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Anaphylaxis & Allergy
Chris McCrossin
Thanks to
Bruce MacLeod
Ian Rigby
Outline: Anaphylaxis and
Allergy
• Anaphylaxis
– Pathophysiology
– Diagnosis
– Management (treatment & disposition)
• Related Issues
– Angioedema
– Anaphylactoid Reactions
• Drug Hypersensitivity Reactions
– Several cases to highlight the various reactions
– Antibiotic Allergies
– Sulfonamide Allergies
Definition
• Definition
– Proposed at the first
symposium on the defn and
mgmt of anaphylaxis
– Believed this will capture
~95% of patients with the
syndrome
– Not validated, keep an open
mind in unclear cases
• Ann Emerg Med 2006;
47:373-380
Epidemiology
• Most fatalities from
insect bites occur
with the first reaction
• Most fatalities from
food allergies occur
in patients with hx of
previous mild
reactions
Alberta Fatalities Due to
Anaphylaxis 1984-2004
5
4
3
2
1
0
Hymenoptera
Food Product
Medication/Blood
Products
Chronic Allergic
Asthma
Immunology 101
• Type I Reactions
– Antigen bridges two IgE molecules on the surface
of basophils and mast cells to release histamine
and leukotrienes in the
•
•
•
•
Skin
Blood vessels
GI tract
Respiratory tract
– Symptoms
• Urticaria, angioedema, nausea, vomiting, SOB,
wheezing, hypotension
Immunology 101
Anaphylactic Signs &
Symptoms
Immunology 101
• Type II Reactions (cytotoxic rxns)
– Antigen specific IgG or IgM antibodies bind with drug
antigens that are bound to the surface of native cells. Once
antibodies bind to the cell coated in drug antigens the
complement & reticuloendothelial system help
destroy/remove the Ab coated cells
• RBC’s
• Platelets
• Keratinocytes
– Consequences
• Antibiotic induced hemolytic anemia & thrombocytopenia
• Autoimmune bullous disease (pemphigus vulgaris)
Immunology 101
• Type III Reactions
– Complexes of IgG (or IgM) antibodies + drug antigens form
in the blood then deposit in tissue. This activates the
complement system and causes local tissue destruction in
• Skin
• Joints
• Other tissues
– Consequences
• Serum Sickness
Immunology 101
• Type IV Reactions (delayed-type hypersensitivity
reactions)
– Mediated by activated T lymphocytes that recognize
antigens from numerous sources (drugs, ingested foods,
creams/lotions, etc)
– Now divided into 4 subtypes. Look this up if you are a
NERD
– Examples
•
•
•
•
Contact dermatitis
SJS
TEN
Maculopapular rashes
Immune Mediated Reactions
Extended Gell and
coombs
classification
Type of
Immune
Response
Pathologic
Characteristics
Clinical Symptoms
Cell Type
Type I
IgE
Mast-cell degranulation
Urticaria,
Anaphylaxis
B cells/Ig
Type II
IgG
FcR dependent cell
destruction
Blood cell dyscrasia
B cells/Ig
Type III
IgG &
Complement
Immune complex
deposition
vasculitis
B cells/Ig
IVa
Th1
Monocyte activation
Eczema
T cell
IVb
Th2
Eosinophilic inflammation
Maculopapular
Bullous exanthema
T cell
IVc
Cytotoxic T
lymphocytes
CD4 or CD8 mediated
killing
Maculopapular
Bullous exanthema
T cell
IVd
T cells
Neutrophil recruitment
and activation
Pustular exanthema
T cell
Type IV
Pathophysiology
• Histamine
– Present in most tissues of the body,
particularly high concentration in lungs,
skin, & GI tract.
