Ketut Suryana

Ketut Suardamana,
Division of Allergy-Immunology
Department of Internal Medicine, Faculty Medicine of
Udayana University
Denpasar
What is anaphylaxis ?
Anaphylaxis is an acute severe, life-threatening,
generalized or systemic hypersensitivity reactions

Why we should know ?

• Anaphylaxis can be fatal
• Unpredictable and suddenly
• Can happen anywhere
• It’s prevalence increased
• Medico legal ?
Classification

anaphylaxis

Immunologic Idiopathic Non-Immunologic

IgE, FcRI Other (IgG, Immune- Physical Other drugs

Foods, venoms, complex-complement exercise, cold
latex, drugs related)
(IgE mediated) Blood products, immune
aggregates, drugs
(Non-IgE mediated)

(WAO, 2004; dikutip Lieberman,2009)

Mechanisms underlying anaphylaxis
ANAPHYLAXIS
Immunologic Non IgE mediated Immunologic Immunologic Non IgE mediated
(Anaphylactic)
Complement activity Substance for histamine release
IgE
Classic Alternative
pathway pathway Arachidonic acid modulation

Mastocyte
C3a, C5a Physical factor
Anafilaktoksin
Idiopathic

Mediator

  vascular permeability
• vasodilatation
• Smooth muscle constraction
• Mucosal gland hypersecretion
• peripheral nerve stimulation

• Erythema, urtica, pruritus (the skin & subcutaneous tissues)

• Nasal congestion, broncho spasm / dyspnea, larynx edema
(respiratory system)
• Nausea, vomiting, abd. cramp, diarrhea (gastrointestinal system)
• Palpitation, hypotention, shock ( cardiovascular system)

Figure 1. Pathophysiology1
EPIDEMIOLOGY
Severe anaphylaxis : 1 - 3/104 people
(Moneret-Vautrin et al; Oct 2005)

0,7 - 10% anaphylaxis dou to penicillin

0.0004% associated with food
0.5 - 5% caused by insect stings
0,22 - 1% dou to Radiographic contrast media
(Neugut, et al; Oct 2005)

Generalized Hypersensitivity/Anaphylaxis : 2/104 total patient

(Ketut Suryana, 2005)

Lethal anaphylaxis : 1 – 3/106 people

Incidece Ricing in parallel with incidence of Food allergy
2.5 x rise in Britain l995 - 1999
(Sheik A et al. Clin Exp Allergy 2001)
AETIOLOGY
The aetiology of Anaphylactic and anaphylactoid :
1. Drugs :
- antibiotic : penicilin most frequens
- aspirin, NSAID
2. Foods :
- Most commonly : fish / sea food, lobster, eggs, cow
milk, nuts.
3. Venoms :
- Heminoptera insects
4. Radiographic contrast media
5. Idiopathic
6. Others :
- Blood products
- Physical factors ( cold & exercise – induced )
PATHOPHYSIOLOGY
• Anaphylactic reaction (IgE mediated reaction)

Figure 2. Anaphylactic reaction / IgE mediated reaction3

• Anaphylactoid reaction (Non IgE mediated)
- Complement activation - Physical factors
- Substance for Histamine released - Idiopathic
- Arachidonic acid modulation
Figure 4. Cross-linking of IgE4
PATTERN OF MEDIATOR (HISTAMINE)
RELEASE ON ANAPHYLAXIS

Histamine released by Mast Cell

Histamine levels

Histamine released by Basophyl

Hour 0 ½ 1 2 3 4 5 6 48-72

Figure 5. Pattern of histamine release on anaphylaxis

CLINICAL FEATURES
Grading system for generalised hypersensitivity
/ anaphylaxis
( Brown SGA . Clinical features and severity grading 0f
anaphylaxis J. Allergy Clin Immunol 2004, 114(2) : 371-6 )

1.Mild (involvement of the skin-mucosal tissues) :

generalised erythema , urtica, periorbital edema or angioedema

2.Moderate (involvment of Respiratory, Cardiovascular, GI syst) :

SOB, Stridor, wheezing, nausea, vomiting, dizziness
(presyncope),diaphoresis, chest / throat tightness, abd. pain /
abd. cramp

3.Severe (hypoxia, hypotention, neurological compromise) :

cyanosis(SpO2  92%), hypotention(adults ;SBP < 90 mmHg),
confusion, collapse, LOC / Loss of Consciousness,
incontinence.

