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Tools of the Allergist: A review of diagnostic techniques. George F. Kroker, MD FACAAI. Tools of the Allergist. Skin Tests Scratch Skin Prick Test Intradermal (ID, IDT) In Vitro Tests Specific IgE RAST (radioallergosorbent test) ELISA (enzyme-linked immunosorbent assay)

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George f kroker md facaai

Tools of the Allergist:A review of diagnostic techniques

George F. Kroker, MD FACAAI


Tools of the allergist
Tools of the Allergist

  • Skin Tests

    • Scratch

    • Skin Prick Test

    • Intradermal (ID, IDT)

  • In Vitro Tests

    • Specific IgE

      • RAST (radioallergosorbent test)

      • ELISA (enzyme-linked immunosorbent assay)

    • Total IgE, other immunological tests


Test preferences vary by specialty
Test Preferences—Vary by Specialty

  • Board Certified Allergist

    • Skin Prick Test (SPT)

    • Intradermal Test (ID)

    • In Vitro Specific IgE

  • ENT Allergist

    • Intradermal Dilutional Test (IDT)

    • Modified Quantitative Test (MQT)

    • In Vitro Specific IgE


George f kroker md facaai

Annals of Allergy

101:580-592, 2008


The importance of the history
The Importance of the History

  • “The clinical history drives the diagnosis of human allergic disease…the clinical history makes the critical link between the allergy skin or blood test results and the allergic disease”

    Pearls and pitfalls of allergy diagnostic testing: report from the ACAAI/AAAAI Specific IgE Test Task Force

    Annals of Allergy 101:580-592, 2008


The importance of history cont
The Importance of History (cont.)

  • “Diagnostic tests should be used to support or exclude a diagnosis of specific allergies based on the history. They should almost never be used as a substitute for a careful history…neither skin tests nor serum IgE tests should be either requested or interpreted outside the context of the clinical history and physical examination…”

    Pearls and pitfalls of allergy diagnostic testing: report from the ACAAI/AAAAI Specific IgE Test Task Force

    Annals of Allergy 101:580-592, 2008


The la crosse method perspective
The La Crosse Method Perspective

We recognize that various allergy testing techniques have their rightful place

Our ultimate goal is to deliver SLIT treatment at the optimum therapeutic level in a streamlined manner

Our testing protocols have been developed to provide a high degree of quantification of the patient’s sensitivities as efficiently as possible


Where are we now
Where are we now?

  • Optimized IDT: streamlined to reduce patient’s time in the office

  • Selective use of In Vitro testing

  • Determine which specific SLIT protocol is best suited for the patient

  • Treat at the therapeutic dose

  • Retest allergens being treated to monitor effectiveness of current dose


How did we get here
How did we get here?

Brief review of skin testing techniques

History of skin testing techniques

Types of techniques

Principles applicable to all techniques

Advantages & disadvantages of each technique


History of the skin test
History of the Skin Test

Charles Blackley, MD

1820-1900

Daily Pollen Counts

May 28-Aug 1, 1866


Types of skin tests
Types of Skin Tests

Epicutaneous

Scratch

Prick-puncture

Modified prick

Intradermal

Single strength

Intradermal Dilutional Titration (IDT)



Factors influencing skin test reactivity
Factors influencing skin test reactivity

Age: Reactivity progressively increases throughout childhood to about age 20-30, then gradually declines until age 50, after which the decline is more rapid

Menstrual cycle: Reactions to allergen & histamine larger at midcycle

Seasonal: Reactions to a seasonal allergen are greater just after the allergy season is finished

Sun Damage: Affects skin mast cell number


Factors influencing skin test reactivity1
Factors influencing skin test reactivity

Site tested: Upper back > lower back> forearm

Clinical status on day of testing: Heavy allergen exposure immediately before testing can enhance reactivity

Other diseases: cancer, etc.

