A N A P H Y LA X IS R EA C TIO N

Marshell Tendean, MD, DPCP

Department of Internal Medicine
UKRIDA, Jakarta
D efi
nition and term s :

Anaphylaxis is a severe, life-

threatening, generalised or systemic
hypersensitivity reaction.
This is characterised by rapidly
developing life-threatening airway
and/or breathing and/or circulation
problems usually associated with
skin and mucosal changes.
 Revised nomenclature for anaphylaxis

Anaphylaxis

Allergic Non-allergic
anaphylaxis anaphylaxis

IgE- Immunologic,
mediated non-IgE-mediated
anaphylaxis anaphylaxis

Johansson SGO et al JACI

2004,113:832-6
 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

Kemp SF and Lockey RF. J Allergy Clin Immunol

2002;110:341-8
Mechanisms of allergic
anaphylaxis

a severe, acute, systemic

allergic reaction caused by
the rapid, IgE-mediated
release of potent mediators
such as histamine from
tissue mast cells and
peripheral blood basophils
 Acutely released mediators of
anaphylaxis

degranulation of mast cells and basophils

causes the release of:
- preformed granule-associated substances, eg
histamine,
tryptase, chymase, carboxypeptidase, and
cytokines
- newly-generated lipid-derived mediators, eg
prostaglandin D2, leukotriene (LT) B4, LTC4, LTD4,
LTE4, and platelet activating factor.

Kemp SF and Lockey RF. J Allergy Clin Immunol 2002;

110:341-8
Primary symptoms of anaphylaxis

Skin: Respiratory:
flushing, itching, urticaria,
angioedema dysphonia, cough, stridor,
wheezing, dyspnea, chest
tightness, asphyxiation, death

Gastrointestinal:
nausea, vomiting, bloating,
cramping, diarrhea Cardiovascular:
tachycardia, hypotension,
dizziness, collapse, death
Other:
feeling of impending
doom,
metallic taste
 Comments about anaphylaxis signs and
symptoms

skin symptoms occur most commonly ( > 90% of patients)

skin, oral, and throat symptoms are often the first ones noted
respiratory symptoms occur in 40% to 70% of patients
gastrointestinal symptoms occur in about 30% of patients
shock occurs in about 10% of patients
signs and symptoms are usually seen within 5 to 30 minutes
the more rapid the onset, the more serious the reaction

Lieberman P. In: Middletons Allergy: Principles and Practice, 6th

edition, Mosby Inc., St. Louis, MO, 2003
 Biphasic and protracted

anaphylaxis
biphasic anaphylaxis is defined as return of symptoms after
resolution of initial symptoms, without subsequent allergen
exposure
usually, symptoms return within 1 to 8 hours (sometimes longer)
up to 20% of anaphylactic reactions are biphasic
patients with biphasic anaphylaxis may require more epinephrine
to control initial symptoms
in protracted anaphylaxis, symptoms may be continuous for 5-32
hrs

Lieberman P. Ann Allergy Asthma Immunol

2005;95:217-26
Biphasic/late-phase reaction
Cellular infiltrates: 3 to 6 hours (LPR)
Eosinophil
CysLTs, GM-CSF,
Histamine IL-4, IL-6 TNF-, IL-1, IL-3, PAF,
ECP, MBP

Allergen
3 to 6 hours Basophil
Histamine,
(CysLTs, PAF, CysLTs, Return
IL-5) TNF-, IL-4, IL-5, IL-6
of
Monocyte Symptoms
PGs CysLTs CysLTs, TNF-,
PAF, IL-1
Proteases

Mast cell Lymphocyte

IL-4, IL-13, IL-5,
IL-3, GM-CSF
EPR 15 min
(Early-Phase Reaction)
Incidence rate

The American College of Allergy,

Asthma and Immunology
Epidemiology of Anaphylaxis Working
group summarised the findings from a
number of important internationally
The overall frequency of episodes of
anaphylaxis using current data lies
between 30 and 950 cases per
100,000 persons per year.
Triggers

Anaphylaxis can be triggered by any

of a very broad range of triggers, but
those most commonly identified
include food, drugs and venom
 Anaphylaxis from immune
causes other than IgE

cytotoxic (Type II)

