Allergy Diagnostic Testing

148 Pages·2008·0.82 MB·English

Practice Parameter
Allergy Diagnostic Testing: An Updated Practice
Parameter
I. Leonard Bernstein, MD; James T. Li, MD, PhD; David I. Bernstein, MD;
Robert Hamilton, PhD, DABMLI; Sheldon L. Spector, MD; Ricardo Tan, MD; Scott Sicherer, MD;
David B. K. Golden, MD; David A. Khan, MD; Richard A. Nicklas, MD; Jay M. Portnoy, MD;
Joann Blessing-Moore, MD; Linda Cox, MD; David M. Lang, MD; John Oppenheimer, MD;
Christopher C. Randolph, MD; Diane E. Schuller, MD; Stephen A. Tilles, MD; Dana V. Wallace, MD;
Estelle Levetin, PhD; and Richard Weber, MD
TABLE OF CONTENTS
I. Preface.................................................................................... S2
II. Executive Summary ......................................................................... S3
III. Collation of Summary Statements .............................................................. S5
IV. Part 1.................................................................................... S15
V. In Vivo Diagnostic Tests of Immediate Hypersensitivity Reactions .................................. S15
VI. Organ Challenge Tests ...................................................................... S29
VII. Tests to Distinguish Clinical Obstructive Diseases Resembling Asthma............................... S33
VIII. In Vivo Diagnostic Tests of Cell-Mediated Immunity ............................................. S34
IX. In Vitro Diagnostic Tests of Immediate Hypersensitivity........................................... S43
X. In Vitro Diagnostic Tests of Cell-Mediated Immunity............................................. S59
XI. Other Diagnostic Immunologic Tests........................................................... S64
XII. Unproven Tests............................................................................ S65
XIII. Part 2.................................................................................... S66
XIV. Allergens ................................................................................. S67
XV. Assessment of Inhalant Allergy ............................................................... S74
XVI. Assessment of Food Allergy................................................................. S102
XVII. Assessment of Stinging Insect Allergy ........................................................ S106
XVIII. Assessment of Drug Allergy................................................................. S109
XIX. Assessment of Allergic Contact Dermatitis..................................................... S115
XX. Acknowledgments......................................................................... S121
XXI. References............................................................................... S122
TheAmericanAcademyofAllergy,AsthmaandImmunology(AAAAI)
andtheAmericanCollegeofAllergy,AsthmaandImmunology AAAAIorACAAIinterpretationofthesepracticeparameters.Any
(ACAAI)havejointlyacceptedresponsibilityforestablishingthe requestforinformationaboutoraninterpretationofthesepractice
AllergyDiagnosticTesting:AnUpdatedPracticeParameter.Thisisa parametersbytheAAAAIorACAAIshouldbedirectedtothe
completeandcomprehensivedocumentatthecurrenttime.Themedical ExecutiveOfficesoftheAAAAI,theACAAI,andtheJointCouncilof
environmentisachangingenvironmentandnotallrecommendations Allergy,AsthmaandImmunology.Theseparametersarenotdesigned
willbeappropriateforallpatients.Becausethisdocumentincorporated forusebypharmaceuticalcompaniesindrugpromotion.
theeffortsofmanyparticipants,nosingleindividual,includingthose ReceivedforpublicationOctober27,2007;Acceptedforpublication
whoservedontheJointTaskForce,isauthorizedtoprovideanofficial November16,2007.
VOLUME 100, MARCH, 2008 S1
PREFACE anticipated to serve as a reference source for current utility
The major emphasis of this updated version of Practice and validity of allergy diagnostic tests.
ParametersforAllergyDiagnosticTestingisfocusedonhow The organization of Practice Parameters on Allergy Diag-
technological refinements and their validations during the nostic Tests is similar to previous Joint Task Force parame-
past decade are being incorporated into the diagnostic arma- ters except that a single algorithm with annotations was not
mentariumofallergists/clinicalimmunologistsandhowtheir appropriatetothemissionoftheparameter.Thebroadrange
optimal use enables confirmation of human clinical sensitiv- ofdiagnostictechniquesforvaryingpurposescouldnotpos-
ity.ThetermallergyinthisPracticeParameterdenotesmajor sibly be stratified into a uniform paradigm encompassing
categories of human hypersensitivity. Pertinent clinical im- diverse clinical sensitivity disorders that require objective
munologic techniques are oriented to this category of adap- confirmatory tests. An Executive Summary is followed by a
tive immunity but not to infection, cancer, or transplantation collation of Summary Statements, which also precede refer-
enced narrative discussions on each subject. The Practice
immunology.
Parameterisdividedinto2parts:part1isadetaileddescrip-
The impetus for Practice Parameters for Allergy Diagnos-
tionofdiagnosticmodalitiescurrentlyavailabletoallergists/
tic Testing originally stemmed from a consensus conference
clinical immunologists. It encompasses both IgE and cell-
sponsoredbytheNationalInstituteofAllergyandInfectious
mediatedinvivo(skinandpatch)andinvitrotestsforawide
Diseases and published as a supplement to the Journal of
spectrum of inhalant, food, and contactant allergens. Organ
AllergyandClinicalImmunologyinSeptember1988.Oneof
challenge tests are discussed in greater detail in this revised
the major conclusions of that workshop was that periodic
Practice Parameter because controlled challenges or super-
reassessment of diagnostic techniques should be mandatory,
visedexposureultimatelyserveastheappropriategoldstan-
and in keeping with that recommendation, the 1995 Practice
dard for assessing whether clinical sensitivity is present.
ParametersforAllergyDiagnosticTestsfurtherreviewedand
Consonant with their recent emergence as diagnostic ad-
considerednewdevelopmentsuptothattime.Inthe13-year
juncts,thesectionconcerningcurrentstatusofcytokinesand
interval since that publication, there has been an exponential
chemokines has been expanded. A new section on “Other
progressionofbasicandtranslationalimmunologicresearch,
ImmunologicTests”hasbeenaddedinrecognitionthatmany
some of which produced novel and practical diagnostic pos-
allergists/clinical immunologists have considerable interests
sibilities. Obviously, these advancements necessitated an
and expertise in a variety of laboratory immunologic tech-
overhaulofthe1995AllergyDiagnosticParametercommen-
niques commonly used to corroborate the diagnosis of non-
surate with the extensive database currently available. The
IgE, non–cell-mediated clinical immunologic diseases. A
ultimate goals were to formulate recommendations based on
discussion about unproven techniques is relevant because
evidence-based literature and to achieve balanced use of
these methods still have advocates who promote them to
classic and new diagnostic methods.
patients desperately seeking alternative approaches for their
TheworkingdraftoftheParameteronAllergyDiagnostic
particular problems.
