Transcript Skin Prick Testing Workshop

GP CME Allergy
Diagnosis Workshop
Waipuna Conference Center
Friday 13 August 2010
Vincent St Aubyn Crump
Plan for Talk
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Overview of Allergy Diagnosis
Skin Prick Test & Prick-Prick Test
ImmunoCAP Specific IgE
Comparison of the two with emphasis on
the diagnosis & follow-up of Food Allergy
Penicillin Allergy
Atopy Patch test
Cases for Discussion
Clinical Assessment
Pre-test Probability score
Specific- IgE Tests
Skin Prick Tests
Prick-Prick Test
Serum IgE levels
Provocation Tests
Oral Challenge
 DBPCFC
Nasal & Bronchial Challenges
oImmuno-CAP (RAST)
Test for Delayed Hypersensitivity
Patch Tests
oContact Dermatitis
oDelayed food reactions
oDrug reactions
Pre-test probability In
Allergy diagnosis
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Is defined as the probability of the
allergic disorder being present, before
a diagnostic test result is known
Is useful in interpreting the results of
all allergy tests
Is useful in deciding whether it's worth
doing the allergy testing at all
High Pre-probability score
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Anaphylaxis* after eating known food
allergen
Very good history temporally compatible
with an IgE-mediated (Immediate) reaction
Reliable witness for reaction
Presence of objective signs of known IgEmediated reactions
Presence of Atopy (Asthma, eczema & hay
fever)
1 of the 8 common food allergen implicated
No other non-allergic explanation for
symptoms
Likelihood Ratio (LR)
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The Likelihood Ratio (LR) is the likelihood
that a given test result would be expected in
a patient with the target disorder compared
to the likelihood that that same result would
be expected in a patient without the target
disorder.
LR positive = sensitivity / (1 - specificity)
LR negative = (1 - sensitivity) / specificity
LR is better than sensitivity & specificity
because it is less likely to change with
prevalence of disorder
Total IgE
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IgE represents <0.001% of total Igs
Majority of IgEs are bound to surface of mast cells
and basophils
~ 50% of patients with allergic rhinitis or asthma
will have elevated IgE
Total IgE more often elevated in AD, and correlates
with severity of AD
Total IgE also elevated in:
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Parasitic Infections
Bronchopulmonary Aspergillosis
Immunodefieciecy, such as HIV infections
Cigarette smoking
Total IgE
Total IgE – Normal Reference Interval
Age (years)
<1
1-4
5 – 10
11 – 15
>15
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Range (IU/ml)
1-52
0-352
0-393
2 – 170
0 – 158
Very high levels of total IgE can give false positive Specific
IgE results (multiple allergens tested positive), due to nonspecific binding of IgE antibodies
Disease indications for
skin prick testing
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To confirm atopy, assisting in the diagnosis of asthma, eczema in
infants
– Especially differentiating transient wheezers in infancy from
persistent / asthmatics
Before initiating immunotherapy
To monitor progress during immunotherapy
Acute Urticaria & Anaphylaxis
All asthmatics requiring therapy
Occupational Diseases including latex allergy
Eczema
Some drug reactions: Penicillin, some herbals such as Echinacea.
In an Australian study ~50 % of cases of allergy to Echinacea,
were thought to be IgE-mediated, and skin prick testing was
helpful in their diagnosis.
Stinging insect anaphylaxis
Rhinitis vs Sinusitis
Diagnosing IgE-mediated food:
Skin Prick Test
 Skin Prick Tests are used to screen patients for
sensitivity to specific foods
 Allergens eliciting a wheal of at least 3 mm greater
than the negative control are considered positive
 Overall positive predictive accuracy is < 50 %
 Negative predictive accuracy > 95 % (negative
skin test results essentially confirm the absence
of IgE-mediated reactions)
Diagnosing IgE-mediated food
hypersensitivity disorders with
ImmunoCAP
 Sensitivity similar to skin prick tests (slightly less)
 Good correlation with other procedures
 Efficiency: Depends on the allergen
 Indicated if SPT are contraindicated (eg, skin disease,
medications)
 Useful if discrepancy exists between history and SPT
 The use of quantitative measurements has shown to be
predictive, for some allergens, of symptomatic IgEmediated food allergy
Comparison of in-vivo (SPT) with
in-vitro Immuno CAP-RAST
Feature
Availability
Speed of results
Sensitivity
Specificity
Standardization
Quantification
of results
Temp. Stability
Reagent stability
Drugs effects
Educational
Importance
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SPT
CAP-RAST
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When should skin prick tests not be
done or should be done with extra
caution?