Medications: Antihistamines, tricyclic antidepressants, H2 antagonists reduce reactivity



Epicutaneous scratch test
Epicutaneous: Scratch Test

  • Method: Knife blade or allergen abrades an area of skin in linear fashion, producing a superficial scratch. Allergen extract applied.

  • Advantage:

    • Time

    • Safety

  • Disadvantage:

    • Lack of uniformity of abrasion

    • Uncomfortable & traumatic

    • Increased false pos & false neg compared to prick/puncture


Epicutaneous puncture test
Epicutaneous: Puncture Test

Method:

Drop of extract is placed on the skin

Testing device (lancet, bifurcated needle) placed perpendicular

to the skin

Device is tapped gently through the drop of extract, and held on the skin with pressure for about 1 second


Epicutaneous modified prick test
Epicutaneous: Modified Prick Test

Method:

Drop of extract placed on skin

Needle is introduced laterally into skin at an angle, through the drop

Skin is lifted up with no downward pressure introducing a minute amount of extract into the skin


Stand alone skin prick tests
Stand-Alone Skin Prick Tests

Stand-alone SPT favored by many allergists for its specificity, safety, and efficiency

Reactions are graded based on wheal size, presence of pseudopods, and in comparison to pos/neg controls

Results graded from 1+ to 4+

Multi-prong device may be used to speed application and provide consistency


Epicutaneous skin testing
Epicutaneous Skin Testing

The skin prick test: “more than meets the eye”

David Bernstein MD Ann Allergy 92: 587-588, June 2004 (editorial)

“Despite its widespread adoption as the premier method used in clinical practice, many characteristics of the skin prick or puncture test are poorly defined…it is concerning that a standard protocol for skin prick testing has yet to be universally adopted. Arcane systems are still being used to grade skin prick test wheal-and-flare responses (i.e., grade 1 to 4+) which greatly impedes communications of results between different clinics.”


Intradermal single strength
Intradermal: Single-strength

Allergy: Principles & Practice, 5th ed 1998

E. Middleton Ed.

“The value of prick tests is limited by low potency extracts producing false negative results.”

“Infrequently, an intradermal test will reveal a clinically relevant reaction in the case of a negative prick test.”


Intradermal single strength1
Intradermal: Single-strength

Joint Task Force on Practice Parameters for the Diagnosis and Treatment of Asthma Ann Allergy Asthma Immunol 75:543-625, 1995.

“Intracutaneous testing may be useful and should be pursued if the prick/puncture test is negative or equivocal to allergens strongly suggested by the patient’s history or exposure.”


Intradermal single strength2
Intradermal: Single-strength

Method: Testing performed with disposable tuberculin syringe and small gauge needle

A small amount (.02ml) of dilute extract is injected into the superficial layers of the skin, making wheals approximately the same size


Intradermal single strength3
Intradermal: Single-strength

  • Advantage

    • More sensitive than prick test

  • Disadvantage

    • Less specific than prick test

    • Rate of systemic reactions, <0.5%

    • Can cause large local reactions

    • First fatality reported 1922 fish ID injection


Epicutaneous skin testing1
Epicutaneous Skin Testing

Jay Portnoy, Ann Allergy 89: 335-336, Oct 2002.

  • What do allergy skin tests really mean?

    • “Categorization of skin test results from 0 to 4+ is analogous to recording the results of a CBC and differential as a moderate white count with 2+ neutrophils, 3+ lymphocytes, and 1+ bands. One could argue that if we are only concerned about white blood cell counts that either are very low or very high, such categorization should be adequate. Even so, most physicians prefer to review the actual numbers so they can interpret the results themselves. Why should we not do the same for skin test results?”


