ANAPHYLAXIS:

DIAGNOSIS, TREATMENT
AND PREVENTION
Heru Sundaru
Drug Allergy and Anaphylaxis Clinic
Division of Allergy Clinical immunology
Department of Internal medicine FKUI/RSCM
Jakarta

DEFINITION OF ANAPHYLAXIS
Anaphylaxis is a severe, acute, life-threatening
generalized or systemic hypersensitivity reaction.
It is commonly, but not always, mediated by an allergic
mechanism, usually by IgE.
Allergic (immunologic) non-IgE-mediated anaphylaxis
also occurs.
Non-allergic anaphylactic reactions, formerly called
anaphylactoid or pseudo-allergic reactions, may also
occur.
Johansson SGO et al JACI 2004,113: 832-6

Why we should know?

Anaphylaxis can be fatal
Unpredictable and suddenly
Can happen anywhere
Its prevalence increased
Medico legal ?

Number of hospital discharges with the primary diagnosis of

anaphylaxis per 100 000 episodes of hospital discharge and cause
of anaphylaxis

Epidemiology :

Prevalence of anaphylaxis
1. 1 : 2300 attendees at ED in UK (Stewart & Ewan,

1996)
2. Anaphylaxis hospital discharge 5.6/100.000 (1991
2) 10.2/100.000 (1994 - 5) (Sheik & Alves, 2000)
3. 13.230 admission for anaphylaxis 1990 - 2000
(Gupta, et al. 2003)
4. 214 death attributed to anaphylaxis in UK 1992
2001 (Pumphrey, 2004)

Anaphylaxis: population study in 5

years
Incidence (annual): 21 per 100.000 person year
133 residents who experienced 154 anaphylactic episode :

- 116 residents 1 episode

- 13 resident 2 episode
- 4 residents 3 episode
53% atopy
68% allergen identified: food, medication and insect sting
52% allergy consultation
7% hospitalization
1 patient died
Yocum, et al. JACI 1999;104:452-6

What is anaphylaxis?
Anaphylaxis is a severe, life-threatening,
generalized or systemic hypersensitivity
reaction

Anaphylaxis

Allergic anaphylaxis

IgE-mediated anaphylaxis

Non-allergic anaphylaxis

Non-IgE-mediated allergic anaphylaxis

Johansson SGO, et al. Allergy 2001;56:813-824

Mechanisms underlying human

anaphylaxis
Human anaphylaxis

Immunologic

Non-Immunologic
Idiopathic

IgE, FcRI

Other

Physical

Other

foods, venoms,
latex, drugs

blood products,
immune aggregates,
drugs

exercise, cold

drugs

Simon FER. J Allergy Clin Immunol 2006;117:367-77

Elicitors of anaphylaxis (including anaphylactoid reactions)

Drugs
Foods
Drug and food additives
Occupational substances (e.g. latex)
Animal venoms
Aeroallergens
Seminal fluid
Contact urticariogens
Physical agents (colt, heat, ultraviolet radiation)
Exercise
Echinococcal cyst
Summation anaphylaxis
Underlying disease
Complement factor 1-inactivator deficiency
Systemic mastocytosis
Idiopathic (?)
Ring J, Brockow K & Behrendt. History and classification of anaphylaxis. In Anaphylaxis. Novartis Foundation 2004:12

The causes of anaphylaxis

Golden DBK, Patterns of anaphylaxis: Acute & late phase features of allergic reactions. In Anaphylaxis.
Novartis foundation 2004: 103

Onset time of reaction in insect venom anaphylaxis.

(from Lockey et al 1988, with permission)

Golden DBK, Patterns of anaphylaxis: Acute & late phase features of allergic reactions. In Anaphylaxis.
Novartis foundation 2004: 105

Grading of anaphylactic reactions according to severity of clinical symptoms

Symptoms
Grade

Dermal

Abdominal

Respiratory

Cardiovascular

Pruritus
Flush
Urticaria
Angiodema

II

Pruritus
Flush
Urticaria
Angiodema (not
mandatory)

Nausea
Cramping

Rhinorrhoea
Hoarseness
Dyspnoea

Tachycardia (> 120 bpm)

Blood pressure change (>
20 mmHg systolic)
Arrhytmia

III

Pruritus
Flush
Urticaria
Angiodema (not
mandatory)

