Transcript Slide 1

Portier and Richet first
coined the term anaphylaxis.
In 1902 when a second
vaccinating dose of sea
anemone toxin caused a
dog's death. The response
was the opposite of
prophylaxis and thus was
referred to as anaphylaxis,
meaning without protection.
Phylaxis= protection
Anaphylaxis- is an acute life-threatening reaction caused
by an IgE-mediated reaction and results from the sudden
systemic release of mast cells and basophil mediators .
Anaphylactoid reaction- reaction that produce the same
clinical picture as anaphylaxis but are not IgE mediated.
Anaphylactic – this term has been used to describe the
clinical reaction (not the mechanism).
IMMUNOLOGY OF ANAPHYLAXIS
PATHOPHYSIOLOGY OF ANAPHYLAXIS
Allergen crosses an epithelial and/or endothelial barrier
Access to the reactive, sensitized cells
–mast cells, basophils
Release of cellular mediators leads to end-organ response in the
skin, respiratory tract , cardiovascular system , gastrointestinal
tract, nervous system.
Histamine
H1 receptor
H1,H2 receptors
H3 receptor
Pruritus
Rhinorrhea
Tachycardia
Bronchospasm
Headache
Flushing
Hypotension
Left ventricular
function
Effects of histamine on airways
Histamine
Bronchoconstriction by stimulation of H1 receptors on smooth muscles.
Mucosal edema from increased microvascular permeability (H1) leading to
transudation of fluid and macromolecules through wide intercellular
gaps (> 12 nm).
Direct stimulation of vagal (cholinergic) nerves can induce airway smooth
muscle contraction
Stimulation of H1 receptors increases mucus secretions, and
stimulation of H2 receptors increases mucus viscosity.
Effects of histamine on the heart
H1 receptors mediate coronary artery vasoconstriction and
increased vascular permeability.
H2 receptors mediate atrial and ventricular contractile forces,
atrial rate, and coronary artery vasodilation.
Decreased diastolic pressure and increased pulse
pressure
Histamine
H1 receptor on
endothelial cell
L-arginine
Nitric oxide
Decreases venous return
Pathologic features of anaphylaxis
Laryngeal edema
Pulmonary hyperinflation
Myocardial edema
Visceral congestion or
hemorrhage
Eosinophilic infiltration
Elevated tryptase levels
Death from cardiovascular
collapse or respiratory
obstruction
The more rapidly anaphylaxis occurs after exposure to an
offending stimulus the more likely the reaction is to be severe
and potentially life-threatening.
Anaphylaxis often produces signs and symptoms within minutes
typically 5-30 minutes , but some reaction , such as aspirin, might
develop after 30 minutes .
Late-phase or biphasic reactions, which occur 8-12 hours after
the initial attack.
The average annual incidence of anaphylaxis is 10-20 cases per 100,000
person-years.
Fatalities from anaphylaxis range from 0.65-2% of patients with
anaphylaxis
The annual incidence of fatal anaphylaxis among hospitalized subjects is
estimated to be 154 per 1,000,000.
ß-lactam antibiotics are tought to cause 400-800 fatal anaphylactic
episodes per year.
An estimated 150 fatalities from food-induced anaphylaxis occur each year
in the united states.
Allergen immunotherapy 1 per 2,000,000 injections.
Insect stings probably cause at least 50 fatalities annually in USA .
Risk factors
Atopy
Route and timing of administration
The longer the interval between
exposures, the less likely an
anaphylactic (IgE-mediated) reaction
will recur.
Asthma
Delay in administration of
DIAGNOSIS
DIAGNOSIS OF SPECIFIC CAUSE OF ANAPHYLAXIS
Skin tests
IgE specific - RAST
Radio-AllergoSorbent Test
Challenge test ( double-blind)
Tryptase
The first documented case of a
food fatal reaction was
described in 1926 by a
pediatrician. A 1 -year-old boy
with atopic eczema experienced
three episodes of generalized
allergic reactions at home after
intake of a few spoons of
mashed peas. In the hospital
setting an oral challenge with
carrots/mashed peas was
performed under the
supervision of a chief nurse.
