Anaphylaxis

Sahala Panggabean

Department of Internal Medicine

Christian University of Indonesia
Okt , 2017
 Definition

 Ana = “away from”

 Phylaxis = “protection”
A term to indicate a lessened
resistance to a toxin which results
from a previous inoculation of the
same material.
 Definitions

 Anaphylaxis: a severe systemic allergic

reaction involving 2 or more systems
* hives/angioedema NOT universally present!
 Anaphylactic Shock: above, plus
hypotension and other signs of shock
 Allergic reactions: localized reaction,
involving a single system; e.g. urticaria,
angioedema, contact dermatitis,
rhinoconjunctivitis
 Definition
 Anaphylaxis is a serious reaction that is rapid
in onset and may cause death1
– Anaphylaxis is a systemic reaction resulting from the sudden
release of multiple mediators (not just histamine) from mast cells
and basophils
– Anaphylaxis is defined by a wide spectrum of symptoms
and their severity
– Although “shock” may occur during anaphylaxis, it most often
occurs in the absence of shock, hypoxia, or collapse
– Quick recognition of anaphylaxis is critical for successful
treatment

NIAID, National Institute of Allergy and Infectious Diseases; FAAN, Food and Allergy Anaphylaxis Network.
Sampson HA, et al. J Allergy Clin Immunol. 2006;117:391-397
 Prevalensi

 The prevalence of anaphylaxis in the general population is at

least 1.6% and likely higher
 Anaphylaxis diagnosis is frequently missed or anaphylaxis is
incorrectly diagnosed
 Recent national survey data:
– Anaphylaxis occurs in at least 1 in 50 up to 1 in 20 adults
– Demonstrates many patients are not adequately equipped to deal with
future episodes
– There is a need for public health initiatives to improve anaphylaxis
recognition and treatment

Wood RA, et al. J Allergy Clin Immunol. 2014;133:461-467.

Lieberman P, et al. Ann Allergy Asthma Immunol. 2006;97(5):596-602.
Simons FER, et al. J Allergy Clin Immunol. 2008;122:1166-1168.
Etiology
 Patient Reported Causes of Anaphylaxis
US National Survey Data: Patient Reported Reaction Trigger (%)
34% 35%
35% 31% 32% Reported Anaphylaxis* (n=344)
30%
Confirmed Anaphylaxis** (n=261)
25%
20% 19%
20%
15% 11% 11%
10% 8%
6%
5% 3% 3%
1% 2%
0%

*Reported reactions were categorized as those involving ≥1 system.

**Confirmed reactions were categorized as those involving ≥2 systems with respiratory and/or
cardiovascular symptoms or those leading to loss of consciousness, even if only that single system
was involved.
Wood RA, et al. JACI. 2014;133:461-7
 Risk Factors
 Patient Factors That Increase Risk of an Event or
Potentiate Its Severity
- History of previous anaphylactic reaction
- Atopy
- Asthma
- Age
» Adolescents and young adults: risk-taking behaviors
» Elderly: comorbidities and medications
- Cardiovascular disease
- Medications (β-blockers, ACE inhibitors, ARBs, tricyclics, MAO inh.)
- Mast cell activating disorders
 Classification
Human Anaphylaxis

Immunologic Non-Immunologic

Idiopathic
IgE, FcRI Non-IgE, Non-FcRI Other Physical
Foods, venoms, Dextran, OSCS, Radiocontrast Exercise,
latex, drugs contaminants media, aspirin, opioids, cold
in heparin, transfusion NSAIDs
reactions

IgE, immunoglobulin E;
FcɛRI, high-affinity IgE receptor;
ANAPHYLACTOID
OSCS, oversulfated chondroitin sulfate;
NSAIDs, nonsteroidal anti-inflammatory drug. 9
Simons FER, et al. J Allergy Clin Immunol. 2010;125:S161-S181.
 Classification

Gell and Coombs classification of

hypersensitivity
Type I Immediate hypersensitivity
Type II Cytotoxic reactions
Type III Immune complex reactions
Type IV Delayed hypersensitivity

Anaphylaxis can occur through Types I, II and III

immunopathologic mechanisms
 Patofisiology 1

 Interaction of antigen with IgE on basophils

and mast cells
 Triggers release of histamine, leukotrienes,
and other mediators that cause:
– diffuse smooth muscle contraction
(bronchoconstriction, vomiting, diarrhea) and
– vasodilation with plasma leakage.
 Patofisiology 2