History of idt
History of IDT

1911: Leonard Noon injected allergy patients with pollen extracts (to induce production of pollen “antitoxin”)

Attempted to determine degree of sensitivity of his pts by making various dilutions of antigens and instilling them into the patient’s conjunctiva

Leonard Noon MD

1878-1913


History of idt1
History of IDT

Noon quantified a patient’s sensitivity by instilling drops of different-strength pollen extracts into the conjunctiva of a known hay fever patient

The strength of extract required to produce a minimal reaction would then represent the patient’s “resistance”: i.e., if a dilution of four “units” was required to institute a reaction, the patient’s “resistance” was rated as 4

These quantified responses could then be used in selecting the appropriate dose for injection therapy



History of idt2
History of IDT

“Three quarters of a century later, a large percentage of the allergy world uses basically non-quantitative techniques of diagnosis and treatment…there is also considerable disagreement regarding an appropriate starting dose for therapy. It has been observed that should William Osler be returned to life, he would be unable to recognize most of the technology in use. If Leonard Noon returned, he could resume his practice as he left it with little difficulty. He would probably continue to seek better quantification.”

Hueston King, MD

Otolaryngologic Clinics of North America,

18: p 703, 1985


History of idt3
History of IDT

French K. Hansel MD

1893-1981

Herbert J. Rinkel MD

1896-1963


History of idt cont
History of IDT (cont.)

1930: French Hansel was the first to perform skin tests using multiple-strength individual extracts instead of single-concentration extracts

He used intradermal injections of antigens in serial 1:10ratiosof varying strengths while measuring the response

He demonstrated that eachantigen has a uniqueresponse in a given patient

He found the strength of a response to different antigens is not the same for all the antigens encountered by a given individual


History of idt cont1
History of IDT (cont.)

Hansel concluded that multiple intradermal skin tests using individual allergens with varying doses produced greater accuracy of information regarding the degree of the patient’s sensitivity

1937: Herbert Rinkel, an allergist working with Hansel, found that an antigenic dilution ratio of 1:5 administered in progressively increasing increments was qualitatively and quantitativelysuperior in measuring allergic skin reactivity. The response was constant through 3 or 4 dilutions in 72% of patients


Goals of idt
Goals of IDT

Reliably identify an inhalant sensitivity by skin testing

Determine a safe starting point at which to initiate therapy (the “threshold dose”)

Allow treatment to be started during patient’s peak allergy season

Treat a variety of allergens of different degrees of sensitivity in a single mix by varying the concentration of individual antigens according to the skin test rxns (“Multi-antigen threshold therapy”)


Principles of idt
Principles of IDT

IDT is based upon the interpretation of the skin response to the injection of weak (nonreacting) dilutions of antigen, proceeding to stronger (reacting) dilutions of the antigen

The first test producing a wheal 2 mm larger than the preceding non reacting wheal is considered the endpoint of the reaction

Treatment based on the endpoint responseis within a safe and therapeutic range


Idt standard technique
IDT: Standard Technique

Allergenic extracts are prepared using 5-fold serial dilutions (Concentrate to a #6)




Idt standard technique1
IDT: Standard Technique

The antigen is injected intradermally, creating a demarcated 4mm wheal containing approx .01 ml of the appropriate dilution

The number 6 dilution of each antigen is administered

The response is measured at 10 min



Idt standard technique2
IDT: Standard Technique

The wheal will normally grow to 5mm within 10 minutes

If less than 2mm growth, the result is interpreted as negative and a stronger dilution is applied

The first dilution to establish a 7mm wheal is considered the “endpoint”

Confirmation: show a clear progression of wheal size of 2mm over 3 consecutive dilutions


Idt typical std titration results
IDT: Typical Std Titration Results

# 6

# 5

#4

#3

#2

#1

4

5

9

4

7

Endpoint

5

5

7

9

Endpoint



Idt standard technique3
IDT: Standard Technique

This process may take several hours and/or 2 or more sessions depending on the number of allergens being tested, the severity of reactions, abnormal skin or whealing responses, etc.