Immediately after the intake of
the test meal the child
developed angioedema,
cyanosis and collapsed. He died
despite emergency treatment.
Food and Anaphylaxis
Clinical aspects and allergenic foods in
life-threatening food anaphylaxis
Moneret-Vautrin, D. A., Morisset, M., Flabbee, J., Beaudouin, E. & Kanny, G.
Epidemiology of life-threatening and lethal anaphylaxis: a review.
Allergy 60 (4), 443-451.
Anaphylactic reactions to foods
almost always occur
immediately.
The majority of reactions are not
fatal.
In general, reactions worsen with
the development of asthma and
as children get older.
The most useful diagnostic tests:
SPT and food challenges
Epinephrine should be available
for use
Exercise-induced anaphylaxis
•This is a rare syndrome that can take
one of two forms:
•The first form is food-dependent,
requiring both exercise and the recent
ingestion of particular foods to cause
an episode of anaphylaxis ~ 50%.
•The second form is characterized by
intermittent episodes of anaphylaxis
during exercise, independent of any
food ingestion. Anaphylaxis will not
necessarily occur during every
episode of physical exertion
Premonitory symptoms can include:
diffuse warmth, itching and erythema,
urticaria generally ensues and
progress to angioedema. Episodes
can include gastrointestinal
symptoms, laryngeal edema, and/or
vascular collapse.
Delaying exercise for about 5 hours
after eating will prevent reaction in
food related exercise-induced
anaphylaxis.
Carry Epipen,
should wear alert identification denoting
their condition,
have a companion with them when
exercising.
idiopathic anaphylaxis
The diagnosis of idiopathic
anaphylaxis a diagnosis of
exclusion.
Nearly 20% of cases of anaphylaxis
are idiopathic.
There are no clinically
distinguishing features, and it may
be fatal.
Management often consists of
prophylactic corticosteroid and
antihistamine therapy.
Drug anaphylaxis
Etiologies of 100 cases of lifethreatening drug anaphylaxis
Moneret-Vautrin, D. A., Morisset, M., Flabbee, J., Beaudouin, E. & Kanny, G.
Epidemiology of life-threatening and lethal anaphylaxis: a review.
Allergy 60 (4), 443-451.
Penicillin and
its metabolites
are haptens,
small molecules
that only elicit
an immune
response when
conjugated with
proteins.
95%
5%
Benzylpenicilloyl (BPO)
Major determinant
Benzylpenicilloate , Benzylpeniloate
Minor determinant
Pre-Pen
Most severe allergic reaction
•Other beta-lactam antibiotics may cross-react with penicillins or may
have unique structures that also act as haptens. The incidence rate of
anaphylaxis to cephalosporins in penicillin-anaphylactic patients
appears to be much less than the 10% frequently quoted.
•Patients with less well-defined reactions to penicillin have a very low
risk (1-2%) of developing anaphylaxis to cephalosporins. The rate of
skin-test reactivity to imipenem in patients with a known penicillin
allergy is almost 50%.
The use of BPO and Penicillin G 10000 unit ( without minor
determinants) can detect 97%-99% of potential life threatening
reactions.
Skin test positive
To BPO and Penicillin G
1.Give alternative drug
2. Desensitize to penicillin
Skin test negative to
BPO and Penicillin G
History of mild
reaction
Graded challenge given
1/100th of dose followed in
30 min by full dose
History of immediate
or severe reaction
1.Graded challenge given
1/1000th of dose followed in
30 min by full dose.