Vomiting
Defecation
Diarroea

Laryngeal oedema
Bronchospasm
Cyanosis

Shock

IV

Pruritus
Flush
Urticaria
Angiodema (not
mandatory)

Vomiting
Defecation
Diarrhoea

Respiratory arrest

Cardiac arrest

Bpm = beats perminute

Ring J, Brockow K & Behrendt. History and classification of anaphylaxis. In Anaphylaxis. Novartis Foundation 2004:12

Grading system for generalized

reactions (from Brown 2004)
Grade

Defined by

Mild (skin and subcutaneous

tissue only)*

Generalized erythema, urticaria,

periorbital oedema or angiodema

Moderate (features
suggesting respiratory,
cardiovascular or
gastrointestinal involvement)

Dyspnoea, stridor, wheeze, nausea,

vomiting, dizziness (presyncope)

Severe (Hypoxia, hypotension Cyanosis or SpO2 92%, hypotension

or neurological compromised (SBP < 90 mm Hg in adults),
confusion, collapse, LOC or
incontinence
* The mild grade does not represent anaphylaxis according to the National Institute of Allergy and
Infections Disease-food Allergy and Anaphylaxis Network (NIAID-FAAN) definition (Box 2), loss of
consciousness; SBP, systolic blood pressure.

Brown SGA. JACI, 2004:114:371-6

Anaphylaxis can be fatal

Be able to recognize the symptoms

Know and avoid the triggers
Have an emergency action plan
Treat it promptly and appropriately

Suspected cause of death 212 reactions

Sting

47

29 wasp, 4 bee, 14 unidentified

Nuts

32

2 almond, 2 brazil, 1 hazel, 10 peanut, 6 walnut, 11 mixed or

unidentified

Food

13

1 banana, 2 chickpea, 2 fish, 5 milk, 2 crustacean, 1 snail

Food?

18

1 ?fish, 5 during meal, 1 ?grape, 3 ?milk, 3 ?nut, 1 ?sherbet,

1 ?strawberry, 1 ?yeast, 1 ?nectarine

Antibiotic

27

1 benzypenicillin, 10 aminopenicillin, 12 cephalosporin, 1

ciprofloxacin, 1 vancomycin, 2 amphotericin

Anesthetic

35

19 suxamethonium, 7 vecuronium, 6 attracurium, 7 at induction

Other drug

15

3 ACE inhibitor, 6 NSAID, 5 gelatines, 2 protamine, 2 vitamin K,

1 Diamox (acetazolamide), 1 etoposide, 1 pethidine, 1 heroin, 1
kabikinase, 1 local anaesthetic

Contrast
media

11

9 iodinated, 1 technetium, 1 fluorescein

Other

1 latex, 1 hair dye, 1 hydatid, 1 idiophatic

Pumphrey RSH, Fatal anaphylaxis in the UK, 1992-2001. In Anaphylaxis. Novartis Foundation 2004:118

Mode of death
Drug

Sting Food Food? Male Female

Lower airways

11

24

11

21

26

Upper + lower airways

13

19

Upper airways

16

12

Shock + asphyxia

21

12

15

Shock

32

18

23

29

Disseminated
intravascular coagulation

Pumphrey RSH, Fatal anaphylaxis in the UK, 1992-2001. In Anaphylaxis. Novartis Foundation 2004:120

Interval from exposure to first arrest. Drug reaction were

fastest, mostly taking less than 5 minutes

Pumphrey RSH, Fatal anaphylaxis in the UK, 1992-2001. In Anaphylaxis. Novartis Foundation 2004:121

CLINICAL FEATURES

Anaphylaxis symptoms
MOUTH

itching swelling of lips and/or tongue

THROAT itching, tightness, closure, hoarseness
SKIN
itching, hives, redness, swelling
GUT
vomiting, diarrhea, cramps
LUNG
shortness of breath, cough, wheeze
HEART
weak pulse, dizziness, passing out
NEURO
headache, visual loss, loss of
consciousness, incontinence, confusion

Frequency of occurrence of
signs & symptoms of
anaphylaxis*+
Signs & symptoms
Cutaneous
Urticaria & angiodema
Flushing
Pruritus without rash
Respiratory
Dyspnea, wheeze
Upper airway angioedema
Rhinitis
Dizziness, syncope, hypotension
Abdominal
Nausea, vomiting, diarrhea, cramping pain
Miscellaneous
Headache
Substernal pain
Seizure