La crosse method optimized idt
La Crosse Method: Optimized IDT

Technique of administration of antigens is identical to standard titration, except for starting dilution

In contrast to giving a number 6 starting dilution for all antigens, varying-strength starting dilutions are used for different antigens, based on clinical experience and the patient’s own history

Goal: to find 2 mm wheal growth response (i.e, 7mm wheal in 10 minutes) with further confirmation by giving additional selected test dilutions as needed


George f kroker md facaai

Optimized IDT Screening Dilutions

Normal Degree of Clinical Sensitivity

Moderate Degree of Clinical Sensitivity: DROP BACK 1 DILUTION

High Degree of Clinical Sensitivity DROP BACK 2 DILUTIONS


Idt technique advantages of optimized vs standard idt testing
IDT Technique: Advantages of Optimized vs. Standard IDT testing

Speeds up testing process

Minimizes the number of skin tests & patient’s discomfort

Minimizes testing expense

Allows better workflow so that more patients can be tested in the same amount of time


Modified quantitative testing mqt
Modified Quantitative Testing (MQT) testing

Krouse JH, et al Otolaryngology Clinic N Am (2003) 855-868

Skin Prick Test (SPT) is first used as a rapid screening measure of reactivity, then selective IDT testing done based on SPT results

Using the Multi-Test II device is estimated to yield a skin response equivalent to a 1:1500 w/v IDT, this first step is similar to a #3 dilution


Multi test
Multi-Test testing

Device allows consistent application of multiple tests to screen initial sensitivity

Rapid, with minimum patient discomfort


Modified quantitative testing mqt1
Modified Quantitative Testing (MQT) testing

Krouse JH, et al Otolaryngology Clinic N Am (2003) 855-868

  • SPT is used in combination with IDT

    • If SPT negative, a single stronger IDT may be administered

    • If SPT positive, a single weaker IDT may be administered

    • The combination of SPT with IDT yields an efficient, rapid estimate of the strength of the allergic response that can be interpreted and used in treatment vial preparation


Mqt algorithm summary
MQT Algorithm Summary testing

Krouse JH, et al Otolaryngology Clinic N Am (2003) 855-868

  • SPT Wheal Size: > 9mm, No ID, Interpret as #6 EP

  • SPT Wheal Size: 3-8 mm, Apply #5 ID

    • If ≤5mm, Interpret as #4 EP

    • If 7-9mm, Interpret as #5 EP

    • If ≥9mm, Interpret as #6 EP

  • SPT Wheal Size: <3mm, Apply #2 ID

    • If ≤6mm, Interpret as NEG

    • If ≥ 7mm, Interpret as #3 EP


Mqt algorithm
MQT Algorithm testing



Special considerations
Special considerations: testing

Know your pollens


Special considerations know your regional pollens
Special considerations testingKnow your regional pollens!


Special considerations1
Special considerations: testing

Know your pollens

Use of Allergen Mixes in testing


Use of allergen mixes testing and slit considerations
Use of Allergen Mixes: testingTesting and SLIT Considerations

  • Testing with allergen mixes

    • Reduces the number of tests

    • Takes advantage of cross-reactivity or co-seasonality

  • For SLIT

    • Inducement of new sensitivities is not a concern


Use of mixes testing and slit considerations
Use of Mixes: testingTesting and SLIT Considerations

  • Easy to describe “mixology”

    • “Non Cross-reactingMix”-a combination of non or slightly cross reacting allergens, i.e., ones that pollinate at the same time (Fall Pollen) or are grouped by type (11-Tree Mix, Mold Mix A).

    • “Cross-reacting Mix”-a combination of highly cross-reactive major allergens, i.e., Mite Mix (equal parts Dp, Df) Ragweed Mix (short, giant) or Standardized Grass (equal parts antigen K grasses).


Use of mixes testing and slit considerations1
Use of Mixes: testingTesting and SLIT Considerations

Contrary to what is often recommended for SCIT treatment, we liberally use mixes for both testing and treatment

If your practice intends to provide both SCIT and SLIT, then continue to test with single allergens and treat the SLIT patients with mixes, using the highest reacting constituent allergen to determine the treatment level

Stay tuned, more to follow during later presentations!


