Clinical Challenges in
Recognizing, Diagnosing and
Treating Anaphylaxis
David Elkayam, MD
Bellingham Asthma, Allergy & Immunology
Bellingham, Washington
SNOW Conference, 10 March 2007
Goals
• Recognize the newer definition of
anaphyalxis.
• Recognize the difference / similarity
between anaphylaxis and anaphylactoid
reactions.
• Recognize biphasic anaphylaxis.
• Optimize treatment:
• Initiate tx early
• IM v. SC Epi
Case Presentation
• CK is a 10 yo male who presents to the school
nurse’s office.
• Onset of sx: ~5-10 mins ago during recess after
lunch.
• Sx: oropharyngeal and palmar itching 
progresses to generalized itching, visible hives
and a sensation of mild throat swelling, w/o
wheezing, coughing, or obvious respiratory
distress.
• Pt has Medic Alert Bracelet that identifies him as
peanut allergic.
Case Presentation
• CK : is he in trouble?
• What else do you need to know?
– VS, PE, PHx: severity of prior rxn? does he have
asthma?
• What do you do?
–
–
–
–
Administer Benadryl?
Administer Epi?
How much?
Call 911?
• What are the consequences of intervention v.
monitoring?
Anaphylaxis: Defined
•
Anaphylaxis is a potentially life-threatening
allergic or allergic-like (anaphylactoid) reaction
resulting from exposure to a substance to
which an individual has become sensitized
•
Most typically, an immediate systemic reaction
caused by rapid, IgE-mediated immune
release of potent mediators from mast cells
and peripheral blood basophils
Lieberman PL. Anaphylaxis. MedGenMed 1(1), 1999 [formerly published in Medscape Pulmonary Medicine eJournal
1(4), 1997]. Available at: http://www.medscape.com/viewarticle/408706. Accessed July 8, 2005.
Anaphylactoid Reaction
• Anaphylactoid rxn: non-IgE, otherwise the
same pathophysiology/ potential severity.
– ASA
– Radiocontrast Dye
– Some drug reactions
Causes of Anaphylaxis
www.emnet-usa.org
Anaphylaxis – Operational
Definition

Two or more organ systems
– skin (e.g., hives)
– respiratory (e.g., swelling of the lips, tongue, or
throat; trouble breathing or shortness of breath;
stridor, wheezing)
– cardiovascular (e.g., hypotension, dizziness or
fainting, altered mental status)
– gastrointestinal (e.g., trouble swallowing, abdominal
pain)
– …or…
Hypotension (SBP <100 mmHg)
www.emnet-usa.org
Incidence of Anaphylaxis
No. of discharges with diagnosis of anaphylaxis/
100,000 discharges
Increase between 1991 and 1995
Cause of anaphylaxis
12
Other
Insect venom
Food
Therapeutic drugs
Unspecified
10
N=876
N=671
8
6
N=415
N=462
1991-2
1992-3
4
2
0
1993-4
Year
Sheikh and Alves, BMJ, 2000
1994-5
Incidence of Anaphylaxis
Continues to Increase: 1995-1999
Food
Unspecified
Serum
Medicinal Substance
Overall
1400
1202
1200
1096
# Patients
1000
840
800
600
400
200
229
158
113
1
558
513
501
312 366
153
406
390
183
235
9
10
3
1996-7
1997-8
1998-9
0
1995-6
Wilson, comment on Sheikh and Alves, BMJ, 2000
Anaphylactic Reaction
Allergen
IgE antibody
Mast cell granules
Mast Cell
Immediate reaction
Wheeze
Urticaria
Hypotension
Abdominal cramping
Late-phase reaction
Phil Lieberman: Anaphylaxis,a clinicians manual
Most Frequent Signs and
Symptoms of Anaphylaxis
Manifestation
Urticaria/angioedema
Upper airway edema
Dyspnea/wheeze
Flush
Hypotension
Gastrointestinal
Tang AW. Am Fam Physician 2003
Percent
88
56
47
46
33
30
Clinical Course of Anaphylaxis
Patterns of Anaphylaxis
•
Uniphasic
–
•
Biphasic
–
•
Symptoms resolve within hours of treatment
Symptoms resolve after treatment but return
between 1 and 72 hours later (usually 1-3 hours)
Protracted
–
Lieberman, 2004
Symptoms do not resolve with treatment and may
last >24 hours
Uniphasic Anaphylaxis
Treatment
Initial
Symptoms
0
Antigen Exposure
Time
Biphasic Anaphylaxis
Treatment
Initial
Symptoms
Treatment
1-8 hours
0
Antigen
Exposure
SecondPhase
Symptoms
Classic Model
1-72 hours
New Evidence
Time
Protracted Anaphylaxis
Initial
Symptoms
0
Antigen
Exposure
Time
Possibly >24 hours
Fatal Anaphylactic Reactions Are
Often Associated With:
•
•
•
•
Delay between time of symptom onset
and administration of treatment
Adverse therapeutic event
History of asthma
However, most fatal reactions are
unpredictable
–
Appropriate management after recovery from a
severe reaction may be protective against a fatal
recurrence
Pumphrey, Curr Opin Allergy Clin Immunol 2004; Sampson et al, N Engl J Med, 1992; Pumphrey, Clin Exp Allergy, 2000
Subsequent Reactions May
Increase in Severity with Time
1st Reaction
60
2nd Reaction
3rd Reaction
% of reactions
50
40
30
20
10
0
Peanut allergen
Tree nut allergen
Proportion of reactions rated severe
Simons et al, J Allergy Clin Immunol, 2004
Anaphylaxis :
Acute Management
Overview of the most important
aspects of in-office and in-the-field
treatments
Treatment
•
Epinephrine is the drug of choice for all
anaphylactic episodes
•
Flexibility in dosing needed to treat effectively
–
–
•
Some patients require more than a single injection
Different doses for pediatrics and adults
Early and aggressive use to maintain airway,
blood pressure, and cardiac output
Medical Clinic Treatment
• Epinephrine
– Up to 35% of patents may need a second dose
•
•
•
•
Antihistamines
Corticosteroids
Oxygen
Impair further absorption
– Local epinephrine, tourniquet
• Supine, elevate legs
• ER, ICU monitor/support (fluids, pressors, etc.)