Tests update was based on an outline jointly conceived by
Part 2 considers optimal utilization and integration of ev-
JamesT.LiandI.LeonardBernsteinandrealizedbyawork
idence-based diagnostic methods for various clinical situa-
group (Robert Hamilton, Sheldon Spector, Ricardo Tan,
tions, which include inhalant, food, insect venom, drug and
David I. Bernstein, Scott Sicherer, David B. K. Golden, and
contact sensitivities. Practice parameters of diagnosis and
David Khan) chaired by I. Leonard Bernstein. As with pre-
management for each of these clinical entities have been
vious parameters, the draft was based on a review of the
previously published with algorithms tailored to fit the spe-
medical literature using a variety of search engines, such as cific clinical situation. Many of the diagnostic recommenda-
PubMed. Published clinical and basic studies were rated by tions of part 2 were extracted or in some cases quoted
categories of evidence and used to establish the strength of verbatim from each of these published guidelines.
recommendations (Table 1). The initial draft was then re- The Joint Task Force acknowledges that rapid advance-
viewed by all members of the Joint Task Force and subse- mentsindiagnostictechnologycouldrenderspecificpastand
quently by the American Academy of Allergy, Asthma and current recommendations obsolete at any time and that at-
Immunology (AAAAI), the American College of Allergy, tempts to revise will have to be undertaken at appropriate
AsthmaandImmunology(ACAAI),andtheJointCouncilof intervals. Nevertheless, whatever the update interim period
Allergy, Asthma and Immunology and a number of experts may be, the allergy/clinical immunology community should
oninvivoandinvitrodiagnosticimmunologyselectedbythe be prepared to accept novel new diagnostic techniques, pro-
supportingorganizations.Commentswerealsosolicitedfrom vided that they are validated by scientifically accepted ap-
thegeneralmembershipofthesesocietiesviatheirWebsites. proaches.
This document therefore represents an evidence-based, The overall objectives of this Parameter on Allergy Diag-
broadlyacceptedconsensusopinion.Thepeerreviewprocess nostic Tests are tripartite: (1) to develop a reliable reference
and general format of the Practice Parameter are consistent resource for selecting appropriate diagnostic tests; (2) to
with recommendations of the American College of Medical provideguidelinesandsupportforthepracticingphysicianon
Quality, which defines practice guidelines. As such, it is how diagnostic tests should be used in an appropriate and
S2 ANNALSOFALLERGY,ASTHMA&IMMUNOLOGY
cost-effectivemanner;and(3)toimprovethequalityofcare allergen challenge tests. This interpretation system also en-
of patients by facilitating prompt and accurate diagnosis of ables easier comparison among physicians. Intracutaneous
their hypersensitivity disorders. tests are generally used for specific allergens (ie, Hymenop-
tera venoms and penicillin), but they may also be applied if
EXECUTIVE SUMMARY prick/puncture test results are negative and there is a strong
There is a wide array of diagnostic modalities for human historical likelihood of clinical allergy to specific allergens.
hypersensitivity diseases. Among these, skin tests for imme- Someclinicianspreferintracutaneoustestswithoutpreceding
diate hypersensitivity and delayed hypersensitivity are of prick/puncture tests, but when this alternative is elected,
paramount importance. As immunologic diagnostic technol- special care must be taken to ensure that intracutaneous
ogy advances, in vitro tests for both IgE- and cell-mediated allergen concentrations are nonirritant and correlative with
immunity have also assumed greater significance. In some end organ sensitivity. However, there are safety concerns
instances, lymphocyte functional assays may be applicable when intracutaneous tests are performed without preceding
for confirmation of humoral or cell-mediated immunity cy- prick/puncture tests. A suggested way of determining appro-
totoxicity syndromes, as well as classic delayed hypersensi- priate intracutaneous test concentrations is a serial end point
tivity reactions. titration regimen, one of which reported that intracutaneous
Specificcellularcomponentsofbothimmediatehypersen- dilutionsbetween1:12,500and1:312,000(wt/vol)werenon-
sitivity– and cell-mediated immunity induced inflammation irritant. Late-phase cutaneous responses, which reflect the
can be identified by their unique transcription markers, pro- persistent IgE allergic inflammatory milieu, may occur after
tein products, or cell surface differentiation markers. An either prick/puncture or intracutaneous tests but are more
increaseineosinophilsandtheirproductsoftenoccursinboth likely to do so after the latter. Preliminary data suggest that
immediate- and late-phase responses of IgE-mediated reac- decrease of late-phase cutaneous response may occur after
tions. The role of the basophil in such reactions can also be successful allergen immunotherapy.
evaluated by basophil histamine release tests and, more re- Theprototypicskintestfordelayedhypersensitivityisthe
cently, the basophil activation test. When tests for IgE-me- tuberculin skin test, which is evaluated by degree of indura-
diatedimmunityareequivocal,organchallengetestingisthe tioninmillimeters48hoursafterapplication.Similartestsare
most direct way of ascertaining whether bona fide clinical no longer commercially available for pathogenic fungi (eg,
sensitivity exists. Histoplasmacapsulatum).Apositive tuberculin readingvar-
Mononuclearcells(monocytes,macrophages,andlympho- ies from 10 to 15 mm in induration, depending on the inci-
cytes) are essential constituents of adaptive immunity. In denceofactivetuberculosiswithintheindigenouspopulation
particular,theirroleincell-mediatedimmunityhaslongbeen ofthepatient.Decreasedcell-mediatedimmunityresponseor
recognized. Lymphocyte subsets, their cytokines, and their anergymaybeevaluatedbydelayedhypersensitivityantigens
chemokinesmaybereadilyidentifiedandmeasurableinbody (ie, tetanus toxoid, Candida, and Trichophyton) to which
fluidsandtissuesites.Severalapplicationsofthistechnology most members of a population have been exposed. Formerly
have become standard clinical tests (eg, CD4(cid:1) cells in ac- the validity of anergy testing was compared with the mean
quired immunodeficiency); others are being vigorously pur- number of positive reactions elicited by 4 to 5 delayed hy-
sued (eg, interleukin [IL] 6, IL-8, IL-10, and transforming persensitivity antigens in a large normal control population.