– Stored in mast cells and basophils
– Increasing cAMP levels in the cell inhibits
histamine release
– Four receptors
• H1, H2, H3, H4
Pathophysiology
• Histamine
– Main actions in humans:
• Stimulation of gastric secretion H1
• Contraction of most smooth muscle (except for
blood vessels)  H1
• Cardiac stimulation  H2
• Vasodilatation  H1
• Increased vascular permeability  H1
Pathophysiology
•Additional Mediators of Inflammation
Differential Diagnosis
Also keep
anaphylaxis on
your differential for
syncope
Case
• 24 yo F with history
of peanut allergy
• Arrives via EMS
after eating one of
Dimmer’s samosas
(which cost her $6!)
• Apparently he used
peanut oil to deep
fry these delicacies
Approach
• The obvious
– ABC’s
– Maintaining a patent airway and managing
shock from vasodilation are the key areas
of concern
– Patient condition can change rapidly
Case (cont)
• Airway
– Talking, no stridor, no drooling, no apparent soft tissue
swelling
• Breathing
– Somewhat anxious and slightly tachypenic, no wheeze but
subjectively SOB
• Circulation
– Normotensive, tachycardic (105)
• Derm
– Urticarial rash
Case (cont)
• Now onto the drugs…
• What is the drug of choice in
anaphylaxis?
Epinephrine
• Stimulation of α-adrenoceptors increases peripheral
vascular resistance thus improving blood pressure
and coronary perfusion, reversing peripheral
vasodilation, and decreasing angioedema.
• Stimulation of β1 adrenoceptors has both positive
inotropic and chronotropic cardiac effects.
• Stimulation of β2 receptors causes bronchodilation as
well as increasing intracellular cyclic adenosine
monophosphate production in mast cells and
basophils, reducing release of inflammatory
mediators.
Management
• Epinephrine
– When do we give it?
Less Likely
More Likely
• Known CAD
• Airway symptoms
• Presence of CAD RF’s
• Cardiovascular instability
• Advancing Age
• Acuity of Onset
• Absence of cardiorespiratory symptoms
• Hx of previous severe
allergic rxns
Management
• Epinephrine
– Bottom Line:
• Consider giving it in anyone with more than just
cutaneous symptoms
• Be cautious in patients with CAD
Management
• Epinephrine
– How do we give it? Where do we inject?
14000
12000
10000
8000
[Epi]peak ug/mL
6000
4000
2000
0
Epi EPI Epi Epi Ctrl
Pen IM T IM A SQ A
IM T
J Allergy Clin Immunol 2001; 108:871-3
Management
• Epinephrine
– Give it in the thigh
– Give it IM (NOT SQ!)
– Peak absorption ~8 +/- 2 minutes
Management
• Epinephrine
– Available in two dilutions:
• 1:10 000 (0.1 mg/mL or 100 mcg per mL)
– 1:10 000 is the crash cart epi and used for IV
administration
• 1:1000 (1 mg/mL)
– 1:1000 is used for IM
Management
• Epinephrine
– Adult dosing
• 0.3-0.5 mL (0.3-0.5 mg) of 1:1000 IM in the
vastus lateralis (thigh) q 5 min prn
– Pediatric dosing
• 0.01 mg/kg of 1:1000 IM in the vastus lateralis
q 5 min prn
Management
• Peds Weight Memory Aid
– Age
– 1
– 3
– 5
– 7
– 9
Wt
10 kg
15 kg
20 kg (threshold for adult epi dosing)
25 kg
30 kg
Cases
• A 1 year old with a probable
anaphylactic reaction; How much epi do
you want to give?
– 1 year old ~ 10 kg
– 10 kg x 0.01 mg/kg = 0.1 mg (100 mcg)
– 0.1 mg of 1:1000 = 0.1 cc
Cases
• 3 year old child with a probable
anaphylactic reaction; how much epi do
you want to give?
– 3 yo ~ 15kg
– 15 kg x 0.01 mg/kg = 0.15 mg
– 0.15 mg of 1:1000 = 0.15 cc
Cases
• 5 yo with a probable anaphylactic
reaction; how much epi do you want to
give?