90%
85-90%
45-55%
2-5%
40-60%
45-50%
50-60%
15-20%
30-35%
25-30%
5-8%
4-6%
1-2%

* On the basis of a compilation of 1865 patients reported in references 1 through 14

+ Percentages are approximations

DIAGNOSIS

DIAGNOSIS OF ANAPHYLAXIS
Clinical diagnosis based on clinical presentation and
exposure history

Flushing and tachycardia are invariably present, other

cutaneous symptoms (hives, itch) may be absent

Anaphylaxis may be difficult to diagnose, especially when

patients present with bradycardia (instead of tachycardia,
which is usual)

Very rarely, patients present only with profound hypotension.

The exposure to some inciting event is one key to the
diagnosis in this rare circumstance
Lieberman PL et al. J Allergy Clin Immunol 2005;115:S483-523

DIAGNOSIS OF ANAPHYLAXIS
(contd)
Careful history to identify possible causes
Can be confirmed by an elevated serum tryptase level
- specific for mast cell degranulation
- remains elevated for up to 6 hours
- may not be elevated, especially in

Refer to allergist for specific testing

food allergy

Anaphylaxis is highly likely when any

one of the following 3 criteria are
fulfilled 1
1.

Acute onset of an illness (minutes to several hours) with

involvement of the skin, mucosal tissue, or both (eg,
generalized hives, pruritus or flushing, swollen lipstongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm,

stridor, reduce PEF, hypoxemia

b. Reduced BP or associated symptoms of end-organ dysfunction
(eg, hypotonia [collapse], syncope, incontinence)
Sampson H, et al. JACI 2006;117:391-2

Anaphylaxis is highly likely when any

one of the following 3 criteria are
fulfilled 2
2.

Two or more of the following that occur rapidly after

exposure to a likely allergen for that patient (minutes to
several hours):
a. Involvement of the skin-mucosal tissue (eg, generalized hives,

itc-flush, swollen lips-tongue-uvula)

b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm,
stridor, reduced PEF, hypoxemia
c. Reduced BP or associated symptoms of end-organ dysfunction
(eg, hypotonia [collapse], syncope, incontinence)
d. Persistent gastrointestinal symptoms (eg, crampy abdominal
pain, vomiting)

Anaphylaxis is highly likely when any

one of the following 3 criteria are
fulfilled 3
3.

Reduced BP after exposure to known allergen for that

patient (minutes several hours)
a. Infants and children: lowsystolic BP (age specific) or greater

than 30% decrease in systolic BP*

b. Adults: systolic BP of less than 90 mm Hg or greater than 30%
decrease from that persons baseline
PEF, Peak expiratory flow; BP, blood pressure
* Low systolic blood pressure for children is defined as less than 70 mm Hg from 1 month to 1 year, less
than (70 mm HG + [2 x age]) from 1 to 10 years, and less than 90 mm Hg from 11 to 17 years.

DIFFERENTIAL DIAGNOSIS OF
ANAPHYLAXIS

Vasovagal reactions

Flushing

Mastocytosis

Carcinoid syndrome

Hyperventilation syndrome

Globus hystericus

Hereditary angioedema

Other types of shock, eg. cardiogenic, septic

Scombroid poisoning

TREATMENT

Emergency management of
anaphylaxis
1. Stop administration of precipitant, assess reaction severity and treat
accordingly:
Call for assistance
Adrenaline I.m (lateral thigh) 0.01 mg/kg up to 0.5 mg
i.v access
Lie flat/elevate legs if tolerated
High flow oxygen, airway/ventilation support if needed
IF HYPOTENSIVE ALSO:
Additional wide bore I.v access (I.e 14G or 16G in adults) for normal
saline infusion
i.v normal saline bolus 20 mL/kg over 1-2 min under pressure
Brown, SGA. Emerg Med Australasia. 2006;18:155-167