Special considerations2
Special considerations: testing

Know your pollens

Use of Allergen Mixes in testing

Recognizing atypical responses


Idt atypical skin test responses
IDT: Atypical Skin Test Responses testing

# 6

# 5

#4

#3

#2

#1

4

5

4

7

Endpoint

21

5

7

7

7

9

11

Endpoint


Special considerations3
Special considerations: testing

Know your pollens

Use of Allergen Mixes in testing

Recognizing atypical responses

Recognizing & recording delayed reactions


Idt atypical skin test responses cont late phase reactions
IDT: Atypical Skin Test testingResponses (cont.): Late Phase Reactions

Endpoint

5

7

7

7

8

“Delayed”

Endpoint


Idt delayed reactions
IDT: Delayed Reactions testing

Day of Testing

24 hrs later

48 hrs later


Idt delayed reactions1
IDT: Delayed Reactions testing

Pt. J.S. 2 weeks

later


Dr keith eaton lrcp lrcs 1936 2002
Dr. Keith Eaton LRCP LRCS testing1936-2002


Moulds yeasts ascospores basidiospores algae and lichens toxic and allergic reactions
Moulds, Yeasts, Ascospores, Basidiospores, Algae and Lichens: Toxic and Allergic Reactions

Eaton, K J Nutr Environ Med 12:321-335 2002

“…delayed reactions should be actively sought in every patient. When this is done it may be noted that moulds in particular may be associated with delayed skin responses, which take various forms.”


Idt delayed reactions2
IDT: Delayed Reactions Lichens:

Often occur in mold allergic patients

Often occur in patients with chronic sinus congestion, fatigue, aching, headaches

Can be effectively treated with sublingual immunotherapy

The safe treatment dose is the strongest wheal dilution with no significant delayed reactivity



Special considerations4
Special considerations: Lichens:

Know your pollens

Use of Allergen Mixes in testing

Recognizing atypical responses

Recognizing & recording delayed reactions

Special testing considerations


Idt special testing situations
IDT: Special Testing Situations Lichens:

  • Young child: # tests=age +2

  • Patient with history of systemic rxn from prior allergy testing & patients on beta blockers

    • Do std titration with few selected antigens beginning at very weak dilutions (#’s 5,6,7)

  • Patient recently on medications potentially influencing skin test response

    • Do histamine control, consider: retesting off meds, RAST/ELISA test


Skin testing histamine control
Skin Testing: Histamine Control Lichens:

  • Concentrate 6 mg/ml

  • Dilution #1: .25 cc conc + 4.75 cc coca

  • Will validate results by documenting skin test reactivity, especially for

    • Very old or very young patients

    • Patients with recent ingestion of medications that may suppress skin test response

  • Usually start with #3 dilution


Idt special testing situations beta blockers
IDT: Special Testing Situations: Beta Blockers Lichens:

  • No prospective study published on safety of IDT testing in patients on beta blockers

  • 12 yr survey of fatal reactions to allergen injections and skin testing: 1990-2001-- none receiving beta blockers

    • Bernstein DI, Wanner M et al JACI 113(6):1129-36, 2004.

  • AAOA sponsored study 2003-2008 : safety of allergy testing and treatment in patients taking beta blocker medication

  • Dr. Veling, AAOA

    • 33 months, 21,000 tests IDT

      • 8 test reactions, incidence .04%, no deaths


Idt special testing situations beta blockers aaaai position paper
IDT: Special Testing Situations; Lichens: Beta Blockers: AAAAI Position Paper

“Systemic reactions to skin testing are rare. Nevertheless, special precautions, when appropriate, should be taken when the patient needs sensitivity testing and cannot stop treatment with a beta-blocking agent.”