– 5 yo ~ 20 kg
– 20 kg x 0.01 mg/kg = 0.2 mg
– 0.2 mg of 1:1000 = 0.2 cc
Cases
• A 7 year old child with a probable
anaphylactic reaction; how much epi do
you want to give?
– 7 yo ~ 25 kg
– 25 kg x 0.01 mg/kg = 0.25 mg
– 0.25 mg of 1:1000 = 0.25 cc
Cases
• A 9 yo with a probable anaphylactic
reaction; how much epi do you want to
give?
– 9 yo ~ 30 kg
– Give adult dosing (0.3-0.5 mg)
Case (cont)
• Your patient’s responded initially to your IM
epinephrine
• 20 minutes later you are called back to the bedside
because the patient is feeling lightheaded,
nauseated, and is having more difficulty breathing
– O/E BP 90/50, HR 110, SaO2 89%, diffuse wheezing bilat
– You give another IM dose of epi, the patient’s BP and resp
symptoms resolve transiently but then starts to deteriorate
again
• What do you want to do now?
Management
• Epinephrine Drips
– IV (adults)
• Can give 1/2 cc of the 1:10 000 (crash cart
epi) if patient is crashing before your eyes
• This means you are giving 50 mcg with each
1/2 cc
• For a drip you want 10 mcg per minute and
titrate up as you need
• Good video on EM:RAP showing how to mix a
drip
Management
• Epinephrine
– Pediatrics
Drugs in Anaphylaxis
• Additional
Considerations
Management
• Antihistamines
– Diphenhydramine
(Benadryl)  H1
– Ranitidine (Zantac)
 H2
– Inverse Competitive
Antagonists
Management
• Antihistamines
– Always given
– Recent Cochrane review
failed to demonstrate
evidence for or against
the use of H1
antihistamines
» Allergy 2007;
62:830-837
– Possible benefit from
using a combination of
H1 & 2 antihistamines
» Ann Emerg Med
2000; 36:482-8
Management
•
Antihistamines
– Bottom line:
1. Should not replace epinephrine in the management of
anaphylaxis
2. May alleviate dermatologic symptoms
3. May play a role in secondary prevention before
exposure
Steroids
• Are we going to pump this patient up
like Arnie?
Management
• Steroids
– Onset 4-6 hours after
administration
– Theoretically prevents
biphasic reaction; standard
in guidelines
– IV methylprednisone
125mg; then PO prednisone
for one week (practice
varies)
Case
• HPI:
– 50 yo M with prev
anaphylactic rxn to shellfish
– Presents now with rapidly
progressive mucosal edema
and swelling, SOB,
tachycardic, hypotensive
• PMHx:
– IHD, DMII, HTN
• He is on an epi infusion and
not getting better, what is
happening? What else can
we do?
Patients on Beta-Blockers
• Patients on BB with
anaphylaxis may be
refractory to
treatment
• Both epinephrine
and glucagon
activate cAMP but
through different
receptors
Patients on Beta-Blockers
• Glucagon
– Dosing 1-5 mg (20-30 mcg/kg in peds) IV
over 5 minutes; then infusion of 5-15
mcg/min titrated to response
– Side Effect: Vomiting! Give ondansetron
prophylactically
• Does it work?
– Two case reports; both report success
» EMJ 2005; 22: 272-276
Summary of Tx
1.
2.
3.
4.