growth factor (cid:1)). Increases in specific cytokines such as Absence of reactivity to all or all except 1 was equated with
macrophageinhibitoryfactor(MIF)andIL-16areassociated completeorrelativeanergy,respectively.Currently,thereare
with active cell-mediated immunity processes. only 3 delayed hypersensitivity antigens for testing (tetanus
Well-established techniques to detect IgG/IgG subclass toxoid,Candida,andTrichophyton),andthesehavenotbeen
antibodiesbyenzyme-linkedimmunosorbentassay(ELISA), evaluatedinalargepopulationasdescribedabove.Therefore,
immunodiffusion, and immunoprecipitation are available for interpretationofanergyusingthese3antigensiscircumspect.
specific antigens and autoantibodies. Antigen antibody com- Concurrent anergy and tuberculin skin testing is no longer
plexes may be associated with increased C1q binding and recommended in patients with human immunodeficiency vi-
cryoglobulins. rus (HIV) suspected of having mycobacterial infections.
Prick/puncture tests or intracutaneous tests are the pre- Allergic contact dermatitis (ACD) is a special form of
ferred techniques for IgE-mediated hypersensitivity. It is ad- delayed hypersensitivity evaluated by epicutaneous or patch
visable to use prick/puncture devices, which are relatively tests. More than 3,700 substances have been reported to
nontraumatic and elicit reproducible results when placed on induce contactant sensitivity. Direct irritants may cause irri-
specificareasofthebody(ie,armsorback).Optimalresults tantcontactdermatitis(ICD),whichoftenismorphologically
depend on use of potent test extracts and proficiency of the indistinguishable from ACD. The irritancy threshold of each
skin tester (ie, demonstration of coefficient of variation testagentmustbepredeterminedtoexcludethepossibilityof
(cid:2)30% at different periods). It is essential that objective ICD.Patchtestingshouldbeconsideredforanydermatitisfor
wheal-and-flare responses be recorded in millimeters (diam- which contactant exposure, either natural or secondary to
eter or area) because cutoff levels (in millimeters) may ob- topical agents, might be implicated. Most ACD can be de-
viate the necessity for confirmatory respiratory and food tectedby65substancesrecommendedbytheNorthAmerican
VOLUME 100, MARCH, 2008 S3
ContactDermatitisResearchGroup.TheonlyavailableFood and stability of the allergen extract being used. For these
andDrugAdministration(FDA)–clearedpatchtestkitisthe reasons,sensitivitytendstobehigheramongpollens,certain
T.R.U.E.test,whichcoversarangeofapproximately25%to foods,dustmite,fungi,andcertainepidermalscomparedwith
30% of the most common ACD contactant allergens. There- venoms, drugs, and chemicals. Recommendations for aller-
fore, customized patch testing is often necessitated. Patch genimmunotherapybasedsolelyonresultsofskinorspecific
tests are read at least twice (48 and 72 to 96 hours after IgE tests without appropriate clinical correlation are not ap-
application)andoccasionally7dayslaterinthecaseofweak propriate.
ACD allergens. Such allergens can also be detected by a IgG and IgG subclasses can be measured using immuno-
repeat open application test protocol. Atopy patch tests to assays similar to those used for allergen specific IgE. Con-
foods and drugs are being investigated as a complementary troversyexistsregardingwhetherincreasesofIgG4arevalid
aid in the diagnosis of food and drug allergies. These tests harbingers of either diagnosis or clinical efficacy after im-
have not yet been validated by a sufficient number of con- munotherapy.SpecificIgG/IgG4resultsdonotcorrelatewith
trolled studies. oral food challenges and are not recommended for the diag-
Laboratory tests may also provide useful information to nosis of food allergy.
evaluate either immediate hypersensitivity or cell-mediated Other less frequently used assays for IgE-mediated reac-
immunereactions.Currently,commercialavailabilityconsid- tions include histamine release from basophils and plasma
erations are such that specific IgE tests are used more fre- tryptase secondary to mast cell degranulation. The latter test
quently than is the case for functional in vitro cell-mediated may be useful in the detection of anaphylaxis and mastocy-
immunityassays.Withinthepastdecade,however,immuno- tosis.
assays of certain cell-mediated immunity products (ie, cyto- Eosinophils and their generated products, such as eosino-
kines or chemokines) may be demonstrating sufficient pre- philiccationicprotein(ECP),arekeycellsinallergicinflam-
dictability to be considered as surrogates of cell-mediated mation,particularlylate-phaseresponses.Increasednumbers
immunity. of these cells in nasal smears and induced sputum may be
The discovery of IgE and availability of IgE myelomas useful indicators of the existence and extent of allergic in-
enabled the production of large quantities of IgE. This per- flammation. In the case of sputum, they may also be indica-
mitted the production of highly specific anti-human IgE an- tiveofasthmaexacerbationorthepresenceofchroniceosin-
tibodies, which led to immunoassays capable of measuring ophilic bronchitis or esophagogastritis.
both total IgE and allergen specific IgE concentrations in The basophil activation test, as detected by the expression
serum and body fluids. A succession of modified assays ofCD63and/orCD203Csurfacemarkersbyflowcytometry,
ensued. Subsequent modifications are calibrated using heter- isbeingvigorouslyinvestigatedforbothdiagnosisandserial
ologous interpolation against the World Health Organization monitoringoftherapeuticefficacy.Thistesthasnotyetbeen
(WHO) 75/502 international human serum IgE reference cleared in the United States by the FDA.