Causes for increased id reactions on follow up idt mqt testing
Causes for INCREASED ID reactions Lichens: on FOLLOW-UP IDT/MQT testing

Falsely suppressed tests on initial visit due to pre-medication

IAQ issues in home: Increased exposure from indoor allergen contamination (animals, dust, mold) in interim

IAQ issues at worksite: “Sick Building” with increased allergen exposures in interim since seen

High allergen load engendered by recent personal activity immediately preceding f/u testing

Testing of seasonal allergen “in season” on f/u visit, whereas it was tested pre-seasonally on first visit

Recent ingestion of a cross-reacting food allergen


Tools of the allergist1
Tools of the Allergist Lichens:

  • Skin Tests

    • Scratch

    • Skin Prick Test

    • Intradermal (ID, IDT)

  • In Vitro Tests

    • Specific IgE

      • RAST (radioallergosorbent test)

      • ELISA (enzyme-linked immunosorbent assay)

      • Phadia diagnostic component testing

    • Total IgE, other tests


In vitro tests
In Vitro Tests Lichens:

Types of tests

Principles & mechanisms

Advantages/disadvantages

Indications

Scoring

Sample panel & hints


Discovery of ige kimishige teruko ishizaka 1967
Discovery of IgE Lichens: Kimishige & Teruko Ishizaka,1967


Types of in vitro tests
Types of In Vitro Tests Lichens:

Assays for total IgE or allergen-specific IgE

  • RAST (radioimmunosorbent test)

    • Introduced in 1972

    • With minor exceptions, now obsolete,

      • “RAST” acronym persists!

  • ELISA (enzyme-linked immunosorbent assay)

    • Variety of commercial systems in use

    • Each use different technology to bind IgE to a surface, tag & meas


Elisa test
ELISA test Lichens:

  • In 1980s, more than a dozen commercial test systems existed

  • Current main methods:

    • TurboRAST (Agilent Tech)

    • Immulite (Siemens Medical)

    • ImmunoCAP (Thermo Fisher)

    • Hycor UltraSensitive EIA

      • Note: results from different systems are not always comparable to each other, even if provided in the same units





In vitro tests elisa
In Vitro Tests: ELISA Lichens:

Food testing with ELISA demonstrates good sensitivity (approx 70-90%) and good specificity (approx 50-80%)

It has been demonstrated with several different inhalants and foods that the probability of symptoms will increase with increasing amounts of IgE

ELISA discloses the presence of food-specific IgE (sensitization), but this does not always correlate with true clinical reactions when the food is ingested (clinical allergy)


In vitro tests advantages
In Vitro Tests: Advantages Lichens:

No risk to patient

Less time-consuming than skin tests

No interference by drugs

Quantifiable measure of IgE antibody which can be followed with treatment

Ideal for assessing systemic IgE-mediated food allergy


In vitro tests disadvantages
In Vitro Tests: Disadvantages Lichens:

Reimbursement restrictions, such as limitations on number of tests performed

Lab-to-lab variability

Results not immediately known

No information provided on “delayed reactions”

Measures IgE in blood and not a specific organ “surrogate marker”


In vitro tests diseases w high yield
In Vitro Tests: Lichens: Diseases w/ high yield

Atopic Dermatitis

Chronic Respiratory/sinus congestion

Asthma

Recurrent infections

Chronic gastrointestinal symptoms

Chronic urticaria

Anaphylaxis


In vitro tests indications
In Vitro Tests: Indications Lichens:

Infants, uncooperative patients

Patients on antihistamines and other medications causing skin test suppression

Pts with severe risk of anaphylaxis

Pts with extensive skin disease, dermagraphism


Typical ige modified class system
Typical IgE Modified Class System Lichens:

Specific IgE Class

Conc in IU/ml

Interpretation


In vitro test typical pt screen
In Vitro Test: Typical Pt Screen Lichens:

“Maximum yield—minimal cost”

Total IgE

“Common Food” panel: eggs, milk, wheat, corn, yeast + “any food they eat a lot” and any food with a history of prior clinical reactivity