Lieberman PL. Anaphylaxis. MedGenMed 1(1), 1999 [formerly published in Medscape Pulmonary Medicine eJournal 1(4), 1997].
Available at: http://www.medscape.com/viewarticle/408706. Accessed July 8, 2005.
Epinephrine
• The most important single medication in the
treatment of acute systemic allergic /
anaphylactic events.
• No strict contraindications
– (including metabisulfite sensitivity).
• Reverses airway edema and spasm, slows/stops
the release of potent vasoactive mediators
– (e.g., histamine, etc.),
• Potent inotropic and chronotropic cardiac effects
– (ie., supports / restores perfusion and BP).
• Frequently underutilized.
Epinephrine Dosing
•
Intramuscular injection in lateral thigh
produces most rapid rise in blood level
–
•
0.01mg/kg in children, 0.3-0.5mg in adults
Data suggest that as many as 30-35% of
patients require more than a single
epinephrine injection
Korenblat and Day, Allergy Asthma Proc, 1999; Webb et al, J Allergy Clin Immunol, 2004
Epinephrine Injection:
Route and Site Do Matter
Injection route
Injection site
C-max: mean ± SEM (pg/mL)
EpiPen IM
Epinephrine IM
Thigh
Thigh
Epinephrine IM
Epinephrine SQ
Arm
Arm
1,821 ± 426
2,877 ± 567
Saline IM
Saline SQ
Arm
Arm
1,458† ± 444
1,495† ± 524
*P < .01 from all arm values. †Endogenous epinephrine
Simons, et al. JACI 2001;108:871-873.
12,222* ± 3,829
9,722* ± 4,801
Epinephrine Injection: IM vs. SQ
Simons et al.: Prospective, randomized, blinded study in children
T-max was 8 ± 2 minutes after injection of epinephrine 0.3 mg from an
EpiPen IM in the vastus lateralis vs. 34 ± 14 minutes (range, 5 to 120) after
injection of epinephrine 0.01 mg/kg SQ in the deltoid region.
Acute Management:
Epinephrine Autoinjector
Overview of Available Auto-Injectors
Twinject™
Available Doses
0.3 mg (single and 2 Pack) &
0.15 mg (single and 2 Pack)
EpiPen
0.3 mg (single and 2-Pak) &
0.15 mg (single and 2-Pak)
Doses Per Injector 2 inseparable doses in one
injector
1 dose per injector
Second Dose
Administration
Requires availability of second
auto-injector
Available
Manual injector included inside
the barrel of Twinject™
Overview of Available Auto-Injectors
Twinject™
EpiPen
Packaging
Permanently attached wrap
label patient instructions
Crush-resistant container with
clip
Updated instructions attached
to auto-injector
New plastic sleeve case with
S clip
Needle Size
Thin 25 gauge
½ inch exposed needle length
22 gauge
½ inch exposed needle length
Noise Level
Quiet operation reduces risk of
removal from injection site
Slightly louder firing
mechanism
Cost / Formulary
Position
AWP Single $68.04
AWP Two-Pack $114.60
Expected 2nd or 3rd Tier
AWP Single $54.38
AWP 2 Pack $104.16
2nd Tier
Epinephrine content vs. Time past expiration
Case Presentation: CK
• Peanut Allergy
– Dangerous: most common cause of food
allergy related deaths in US.
– Added risk factors:
• severity of prior event
• level of anti peanut sIgE
• Presence of asthma
– In this setting, treat early, aggressively
(injected Epi + other tx’s)
Inadequate Management Post ER for
Food Anaphylaxis
45
40
40
35
30
25
% of Patients
20
16
12
15
10
5
0
Instructed to Avoid
Allergen
Clark et al, J Allergy Clin Immunol, 2004
Dispensed Epinephrine
Referred to Allergist
Anaphylaxis Conclusions
• Anaphylaxis is a life-threatening acute reaction which is
under-reported, frequently misdiagnosed and undertreated
– More common than previously thought; increasing incidence and
prevalence
• Rapid and proper administration of epinephrine is the
standard of treatment
– Many patients require a second epinephrine injection to treat
anaphylaxis
• Patients education needed – delays in treatment,
improper administration and outdated epinephrine
– Written Action Plan
– Medical Alert Bracelet
Anaphylaxis: Conclusions & Questions
• Prior to this presentation, how aware were
you
– Of the new practice parameters?
– Difference/similarity b/w anaphylaxis and
anaphylactoid reactions.
– Uniphasic, protracted & biphasic anaphylaxis?
– Underutilization of epinephrine in fatal
attacks?
– 35% of patients may need a second dose?
Thank You !
• Questions?
• Please feel free to write me at:
• David Elkayam, MD
• ddelkayam@hinet.org