Download GLORIA MODULE 9: Diagnosis of IgE Sensitization

Nomenclature of allergy
Diagnosis of IgE
Sensitization
Allergic
hypersensitivity
(immunological
mechanism
defined or strongly
suspected)
Non-allergic
hypersensitivity
(immunological
mechanism
excluded)
IgE-mediated Not IgE-mediated
Johansson SGO et al. Allergy 2001 and JACI 2004
Atopy
Allergic disease progression
with age
Atopy is a personal and/or familial
tendency, usually expressed
anytime in life from childhood and
adolescence, into maturity, to
become sensitized and produce IgE
antibodies in response to ordinary
exposures to allergens, usually
proteins.
As a consequence, atopic persons
can develop IgE-mediated allergic
diseases including asthma,
rhinoconjunctivitis, or eczema.
WAO Nomenclature Review
Committee
Johansson et al. J Allergy Clin
Immunol 2004;113:832-6
Saarinen UM et al. Lancet
1995
The essential components
of allergy diagnosis
Clinical History and Physical Examination
Symptoms versus Exposure
Diagnostic Confirmatory Test
Skin Test (Puncture, Intradermal)
Allergen-specific IgE antibody serology
Provocation Test
Oral, Nasal, Bronchial Challenge
Key concepts in allergy
diagnosis
• A proper allergy history involves determining the
symptom complex, any relationship to allergen exposure
and a careful physical examination, looking for the
specific signs of allergy.
• Once allergic disease is suspected, a confirmatory test
(skin test or IgE antibody serology) is performed to
verify sensitization by the presence of allergen specific
IgE antibody.1-3
• Where it can be performed and interpreted, skin prick
testing (SPT) remains the primary confirmatory test
because it is fast, safe, sensitive, minimally invasive and
results correlate with nasal and bronchial challenges.
• Quantitative IgE antibody serology is an accepted
alternative.
• SPT and/or IgE serology are essential adjuncts to
history and physical exam when making the diagnosis of
allergy.
• Provocation tests are sometimes needed to confirm
sensitization.
1. Oppenheimer Ann Allergy 2006;S1:6-12,
2. 2. Bousquet Clin Allergy 17:529-36, 1987
3. Cockroft Am Rev Respir Dis 135:264-7., 1987
Allergy History
•
•
•
•
Demographics (age)
Symptoms: frequency and severity
Pattern: intermittent, persistent or seasonal
Response to environmental factors:
– Temperature changes, odors, humidity,
alcohol
• Occupation and hobbies
• Identification of allergens/irritants in the
home, office or environment
• Treatment, past and present: efficacy,
compliance, side effects
Allergy Symptoms
Clinical History Drives the Diagnosis
• Hypersensitivity to an injected,
ingested, or inhaled antigen in
response to a first exposure.
–
–
–
–
Skin: itch, rash, swelling, redness
Eyes: itchy, tears, watery, redness, crusting
Nose: runny, itchy, congestion, sneezing
Lung: wheezing, cough, tightness, shortness of
breath
– Stomach-Intestines: nausea, vomiting, bloating,
diarrhea
– Heart-Blood Vessels: anaphylaxis, syncope,
faintness, death
Allergy Physical Examination:
The Everted Eyelid
Allergy Physical Examination:
The Swollen Nasal Mucosa
Allergen extracts
• An allergen extract used for
diagnosis or treatment is prepared
by incubating the allergenic
material in a physiological buffer
followed by lipid extraction.
Selection of aeroallergens
• An evidence-based approach that
minimizes irrelevant test antigens
can reduce patient discomfort
and costs.
• An understanding of pollen
aerobiology and knowledge of
allergenic cross-reactivity
between regional pollinating
plant families is necessary in
selecting appropriate
aeroallergen test panels.
Practice Parameters for Allergy Diagnostic Testing
Ann Allergy 1995; 75:543-625
Skin testing and IgE antibody
serology
Powerful adjuncts for confirming
allergy in:
•
•
•
•
•
•
Rhinitis and sinusitis
Asthma, cough, dyspnea
Eczema
Food allergy
Insect sting allergy
Drug allergy (some i.e. beta-lactams and
local anesthetics)
• Occupational (some)
• Anaphylaxis
Confirmatory Skin
Testing
Use of skin prick tests
(SPT)
• Diagnosis of allergy
• Confirmatory evidence (positive, negative)
of IgE sensitization in support of the
clinical history
• Identifies the allergen against which IgE is
specifically directed, which is essential for
allergen avoidance measures
• Educational value: visual reinforcement
strengthens compliance of verbal advice
Skin prick testing
• SPT is easy to perform and rarely causes
generalized reactions.
• Patients may have positive SPT but no clinical
disease. A positive SPT indicates the presence
of IgE antibodies against that allergen but
does not indicate clinical sensitivity. A
correlation between the history and SPT is
essential.
• The results can be unreliable if the patient
takes certain drugs, such as anti-histamines
and tricyclic anti-depressants.
General rules for
successful SPT
• It is imperative that the technician performing the
skin tests as well as the clinician
ordering/interpreting these tests understands the
characteristics of the specific tests they are
administering.