If sensitive to specific pollens or latex, consider testing for concomitant food allergens

Measure specific IgE to strongest clinically relevant inhalant allergen(s) by history/skin test as another “benchmark”


In vitro test interpretation clinical considerations
In Vitro Test Interpretation: Clinical Considerations Lichens:

Two allergens may have similarly positive scores, but differ markedly in the clinical symptoms elicited (i.e. have different “target organs”)

A food allergen may have a falsely low IgE score if it has been avoided for a prolonged period

Remember: you are measuring systemicunbound IgE—studies show that sometimes one may not detect systemic elevation in IgE yet when local mucosa is analyzed (nasally & in the gut) one may detect elevated allergen-specific IgE

The “x-ray” analogy


In vitro test interpretation clinical considerations cont
In Vitro Test Interpretation: Clinical Considerations (Cont) Lichens:

“After additional analysis, if the ELISA test results (or skin testing) remain inconsistent with the patient’s clinical history, the overriding criteria in making the final diagnosis should be the clinical history and physical examination…”

Pearls and pitfalls of allergy diagnostic testing: report from the ACAAI/AAAAI Specific IgE Test Task Force

Ann Allergy 101: 580-592, 2008


Elisa food test a limitation
ELISA Food Test—a limitation Lichens:

“Measuring the whole food may not tell the whole story”

Certain components of a food may be more allergenic than others—how can we investigate this? Is it clinically relevant?


Allergen component diagnostic testing
Allergen Component Diagnostic Testing Lichens:

  • New type of allergy testing available through Thermo Fisher

  • www.pirllab.com

  • Addresses limitations of current ELISA:

    • Current tests define allergen sources, not specific allergenic molecules



Panallergens of importance
Panallergens of Importance Lichens:

  • PR-10 proteins (BetV1 homologue)

    • Heat labile, causes OAS

  • Lipid Transfer Proteins (LTP)

    • Heat stable, systemic reactions

  • Profilins

    • Seldom cause serious clinical symptoms

  • Tropomyosins

    • Cross-reactivity shellfish, mites, cockroach



Clinical utility of component testing
Clinical Utility of Component testing Lichens:

Reveals original sensitizing source

Risk estimation for severity of reactions

Risk estimation for reaction to cooked food

Resolving cross-reactivity issues

Establishing priorities for immunotherapy


Food component testing clinical utility example 1
Food Component Testing: Clinical Utility: Example #1 Lichens:

“Is my child at high risk of peanut anaphylaxis with a very positive peanut ELISA test?”

Solution—do peanut component test:

Elevated r Ara h 2 ?—yes!

Elevated r Ara h 8—no!


Food component testing clinical utility example 2
Food Component Testing: Clinical Utility: Example #2 Lichens:

“My child is ELISA positive to egg—what does this mean?”

Ovomucoid -: tolerance to hard-boiled egg and egg in baked goods

Ovomucoid +: confirmed egg allergy; will not tolerate any kind of egg


Component testing and lcm conclusions
Component Testing and LCM: Conclusions Lichens:

  • Component testing may be of help in in establishing priorities in SLIT treatment

    • Assessment may direct treatment priority in a patient with multiple fruit sensitivities

    • Example: a patient with birch pollen allergy and OAS symptoms from apple, peach, cherries could benefit from aggressive treatment of birch allergen if Bet v 1 positive on testing


The mystery of delayed food allergy
The Mystery of Delayed Food Allergy Lichens:

The most beautiful thing we can experience is the mysterious.