Epinephrine 0.5 mg IM lat thigh
Diphenhydramine (Benadryl) 50 mg IV
Ranitidine 50 mg IV
Methylprednisone 125 mg IV x 1; then,
Prednisone 50 mg PO
5. Consider: Glucagon in patient on BB
6. Consider Ventolin if asthmatic or if
patient continues to struggle
Disposition
Disposition
• Things to consider
–
–
–
–
–
–
Biphasic Reactions
Epi-pen prescription
Medic alert bracelet
Referral to allergist
When to return to ED
When to call 911
Biphasic Anaphylaxis
• Occur 1-20% of
patients
• No way to predict
who will get it
• Tend to have same
organ systems
involved as with first
reaction
Biphasic Anaphylaxis
• Study*
– Prospective analysis done to look at biphasic reactions; N =
134
• Results & Conclusions
– 20% had biphasic reactions
• 35% milder; 40% life threatening; 20% required more aggressive measures
– Range of biphasic onset between 2-38 hours; mean 10 hours
– Found an association between time to resolution of first episode
and chance of recurrence
– Some association with less epi and steroid treatment
» Ann Allergy Asthma Immunol 2007; 98:64-69.
Biphasic Anaphylaxis
Macleod Approach
• Decisions based on judgment not science
– Observation Period
•
•
•
•
Observe those with serious initial symptoms in ED
Extra caution with asthmatic patients
Advise not to leave city for 24 hours
Reliable companion is desirable
– Discharge Medications
• Epi pen
• Corticosteroids - 24 hour coverage is standard
– No clinical trials to support
– Many case reports where it didn’t help
– Theoretical advantage
Disposition
• Bottom Line:
– Risk of recurrence of anaphylaxis is
unpredictable (but atopic type/asthmatic
patients are at a higher risk)
– Severity of initial reaction is NOT a good
predictor of future reactions
Case
• 5 yo child
• HPI:
– Experiences generalized
urticaria after a
hymenoptera sting. Has no
other symptoms.
• PMHx:
– Asthma
• Does this patient need an
epi-pen prescription when he
goes home? If yes which
one (Jr or adult?)
Disposition
• Recent systematic review found no
universally accepted anaphylaxis
management plan
» J Allergy Clin Immunol 2008; 22:353-361
• All patients who experience
cardiovascular or respiratory symptoms
should receive an epi-pen
» J Allergy Clin Immunol 2005 (Practice
Guidelines)
Disposition
• Epi-Pen
– No clear cut guidelines on when to
prescribe
– Not indicated for local insect sting
reactions
– Risk of anaphylaxis in children presenting
with generalized cutaneous symptoms
have 10% risk of future anaphylaxis
– Children with asthma are at higher risk of
adverse outcomes
Disposition
• Epi-Pen
– Adult Dose
• 0.3 mg
– Pediatric
• 0.15 mg
• If < 20 kg prescribe
epi-pen jr
• If > 20 kg prescribe
adult epi-pen
Disposition
• Epi-Pen
– You decide to give the patient a prescription for an epi-pen
because of his hx of asthma. Mom asks: Doctor, when
should my child use the epi-pen?
– Two extremes:
• Inject after any possible exposure even in the absence of
symptoms
• Wait until patient experiences progressive respiratory and/or
cardiovascular symptoms
• Truth is somewhere in between: consider comorbid illness,
specific allergy (peanut, shellfish, insects tend to cause the
most severe reactions)
» J Allergy Clin Immunol 2005; 115: 575-583
Epi-Pen
• Bottom line
– Clinical judgment call
when to prescribe
epi-pens
» J Allergy Clin
Immunol
March 2005
Disposition
• Other
considerations
– Medic alert bracelet
– F/u with allergist
– Advise on biphasic
rxn
– When to call 911
– Refer pt to
community education
www.foodallergy.org
Additional Notes and
Considerations
Case
• 40 yo F presents with mild oral itching
and swelling of the lips and mouth after
eating an apple
• PMHx: Healthy, seasonal hay fever, no
previous food or drug reactions
• What is the diagnosis?
