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The Diagnosis of Allergic Diseases

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Title: The Diagnosis of Allergic Diseases


1
GLORIA is supported by unrestricted educational
grants from
2
Global Resources in Allergy (GLORIA)
  • Global Resources In Allergy (GLORIA) is the
    flagship program of the World Allergy
    Organization (WAO). Its curriculum educates
    medical professionals worldwide through regional
    and national presentations. GLORIA modules are
    created from established guidelines and
    recommendations to address different aspects of
    allergy-related patient care.

3
World Allergy Organization (WAO)
The World Allergy Organization is an
international coalition of 74 regional and
national allergy and clinical immunology
societies.
4
WAOs Mission
WAOs mission is to be a global resource and
advocate in the field of allergy, advancing
excellence in clinical care, education, research
and training through a world-wide alliance of
allergy and clinical immunology societies
5
GLORIA MODULE 9The Diagnosis of Allergic
DiseasesDiagnosis of IgE SensitizationAuthorsM
ichael A Kaliner, USAStephen R Durham, UKRobert
Hamilton, USAS.G.O. Johansson, SwedenConnie
Katelaris, AustraliaJohn Oppenheimer,
USAReviewers Joaquin Sastre, Spain Cassim
Motala, South Africa
6
Nomenclature of allergy
Not IgE-mediated
Johansson SGO et al. Allergy 2001
and JACI 2004
7
Atopy
  • 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 2004113832-6
8
Allergic Disease Progression with Age
Saarinen UM et al. Lancet 1995
9
Pathophysiology of an Allergic Reaction
10
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
11
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 2006S16-12, 2.
Bousquet Clin Allergy 17529-36, 1987 3. Cockroft
Am Rev Respir Dis 135264-7., 1987
12
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

13
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

14
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15
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16
Allergy Physical Examination The Everted Eyelid
17
Allergy Physical Examination The Swollen Nasal
Mucosa
18
What is an Allergen?
  • An antigen causing an allergic disease is called
    an allergen.
  • Most allergens initiating an IgE-antibody
    mediated allergic reaction are glycoproteins with
    a molecular weight of 5 to 100 kD, most around 20
    kD.
  • Many pollen allergens are surface enzymes.
  • Some food allergens are remarkably stable and are
    stable even after cooking.
  • A genetically predisposed (atopic) person can
    become IgE-sensitized after several years of
    inhaling lt1 µg of grass pollen allergen per
    season.

19
Spectrum of Allergen Sources
20
Allergen Extracts
  • An allergen extract used for diagnosis or
    treatment is prepared by incubating the
    allergenic material in a physiological buffer
    (e.g., phosphate buffered saline) followed by
    lipid extraction.
  • The allergen content was commonly expressed in
    crude terms such as protein nitrogen units (PNU)
    or weightvolume, but it may now be expressed as
    micrograms of specific allergen per ml.
  • Several commercial extracts used in skin testing
    are standardized regarding allergen protein
    concentration, composition and lack of irritating
    contaminants.
  • In some countries such as the USA, grass,
    ragweed, dust mite and cat allergens are
    currently standardized

21
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.
  • Extensive allergenic cross-reactivity exists
    between northern pasture grasses, permitting the
    use of a single northern grass pollen for testing
    in most regions outside of southern regions of
    North America and Europe

Practice Parameters for Allergy Diagnostic
TestingAnn Allergy 1995 75543-625
22
Allergy Diagnosis - Definitions
  • Sensitivity proportion of subjects with allergy
    who test positive
  • Specificity proportion of subjects without
    allergy who test negative
  • PPV probability that a subject has allergy if
    they test positive
  • NPV probability that a subject does not have
    allergy if they test negative
  • Efficiency of allergy patients correctly
    classified as diseased and not diseased

23
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

24
Confirmatory Skin Testing
25
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

26
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.

27
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.

28
Skin Prick Testing Solutions
29
Skin Prick Testing
30
Not all Allergens are Available as a Skin Test
Extract Fruit Prick-Prick Test
31
Prick-Prick Test Reactions
32
Skin Testing with Natural Foods in Subjects
Suspected of Having Food Allergy
  • 22 patients with highly suspected food allergies
    but with negative SPT to commercial extracts had
    positive prick-prick skin tests with fresh
    natural foods - 7 fish and seafood- 4 fruit
    and vegetable- 9 peanut and tree nuts- 1 milk-
    1 egg

Rosen. J Allergy Clin Immunol 1994931068
33
Puncture Skin Testing Devices
  • There are several different devices available for
    skin prick testing.
  • 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.