It is the source of all true Art and Science

--Albert Einstein

Food intolerance is often highly individual and…

Mysterious

--Andrew Weil MD


Delayed onset food sensitivity
Delayed-Onset Food Sensitivity Lichens:

  • “Hidden food sensitivity” causing chronic symptoms

  • Common symptoms include:

    • Fatigue, cognitive impairment, gastrointestinal distress, headaches, myalgias, fluid retention, sinus congestion

  • Symptoms occur typically 6-36 hours after ingestion, with peak 12-24 hours


Delayed onset food sensitivity1
Delayed-Onset Food Sensitivity Lichens:

  • “A bad illness in search of a good test”

  • Usually IgE tests are negative

  • Paucity of scientific studies on tests to determine diagnosis

  • No widely accepted test available

  • Complicating factors:

    • Lack of interest by allergy profession

    • Symptoms outside of allergist’s “comfort zone”


Delayed onset food sensitivity commercial tests
Delayed-Onset Food Sensitivity Lichens: Commercial Tests

  • IgG ELISA

    • http://www.gdx.net/product/10145

  • ALCAT

    • https://www.alcat.com/

  • Mediator Release Test (MRT)

    • http://www.nowleap.com/about_us.html


Igg elisa test
IgG ELISA Test Lichens:

  • Principle of testing is the same as measuring IgE but using IgG instead

  • Multiple labs provide test—Genova Diagnostics, Meridian Valley, Great Plains Lab, etc.

  • May have more inter-lab reproducibility than cell-based assays

    • Reproducibility and Reliability of Two Food Allergy Testing Methods

      Hodsdon, et al. Natural Medicine Journal, March 2010


Alcat test
ALCAT Test Lichens:

The ALCAT test: An Evaluation of Efficacy and

Clinical Applicability

Andrea Martinson



Delayed food allergy tests problems
Delayed Food Allergy Tests: Lichens: Problems

  • Specificity, sensitivity, reproducibility not universally validated

  • False positives occur frequently, especially at low reactivity to a food

  • False negatives occur:

    • Food previously avoided

    • Food reaction non-immunologic


Delayed onset food sensitivity2
Delayed-Onset Food Sensitivity Lichens:

Commercial tests serve as only an initial screening tool for diet design

“Gold standard” for diagnosing is an elimination/challenge diet

Implementation & review of a patient’s diet diary can be helpful in designing a trial elimination diet


Delayed onset food sensitivity clues
Delayed-Onset Food Sensitivity Lichens: Clues

Pts often present with a diagnosis of chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, migraine

Patient may have “cravings” for certain foods, and eat them excessively

Unexpected dietary changes may result in unexpected changes in baseline symptoms


Delayed onset food sensitivity clues cont
Delayed-Onset Food Sensitivity Lichens: Clues (Cont.)

Patient tries a high protein diet for weight loss and feels “wonderful”

Patient travels overseas and headaches go away

Patient visits sister and in 3 days her fibromyalgia “disappears”


Delayed onset food sensitivity clinical pearls
Delayed-Onset Food Sensitivity Lichens: “Clinical Pearls”

  • Many patients with delayed food allergy have had previous IgE mediated illness

  • Delayed food allergy often co-exists with delayed inhalant allergy

  • Typical foods responsible include dairy, corn, gluten, eggs, soy

  • Delayed food sensitivity often occurs in the setting of heightened intestinal permeability (“leaky gut”)

  • Gluten and Candida can cross-react due to “molecular mimicry”


Delayed onset food sensitivity clinical pearls1
Delayed-Onset Food Sensitivity Lichens: “Clinical Pearls”

  • Multiple delayed food allergies often signal heightened intestinal permeability (i.e, “leaky gut”)

  • Rapid weight gain and loss suggests fluctuating edema from delayed onset foodallergies

  • Gluten and Candida can cross-react due to “molecular mimicry”


One final thought
One Final Thought… Lichens:

  • “The message which will guarantee our survival as a specialty is that our knowledge is broader than the atopic diatheses, and we have expertise that is of value in the management of other interesting medical arenas. That is what gives us value and credibility.”

    • Richard Weber, MD FACAAI

      • “Message from the President”


Thank you
Thank You Lichens:

Next:La Crosse Method™ Practice Protocol Dosing Guidelines

Mary Morris MD