Pollen-Food Syndrome
• Triggered in patients with a pollen
allergy who eat raw fruit or vegetables
• Local IgE mediated response
• Symptoms rarely involve other organs
• ~2% of patients with this syndrome
develop anaphylaxis
• Epi-pen prescription is optional
» J Allergy Clin Immunol 2005; 115: 575-83
Anaphylaxis and Asthma
• Concomitant asthma increases the risk
for adverse outcome in anaphylaxis
• 50% risk of possible peanut allergy with
asthmatics
» J Allergy Clin Immunol 2005; 115: 575-583
Exercise Induced
Anaphylaxis
• Epidemiology
– Only one reported death in the literature*
– Most are unaware of their condition
• Clinical Features
– Varies from mild urticaria to anaphylaxis
– May present as syncope during exercise
– Resp symptoms (59%), GI (30%), Headache, dermatologic
symptoms
» Am Fam Phys 2001; 64:1367-72
Exercise Induced
Anaphylaxis
• Treatment
– Recognition is key
– As per any anaphylactic
presentation
• Prevention
– Activity modification
– Prophylactic antihistamines
may blunt skin symptoms
making diagnosis more
difficult
Immunotherapy for
Hymenoptera
• What insects are
included in the
taxonomic order
Hymenoptera?
–
–
–
–
–
Ants
Bees
Hornets
Wasps
Yellow Jackets
Immunotherapy for
Hymenoptera reactions
• Venom immunotherapy may
reduce the risk of systemic
reaction after a subsequent
sting from 32% in untreated
patients to less than 5 %
» NEJM 2004;
351:1978-84
• Protection may last for > 20
years
Immunotherapy
• Who should be referred:
– Pts who experience anaphylaxis
– Controversial: Adults with exclusively
dermal reactions (urticaria and
angioedema)
• Who doesn’t need to be referred:
– Local reactions; even if they are large
– Children under 16 with exclusively dermal
reactions (urticaria and angioedema)*
Anaphylactoid Reactions
• Pathophysiology
– Direct degranulation of mast cells
– May occur with first time exposure
• Clinical features
– Dose dependent reactions
– Can be clinically indistinguishable from
anaphylaxis
Anaphylactoid Reactions
• Common etiologies
– NAC
– Radiologic contrast material
– Some antibiotics (Vancomycin; so called
“red man syndrome”)
Anaphylactoid Reactions
• Management
– Treat severe symptoms same as
anaphylaxis
– Stop offending agent for a period of time
then restart by infusing at a slower rate
– Prophylactic antihistamines
Drug Reactions
1. Drug Hypersensitivity Reactions
2. Penicillin Allergies
3. Sulfur Medication Allergies
Drug Hypersensitivity
Reactions
Drug Hypersensitivity
Reactions
•
•
•
•
•
•
•
•
Anaphylaxis
Angioedema
Urticaria
Serum Sickness
SJS
TEN
Drug Hypersensitivity Syndrome
…These are not all encompassing
Drug Reactions
•
How drugs stimulate the immune system
1.
2.
Drugs (or their metabolites) can bind to native proteins and
change their shape so that they become immuogenic and induce
cell-mediated or humoral immune responses
Drugs can directly stimulate the immune system by binding to Tcells that have receptors able to recognize the drug
Case
•
•
•
•
14 mo old M
Started on amoxil 6 days
previous for sinusitis
Presented yesterday with an
“urticarial like rash” - Amoxil
d/ced and benadryl prescribed
What is this rash?
Serum Sickness
• Typically develops 1-2 weeks after exposure to the
offending agent
• Clinical Features
– Fever, rash, polyarthralgias (child refusing to walk),
lymphadenopathy, proteinuria, edema, abdominal pain
– Typically non toxic appearance
• Pathophysiology
– Type III, occurs with a number of Abx and drugs
• Differential diagnosis:
– EM, Kawasaki’s, disseminated gonococcal/meningococcal
infections
Ann Emerg Med
2007; 50:350
Case
• 8 year old boy
• Clinical symptoms
– Pruritic, T38.0
• Diagnosis?
– Morbilliform drug rxn to
ampicillin
– Increased likelihood to react
like this with concurrent viral
illness
• Mgmt?