34
Intracutaneous Skin Testing (ICT)
  • ICT should be interpreted cautiously. Many
    positive reactions (up to 70 according to some
    published reports) are not clinically relevant.
  • Because ICT uses larger volumes of injected
    allergen preparations, there may be some irritant
    reactions not mediated by an allergic mechanism.
    Many drugs may directly stimulate mast cells to
    release mediators.
  • The incidence of severe systemic effects, while
    rare, are more likely to occur with ICT than with
    SPT

35
Comparison of SPT and ICT
  • Advantages of SPT Advantages of ICT
  • Safer More sensitive
  • More rapid (300 to gt1000 fold)
  • Less discomfort to patient More reproducible
  • Technically less demanding More positives
  • More specific
  • More allergens in one session
  • Allergen more stable (50 glycerin)
  • Positive and negative tests more easily
  • distinguished
  • Steeper dose response curve
  • Positive tests correlate better with clinical
    disease

36
Recording Skin Test Responses
  • Results of both SPT and ICT skin tests should be
    reported in the most quantitative
  • terms possible.
  • Reports of minimal usefulness include
  • Positive or negative
  • 0 to 4 (unless accompanied by an indication of
    what these numbers represent).
  • Useful to report both wheal and flare
    measurements in mm
  • A superior method is to measure the reaction in
    mm across the cross-diameter
  • Area (cross-diameter in mm) of the wheal and
    erythema is the most accurate way to present
    results.
  • Measurements of
  • the product of the orthogonal diameters
  • the sum of the orthogonal diameters
  • the longest diameters
  • Correlate very well with area (r values greater
    than 0.9).

Ownby JACI 198269536-8
37
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38
Are Skin Tests Easy to Interpret?
39
Reproducibility of Skin Test Scoring and
Interpretation by Board-Certified/Eligible
Allergists
  • Methods
  • Series of SPT were digitally photographed
  • 22 tests with controls
  • a questionnaire regarding interpretation was sent
    to 70 allergists to assess
  • positive, negative or intermediate
  • positive or whether a ICT test was desired

McCann Ann Allergy Asthma Immun 200289368-71
40
Reproducibility of Skin Test Scoring and
Interpretation by Board-Certified/Eligible
Allergists
  • Results
  • 33 interpretable responses
  • 24 relied on a grading scale (0-4)
  • 2 measured in mm,
  • 7 provided only interpretation with no grading
  • Greatest agreement with median/mode score 4
  • Least agreement with median/mode score 1-2
  • Range of requested ICT test was 0-11 tests
  • Conclusion
  • Significant variability in scoring and
    interpreting skin tests
  • Reinforces the need to report skin test reactions
    by measuring and recording reaction size in mm

McCann Ann All Asthma Immun 200289368-71
41
Inter-Individual Variation in SPT
  • CV
  • 55.9
  • 16.6
  • 42.8
  • 24.7
  • 43.3
  • 26.5

CV inter-individual coefficient of variation,
Target lt 25 Vohlonen I et al. Allergy 1989
44 525-531
42
www.AAAAI.ORG
43
Suppression of Skin Tests by Medication
  • Most antihistamines and anti-depressants suppress
    skin tests for 3-7 days. Astemizole suppresses
    for 1-3 months.
  • 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 19735171-7 Rao KS J
Allergy Clin Immunol 198882752-7 Miller J J
Allergy Clin Immunol 198984895-99 Slott RIJ
Allergy Clin Immunol 1974554229-34
44
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 198779660-77 Reid JACI
1993926-15 Bernstein JACI 20041131129-36
45
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.