2. desensitize
NSAIDs ALLERGY
Aspirin (ASA), by irreversibly inhibiting platelet cyclooxygenase1 enzyme (COX-1), prevents platelet aggregation
ASA can also cause a hypersensitivity reaction:
• respiratory sensitivity (asthma and/or rhinitis)- These patients
have marked cross-reactivity between aspirin and most NSAIDs.
cyclo-oxygenase pathway
Arachidonic acid
lipoxygenase pathway
leukotrienes
•cutaneous sensitivity (urticaria and/or angioedema)
•systemic sensitivity (anaphylactoid reaction) mechanism that is
more consistent with IgE-mediated anaphylaxis. With true anaphylaxis, the different
cyclooxygenase inhibitors do not appear to cross-react.
Latex is the name for the milky sap collected from
the rubber tree- hevea brasiliensis
The latex has a crossreactive epitopes of
foods: banana,
avocado, chestnut.
3 groups are at higher risk:
health care workers: 4.5-14.4% sensitivity. ,
children with spina bifida and genitourinary abnormalities: 34100% sensitivity.
workers with occupational exposure to latex.
Dig : SPT better than RAST
Patients with spina bifida – regardless of a
HISTORY OF LATEX ALLERGY should have all
medical-surgical-dental procedures performed in a
latex-safe environment.
Hymenoptera sting anaphylaxis
Yelow jacket
Anaphylaxis occur with 0.5-1.5% of
stings.
Vespa orientalis
Wasp
Bumble bee
Bee
Diagnosis : Skin test
RAST
Sting Challenge test
Treatment : immunotherapy
Epipen
Epinephrine is the medication of choice for treating an
anaphylactic episode .
The recommended dose of epinephrine is 0.01 mg/kg I.M to as much as 0.3
mg-in children, and it may be repeated within 5 minutes if symptoms worsen
or severe symptoms persist. (1:1,000 aqueous solution (1 mg/mL) ).
The lateral aspect of the thigh appears to be the optimal
location of administration.
There are 2 doses of self –injectable epinephrine : Epipen jr 0.15mg , Epipen
0.3mg.
Use of I.V should be reserved for the most extreme conditions ( more
adverse reaction).
The more advanced the anaphylactic reaction- development of hypotensionthe less likely epinephrine is to reverse the reaction.
.
Epinephrine should be administered I.V only during cardiac arrest or to
profoundly hypotensive subjects who have failed to respond to intravenous
volume replacement and several injected doses of epinephrine.
Epinephrine administered during
anaphylaxis to patients taking ßadrenergic antagonist might be
ineffective . In this situation both
glucagon administration and isotonic
volume expansion is needed. Glucagon
causes bronchodilatation and
reverses anaphylaxis by increasing
intracellular cAMP and release of
catacholimies.
Glucagon 20-30 µg/kg –maximum 1mg
in children , in adults up to 5mg;
administrated i.v over 5 minutes
followed by infusion 5-15 µg/min.
Fluid resuscitation
Changes in vascular permeability during anaphylaxis might
permit transfer of 50% of the intravascular fluid into the
extravascular space within 10 minutes.
The patients whose hypotension persists despite
epinephrine should receive intravenous crystalloid solutions
(saline) or colloid volume expanders.
Adults – 1-2 liters ; 5-10ml/kg in 5 minutes.
Children- up to 30ml/kg in the first hour.
Corticosteroids :
systemic corticosteroids have no role in the acute management of
anaphylaxis because they might have no effect for 4-6 hours.
They might potentially prevent protected or biphasic anaphylaxis.
They provide additional benefit for patients with asthma.
If given , Corticosteroids should be administered early in the treatment
of anaphylaxis at a dosage equivalent to 1-2 mg /kg/d of
methylprednisolone every 6 hours. Oral prednisone 0.5 mg/kg is
sufficient for milder attacts.
H1 and H2 antagonists
Antihistamines are supportive in the treatment of anaphylaxis.
Antihistamines use in anaphylaxis should be considered
second line treatment after the adminstration of epinephrine.
They are useful in the treatment of urticaria or pruritus .
The role of H2 antagonist is more controversial , but some
reports ghave demonstrated that H1+H2 are more effective than
H1.