preparation,therebyestablishingauniformsystemofspecific Cell types that contribute to cell-mediated immunity reac-
IgEantibodyinquantitativekilointernationalunits(kIU)per tions include lymphocytes, monocytes, macrophages, den-
liter (ie, 1 kIU (cid:3) 2.4 ng IgE). The method of total and driticcells,Langerhanscells,andgranulocytes.Mostlabora-
specific IgE assays are discussed in detail, including the tory tests of cell-mediated immunity quantify lymphocyte
indications, advantages, and limitations of these assays. The function with respect to (1) proliferation; (2) production of
FDA guideline regulations now stipulate guidance regula- inflammatory mediators, cytokines, and chemokines; (3)
tions for all IgE methods, including semiautomatic, auto- monitoring of cytotoxic reactions; and (4) regulation of im-
matic, and multiplexed systems. According to these quality mune responses. Techniques to measure each of these func-
assurancesuggestions,eachallergenassayshouldincludeits tions are discussed in the context of advantages and disad-
specific homologous reference serum (ragweed vs ragweed vantages of each method. Several nonradioactive assays of
reference serum) as an additional internal control whenever lymphocyte proliferation and cytotoxicity are now available.
sufficient quantities of specific reference sera can be ob- Although a functional assay of macrophage inhibition is not
tained. It is anticipated that multiplexed arrays for assays of commerciallyavailable,thecytokineresponsibleforthistest,
IgE will soon be generally available. Secondary antibody MIF, can be measured by immunoassay. Other cytokines or
detector systems for these modified techniques include chemokinesofspecialimportancetocell-mediatedimmunity,
chemiluminescence and fluorescence. Allergen specificity suchasIL-12,IL-16,andmonocytechemoattractantproteins
and cross-allergenicity may be determined by an inhibition (MCPs) 1, 2, and 3, can also be measured by ELISA immu-
technique. Although correlation of higher kIU levels of spe- noassays.
cific IgE to clinical sensitivity for some allergens is equiva- Evaluation of non-IgE and non–cell-mediated immunity
lent to prick/puncture tests, skin prick/puncture tests gener- clinicalimmunologicdiseasesmayincludelaboratoryscreen-
ally have better overall predictability and are the preferred ing for (1) primary and acquired immunodeficiency, (2) im-
initial diagnostic approach. mune-mediated gammopathies, (3) complement activation
Interpretation of both skin and serum specific IgE tests is disorders, and (4) a diverse spectrum of autoimmune and
highly dependent on the constitutive allergenicity, potency, vasculiticdiseases.Briefsummariesofdiagnostictechniques
S4 ANNALSOFALLERGY,ASTHMA&IMMUNOLOGY
available for these entities are discussed in part 1. Many of current diagnostic roles of 2 new noninvasive methods (ex-
them have evolved to ELISA and Western and immunoblot haled nitric oxide and exhaled breath condensate) are sum-
assays, although indirect immunofluorescence tests are still marized.
required for confirmation in certain autoimmune diseases. Abriefreviewofunproventestsisincludedneartheendof
Tests of complement activation are especially important in part 1. The unproven nature of these tests is supported by
patients who present with signs of leukocytoclastic vasculit- placebo-controlled studies in some instances. In other situa-
ides. tions, clinical samples submitted for diagnostic evaluation
Specific organ challenge tests may facilitate or confirm yielded completely false results.
clinical diagnosis under certain circumstances: (1) investiga- Thesectiononallergenshasbeenretainedbecauseitisone
tionofpotential“new”allergens,(2)confirmationofclinical ofthemostreliablesourcesofplant,animal,andchemicalsto
diagnosis when the history is suggestive but skin and/or in
which North American patients are exposed. As cited previ-
vitrotestresultsarenegative,(3)confirmingfoodallergy,(4)
ously, the number of positive allergenic contactants exceeds
monitoring of therapy, and (5) substantiating occupational
3,700.Areliablereferencesourceforsuchcontactsubstances
sensitivity. This section has been expanded substantially to
may be found in the patch test discussion of part 1. The
include detailed descriptions of the indications and objective
allergens section also reviews essential information about
techniques for evaluating allergen-specific conjunctival, na-
cross-allergenicity,whichshouldaidtheclinicianinspecific
sal, and bronchial challenges. Protocols for food challenges
decisionsaboutskintestsandallergenimmunotherapy.(Also
are discussed in the part 2 section on “Evaluation of Food
see Allergome – a database of allergenic molecules – http://
Allergy.” Details of laboratory supervised and workplace
www.allergome.org.)
challengesforconfirmationofoccupationalasthma(OA)are
Part2ofthisparameterprovidesevidence-basedlikelihood
also included.
decisions on selecting confirmatory laboratory diagnostic
A new section, “Inflammatory Biomarkers of Upper and
tests for inhalant, food, insect venom, drug, and contactant
Lower Airway Fluids,” has been added because such tech-
allergies. When the data are not sufficiently evidence based
niques often provide confirmatory evidence of suspected
forsuchchoices,alternativepathwaysaresuggested.Ineach
clinical diseases (eg, eosinophilic vs neutrophilic asthma;
bronchoalveolar lavage (BAL) CD8(cid:1) lymphocytic alveolitis oftheseclinicalsubsections,discussionsaboutuseofinvivo
vs in vitro tests are commensurate with Category I evidence
as an indicator of hypersensitivity pneumonitis). In addition,
criteria. All clinical topics in part 2 provide a basis for
integrating historical features, physical signs, and diagnostic
Table1.ClassificationofRecommendationsandEvidenceCategory recommendations of previously published Practice Parame-
ters(DiseaseManagementofDrugHypersensitivity:APrac-
CategoryofEvidence
IaEvidencefrommeta-analysisofrandomized tice Parameter; Allergen Immunotherapy: A Practice Param-
controlledtrials. eter; Stinging Insect Hypersensitivity: A Practice Parameter;
IbEvidencefromatleast1randomizedcontrolled FoodAllergy:APracticeParameter;andContactDermatitis:
trial. A Practice Parameter), with the current updated diagnostic
IIaEvidencefromatleast1controlledstudy techniques presented in part 1.
withoutrandomization.