(1 = acute hypersensitivity reaction) (2 &3 = anaphylaxis)

Gambar 6. Angioedema3
Clinical Criteria for Diagnosing Anaphylaxis
(Sampson HA, et al. JACI 2006)

1. Acute onset of an illness ( minutes to several hours)

with involvement of the skin, mucosal tissues, or both
( eg, generalized hives, pruritus or flushing, swollen
lips-tongue-uvula) 
AND AT LEAST ONE OF THE FOLLOWING  
a. Respiratory compromise (eg, dyspnea, wheeze-
bronchospasm, stridor, reduced PEF, hypoxemia) 
b. Reduced BP or associated symptoms of end-organ
dysfunction (eg, hypotonia /collapse, syncope,
incontinence)
Clinical Criteria for Diagnosing Anaphylaxis
(con’t)
(Sampson HA, et al. JACI 2006)

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, itch-flush, swollen lips-tongue-uvula)
b. Respiratory compromise (eg, dyspnea, wheeze-
bronchospasm, stridor, reduced PEF, hypoxemia)
c. Reduced BP or associated symptoms (eg, hypotonia
collapse, syncope, incontinence)
d. Persistent gastrointestinal symptoms (eg, crampy
abdominal pain, vomiting)
Clinical Criteria for Diagnosing Anaphylaxis
(con’t)
(Sampson HA, et al. JACI 2006)
3. Reduced BP after exposure to known allergen for that patient

( minutes to several hours ) :

a. Infants and children: low systolic 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 person's baseline
Clinical Criteria for Diagnosing Anaphylaxis
(Sampson HA, et al. JACI 2006)

Acute onset of Cardiovascular

( Reduced BP )
3 anaphylaxis
after exposure to known allergen
for that patient

Acute onset of the Skin &

4 Acute hypersensitivity /
Subcutaneous tissues only
Acute allergic reaction
( Urtica & Angioedema )
• Laboratory Findings
Laboratory test are seldom necessary or helpful
initially, although certain test may be used later to
assess and monitor treatment and to detect
complications.
• Blood cell counts ( haemoconcentration ? )
• Eosinophil counts, stool examination
• IgE total
• ECG
• Chest X – ray
• Others : dou to progress note ( eg ; Electrolyte,
Blood Gas Analyse, Blood Suger )
Differential diagnosis
Clinical Features Differential Diagnosis
Shock Septic shock
Hypovolemic shock
Cardiogenic shock
Vasovagal reaction
Respiratory distress with Corpus alienum in Resp.
wheezing or stridor tract
Asthma bronchiale
COPD
Vocal cord disfunction
FACTORS ASSOCIATED WITH
SEVERITY REACTIONS
• Age
• Allergen
• Atopy
• CVD (Cardiovascular Disease)
• COPD (Chronic Obstructive Pulmonary Disease)
• Asthma Bronchiale
• Acid base and electrolyte inbalance
• Drugs ( eg, beta-blocker, ACE-inhibitor)
• Interval of epinephrine injection after exposure
 Management acute hypersensitivity /
anaphylaxis
Acute hypersensitivity reaction
(involvement of the skin, mucosal
tissues, or both only)
Anaphylaxis reaction
(involvement of 2 or more system /
organ)

Dipenhydramine inj (10-20 mg) IM Management of anaphylaxis

Observation for 4-6 hours Observation

No Response
Good Response No worsening (be worsen)
(no clinical response
manifestation) Explore the
prognostic factors

In patient
Another treatment
Ambulatory IVFD (due to the problem)

AH1 inj i.m
Oral
antihistamie AH2 inj i.v
for 3 days Steroid inj No Response
Good Response
(be worsen)
MANAGEMENT OF ANAPHYLAXIS
History of severe allergic reaction with respiratory difficulty or hypotension,
especially if skin changes present

Stop administration of precipitant

Oxygen high flow

Adrenalin / epinephrine (1 : 1000) 0,3 – 0,5 ml IM (0,01 mg/kg BW)

Repeat in 5-15 minutes if no clinical improvement

Antihistamine 10-20 mg IM or slowly Intravenously

In addition
 Give 1-2 l of fluid intravenously if clinical manifestation of shock do not respond to drug
treatment
 Corticosteroid for all severe or recurrent reactions & patients with asthma.
- Methyl prednisolone 125-250 mg IV
- Dexamethasone 20 mg IV
- Hydrocortisone 100-500 mg IV slowly
continue by maintenance dose
 Inhaled short acting -2 agonist may used if bronchospasm severe
 Vasopressor (dopamine, dobutamine) with titration dose
Observation for 2 - 3 x 24 horus, for mild case just need 6 hours
Give Corticosteroid and antihistamine orally for 3 x 24 horus
Elderly ( 60 y.o), CVD  adrenalin dose 0,1-0,2cc IM with interval 5-10 mnt
Adrenaline / epinephrine

