The Diagnosis of Allergic Diseases

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  and national presentations. GLORIA modules are
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  allergy-related patient care.

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The World Allergy Organization is an
international coalition of 74 regional and
national allergy and clinical immunology
societies.
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WAOs mission is to be a global resource and
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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
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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
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Allergic Disease Progression with Age
Saarinen UM et al. Lancet 1995
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Pathophysiology of an Allergic Reaction
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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
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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
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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

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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

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Allergy Physical Examination The Everted Eyelid
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Allergy Physical Examination The Swollen Nasal
Mucosa
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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.

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Spectrum of Allergen Sources
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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

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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
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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

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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

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Confirmatory Skin Testing
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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

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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.

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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.

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Skin Prick Testing Solutions
29
Skin Prick Testing
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Not all Allergens are Available as a Skin Test
Extract Fruit Prick-Prick Test
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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.

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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

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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

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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
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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
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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
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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
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www.AAAAI.ORG
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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
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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
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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.

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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

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Confirmatory Total and Allergen-Specific IgE
Antibody Serological Testing
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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)

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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

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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
  

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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)
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414 276 1791 Fax [phone] Email
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