IIbEvidencefromatleast1othertypeofquasi-
experimentalstudy. COLLATION OF SUMMARY STATEMENTS
IIIEvidencefromnonexperimentaldescriptive SummaryStatement1.Firstdescribedin1867byDrCharles
studies,suchascomparativestudies,correlation
Blackley,skintests(prick/punctureandintracutaneous)have
studies,andcase-controlledstudies.
evolvedasreliable,costeffectivetechniquesforthediagnosis
IVEvidencefromexpertcommitteereports,the
of IgE-mediated diseases. (B)
opinionorclinicalexperienceofrespected
authorities,orboth. Summary Statement 2. Prick/puncture tests are used to
LBEvidencefromlaboratory-basedstudies. confirm clinical sensitivity induced by aeroallergens, foods,
StrengthofRecommendation some drugs, and a few chemicals. (B)
ADirectlybasedoncategoryIevidence. Summary Statement 3. A number of sharp instruments
BDirectlybasedoncategoryIIevidenceor (hypodermicneedle,solidboreneedle,lancetwithorwithout
extrapolatedfromcategoryIevidence.
bifurcated tip, and multiple-head devices) may be used for
CDirectlybasedoncategoryIIIevidenceor
prick/puncture tests. (C)
extrapolatedfromcategoryIorIIevidence.
Summary Statement 4. Although a number of individual
DDirectlybasedoncategoryIVevidenceor
extrapolatedfromcategoryI,II,orIIevidence prick/puncture comparative studies have championed a par-
EDirectlybasedoncategoryLBevidence. ticular instrument, an objective comparison has not shown a
FBasedonconsensusoftheJointTaskForceon clear-cut advantage for any single or multitest device. Fur-
PracticeParameters. thermore, interdevice wheal size variability at both positive
NRNotrated
and negative sites is highly significant. (C)
VOLUME 100, MARCH, 2008 S5
SummaryStatement5.Optimalresultscanbeexpectedby recentretrospectivesurvey,1deathwasreportedinapatient
choosingasingleprick/puncturedeviceandproperlytraining who received 90 food prick/puncture tests at one time. (C)
skin technicians in its use. (C) SummaryStatement19.Intracutaneoustestswillidentifya
Summary Statement 6. Although prick/puncture tests are largernumberofpatientswithlowerskintestsensitivityand
generally age, sex, and race independent, certain age (chil- are used when increased sensitivity is the main goal of
drenyoungerthan2yearsandadultsolderthan65years)and testing. (B)
racial (African American children) factors may affect their Summary Statement 20. Intracutaneous tests are useful for
interpretation. (C) evaluation of anaphylaxis, particularly drug (ie, penicillin)
Summary Statement 7. Skin test allergens used for prick/ and Hymenoptera venom anaphylaxis. (A)
puncture tests should be potent and stable. (B) Summary Statement 21. When compared with specific na-
Summary Statement 8. To ensure proper interpretation, sal challenge, skin end point titration (SET) is equivalent to
positive(histamine)andnegative(salineor50%glycerinated prick/puncture skin tests. (B)
humanserumalbumin[HSA]–saline)shouldbeperformedat Summary Statement 22. Intracutaneous tests should be
the same time as allergen tests. (B) performed with small volumes (approximately 0.02 to 0.05
Summary Statement 9. The peak reactivity of prick/punc- mL) of allergens injected intracutaneously with a disposable
ture tests is 15 to 20 minutes at which time both wheal and 0.5- or 1.0-mL syringe. (C)
erythemadiameters(orareas)shouldberecordedinmillime- SummaryStatement23.Asageneralrule,thestartingdose
ters and compared with positive and negative controls. (B) ofanintracutaneousallergentestrangesfrom100-to1,000-
SummaryStatement10.Qualitativescoring(0to4(cid:1);pos- fold more dilute than the allergen concentration used for
itive or negative) is no longer used by many clinicians be- prick/puncture tests. (C)
cause of interphysician variability in this method of scoring SummaryStatement24.Intracutaneoustestsareread10to
and interpretation. (B) 15 minutes after injection and both wheal and erythema (in
Summary Statement 11. The diagnostic validity of prick/ millimeters) should be recorded. (B)
puncture tests has been confirmed not only in patients ex- SummaryStatement25.Thediagnosticsensitivityofintra-
posed to allergens under natural conditions but also in pa- cutaneous tests is probably greater than prick/puncture tests
tients undergoing controlled organ challenge tests. (B) when testing for penicillin, insect venom, or certain drug
Summary Statement 12. Although prick/puncture testing class(eg,insulin,heparin,musclerelaxants)hypersensitivity.
often correlates with exposure history, there are significant (C)
exceptions to this observation. (B) Summary Statement 26. The greater sensitivity of titrated
Summary Statement 13. Many studies have verified the intracutaneoustests,especiallyintheerythemacomponent,is
sensitivity and specificity of prick/puncture tests for both an advantage for determining biologic potency of allergen
inhalant and food allergens when correlated with nasal and extracts and biologic allergy units (BAU) as based on intra-
oral challenge tests. (B) cutaneouserythemaassaysinsensitivehumanvolunteers.(B)
Summary Statement 14. Compared with clinical history SummaryStatement27.Atdilutionsbetween10(cid:4)2and10(cid:4)3
alone,thediagnosticaccuracyofprick/puncturetestsshowed (wt/vol), intracutaneous tests for most allergens exhibit poor
more limited capacity to predict clinical sensitivity for both efficiency in predicting organ challenge responses and cor-
inhalant and food allergens. (C) relating with the presence of detectable serum specific IgE.