• A quick-acting hormone

• Secreted by Suprarenal gland

• A direct-acting sympathomimetic
(-adrenergic, -adrenergic agonist)

• A narrow toxic-therapeutic index (risk-to-benefit ratio)

• No absolute contra indications

• The first-aid treatment of anaphylaxis

Epinephrine

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

receptor receptor

  vasoconstriction   insulin release   inotropic   bronchodilator

  peripheral   noreepinephrine   chronotropic   vasodilatation
vascular resistance release
  glycogenolysis
  mucosal edema
  mediator release

Figure 7. Pharmacology of epinephrine9

 Dosage and route of injection
• Dose epinephrine and route of injection :
• 0,3-0,5 ml inj SC/IM lateral thigh / deltoid
(North American Guidelines, Indonesia)
• 0,5-1 ml inj SC/IM lateral thigh / deltoid
(European Literature)
• Pharmacokinetic and pharmacodynamic epinephrine

Intramuscular inj
8 ± 2 minutes

Subcutaneus inj.
34 ± 14 (5-120) minutes

5 10 15 20 25 30 35

Time of Cmax after injection (minutes)

Figure 8. Absorption of epinephrine9

The epinephrine injection vs oral H1antihistamine
controversy
• H1 anti-histamines are commonly used to relieve cutaneous signs &
symptoms ( eg, itching, flushing, urtica)
• H1 anti-histamines :

• play little in relief of bronchospasm,

gastrointestinal symptoms
• fail to relieve upper airway edema or hypotention
• in usual doses, do not reduced the explosive release of
histamine and other mediators inflammation
(mast cells & basophils )
• Epinephrine injection would need to be given immediately after
exposure by correct doses and route; decreased morbidity &
mortality
PREVENTION
a. Explore the major risk factors for anaphylaxis include a prior
history of such reactions, -adregenric blocker or possibly ACE
inhibitor therapy, and the multiple antibiotic sensitivity
syndrome, atopic background.
b. Application the rationale therapy
c. Informed consent
d. Patients & their families education maybe the most important
preventive strategy; be carefully instructed about hidden
allergens, cross-reactions to various allergens, unforeseen risk
during medical procedures, when and how to use self-
administration epinephrine (if available).
e. In a future; injection anti IgE antibody with regular interval could
be prevent the risk or the severity of anaphylaxis reactions
 Why, follow up is needed ?
 Anaphylaxis can occur repeatedly / episodics
 The trigger need to be confirmed

 Long term preventive strategies

need to be implemented
SUMMARY
• Anaphylaxis reaction
is a severe, life-threatening, generalized or systemic
hypersensitivity reaction
Anaphylaxis reaction (IgE mediated)
Anaphylactoid reaction (non IgE mediated)

• Epidemiology
The true incidence of anaphylaxis is unknown

• Aetiology
The common etiologies of anaphylaxis include drugs, foods,
insect sting and physical factors/exercise, idiopathic

• Pathophysiology
Mostly based on IgE mediated
• Clinical Manifestations
Various from mild (involve the skin-mucosal only: urtica,
pruritus, angioedema) to severe (shock, death)
• Acute management due to emergency concept will
reduce the morbidity and mortality by giving :
Adrenaline, antihistamine, corticosteroid, etc
• Prevention
Explore the clinical history, rationale therapy, informed
consent, education (primer prevention, secondary prevention )
Anti IgE antibody injection with regular interval  reduce the
risk and severity
 Allergen exposure

(drugs, food, insect sting)

minute - 6 hours

Clinical Features

• Mild
(acute hypersensitivity reaction)
• Age
• Moderate, severe (anaphylaxis) • Allergen
• CVD
• COPD
• Asthma bronchiale
• Acid base, electrolyte inbalance
Management • Drugs (-blocker, ACE-inhibitor)
• Interval injection adrenaline after
exposure
- Antihistamines ( AH-1 & AH-2 )
- ABC, Adrenalin, Anti-histamine,
Corticosteroid, fluid, others)

48-72 hours
Outcome (?)