– Stop offending agent
– Benadryl/steroids
Case
• Diagnosis?
• TEN
Drug Reactions
• TEN
– Widespread erythematous or purpuric
macules & targetoid lesions
– Full thickness epidermal necrosis with
involvement of more than 30% of BSA
– Common to have mucous membrane
involvement
– Drugs involve > 65% of the time; PCN &
sulfonamide most common
Drug Reactions
• Stevens-Johnson Syndrome
– Widespread purpuric macules and
targetoid lesions
– Rate of epidermal detachment is less than
10%, mucosal involvement is common
(>90%)
– Mortality rate less than that for TEN (~5%)
Drug Reactions
• Erythema Multiforme
– Targetoid lesions
– May have oral mucosal involvement
– Low morbidity and no mortality
Drug Reactions
• Pathophysiology of TEN, SJS, EM
– Thought to be a combination of patient factors (genetic
defects) that allows accumulation of toxic metabolites and
the ability of drugs to alter proteins and stimulate an
immunologic response (Type II and or III reactions)
– Cytotoxic T lymphocytes may also invade the epidermis and
cause local tissue destructions (Type IV reactions)
– Steroids & IVIG have been used as treatment because of
this hypothesized immunopathophysiology (controversial)
Antibiotic Allergies
Antibiotic Allergies
• Case
– 47 yo F with a cellulitis. You are
considering starting her on cefazolin
(ancef)
– PMhx: Allergy to penicillin
• Reaction: makes my stomach upset
– Is cefazolin safe in this situation?
– What about cloxacillin?
Antibiotic Allergies
• Confusing topic; these are the issues:
– Some literature, pretty much all retrospective
– Guidelines don’t always reflect clinical practice
– How good is the patient’s history?
• What % of patients who report allergy have a true allergy?
• What % of patients who report allergy but describe a benign
history could potentially suffer an anaphylactic reaction?
– How often does a patient with a true PCN allergy have a true
allergy to cephalosporins? Does it matter what generation of
cephalosporin?
Antibiotic Allergies
• The Guidelines
Antibiotic Allergies
• Guidelines from the
diagnosis and
management of
anaphylaxis: An
updated practice
parameter
– J Allergy Clin
Immunol March 2005
Antibiotic Allergies
• Guidelines from the
diagnosis and
management of
anaphylaxis: An
updated practice
parameter
– J Allergy Clin
Immunol March 2005
Antibiotic Allergies
• AAP endorse the
use of
cephalosporin
antibiotics for
patients with PCN
allergies
• Pichinchero
reviewed evidence
on the topic in 2005
Antibiotic Allergies
• The Facts
Antibiotic Allergies
• “Only 15% of patients with a history of
allergy to penicillin have positive skin
tests and, of those, 98% will tolerate a
cephalosporin. However, those patients
who react (less than 1%) may have fatal
anaphylaxis”.
• Ann allergy Asthma Immunol 1999; 83:655-700
Antibiotic Allergies
• True penicillin allergy occurs 1/50001/10000 courses administered
» NEJM 2006; 354:601-609
» J Allergy Clin Immunol March 2005
Antibiotic Allergies
• The most common allergic type
reactions to antibiotics are
maculopapular skin eruptions, urticaria,
and pruritus and are typically delayed*
• Not all of these reactions are IgE
mediated
Antibiotic Allergies
• Common quote of ~10% cross-reactivity
of cephalosporins in patients with PCN
allergy is an over estimate because
historically 1st generation
cephalosporins used to contain small
amt of PCN
» NEJM 2006; 354(6): 601-609
Antibiotic Allergies
• Another review found that allergic
reactions to cephalosporins occurred in
4.4% of patients with positive skin tests
to PCN vs 0.6% of patients with
negative skin tests
• These authors did not discuss
sulfonamide allergies in these patients
» NEJM 2001; 345:804-809
Antibiotic Allergies
• Study
– Retrospective cohort analysis; databank of > 500,000 pts receiving
cephalosporins after PCN in the UK
– Only 25 patients in their study had anaphylaxis, 1/25 had a second
anaphylactic rxn with a cephalosporin
• Conclusions
– Allergic events with cephalosporins are increased with hx of rxn to
penicillin but to a similar degree as those who have had rxns to
SMX therefore unlikely that rxns are a class effect and it is safe to
use cephalosporins in pts with reported allergy to pcn
» Am J Med 2006; 119: 354e11-354e20
Study Protocol
Antibiotic Allergies
• The Problems
Antibiotic Allergies
• How do I know if a patient’s reaction is
immune mediated?