Summary Statement 15. The reliability of prick/puncture (C)
tests depends on the skill of the tester, the test instrument, SummaryStatement28.Therearelimiteddataaboutequiv-
color of the skin, skin reactivity on the day of the test, age, alency of sensitivity, specificity, and predictive indices be-
and potency and stability of test reagents. (C) tween intracutaneous and prick/puncture tests when com-
Summary Statement 16. False-positive prick/puncture test pared with organ challenge tests. One study demonstrated
results may occur (1) to tree pollens in honey bee–sensitive that more dilute intracutaneous concentrations were compa-
patients due to cross-reactive carbohydrate determinants rabletoprick/puncturetestsinpredictingpositivenasalchal-
presentinhoneybeevenomand(2)intree-sensitivepatients lenges. (C)
being tested to tree pollens no longer indigenous to the area. Summary Statement 29. Similar comparative equivalency
(C) studies based on history and symptoms alone revealed that
Summary Statement 17. The rare occurrence of specific intracutaneous tests were comparable to prick/puncture tests
positive organ challenge test results in patients with both only at intracutaneous titration end points between 10(cid:4)5 and
negative prick/puncture and intracutaneous test results sug- 10(cid:4)6 g/mL (wt/vol). (B)
gests that alternative pathways, including locally secreted Summary Statement 30. Because clinical use of intracuta-
IgE, IgE-independent, or nonimmune stimuli may activate neous tests is usually restricted to a single dose (ie, 1:1,000
mediator release in the end organ. (C) wt/vol), which may be irritant, predictive accuracy of these
Summary Statement 18. Life-threatening generalized sys- tests at this concentration is often confounded by false-posi-
temicreactionsarerarelycausedbyprick/puncturetests.Ina tive results. (C)
S6 ANNALSOFALLERGY,ASTHMA&IMMUNOLOGY
SummaryStatement31.Formostallergens,afixeddilution some cases they may also be helpful in investigating nasal
(1:1,000wt/vol)ofintracutaneoustestshaspoorefficiencyin allergy. (B)
predicting organ challenge responses. (A) Summary Statement 46. Conjunctival challenge tests are
Summary Statement 32. Intracutaneous tests are occasion- evaluated by symptoms of itching and objective indices,
ally negative in venom-sensitive patients who experience including tear volume, amount of mucus, and palpebral or
life-threatening reactions. (C) bulbar erythema. (B)
Summary Statement 33. Repetitive ((cid:2)2) intracutaneous SummaryStatement47.Nasalchallengesprovideobjective
penicillintestingmaysensitizeasmallnumberofindividuals evidenceofclinicalsensitivitywhenthediagnosisisinques-
to penicillin. (C) tion or in situations when it is desirable to evaluate efficacy
Summary Statement 34. Immediate systemic reactions are of therapeutic management. (B)
more common with intracutaneous tests; 6 fatalities were Summary Statement 48. Nasal challenge responses are
reported in a recent retrospective survey. (C) evaluated by subjective symptoms and objective measure-
Summary Statement 35. Prescreening with prick/puncture mentsofnasalairwayresistance,thenumberofsneezes,and
tests is a practical way to avoid life-threatening reactions to the measurement of inflammatory mediators in nasal secre-
intracutaneous tests. (C) tions. (B)
Summary Statement 36. If prick/puncture prescreening is Summary Statement 49. Specific (allergic) bronchial chal-
not used, preliminary intracutaneous serial threshold titra-
lengeprovidesameasureoflowerairwayclinicalsensitivity
tionsshouldbeconsidered,startingathighdilutions(eg,10(cid:4)5
when there is uncertainty or dispute. (B)
to 10(cid:4)8 g/mL [wt/vol]). This is of particular importance if
SummaryStatement50.Guidelinesfortheperformanceof
exquisite sensitivity (eg, anaphylaxis to foods and drugs) is
specificbronchialchallengeincludefactorssuchaswithhold-
suspected. (D)
ingcertainmedicationsbeforethetest,determiningtheinitial
SummaryStatement37.Thelate-phasecutaneousresponse
allergen dose by preliminary skin or methacholine challenge
is a continuation of either prick/puncture or intracutaneous
testing, a beginning forced expiratory volume in 1 second
testing,generallythelatter,andischaracterizedbyerythema,
(FEV ) baseline of 70% or better, the amount or duration of
induration or edema, and dysesthesia. (B) 1
exposuretoallergen,measurementofFEV atintervalsafter
SummaryStatement38.Thelate-phasecutaneousresponse 1
the exposure, careful observation for late-phase responses,
may occur after both immune and nonimmune activation.
comparison to a placebo-controlled challenge usually per-
Many allergens have been implicated. (B)
formedthedaybeforethespecificchallenge,and,optionally,
SummaryStatement39.Thelate-phasecutaneousresponse
repetition of methacholine challenge 24 to 48 hours after
shouldbereadbetweenthe6thand12thhoursaftertheskin
specificchallengeforevaluationofinducedbronchialhyper-
testsareapplied;measurementsofmeandiameterand/orarea
responsiveness. (B)
of induration or edema should be recorded. (B)
Summary Statement 51. Occupational challenge testing
SummaryStatement40.Althoughtheclinicalrelevanceof
requiresspecialprecautionswithrespecttotheinnatetoxicity
late-phase cutaneous response is not as yet fully established,
of the suspected allergen and special apparatuses used to
severalrandomized,controlledstudiessuggestthatreduction
measure and control the quantity of challenge substances,
insizesoflate-phasecutaneousresponsemayparallelclinical
such as potentially irritating volatile agents and dust. (B)
response to immunotherapy. (B)
Summary Statement 52. A practical clinical method of
SummaryStatement41.Thesameprinciplesthatpertainto
assessingOAisprospectivemonitoringoftheworkeratand
safety of skin tests apply to late-phase cutaneous responses.