46
Food Allergy Diagnosis Oral Food challenges
  • Challenge typesOpen useful when the history
    is vague and when the reaction is likely to
    be negative (-ve specific IgE antibodies and
    unconvincing history)Single blind
    useful to confirm negative reactions useful to
    confirm non-subjective reactionsDouble Blind
    Placebo Controlled (DBPCFC) gold standard -
    mandatory for research studies usually
    definitive excellent for subjective reactions
    alternate placebo and active randomly

47
Confirmatory Total and Allergen-Specific IgE
Antibody Serological Testing
48
Serological Tests Performed in Diagnostic Allergy
Laboratories
  • Allergen-specific IgE (over 400 allergen
    specificities)
  • Pollen (weeds, grasses, trees), Epidermals, Dust
    Mites, Molds, Foods, Venoms, Drugs, Occupational
    allergens (Ispagula, Natural Rubber Latex)
  • Total Serum IgE (Xolair anti-IgE ABPA)
  • Phadiatop (Multi-allergen screen) IgE (define
    atopy)
  • Fx5e (Multi-allergen screening test for foods)
  • Mast Cell Tryptase (indicator of anaphylaxis)
  • Eosinophil Cationic Protein (eosinophil
    activation marker)
  • Precipitin-IgG antibody (Hypersensitivity
    Pneumonitis, anaphylactic reactions to dextran)

49
Total Serum IgE Levels in Allergy
  • Patients with allergic asthma may have increased
    total serum IgE concentrations, but this is not
    an allergy-specific finding
  • 60 of allergic asthmatics have increased IgE
  • 40 of allergic rhinitis patients have
    increased IgE
  • Measurement of total serum IgE may be of value in
    patients with
  • Gastrointestinal symptoms/eosinophilic
    esophagitis
  • Suspected occupational allergy with unclear
    genesis
  • Anaphylaxis
  • Allergic Bronchopulmonary Aspergillosis (ABPA)
  • Allergic Fungal Sinusitis
  • Total serum IgE may be measured to determine the
    dosage of omalizumab

50
Some Disorders with Elevated Total Serum IgE
Levels
  • Helminth infestation, e.g. Ascaris, Schistosoma
  • Infections with Staphylococcal strains containing
    enterotoxins, so called super-antigens
  • Virus infections, e.g. cytomegalovirus (CMV)
  • ABPA and Allergic fungal sinusitis
  • Graft Versus Host Disease (GVHD)
  • Hyper-IgE Syndrome

51
Serological Testing for Allergen-IgE Antibody is
Recommended when In-Vivo Tests Cannot be Used
  • 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

52
Allergen-Specific IgEIn-Vitro and In-Vivo Tests

  • In-vitro In-vivo
  • IgE
    Antibody SPT
  • Serology
  • High sensitivity Yes Yes
  • High specificity Yes Yes
  • High reproducibility Yes Yes
  • Quantitative results in kIU/L Yes No
  • WHO Standard calibrated Yes No
  • Quality assurance test program Yes No
  • Can be used independently Yes No
  • of pharmaceutical treatment
  • Can be used independently Yes No
  • of patient skin status
  • Time factor 1-7 days 15-30 minutes
  • Cost factor more expensive inexpensive
  • Usefulness in motivating patients obscure dramatic

53
Evolution in Specific IgE Antibody Assay
Technology
  • 1st generation manual chemistries
  • RAST Radio Allergo Sorbent test, Phadia 1974
  • Hycor Hy-Tec (paper disc based)
  • FAST Allergenics/Biowhittaker, fluorescent
    allergosorbent test
  • MAST Hitachi thread pipette
  • EAST Sanofi Dignostics Pasteur
  • Magic Lite ALK/Corning/Bayer
  • Matrix Abbott
  • 2nd generation (semi-automated chemistries)
  • Alastat, Diagnostic Products Corp. (DPC,
    biotin-allergen)
  • Pharmacia CAP System , ImmmunoCAPTM 3D Solid
    Phase, Phadia 1989
  • 3rd generation (autoanalyzers)
  • Immulite 2000 Diagnostic Products Corporation
  • ImmunoCAP 250TM, 1000) Phadia 2001
  • Phadia is the new name of Pharmacia Diagnostics
    (2006)

