helminthic)
Angioedema
Non-IgE-mediated
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Cyclooxygenase inhibition (ASA and other
NSAIDS)
Angiotensin converting enzyme inhibition
Angioedema
Systemic diseases
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Systemic lupus erythematosis
Hypereosinophilia
Lymphoma:
abnormal antibodies activate complement
system
Angioedema
Physical causes
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Cold
Cholinergic
Solar
Vibratory
Other
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Some contact reactions
Autoantibodies to C1-esterase inhibitor
Unopposed complement activation
Angioedema
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Angioedema occurs most commonly with
urticaria (40% cases)
May occur in isolation (10% cases)
Hereditary Angioedema (HAE)
Type 1*
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Autosomal dominant
Markedly suppressed C1 esterase
inhibitor protein levels
* Accounts for 85% cases
Hereditary Angioedema (HAE)
Type 2*
Autosomal dominant, with a point
mutation leading to synthesis of a
dysfunctional protein
 Functional assay required for diagnosis
as level may be normal
* Accounts for 15% cases
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Hereditary Angioedema (HAE)
Epidemiology
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1:10,000 - 1:150,000 with no racial or
gender predilection
Hereditary Angioedema (HAE)
Clinical manifestations
 Usually manifests in 2nd decade
 May be seen in young children
 Oedema may develop in one or several
organs
 Presentation depends upon site of swelling
 Attacks last 2- 5 days before spontaneous
resolution
Nzeako Arch Intern Med, 2001
Hereditary Angioedema (HAE)
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Angioedema may develop in subcutaneous
tissues of extremities, genitalia, face,
trunk.
Oedema of wall of intestine may present
as an acute abdominal emergency.
Submucosal oedema of larynx or pharynx
may cause asphyxiation – this may occur
on first presentation
Hereditary Angioedema (HAE)
Laryngeal oedema
Commonest cause of mortality in HAE
 Time from onset of swelling to death 1- 14
hours (mean 7 hours)
 May be presenting feature
 Death may occur in those with no previous
laryngeal oedema episodes
 Increased risk within certain families
 Early symptoms - lump in throat, tightness in
throat
 Hoarseness, dysphagia, progressive dyspnoea
Hereditary Angioedema (HAE)
Diagnosis
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Clinical presentation
For screening - quantitative and functional
assays of C1 inhibitor
C4 and C2 levels reduced in acute attack
C4 persistently low in most patients
Hereditary Angioedema (HAE)
C1 inhibitor
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Single chain glycoprotein; molecular
weight 104,000; serine protease family
Important regulatory protein of
complement cascade
Inactivates C1 esterase complex
Regulates coagulation, fibrinolytic, kinin,
complement systems
Hereditary Angioedema (HAE)
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Lack of C1 inhibitor leads to abnormal
activation of complement pathway,
reduced C2 and C4 levels
Hageman factor induces formation of
kallikrein from prekallikrein
Bradykinin is released from high molecular
weight kininogen
All these mediators increase capillary
permeability and are responsible for
attacks of angioedema
Hereditary Angioedema (HAE)
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Autosomal dominant; all patients
heterozygous
25% no prior family history - spontaneous
mutations
More than 100 different mutations
reported
Varied clinical pattern may be explained by
variable effect of mutations on C1 inhibitor
synthesis
Hereditary Angioedema (HAE)
Acute attacks
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Treatment of choice is C1 inhibitor concentrate,
500 - 1,000U intravenous infusion
Safe and effective - no long term side effects
reported
Excellent and prompt response in most patients
Not available in USA, but in clinical trials
Hereditary Angioedema (HAE)
Acute attacks when C1 inhibitor
concentrate not available
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Intubation and respiratory support may be
necessary when laryngeal oedema present
Fresh frozen plasma (FFP) has been used
successfully for acute attacks.
Exacerbation of symptoms by supplying
more kallikrein substrate is a theoretical
consideration but is rarely seen
Hereditary Angioedema (HAE)
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Avoid oral contraceptive pill, ACE inhibitor
medication
Premedicate before procedures requiring
radiocontrast media or streptokinase as
they may decrease C1 inhibitor levels
Angioedema (ACEI)
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Angioedema develops in 0.1% to 0.5% of those
receiving the drug
Onset from 1st week of use to 2 - 3 years of use
Symptoms resolve within 24 - 48 hours of
cessation of drug
Most commonly seen with captopril and enalopril
but described with all in class
Genetic factors may be important
Subjects with a history of angioedema from
other causes are more susceptible to ACEinduced angioedema
Angioedema
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Most often occurs in association with urticaria
When angioedema occurs alone, consider HAE,
AAE
HAE is a rare disease but must be identified as it
can be life-threatening
Refer to appropriate specialist for ongoing
management
ACE-inhibitor induced angioedema is an
important cause in older people
“There are no contraindications to the
use of epinephrine for a life-threatening
allergic reaction”
AAAAI board of Directors JACI 1998;102:173-76
Reference
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GLORIA - world allergy congress 2006
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Ann Allergy 1993 May; 70(5): 396-8
Myocardial infarction induced by coronary vasospasm after selfadministration of epinephrine.
Saff R, Nahhas A, Fink JN.
Department of Medicine, Medical College of Wisconsin, Milwaukee.
"A case of a 30-year-old man who developed a myocardial infarction
after self-administering an Epi-Pen for an episode of idiopathic
anaphylaxis is reported. The patient had numerous risk factors for
coronary artery disease, and it was suspected that epinephrineinduced coronary spasm caused the infarct. The Epi-Pen Junior may
be indicated in such adults with numerous risk factors for coronary
artery disease who are at risk for recurrent anaphylaxis."