Anaphylactic vs Anaphylactoid

• Anaphylactic - an immediate systemic reaction caused by rapid, IgE-

mediated immune release of potent mediators from tissue mast cells
and peripheral blood basophils

• Anaphylactoid - immediate systemic reactions that mimic anaphylaxis

but are caused by nonimmune-mediated release of mediators or
complement activation
 Patofisiology 3

Anaphylactoid reactions:
• These reactions are clinically indistinguishable from anaphylaxis but
do not involve IgE and do not require prior sensitization.
• They occur via direct stimulation of mast cells or via immune
complexes that activate complement.
• The most common triggers are iodinated radiographic radiopaque dye,
aspirin, other NSAIDs, opioids, blood transfusions, Ig, and exercise
 Signs and Symptoms 1
 Skin:
flushing, itching, urticaria,
angioedema
 Gastrointestinal:
nausea, vomiting, bloating,
cramping, diarrhea

 Respiratory:
dysphonia, cough, stridor,
wheezing, dyspnea, chest
tightness, asphyxiation, death

 Cardiovascular: tachycardia,
hypotension, dizziness, collapse, • Other:
death feeling of impending doom,
metallic taste
 Signs and Symptoms 2
Frequency and Occurrence of Signs and Symptoms of Anaphylaxis
Signs and Symptoms Percent*
Cutaneous
Urticaria and angioedema 85-90
Flushing 45-55
Pruritus without rash 2-5
Respiratory
Dyspnea, wheeze 45-50
Upper airway angioedema 50-60
Rhinitis 15-20
Hypotension, dizziness, syncope, diaphoresis 30-35
Abdominal
Nausea, vomiting, diarrhea, cramping pain 25-30
Miscellaneous
Headache 5-8
Substernal pain 4-6
Seizure 1-2
Angor animi ––

*Percentages are approximations.

Lieberman P, et al. J Allergy Clin Immunol. 2010;126:477-480.
 Diagnosis
Acute onset of an illness 2 of the following that Reduced BP after
(minutes to several hours) OR occur rapidly after OR exposure to known
with involvement of the exposure to a likely
allergen (minutes to allergen (minutes
skin, mucosal tissue,
several hours): to several hours):
or both

AND AT LEAST 1
OF THE FOLLOWING
a. Involvement of the a. Infants and children:
skin-mucosal tissue (eg, low SBP* (age specific) or
generalized hives, >30% decrease in SBP
Respiratory Reduced BP itch-flush, swollen b. Adults: SBP of <90 mm Hg
compromise or associated lips-tongue-uvula) or >30% decrease from that
(eg, dyspnea, symptoms b. Respiratory compromise person’s baseline
wheeze- of end-organ c. Reduced BP or associated
bronchospasm) dysfunction symptoms
d. Persistent gastrointestinal
symptoms (eg, crampy
abdominal pain, vomiting)
*Low SBP for children is defined as <70 mm Hg from 1 month to 1 year, <70 mm Hg plus (2x age)
from 1 to 10 years, and <90 mm Hg from 11 to 17 years.
BP, blood pressure; SBP, systolic blood pressure.
16
Sampson HA, et al. Ann Emerg Med. 2006;47:373-380.
 Differential diagnosis
 vasovagal reactions
 flushing
 mastocytosis
 carcinoid syndrome
 hyperventilation syndrome
 globus hystericus
 hereditary angioedema
 other types of shock, eg. cardiogenic, septic
 scombroid poisoning
 Patterns of Anaphylaxis

 Uniphasic
– Isolated reaction producing signs and symptoms within minutes
(typically within 30 minutes) of exposure to an offending stimulus
 Biphasic
– Late-phase reactions that can occur 1 to 72 hours (most within 10
hours) after the initial attack (1%-23%)
 Protracted
– Severe anaphylactic reaction that may last between 24 and
36 hours despite aggressive treatment
 Uniphasic Anaphylaxis
Treatment

Initial
Symptoms

0 Time
Antigen Exposure
19
 Biphasic Anaphylaxis
Treatme Treatme
nt nt
Symptom Score

8 to 12 hours1

Antigen
First Phase Asymptomatic Second Phase
Exposure

Classic Model
30 minutes to 72 hours2
New Evidence
Tim
2. Lieberman P. Allergy Clin Immunol Int. 2004;16(6):241-248. e
1. Lieberman P. J Allergy Clin Immunol. 2005;115:S483-S523. 20
 Protracted Anaphylaxis

Initial
Symptoms

0 Time
Antigen
Up to 32 hours1
Exposure
1. Lieberman P, et al. J Allergy Clin Immunol. 2005;115:S483-S523. 21
 Patient Assessment
 Always start with a Primary Assessment
Many times in the management of
Anaphylactic Shock, therapeutic
interventions will be needed immediately
after the primary survey is completed to
correct life threatening airway conditions.
 Patient Assessment cont.