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For mass screening in the general population. Up to
40% of adults will have positive skin prick tests to
insect venoms, but only a small percent experience
anaphylaxis to venoms. Having a positive skin prick
test to a venom will not predict if that individual will
get anaphylaxis, if stung by that insect
In presence of dermographism
Patient unable of unwilling to stop medications like
antihistamines and some antidepressants
Allergy to fruits & Vegetables. Do prick-prick test
instead
Within 6 weeks of an anaphylactic reaction.
If therapy for anaphylaxis is not readily available
Extreme caution in pregnancy
Drugs affecting Skin Prick
Test
Drug
Degree of supression
Duration of supression
Loratidine
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3 – 5 days
Cetirizine
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3 -5 days
Phenergan
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3 – 10 days
Astemizole
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>1 month
Cimetidine
0 to +
not significant
Ranitidine
+
not significant
Famotidine
0 to +
probably not significant
Ketotifen
++++
> 5 days
Imipramines
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>10 days
Phenothiazines
++
Nasal steroids
0
Topical steroids
0 to ++
Systemic steroids > 2 weeks & > 20mg / day reduces wheal & flare
Montelukast
0
Cyclosporin
0
EMLA cream reduces the flare but not the wheal
Skin Prick Test Form
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Practice name / Ordering physician:
Street address
City
Telephone
Fax
Patient name: ______________________________ Date of birth: __/__/__
Testing Technician: _______________________
Last use of antihistamine (or other med affecting response to histamine): ___ days
medication __________________
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Testing Date (s) and Time: Percutaneous __/__/_____________AM PM
Intradermal __/__/_____________AM PM
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General information about skin test protocol
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Percutaneous reported as: Allergen: Testing concentration: Extract company (*see below)
Location: back__ arm___
Device: _________Intradermal: 0.__ml injected,
Location: arm Testing concentration: 1:___ w/v or BAU or AU/ml, PNU
Results Longest diameter (Left in this example) or longest diameter and orthogonal diameter (Right in
this example) of wheal (W) and erythema (flare) (F) measured in millimeters at 15 minutes
– Blank in results column indicates test was not performed, O=negative
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* Extract manufacturer abbreviations:, STG= Stallergens, AK=ALK Abello, AD=ALK (Denmark), H=Hollister–Stier,
Allergen:Concentration:
Skin Prick Test Allergen: Concentration:
Skin Prick Test .
Extract Manufacturer.
Wheal Flare *Extract Manufacturer. *
Wheal Flare
Allergens
(W)
(F)
Allergens:
(W)
(F) .
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House dust mites
Milk
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Cat
Egg
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Dog
Wheat
–
Interpretation of Test
Results
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The wheal & flare should be recorded in millimeters
3 mm is considered the cut-off for positive, but may
overestimate clinical allergy!
All results should be compared to the negative and
positive control
If negative control is positive the patient has
dermographism, and entire test is invalid
If histamine control is negative, the results are
probably being inhibited by antihistamines (Patients
do forget!)
In hyperpigmented skin the indurations might have
to be palpated
Remember that sensitivity (positive skin prick tests)
does not mean clinical reactivity or allergy.
Size of SPT wheal (mm) 100%
likelihood of + Challenge
Milk
>6
Children: all ages (medium =3 yrs) >8
Children: 0-2 years of age
Egg
Peanut
>5
>7
>4
>8
Note: Results may vary widely due to lack of standardization of
SPT (extracts, devices)
(Clin Exp Allergy 200; 30:1540-1546)
Comparison of Skin Test
(>3mm) vs. DBPCFC
NPV
PPV
Food
High Risk
Low Risk
High Risk
Low Risk
Egg
90 %
99%
85%
17%
Milk
90%
99%
66%
2%
Peanut
75%
99%
55%
15%
Soy
84%
97%
35%
12%
Wheat
94%
98%
35%
15%
Fish
80%
99%
77%
30%
History of RAST
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RAST (radioallergosorbent test) invented and
marketed in 1974
The suspected allergen is bound to an insoluble
material and the patient's serum is added
If the serum contains antibodies to the allergen,
those antibodies will bind to the allergen
Radiolabeled anti-human IgE antibody is added
where it binds to those IgE antibodies already
bound to the insoluble material
The unbound anti-human IgE antibodies are
washed away.