awayfromworkbyserialpeakexpiratoryflowrates(PEFRs)
(C)
SummaryStatement42.Preadministrationofdrugs,suchas or FEV1 values if this can be arranged by mutual agreement
calcineurin inhibitors, misoprostol, prednisone, and azelas- of employee and employer. (B)
tine, before application of skin tests partially or completely SummaryStatement53.Manyinflammatorycorrelatescan
inhibit the late-phase cutaneous response. (B) be evaluated and studied serially in respiratory and other
Summary Statement 43. The number of skin tests and the bodyfluids,suchasnasalsmearsorlavage,inducedsputum,
allergensselectedforskintestingshouldbedeterminedbased or BAL. These may define specific phenotypes or in some
on the patient’s age, history, environment and living condi- cases predict severity. (B)
tions (eg, region of the country), occupation, and activities. SummaryStatement54.Exhalednitricoxideisanoninva-
Routineuseofalargenumberofskintestsorroutineannual sive measure of airway inflammation and is useful for mon-
tests without a definite clinical indication are clearly not itoring objective responses to topically administered cortico-
justified. (D) steroids. (B)
Summary Statement 44. Respiratory challenge tests are Summary Statement 55. Although breath condensate anal-
usedwhenanobjectivegoldstandardforestablishingclinical ysis is an evolving noninvasive method for evaluation of
sensitivity is indicated. (B) asthma, results are still variable and further refinements are
Summary Statement 45. Conjunctival challenge tests are required before it can be accepted as a valid diagnostic
usually conducted for suspected localized eye allergy but in method. (C)
VOLUME 100, MARCH, 2008 S7
Summary Statement 56. Bronchoalveolar lavage obtained approach. Recall antigen anergy in HIV patients has also
through flexible bronchoscopy is useful in phenotyping been investigated as an indicator of staging, progression of
asthma. The finding of lymphocytic alveolitis may suggest a disease, and response to therapy. (C)
diagnosis of hypersensitivity pneumonitis. (B) Summary Statement 70. Although the standardized PPD
Summary Statement 57. Cystic fibrosis may not only be antigenhasbeenusedformanyyearsasapredictorofactive
confused with asthma but certain genetic variants may be orlatenttuberculosisinfection,confounders,suchassuscep-
associated with increased asthma risks. (B) tible populations, BCG vaccination, and cross-sensitization
Summary Statement 58. Although major phenotypes of with other atypical mycobacterial species have all affected
(cid:3)-antitrypsin deficiency do not occur in asthma, recent sur- the diagnostic accuracy of the tuberculin skin test and, by
1
veysdemonstratedahighprevalenceofasthmainyoungZZ extrapolation, other delayed-type hypersensitivity tests. (C)
homozygous antitrypsin deficiency patients. (B) Summary Statement 71. The gross appearance of a late-
Summary Statement 59. Purified protein derivative (PPD) phase cutaneous response and delayed-type hypersensitivity
oftuberculinistheprototypeantigenrecalltestandprovides reactions may not be completely distinguishable except that
direct evidence that hypersensitivity, as opposed to toxicity, thelatteraremorecharacterizedbyprolongedinduration.(B)
is elicited by the antigens in Mycobacterium hominis or SummaryStatement72.Althoughsystemiccorticosteroids
related mycobacterial species. (B)
will render delayed-type hypersensitivity skin test results
SummaryStatement60.Thetuberculinskintestiselicited
uninterpretable, 28 days of treatment with high-dose inhaled
by the intracutaneous injection of 0.1 mL of standardized fluticasone (220 (cid:4)g, 2 puffs twice a day) did not suppress
PPD starting with the intermediate strength of 5 tuberculin
delayed-type hypersensitivity to PPD in healthy volunteers.
units. (C)
(B)
Summary Statement 61. Recall antigen skin tests are used
SummaryStatement73.Neitheranergynortuberculintest-
to evaluate cellular immunity in patients with infection (eg,
ingobviatestheneedformicrobiologicevaluationwhenthere
life-threatening sepsis), cancer, pretransplantation screening,
is a suspicion of active tuberculosis or fungal infections. (F)
endstage debilitating diseases, and the effect of aging. (C)
Summary Statement 74. Several new in vitro assays (ie,
Summary Statement 62. Reduced or absent recall antigen interferon-(cid:5) and polymerase chain reaction) appear to be
testsaretermedanergy,whichdevelopsfrequentlyincertain
more reliable in predicting active tuberculosis in BCG-vac-
diseases,suchashematogenoustuberculosis,sarcoidosis,and
cinated persons or when cross-sensitivity to atypical myco-
atopic dermatitis. (C)
bacteria may coexist. (C)
Summary Statement 63. Candida albicans, Trichophyton
Summary Statement 75. Immediate hypersensitivity reac-
mentagrophytes, and Tetanus toxoid, the currently available
tions, including anaphylaxis, have been reported after tuber-
recallantigens,areinjectedintracutaneouslyinthesameway
culin skin tests. (D)
as the PPD test. (C)
Summary Statement 76. The number of skin tests for de-
Summary Statement 64. The size of the delayed skin test
layed,cell-mediatedhypersensitivityreactionsislimited.(C)
reactionismeasured48hoursafterantigenchallenge,andthe
Summary Statement 77. First introduced by Jadassohn in
largest diameter of the palpable firm area that outlines the
1896, the epicutaneous patch test has evolved as the defini-
induration response should be measured to the nearest milli-
tivediagnostictechniqueforthediagnosisofallergiccontact
meter. (C)
dermatitis (ACD). (A)
Summary Statement 65. When a single intracutaneous an-
SummaryStatement78.Whenclinicalevaluationssuggest
tigen (other than PPD) is used to evaluate prior sensitization
thatexposuretoaspecificcontactanthasoccurredeitherinan
to a potential pathogen, a reaction of 5 mm or greater may
occupationalornonoccupationalclinicalsetting,patchtesting
suffice as the cutoff point for positive tests, but smaller
reactions (2 to 4 mm) may be clinically important. (C) can be used to confirm the diagnosis. (C)
Summary Statement 66. The absence of delayed-type hy- Summary Statement 79. From a public health perspective,
persensitivitytoallthetestantigenswouldsuggestananergic patch testing is useful to identify potential health hazards of
state. (C) unknown and newly introduced contact allergens for the
Summary Statement 67. The most important use of de- medical community and industrial hygienists. (C)
layed-type hypersensitivity skin testing is epidemiologic SummaryStatement80.Themostcommonpatchtesttech-
screeningofsusceptiblepopulationsexposedtobacterialand niques are the individual Finn Chamber and the T.R.U.E.
fungal pathogens. (C) TEST, an FDA-approved screening method for screening
Summary Statement 68. The widest application of recall contactant allergens. The T.R.U.E. TEST is preloaded with
antigen testing is the detection of anergy and as an in vivo 23 common contactants and vehicle control that have been
clinicalcorrelateofcell-mediatedimmunoincompetency.(C) previously incorporated into a dried-in-gel delivery system,
Summary Statement 69. Although anergy testing was for- which is coated onto a polyester backing to form a patch
merly conducted frequently in HIV patients to determine template. (B)
whetheraconcurrentnegativetuberculinskintestresultrules Summary Statement 81. If photocontact sensitivity is sus-
outactivetuberculosis,recentevidencemitigatesagainstthis pected,theappropriateallergensshouldbesubjectedtopho-
S8 ANNALSOFALLERGY,ASTHMA&IMMUNOLOGY
topatchtestsprimarilyin the UV-Arangeof320to400nm. Summary Statement 94. Negative patch test reactions may
(C) occur even when the tests are performed with the correct
SummaryStatement82.Traditionally,patchtestsremainin sensitizing materials because the test fails to duplicate the
place for 48 hours. After the 48-hour patch test reading, conditions under which the dermatitis developed (eg, abra-
additional readings at 3 to 4 days and in some cases 7 days sions,frequentuseofirritatingsoaps,washingthehandswith
after the original application of the patch yield the best solvents). (C)
overall reading reliability. (C) Summary Statement 95. Systemic ACD after patch testing
SummaryStatement83.Adescriptivereadingscaledevel- is rare, as is reactivation of patch test reactions after oral
oped by 2 major international ACD research groups is the ingestionofrelatedallergensorevenbyinhalationofbudes-
current standard for interpreting patch test results. (C) onideinpatientswithsensitizationtotopicalcorticosteroids.