54
Evolution from Qualitative to Quantitative IgE
Antibody Results
  • 1974-80 PRU/ml Phadebas Relative Units
  • 1980s-1990s AU/ml AU allergen unit
  • Normalized Counts, ASM (adjusted counts)
  • sIgE/ml, IU/ml, FSU/ml, VRU/ml
  • EAU/ml Classes
  • 1997 Clinical and Laboratory Standards
    Institute LA20A Evaluation Methods and
    Analytical Performance of Immunological assays
    for human IgE Antibody (www. CLSI.org)
  • 1989-present kIU/L or kIUa/L (interpolation from
    total serum IgE heterologous dose response curve
    traceable to WHO 75/502 IgE Serum Standard) 1U
    2.44 ng of IgE

55
Design of Serological Assays for Allergen
Specific IgE Antibody
  • Step 1
  • Separate allergen-specific IgE from other
    antibodies present with a solid phase
    allergosorbent
  • Step 2
  • A buffer wash separates bound IgE from unbound
    antibodies
  • Step 3
  • Bound IgE is detected with a labeled anti-human
    IgE reagent

JACI 2003111S687-701
56
Solid Phase Allergosorbent
  • As with skin testing, the allergen used in the
    solid phase is critical to the validity of the
    test
  • Characterization of allergen
  • Ensure that critical antigen epitopes are on the
    solid phase
  • Antigen epitopes should be present in excess to
    maximize binding of IgE antibody
  • If not in excess, can have competitive binding
    from antibody of other isotypes (IgG)
  • Antigen excess binds IgE in an affinity-independen
    t fashion

57
Illustration of a Widely Used Assay (ImmunoCAP
System) for Allergen Specific IgE Quantification
Patient IgE
Allergen coupled to ImmunoCAP
Conjugate Enzyme Anti-IgE
Patient IgE ab bound to ImmunoCAP allergen
Fluorogenic substrate
Conjugate bound to patient IgE
Conjugate enzyme reacts with substrate forming a
fluorescent product
58
The Clinical Validity of IgE Antibody Serology
Testing
Sensitivity 89 Specificity 91
UniCAP Specific IgE Physicians
conclusion Positive Negative Total Positive
1121 144 1265 Negative 360 3545 3905 Total 1481 3
689 5170
  • The clinical performance of UniCAP Specific IgE
    was documented in clinical trials in six
    countries Italy, Spain, Germany, The
    Netherlands, Sweden and Great Britain, on 894
    patients with suspected allergy.
  • Clinical sensitivity and sensitivity were
    calculated as agreement between the test result
    and a specialist diagnosis based on the
    established diagnostic routines of the clinic.

Paganelli R et al., Allergy 1998 53 763-8
59
Proficiency and Quality Control
  • Clinical and Laboratory Standards Institute
    Guideline
  • Evaluation of Methods and Analytical Performance
    Characteristics of Immunological Assays for Human
    Immunoglobulin E Antibodies of Defined Allergy
    Specificities
  • Recommends quality control for daily performance
    of testing with minimal performance targets for
    IgE antibody assays
  • Intra-assay and Inter-assay coefficient of
    variation in IgE antibody assays should not
    exceed 10 and 15, respectively.
  • Laboratories encouraged to participate in an
    inter-laboratory external proficiency testing
    program 3 cycles per year, 5 or 6 sera per
    cycle, measure total IgE, multi-allergen screen,
    specific IgE to 5 allergen specificities in each
    cycle
  • Laboratories should be credentialed (licensed) by
    appropriate government agencies
  • Document available from CLSI (www.CLSI.org I/LA20
    guideline)

60
Interpretation of Allergen-Specific 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 IgE-mediated symptoms.
  • With precise, quantitative assays, IgE antibody
    production can be detected at an early stage,
    even before clinical symptoms have fully
    developed.

61
Controversial Unproven In-Vitro Allergy Tests
  • Tests with no diagnostic value for any disease
    under any circumstance (not based on sound
    scientific principles)
  • Cytotoxic test,
  • Antigen leukocyte cellular antibody test
    (ALCAT)
  • Tests intrinsically capable of valid
    measurements effective/appropriate for
    diagnosing certain diseases but not for allergy
  • Serum IgG antibodies
  • Total serum immunoglobulin (IgG/IgA/IgM)
  • Cytokine/cytokine receptor assays
  • Lymphocyte subset counts, lymphocyte function
    assays
  • Chemical analysis of body fluids/tissues
  • Food immune complex assays
  • Practice Parameters for Allergy Diagnostic
    Testing. Ann. Allergy 1995 75 616