Antibiotic Allergies
•
Three classes of reactions
1.
2.
3.
Immediate
Accelerated
Delayed
•
•
•
•
•
May take >72 hours to occur
TEN
Interstitial nephritis
Serum sickness
Maculopapular rashes (most
common)
Antibiotic Allergies
NJEM 2006; 354(6): 601-609
Antibiotic Allergies
• How good is a patient’s self reported
history at identifying a true allergy?
• Can I rely on a benign history as being
truly benign?
Antibiotic Allergies
• Patient history
– One study done on this topic
• Solensky et al lit review to determine how many patients with a
vague history of allergy had positive skin test reactions to
penicillin
• Vague history defined as “rash, GI symptoms, or unknown
reaction”
• Rational: many physicians proceed less cautiously if a patient
provides a vague history of a penicillin reaction, is this
appropriate?
» Ann Allergy Asthma Immunol 2000; 85:195-199
Antibiotic Allergies
• Patient history (cont)
– Results:
• 33% of patients with a positive skin test reported a vague history of a
penicillin reaction
– Conclusion:
• A large proportion of patients who have IgE antibodies on skin testing
have vague PCN allergy histories
• Patients with vague histories should be treated the same as patients
with more convincing histories
» Ann Allergy Asthma Immunol 2000; 85:195-199
Antibiotic Allergies
• Additional Considerations
Antibiotic Allergies
• Special Cases
– HIV
• Higher frequency of allergic reactions to many Abx
• Frequency is declining with HAART
– CF
• 30% of pts with CF develop allergies to 1 or more Abx
– Infectious Mononucleosis
• Likelihood of cutaneous reaction to penicillins is increased in
patients with mono
• Viral infection alters the immune status of the host
• Abx ok once infection has resolved
Antibiotic Allergies
• An Approach
Antibiotic Allergies
• An approach:
– Take the history
–
–
–
–
–
–
What rxn? Can the reaction be attributed to the abx?
How quickly did the reaction occur?
How long ago? First exposure?
Severity?
Was the reaction a known side effect of the drug?
Look in the chart (preop abx may not be known by the patient)
– Patients with reactions that occurred a long time ago are
less likely to still be allergic
» Immunol Allergy Clin N Am 2004; 24:45-461
» NEJM 2006; 354: 601-609
Antibiotic Allergies
• An approach (cont):
– Does it sound like a true IgE mediated reaction that happened
recently? Hx of atopy and/or asthma?
• Yes: Avoid 1st generation cephalosporins, watch the patient regardless
of the drug class
– Does it sound like a non-IgE mediated reaction non immune side
effect? No comorbidities?
• Yes: Safe to give cephalosporin, watch the patient if in doubt
Antibiotic Allergies
• Bottom line:
– Although biologically plausible there is no good evidence to
support cross reactivity between PCN’s and cephalosporins
based on class effect alone
– Patients with a true anaphylactic history to penicillin are at
risk of reacting to other abx, not just cephalosporins
– Patients with asthma generally have poorer outcomes (be
more cautious with these patients)
– As Emerg docs we have the advantage of being able to treat
adverse reactions quickly
Antibiotic Allergies
• Bottom line (cont)
– Be reassured that true allergies occur
infrequently
– Be cautious that when a reaction does
occur it has the potential to be fatal
Antibiotic Allergies
Antibiotic Allergies
Sulfur Medication Allergies
“Sulfa” Allergies
• Mrs K is a 55 yo who
presents with new symptoms
consistent with CHF
• PMhx:
–
–
–
–
DM II
HTN
Smoker
Sulfa allergy
• Do you give her lasix?