Emergency management of anaphylaxis

2. If there is inadequate response, an immediate life threat, or deterioration:
Start an I.v adrenalin infusion as per hospital guidelines/protocol
OR
Repeat i.m adrenalin every 3-5 min as needed
And consider also:
Hypotension
o Repeat normal saline boluses 10-20 mL/kg as needed, up to 50mL/kg total over the first
30 min
o i.v atropine 0.02 mg/kg if severe bradycardia (minimum dose 0.1 mg)
o i.v vasopressors to overcome vasodilation (vasopressin 10-40 units in adults, or
metaraminol 2-10 mg in adults)*. For anaphylactic cardiac arrest, rapid escalation to
high dose adrenaline (3-5) mg every 2-3 min) might be effective
o I.v glucagon/phosphodiesterase inhibitors/ballon pump if -blocked or heart failure:
Glucagon dose in adults: load with 1-5 mg over 5 min, followed by 5-15 g/min*
Bronchospasm
o Continuous salbutamol nebulizers or continuous actuations of metered dose inhaler into
ventilation circuit if intubated)
o i.v. hydrocortisone 5 mg/kg 6 hourly followed by oral prednisone 1 mg/kg (max. 50 mg)
for 4 days
Upper airway obstruction
o Nebulized adrenaline (5 mg in % mL, I.e. 5 mL of 1:1000 may provide some relief
o Prepare for surgical
Brown, SGA. Emerg Med Australasia. 2006;18:155-167

Emergency management of anaphylaxis

3

Observe for an adequate period and arrange appropriate follow up:

i. Observe for a minimum of 4 h after the resolution of all symptoms
and signs
Take blood for serum mast cell tryptase on arrival, 1 h after arrival
and prior to discharge.
Admit longer (overnight) those with severe reactions, a history of
life-threatening reactions or poorly controlled
Asthma, and those who present late in the evening
ii.

Outpatient follow up by a specialist allergist is recommended for all

those with moderate-severe reactions, and with mild reactions to
food if the patient also has asthma
Prior to discharge allergen avoidance measures (including Medic
Alert). Ensure that an alert is placed in hospital /practice
records/computer system, and ensure that your referral
letter/summary contains a detailed record of reaction features &
timing, possible precipitants and times of exposure

iii. Arrange for an EpiPen, demonstrate correct use with an EpiPen

Trainer and provide a written action plan (http://www.allergy.org.au)
if there is a significant risk of re-exposure and outpatient follow up
will be delayed

Pharmacology of epinephrine
Epinephrine

1-receptor

vasoconstriction
peripheral vascular resistance
mucosal edema

2-receptor

insulin release
neropinephrine release

1-adrenergic
receptor

inotropy
chronotropy

Estelle FER. J Allergy Clin Immunol 2004;113:837-44

2-adrenergic
receptor

bronchodilation
vasodilation
glycogenolysis
mucosal edema

Absorption of epinephrine is faster

after intramuscular injection than after
subcutaneous injection
Intramuscular
epinephrine
(Epipen)

8 2 minutes

Subcutaneous
epinephrine

34 14 (5-120) minutes
p < 0.05

10

15

20

25

30

Time to Cmax after injection (minutes)

Estelle FER. J Allergy Clin Immunol 2004;113:837-44

35

PREVENTION

As
se
s

ACUTE

sk
Ri
ce
du
at
Re
Tre

Ri
Re
sk
cog
niz
e

LONG TERM

Prevent

Educate
FIG 2. The dual role of the allergy-immunology specialist in anaphylaxis
Simons F.E.R JACI 2006;117:367-377

Why is follow up is needed ?

Anaphylaxis can occur repeatedly
The trigger need to be confirmed
Long-term preventive strategies
need to be implemented

Education of anaphylaxis

Individuals and their families

Caregivers
Health case professional (doctors, nurses)
First respondent
Emergency medical services
Teachers coaches, child care providers
Food industries, restaurant, law makers

1. Prior History - Identification

2. Medical alert brachelet1

Medical alert brachelet2

Prevention1

3. Emergency Kit

Prevention2

Pharmacologic prophylaxis : RCM

Immunotherapy
Hidden allergens, cross reactivity
Waiting 30 minutes after injections

Sample Chef Card

To the Chef:
WARNING! I am allergic to peanuts. In order to avoid a life-threatening
reaction, I must avoid the following ingredients:
Artificial nuts
Beer nuts
Cold pressed, expelled, or extruded peanut oil
Ground nuts
Mandelonas
Mixed nuts
Monkey nuts
Nut pieces
Peanut
Peanut butter
Peanut flour
Please ensure any utensils & equipment used to prepare my meal, as
well as prep surfaces, are thoroughly cleaned prior to use. Thanks for
your cooperation
Munoz. Anaphylaxis 2004. Wiley, Chichester. P. 265-75