62
Cytotoxic Test Unproven Diagnostic Utility
  • Method
  • Buffy coat from centrifuged whole blood is placed
    on
  • Siliconized microscope slide previously coated
    with dried extracts of up to 150 to 200 foods.
  • Interpretation
  • Unstained cells are viewed microscopically at
    varying
  • intervals up to 2 hours for changes in shape and
    appearance of
  • leukocytes. Swelling, vacuolation, crenation,
    lack of movement
  • evidence of allergy to food.
  • Concerns
  • Incubation time, pH, osmolarity not standardized.
  • Controlled studies show results are
    non-reproducible and do not
  • correlate with clinical evidence of food allergy.
  • Practice Parameters for Allergy Diagnostic
    Testing. Ann. Allergy 1995 75 616

63
Performance Characteristics and Clinical
Utility of Diagnostic(Skin and Serology)
Confirmatory Tests
64
Prick Skin Tests Correlate with Nasal Challenge
1215
Relationship between nasal challenges with pollen
grains and skin prick test Endpoints in patients
allergic to Dactylis glomerata Bousquet Clin
Allergy 198717529-38
405
Nasal Challenge (Pollen Grains)
135
45
15
0
5
7
8
6
0
1
2
3
4
Prick Test Endpoint (Log3 Allergen Dose)
Rs 0.54 plt 0.005
65
Even SPT May Result in False Positivesin
Respiratory Allergy
  • Skin prick tests are positive in many patients
    who have no respiratory symptoms- 42 with a
    positive family history for asthma or rhinitis
    may have SPT and no disease.
  • - 29 of those with a negative family history
    for asthma or rhinitis may have SPT.
  • 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

Adinoff Nelson. JACI 199086766
66
SPT vs ICT Skin Tests inDiagnosis of Allergic
Diseases
In patients who had history of spring
allergy-like symptoms but a negative SPT to
timothy grass, there was no difference in nasal
challenge or correlations between symptoms and
pollen counts during the grass season in those
with positive or negative ICT to grass.
Nelson. JACI 1996971193-1201.
67
Evidence Based Medicine
  • Likelihood ratio
  • the ratio of post-test odds after a test result
    to the pre-test odds indicates how much the odds
    change after a test
  • Likelihood ratios (positive negative)
  • gt5.0 or lt 0.2 generate moderate to large shifts
    in disease probability
  • 1.0 to 2.0 and 0.5 to 1.0 generate very small and
    often clinically insignificant changes in disease
    probability

Jaeschke JAMA 1994271703-7
68
SPT vs ICTComparison Using Evidenced Based
Medicine
Conclusion SPT relate closely to disease, while
ICT do not (there are presently no available data
in children or in allergens other than cat and
grass).
Gendo Ann Int Med 2004140278-89
69
Allergy Skin Testing (SPT vs ICT) Conclusions
  • Skin Prick Tests
  • - Diagnostically sensitive, safest, easy to
    perform and may even detect
  • asymptomatic sensitivity- Correlate well
    with clinical rhinitis asthma
  • - Correlate well with challenge tests and
    IgE antibody serology
  • measurements
  • Intradermal Skin Tests
  • - Do not differentiate clinically allergic from
    non-allergic subjects in
  • epidemiologic studies or in studies of cat
    and grass sensitivity in
  • adults.

70
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.

71
IgE Antibodies to Food Early in Life Predict
Later IgE Antibodies to Inhalants
Development of positive Dermatophagoides
pteronyssinus IgE Values at 5 yrs of age
RAST IgEs at



No.
n

six months of age
Specific IgE for egg white
54
46
85
Positive finding
54
8
15
Negative finding
Specific IgE for cow's milk
31
29
94
Positive finding
77
25
Negative finding
32
Specific IgE for soy
16
16
100
Positive finding
41
92
38
Negative finding
plt0.001, by chi-square test
Reference Data from Sasai et al., J Pediatr
1996 128 834-840
72
Asymptomatic Skin Sensitization to Birch May
Predict Development of Birch Pollen Allergy in
Adults
  • Methods
  • Asymptomatic adults were followed through use of
    daily diary cards during 3 consecutive birch
    pollen seasons
  • 15 SPT for birch
  • 15 non-atopic controls
  • 6 birch pollenallergic patients
  • At the 3-year follow-up visit, conjunctival and
    nasal challenges, intradermal late-phase reaction
    evaluation, and measurement of birch specific IgE
    were performed.