The amount of radioactivity is proportional to the
serum IgE for the allergen
Immuno CAP Specific IgE
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In 1989, Pharmacia Diagnostics AB
replaced RAST with a superior test
named the ImmunoCAP Specific IgE
blood test
Also describe as CAP RAST or CAP
FEIA (fluoroenzymeimmunoassay)
ImmunoCAP (RAST)
Food Specific Ige (immuno-CAP RAST) values
at /or above which there is a 95% risk of
Clinical Allergy (no challenge necessary)
Food___
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_Serum IgE (kIU/L) for 95% PPV
Egg (child)
Egg (age <2 yr)
Cow’s milk (child)
Cow’s milk (age <2 yr)
Peanut
Fish
>7
>2
>15
>5
>14
>20
ImmunoCAP Sensitivity
compared to skin test and
clinical diagnosis: Caveat
For animal and mould allergens, a high
proportion of positive skin test results were
disregarded (i.e. considered as false
positive)
compared to
Allergen
Clinical diagnosis
SPT
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Cat
Mould
84%
79%
66%
58%
Performance characteristics of
diagnostic tests for peanut
allergy
Diagnostic test
Sensitivity % Specificity % PPV % NPV %
Skin Prick Test
>95
30-60
<50
>95
CAP-RAST
(If >15kU/L)
57
100
100
36
Food Challenge
~100
~100
~100
~100
Specific IgE level related to the
probability of a food reaction
Food-specific IgE level (measured by ImmunoCAP-specific IgE blood test)
and probability of reacting to that food after challenge
Predicted relationship
between specific IgE and
challenge for peanuts
Predicted relationship between skin
prick test result and challenge for
peanuts.
Improved screening for peanut
allergy by combining SPT to
raw peanut & ImmunoCAP
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SPT with raw peanut extract superior to commercial
extract
If SPT to raw extract <3mm: 100% certainty child is not
allergic to peanut
If SPT to raw extract >3mm: 74% certainty of allergy
However, if raw extract > 16mm: 100% certainty of
peanut allergy
If ImmunoCAP > 57KU (A) / L = 100% positive
predictive value
DBPCFC can be avoided if:
– SPT to raw extract <3mm and ImmunoCAP <57
KU/L and also when
– SPT to raw extract >16mmm or CAP > 57 KU/L
JACI Vol 109, 6,June 2002, Pg 1027-33
Diagnosing food hypersensitivity
disorders: Summary
Skin tests
Prick:
Reproducible, sensitive, not irritant
Prick-prick:
Use raw or cooked food. Highly recommended
for fruits and vegetables (commercially
prepared extracts are generally inadequate
because of the lability of the allergens, so the
fresh food must be used for skin testing)
 CAP-RAST: Good for follow-up for out-grown allergy.
 Patch test:
Atopic dermatitis, delayed reactions, fresh
food is recommended
ImmunoCAP RAST for
diagnosis of peanut, tree
nut & seed allergy
Patients referred for peanut or tree nut allergy
Organ system involvement with
peanut, tree nut, and seed
reactions.
A, Tree nut allergy and sensitization rates in patients
with peanut allergy (n 5 234). B, Tree nut allergy
rates in relation to peanut allergy for patients with tree
nut allergy (n 5 128). TN, Tree nut.
Peanut
Tree Nut
Penicillin Skin Prick Test
& Intradermal testing
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Benzyl Pennicillin
Penicillin Polylysine (major
determinant)
Minor determinant mixture
Amoxycillin
Augmentin
Flucloxacillin
Skin Testing in suspected
penicillin allergy
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In USA study: 566 history positive pts with
negative SPT received penicillin:
– 1.2% had possible IgE rxn
– None of the 568 history negative and SPT
negative pts had any rxn
– Of the 167 SPT positives, 9 received penicillin
and only 2 had IgE-compatible rxn
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Conclusion: Skin testing for penicillin is
sensitive but not very specific
Penicillin skin testing
contd.
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Review by Weiss & Adkinson in 1988:
– In pts with positive history & positive SPT only a
50 – 70% risk of drug rxn
– Benzylpennicilloyl –specific IgE detetcted in 6095% of pts with positive SPT to
peniilloylpolylysine
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1983-90, 175 pts referred by GPS to allergy
clinic, with h/o immediate rxn to penicillin.