- transfusion reactions to cellular

elements (IgG, IgM)
immune aggregates (Type III)

- intravenous immunoglobulin
- Dextran (possibly)

Kemp SF and Lockey RF, J Allergy Clin Immunol

2002;110:341-8
 Anaphylaxis: non-
immunologic causes
MULTIMEDIATOR COMPLEMENT ACTIVATION/ACTIVATION
OF CONTACT SYSTEM

radiocontrast media
ethylene oxide gas on dialysis tubing (possibly
through IgE)
protamine (possibly)
ACE-inhibitor administered during renal dialysis
with sulfonated polyacrylonitrile, cuprophane, or
polymethylmethacrylate dialysis membranes

Kemp SF and Lockey RF, J Allergy Clin Immunol

2002;110:341-8
 Anaphylaxis: non-immunologic
causes
NONSPECIFIC DEGRANULATION OF MAST
CELLS
AND BASOPHILS
opiates
physical factors:
- exercise (no food or medication co-trigger)
- temperature (cold, heat)

Kemp SF and Lockey RF, J Allergy Clin Immunol

2002;110:341-8
 Idiopathic anaphylaxis
common in adults who are referred to allergists for evaluation of
anaphylaxis
uncommon in children
negative skin tests, negative dietary history, no associated
diseases eg. mastocytosis
preventive medication: oral corticosteroids, H 1 & H2
antihistamines, anti-leukotrienes
deaths rare
may gradually improve over time

Lieberman PL et al. J Allergy Clin Immunol

2005;115:S483-S523
Severity ofanapylaxis reaction
 Patients can have either an A or B or C problem
or any combination. Use the
ABCDE approach to recognise these.
Airway problems:
Airway swelling, e.g., throat and tongue swelling
(pharyngeal/laryngeal oedema). The patient has
difficulty in breathing and swallowing and feels
that the throat is closing up.
Hoarse voice.
Stridor this is a high-pitched inspiratory noise
caused by upper airway obstruction.
Breathing problem s:

Shortness of breath increased

respiratory rate.
Wheeze.
Patient becoming tired.
Confusion caused by hypoxia.
Cyanosis (appears blue) this is
usually a late sign.
Respiratory arrest.
 Circulation problems (often referred
to as anaphylactic shock) can be
caused by direct myocardial
depression, vasodilation and
capillary leak, and loss of fluid from
the circulation. Bradycardia (a slow
pulse) is usually a late feature, often
preceding cardiac arrest.
Cutaneous and m ucosalm anifestation

They are often the first feature and present in over 80% of
anaphylactic reactions.
They can be subtle or dramatic.
There may be just skin, just mucosal, or both skin and
mucosal changes.
There may be erythema a patchy, or generalised, red rash.
There may be urticaria (also called hives, nettle rash, weals
or welts), which can appear anywhere on the body. The
weals may be pale, pink or red, and may look like nettle
stings. They can be different shapes and sizes, and are often
surrounded by a red flare. They are usually itchy.
Angioedema is similar to urticaria but involves swelling of
deeper tissues, most commonly in the eyelids and lips, and
sometimes in the mouth and throat
Laboratory tests in the diagnosis of
anaphylaxis

Plasma histamine
Serum tryptase
24-hr Urinary histamine
metabolite

0 30 60 90 120 150 180 210 240 270 300 330

Prevention
Beta blockers are contraindicated for those at risk
especially those sensitive to Hymenoptera venom or those
undergoing immunotherapy for respiratory system allergy
Always know crossreactivity between drugs
A prick or scratch skin test should precede an intradermal
skin test (for it might cause anaphylaxis)
Desensitization with most antibiotics and other classes of
therapeutic agents can proceed by the IV, SQ or oral route
Giving graded quantities of drug at regular intervals
Development of blocking antibody of the IgG class that interacts
with antigen so that less reaches the sensitized tissue mast cells
Modification of outdoor activities
Wearing informational bracelet and access to unexpired
auto-injectable epinephrine kit
Factors affecting prognosis

Factor Poor Good

Prognosis Prognosis
Onset of symptoms Early Late
Initiation of treatment Late Early
Route of exposure Injection Oral*
-adrenergic blocker use Yes No
Presence of underlying disease Yes No

* true for drugs, not foods