JACI 2003111149-54.
73
Asymptomatic Skin Sensitization to Birch May
Predict Development of Birch Pollen Allergy in
Adults
  • Results
  • Asymptomatic SPT subjects had both birch
    specific IgE levels and positive conjunctival
    provocation testing.
  • Sixty percent (n 9) of the asymptomatic
    sensitized subjects developed clinical allergy in
    the three year period.
  • The development of clinical allergic disease was
    associated with an initial birch skin prick test
    wheal diameter of gt4 mm.
  • IgE antibodies 0.7kU/L (class 2) was 87.5
    predictive of allergy development
  • Conclusion Positive skin prick test in an
    asymptomatic patient may
  • indicate potential for development of allergy in
    the future.

JACI 2003111149-54
74
A Comparison of SPT, ICT and IgE Serology in the
Diagnosis of Cat Allergy
  • Methods
  • 120 patients with asthma, with or without a
    history of cat allergy were challenged with a
    characterized cat challenge model after a
    clinical history, SPT, ICT and IgE Serology
    (ImmunoCAP System).
  • Challenge was positive if upper respiratory
    symptom score was gt0.5, mean lower respiratory
    symptoms score was gt 0.4 or maximum fall in FEV1
    was gt 15

RA Wood, et al. JACI 1999103773
75
Diagnosis of Clinically Significant Cat
Sensitivity
  • Category Positive Cat Challenge
  • SPT 38/41 (92.7)
  • SPT - 10/39 (25.6)
  • ICT 6/26 (23.1)
  • ICT - 4/13 (30.8)
  • IgE anti-Cat Serology 27/27 (100)
  • IgE anti-Cat Serology - 11/44 (25.0)
  • In patients with a negative SPT, there was no
    correlation between positive or negative ICT and
    challenge results

RA Wood, et al. JACI 1999103773
76
Utility of In vivo and In 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.
  • ICT results added little to the diagnostic
    evaluation, exhibiting a low diagnostic
    efficiency (38.5)
  • RA Wood, et
    al. JACI 1999103773

77
Quantification of IgE Antibodies in Diagnosing
Food Allergy
Objective Compare results of CAP system
FEIA to outcome of SPTs and Double Blind
Placebo Controlled Food Challenge
(DBPCFC) Population 196/320 well characterized
pediatric patients Age mean 5.2 years
range 0.6-18 years Gender 117 male 79
female Evaluation IgE mediated reactions by
history, SPTs, DBPCFC and open challenges
Sampson and Ho 1997 100 444-51
78
Performance Characteristics of ImmunoCAP at
Cut-off 0.35 kU/L
Sampson, Ho.1997100
79
Tests for Diagnosis of Food AllergySkin tests vs
Challenge Test
  • PPV of positive SPT - lt50 vs DBPCFC
  • NPV of negative SPT - gt95 vs DBPCFC

80
Performance Characteristics of SPT at 3mm vs
DBPCFC
Sampson, Ho, 1997100
81
Size of SPT with 100 Likelihood of Positive Open
Challenge
Sporik et al Clin Exp Allergy 200030
82
Predictive Values for CAP RASTS vs Challenges
  • 95 predictive value
  • Egg 7 Ku/L (2 Ku/L)
  • Milk 15 Ku/L (5 Ku/L)
  • Peanuts 14 Ku/L
  • Fish 20 Ku/L
  • Negative Predictive value 95
  • Sampson H. Ho D. JACI 2001

83
Diagnosis of Allergic DiseasesSummary
  • The decision that the patients 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.

84
World Allergy Organization (WAO)
For more information on the World Allergy
Organization (WAO), please visit
www.worldallery.org or contact the WAO
Secretariat 555 East Wells Street, Suite
1100 Milwaukee, WI 53202 United States Tel 1
414 276 1791 Fax 1 414 276 3349 Email
info_at_worldallergy.org
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