– 132 tested & 4 had positive ImmunoCap RAST
– The 128 that tested negative challenged with
oral penicillin and none reacted
– So, Clinical sensitivity is good
Immuno CAP vs SPT to
penicillin
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Specificity of CAP RAST to Pen G, Pen
V, Ampicillin and amoxil was 89%
when compared to negative SPT in
105 pts with positive history
Penicillin allergy: Incidence
of positive SPT &
ImmunoCAP
300 children with suspected penicillin allergy evaluated in OPD:
SPT with Benzylpennicilloyl-polylysine (Major determinant) & Minor determinant mixture
(MDM)
RAST performed with Benzylpennicilloyl and phenoxymethylpenicilloyl conjugated on disc
Procedure
Skin Tests
– Major determinant
– Minor determinant
– Both
RAST
SPT & RAST
Skin Test only
RAST only
Children with positive results
48
(16) *
30
11
7
42
33
15
9
*% of total number of children
(14)
(11)
(5)
(3)
57 (19)
Relationship of positive penicillin
test to time elapsed since adverse
reaction
Time interval (months)
1–3
4 – 12
13 – 60
> 60
% with pos results
18.6
9.3
4.5
1.9
Archives of Childhood Disease, 1980, 55, 857-860
Relationship of positive
result to speed of adverse
reaction
Duration of Rx with Pen
% with positive
results
Before rxn (hrs)
_______________________________________________
<12
21.2
13 – 24
11.9
25 – 48
6.3
49 – 72
2.1
>72
1.9
Archives of Childhood Disease, 1980, 55, 857-860
Relationship of positive
results to the type of
adverse rxn
Manifestation
Accelerated skin rash*
Delayed skin rash**
Urticaria
Angioedema
Serum Sickness
Anaphylaxis
% with positive results
25
5.6
36.7
54.4
100
100
*Skin rash appearing within 24 hrs of Rx
** Skin rash observed >24hrs after starting pen
Steroid Testing:
Skin Prick & I/D
(or Patch Test)
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Prednisolone
Triamcinaline
Methylprednisolone
Hydrocortisone
Dexamethasone
Other Drug Tested
(ImmunoCAP & skin testing)
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Cefaclor
Insulin (Bovine, human, Porcine)
Isocyanate (painters)
Local Anaesthetic
General Anaesthetic
Gelatin (vaccine rxn)
(Venoms intradermal testing)
Recommended interpretation of food
allergen-specific IgE levels (kU/L) in the
diagnosis of food allergy
Egg Milk Peanut Fish Soy Wheat
Reactive if > (no challenge needed)
7
Possible reactive ( MD challenge*)
Unlikely reactive If < (home challenge) 0.35
15
14
20
65
80
0.35
0.35
(values between)
0.35
0.35
0.35
Uses of skin prick tests (SPT) and
radioallergosorbent testing (RAST)
Things SPT/RAST can tell us
 That a patient is sensitised to an allergen
 The likelihood of reacting after a food challenge
(restricted range of foods)
 That a patient is not sensitised to an allergen and
therefore an IgE-mediated reaction to that allergen
is very unlikely
Things SPT/RAST cannot tell us
 The severity of a reaction if a sensitised patient
were exposed
 Whether the patient’s symptoms are caused by the
allergen
Mast cell Tryptase
The increased levels of tryptase can normally be detected
up to three to six hours after the anaphylactic reaction.
Levels return to normal within 12 - 14 hours after release
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Normal <11.4
Types of challenge testing
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Double -blind
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Single-Blind
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Open
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Double-blind placebo controlled (DBPCFC)
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Exercise + oral challenge
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Inhalation challenge
Indications for Patch Test
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Atypical Eczema & non-immediate skin
reactions
Allergic Contact Dermatitis
Occupational asthma & dermatitis
Drug Reactions, especially delayed
Non-immediate Food Reactions
Predictive values of SPT & APT vs
DBPCFC in patients with AD
Technique
SPT (early reaction)
PPA
NPA
9%
95%
SPT (late-phase reaction)
41%
81%
APT
81%
93%
Niggemann et al, Allergy 2000;
55::281-285
NPA = Negative predictive accuracy
PPA = Positive predictive accuracy
Food Protein-Induced Enterocolitis
Syndrome (F Pies)
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Profuse vomiting & diarrhea-> dehydrated
Presents in 1st weeks or months or later in
exclusively breast fed child upon introducing
solids or formulae
Often misdiagnosed as “tummy bug”
Triggers:
– Cow’s milk, soy
– Oats, rice, Barley
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Diagnosis:
– Negative SPT & RAST
– Atopy Patch Test: milk, soy, oats, wheat, barley,
rice
Eosinophilic Esophagitis
(EE)
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Presents as reflux
Poor response to omeprazole
Atopic
Diagnosed with:
– SPT, RAST & APT
– Biopsy of esophagus: High eosinophils >15/hpv
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Triggers:
– milk, eggs, peanuts, shellfish, peas, beef,
chicken, fish, rye, corn, soy, potatoes, oats,
tomatoes and wheat
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Rx: Swallowed Fluticasone
Unproven (useless) Tests
widely available in NZ
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IgG antibody tests (Great Smokies lab)
Applied kinesiology (Muscle Testing)
Hair analysis
Electrodermal Tests (Vega Testing)
Iridology
Cytotoxic Test (Changes in WBC)