• This includes:
– type of skin testing
– device used
– placement of tests (location and adjacent
testing)
– the particular extracts (source, concentration)
being used
– the potential confounder of medications that
may suppress skin test response.
Skin Prick Testing Solutions
Skin prick testing
Prick-prick test reactions
Not all allergens are available as a
skin test extract: fruit prick-prick
test
Puncture skin testing
devices
• There are several different
devices available for skin
prick testing.
QTS
GTK
• These devices result in
varying degrees of trauma
to the skin with differing
levels of skin test
reaction.
• Thus, the physician
should be familiar with
the characteristics of the
device used in his/her
practice, as each require
different criteria for what
constitutes a positive
reaction.
M
T
2
AS QT ST GP
QNT
Suppression of skin tests by
medication
• Most antihistamines and anti-depressants
suppress skin tests for 3-7 days.
• H2 antagonists have no, or a very minor,
effect.
• Bronchodilators do not affect skin tests.
• Short-term and low dose oral
corticosteroids have no effect.
– Reports vary on long-term high-dose
use.
Cook J Allergy Clin Immunol 1973;51:71-7
Rao KS J Allergy Clin Immunol 1988;82:752-7
Miller J J Allergy Clin Immunol 1989;84:895-99
Slott RIJ Allergy Clin Immunol 1974;554:229-34
Skin test safety
Review of surveys of fatal reactions
to skin testing between 1959-2001
• 9 deaths associated with skin testing
• 1 death associated with SPT
– History of unstable asthma with
FEV-1 36% 1 week prior
– Tested to 90 foods
Lockey JACI 1987;79:66077
Reid JACI 1993;92:6-15
Bernstein JACI
2004;113:1129-36
In-Vivo provocation tests
• Provocation tests involve the challenge of the
affected organ by serial
dilutions of an allergen extract or by the actual,
suspected allergen source
material, e.g. food or drug.
• A provocation test is time-consuming. It can
result in dangerous clinical
reactions and should only be performed by
experienced persons with
access to lifesaving equipment.
Due to space limitations, details of nasal, lung and
insect sting challenge tests will not be discussed
further in this presentation.
Confirmatory
Total and Allergen-Specific IgE
Antibody Serological Testing
Serological testing for allergen-IgE
antibody is recommended when InVivo tests cannot be used
Skin testing
• When the patient is taking anti-histamines or
other confounding medications for skin tests
• When the patient has eczema or
dermographism
• Immediately (up to 6 weeks) following an
anaphylactic event
• If the patient is morbidly afraid of skin
testing
Interpretation of allergenspecific IgE antibody
results
• Presence of allergen-specific IgE antibodies
in serum indicates sensitization. It does
not equal clinical symptoms.
• Serum IgE antibody is an absolute
prerequisite for the development of IgEmediated symptoms.
• With precise, quantitative assays, IgE
antibody production can be detected at an
early stage, even before clinical symptoms
have fully developed.
In Vitro testing
• Allergen
• IgE that is
specific IgE
free floating
that is bound
in patient’s
to patient’s
serum
mast cells
Clinical Utility of
Diagnostic
(Skin and Serology)
Confirmatory Tests
Prick skin tests correlate with
nasal challenge
Nasal Challenge (Pollen Grains)
1215
Relationship between
nasal challenges
with pollen grains and
skin prick test
Endpoints in patients
allergic to
Dactylis glomerata
405
135
45
15
0
0 1
2 3
4
5 6
Even SPT may result in
“false positives”
in respiratory allergy
• SPT results need to be interpreted
carefully. There MUST be a
correlation with the history
• Skin tests are a diagnostic tool, an
adjunct to the history, and do not
make the diagnosis
7 8
Prick Test Endpoint (Log3 Allergen Dose)
Rs= 0.54
p< 0.005
Bousquet Clin Allergy 1987;17:529-38
IgE antibody determination
allows evaluation of disease
prognosis
Early sensitization can be predictive of future
allergies:
• IgE antibodies to food early in life may be
associated with a high risk of developing IgE
antibodies to inhalants later in life.
• IgE antibodies to inhalants prior to
symptoms also predict evolving allergic
disease.
• Even low levels of IgE antibodies to an
allergen are of importance, since they can
predict a later development of symptoms
caused by this allergen.
Adinoff & Nelson. JACI 1990;86:766
Utility of In-vivo and I-vitro
diagnostic methods for cat
allergy: conclusions
• Both the SPT and IgE antibody serology
(Immuno-CAP System) exhibited an
equivalent excellent efficiency (83.1%, 83.4%)
in the diagnosis of cat allergy.
RA Wood, et al. JACI 1999;103:773
Tests for diagnosis of food
allergy
skin tests vs challenge test
• PPV of positive SPT - <50% vs
DBPCFC
• NPV of negative SPT - >95% vs
DBPCFC
Diagnosis of allergic diseases
summary
• The decision that the patient’s
symptoms and clinical signs represent
an allergic disease is made by an
experienced clinician on the basis of
the case history, physical examination,
and symptoms following allergen
exposure.
• Measurement of IgE antibodies by SPT
or serological assays confirm the
presence of specific IgE antibodies and
are an essential adjunct in making a
definitive diagnosis of allergic disease.