– The airway portion of the primary survey

should be assessed for laryngeal edema,
tongue swelling, stridor or barking cough.
– All these abnormalities are warnings of
impending complete airway obstruction.
 Secondary Assessment
 A complete head to toe survey must be
completed, paying special attention to the
early and frequent assessment of vital signs.

 The patient’s neck and face should be

continually assessed for swelling, hives
(uticaria), and redness (erythemia).

 Ongoing assessment of lung sounds is of

primary importance due to the rapid onset of
bronchospasm.
 Assessing the reaction
 Is it chronic or acute?
 The patient’s history will determine.

 Is it mild or severe?
 If any sign or symptom includes any facial, oral,

or neck swelling or edema, it is severe.

 Is it local or systemic?
 It it has spread past the injection site or spread to

any organ system, it is systemic.

 If the reaction is acute, severe, or systemic, expect
airway compromise.
 Treatment
Epinephrine has the ability to reverse many of the effects of
histamine release. This is accomplished by:
– Bronchodilation
– Vasoconstriction
– Increased cardiac output

In severe cases, the first dose of Epinephrine should be given

subcutaneously (SQ) or by Epi pen (for EMTs) prior to
establishing an IV.
 Action of Epinephrine
Epinephrine

1-adrenergic 2-adrenergic 1-adrenergic 2-adrenergic

receptor receptor receptor receptor

 Vasoconstriction  Insulin release  Inotropy  Bronchodilation

 Peripheral vascular  Chronotropy  Vasodilation
resistance  Glycogenolysis
 Heart rate  Mediator release
 Mucosal edema

28
Simons KJ, Simons FER. Curr Opin Allergy Clin Immunol. 2010;10:354-361.
 Absorption of Epinephrine
Faster With IM vs SC Injection
50 34 ± 14 min SC epinephrine

45 IM epinephrine
40
P<.05
35
30
Minutes

25
20
15 8 ± 2 min
10
5
0
Time to Cmax After Injection (minutes)
SC, subcutaneous.
29
Adapted from Simons FER, et al. J Allergy Clin Immunol. 2004;113:837-844.
 Available Auto-injectors: EpiPen

30
Available at: http://www.epipen.com/pdf/EPI_HowtoTearSheet.pdf.
 Treatment
 The first step is maintenance of the airway
– Give 100% Oxygen
 Give Epinephrine 1: 1,000 0.5 mg SQ
 Epinephrine auto-injector

Place the tip on the lateral aspect of the thigh, midway

between the hip and knee. Push firmly against the
thigh until it activates. Hold in place for 10 seconds.
 Why Not an Antihistamine?
 Anaphylaxis is not mediated by histamine
alone*
 Antihistamines antagonize only histamine
and have slower onset of action than
epinephrine
 Guidelines state that antihistamines are
second line to and should not be
administered in lieu of epinephrine
 Practice Parameter Guidelines:
Corticosteroids
 Corticosteroids should never be used in place
of or
prior to epinephrine and are not helpful acutely
 However, they theoretically have the potential
to prevent recurrent or protracted anaphylaxis
although there is no conclusive evidence that
the administration of corticosteroids prevents a
biphasic response
 Corticosteroids have a slower onset of action
 Supportive therapies

 Patients who have stridor and wheezing

unresponsive to epinephrine should be
given O2 and be intubated.
 Early intubation is recommended because
waiting for a response to epinephrine may
allow upper airway edema to progress
sufficiently to prevent endotracheal
intubation and require cricothyrotomy
 Supportive therapies (2)

 Hypotension can usually be treated with 1

to 2 L (20 to 40 mL/kg in children) of
isotonic IV fluids (eg, 0.9% saline).
 Hypotension refractory to fluids and IV
epinephrine may require vasopressors (eg,
dopamine 5 μg/kg/min).
 Referencess

1. Harrison Principles of Internal Medicine, 19th

Edition, 2015.
2. Current Medical Diagnosis and Treatment, 2015
THANK YOU