• What drugs contain sulfa?
Sulfur Medication Allergies
• 8% of patients
treated with SMX
have an adverse
reaction
• 3% rxn represent
hypersensitivity
• Largest % abx
induced cases of
TEN and SJS
Sulfur Medication Allergies
• Actually consists of
three different
classes
– Sulfonylarylamines
(abx)
– Non-arylamine
sulfonamides
(thiazides, loop
diuretics)
– Sulfones (Dapsone)
Sulfur Medication Allergies
• Sulfonamide antibiotics (ie Septra) differ from other
sulfonamide containing medications (have an extra
amine group)
• Despite drug label warnings it would be safe to give
lasix in a patient with a septra allergy (patients with
rxns to both drugs tend to have a general sensitivity
unrelated to the drug itself)
– NEJM 2006; 354: 601-609
Sulfur Medication Allergies
• Loop diuretics
– Ethacrynic Acid is the only loop diuretic that doesn’t contain
sulfur
– Loop diuretics that contain sulfur can cause allergic rxns but
much less frequently than SMX
– Many anecdotal reports of furosemide safety in patients with
known SMX sensitivity
– Rxns to other non-antimicrobial sulfur containing medication
warrants graded dose challenges or alternative drug choice
(e.g. ethacrynic acid)
Sulfur Medication Allergies
• Commonly
prescribed non
antibiotic sulfur
containing
medications in
Canada
Case
• HPI
– 44 yo M presents with a
6 hour hx of a sore throat
– Awoke feeling like there
was something stuck in
his throat
• Exam
– Afebrile, no drooling
– Muffled voice, occasional
gagging
– No lymphadenopathy
• Thoughts?
Angioedema
• Pathology
– 1 IgE mediated
– Other mech:
•
•
•
•
•
Complement mediated (hereditary, serum sickness)
Bradykinin (ACEI)
Direct mast cell stimulation (opioids, abx)
AA metabolism (NSAIDS, ASA)
C1 inhibitor deficiency (Hereditary)
• Clinical Features
– Pruritis absent
– Can be acute (<6 weeks) or chronic (> 6 weeks)
Angioedema
• Management
–
–
–
–
–
–
Assess airway (voice change, stridor, drooling, dyspnea)
ACEI increases likelihood of needing airway intervention
Steroids & Antihistamines
Epinephrine if concerning clinical picture
FFP (controversial - may worsen laryngeal edema)
ENT surgery may be indicated
Summary
• The dose of epi in adults is 0.3-0.5 cc of
1:1000
• The dose of epi in peds is 0.01 mg/kg
which is the same as 0.01 cc/kg of
1:1000
• Give it IM in the thigh
• Use 1/2 a cc at a time of crash cart epi if
patient crashing in front of you
Further Reading
•
•
•
•
Sampson HA, et al. Second Symposium on the Definition and management of anaphylaxis: summary report
- second national institute of allergy and infectious disease/food allergy and anaphylaxis network
symposium. Ann Emerg Med 2006; 47:373-380.
Lieberman P, et al. The diagnosis and management of anaphylaxis: an updated practice parameter. J
Allergy Clin Immunol. 2005; 115:571-574.
Sicherer SH, et al. Quantries in prescribing an emergency action plan and self injectable epinephrine for
first-aid management of anaphylaxis in the community. J Allergy Clin Immunol 2005; 115: 575-583.
McKenna JK, Leiferman KM. Dermatologic drug reactions. Immunol Allergy Clin N Am 2004; 24:399-423.