SummaryStatement84.Althoughpatchtestsareindicated (B)
inanypatientwithachroniceczematousdermatitisifACDis SummaryStatement96.Itispossibletosensitizeapatient
suspected, patch tests are especially important in identifying whohadnotbeenpreviouslysensitizedtotheallergenbeing
both ICD and ACD in the occupational setting. (C) tested. This is particularly true of plant contactants, such as
SummaryStatement85.Otherimportantexposuresassoci- poison ivy or oak and aniline dyes. (B)
atedwithACDincludetheuseoftopicalmedication,includ- Summary Statement 97. Two major variants of traditional
ing corticosteroids, plant-induced ACD, and dermatitis oc- patch tests are available: the atopy patch test (ATP) and
curring after the use of cosmetics and personal hygiene repeated use test (RUT). (B)
products. (C) Summary Statement 98. Atopy patch tests have been eval-
Summary Statement 86. Unprotected work and repetitive uated in patients with atopic dermatitis and eosinophilic
exposure to surfactants may predispose patients to occupa- esophagitis as an adjunct for the diagnosis of inhalant and
tional dermatitis, including ICD and ACD. (C) food allergy. (B)
SummaryStatement87.Certaincontactantallergensinthe Summary Statement 99. Atopy patch tests for foods are
T.R.U.E.TESTpanel,suchasnickelandsomerubberchem- prepared with dried or desiccated foods mixed into an aque-
icals, have a high degree of relevant (approximately 75%) ous solution and placed in 12-mm Finn Chambers before
correlation with clinical sensitivity but others do not (eg, positioning on the patient’s back. (B)
hydroxycitronellal, thimerosal). (B) SummaryStatement100.Atopypatchtestsforthediagno-
SummaryStatement88.Patchtestsaremosteffectivewhen sis of drug allergy are performed by incorporating liquid or
the patients are selected on the basis of a clear-cut clinical powdered drugs into petrolatum or aqueous solvents, which
suspicion of contact allergy and they are tested with the are added to 12-mm Finn Chambers and placed on the back.
chemicals relevant to the problem; these conditions satisfy (B)
the prerequisites of high pretest probability. (C) Summary Statement 101. Use tests have been developed
Summary Statement 89. Although the diagnostic accuracy forweaksensitizers(repeatedopenapplicationtest[ROAT]),
of contactants cannot be compared with other in vivo or in substances with poor percutaneous absorption (strip patch
vitro tests, diagnostic concordance between patch test sensi- test), and several premarketing dose response provocation
tivity and the outcomes of repeated open provocation tests testsfordeterminingtheminimalsensitizingdoseofpotential
has been demonstrated for some contactants. (B) contactants in human volunteers. (B)
Summary Statement 90. The chief limitation to traditional SummaryStatement102.Inthestrippatchtestpenetration
patchtestingforthediagnosisofACDisthelackofasuitable ofsubstancesisenhancedbyrepeatedadhesivetapestripping
gold standard by which it can be evaluated in terms of beforeapplicationofthecontactantpatchtothestrippedarea.
diagnostic accuracy predictors and likelihood ratios. (C) (B)
Summary Statement 91. Other technical limitations of SummaryStatement103.TheROATisanexaggerateduse
patchtestsincludetheinclusionofrelevantcontactallergens, test designed to determine a patient’s biologic threshold or
useofthepropervehicle,applicationtotheproperskinarea, response to a suspected contactant, especially if this has not
proper reading and interpretation, and the ability to correlate been achieved with prior open or closed patch testing. (B)
the tests with the patient’s specific exposure. (A) Summary Statement 104. Although clinical relevance is
Summary Statement 92. Other limiting factors concern still evolving with regard to the APT, several investigative
reproducibility, lack of information about irritant thresholds, groups have reported that this test may be an adjunct in
and minimal elicitation concentrations (MECs) for many detectionofspecificallergensinatopicdermatitisandeosin-
common chemicals in the human environment. (C) ophilic esophagitis. (B)
Summary Statement 93. The inability to separate irritants Summary Statement 105. The role of the atopy patch in
fromallergicresponsesisoftenencounteredintheangryback determining clinical allergy to food is indeterminate. (B)
syndrome,whichoccursinapproximately6%ofcasesandis Summary Statement 106. The lack of standardization of
likely to develop in patients with a longer duration of the APTsfordiagnosisofbothfoodanddrugallergyisthechief
primary dermatitis. (C) limitation. (C)
VOLUME 100, MARCH, 2008 S9
SummaryStatement107.AlthoughthepurposeofAPTsis tive value of both prick/puncture and specific IgE tests gen-
to test for food and drug nonimmediate reactions, the possi- erally tend to be higher among pollens, stable anaphylacto-
bilityofanaphylaxismustbeconsideredbecausetherecould genic foods, house dust mite, certain epidermals, and fungi
be significant percutaneous absorption of proteins and/or compared with venoms, drugs, and chemicals. (C)
simple chemicals with high anaphylactogenic potential. (B) Summary Statement 119. Proper interpretation of specific
SummaryStatement108.Theappropriatenumberofatopic IgEtestresultsneedstotakeintoconsiderationvariablessuch
patch tests is indeterminate because they are not routinely as the binding affinity or avidity of allergens, solid-phase
performed. (D) systems, cross-reactive proteins and glycoepitopes, specific
Summary Statement 109. Because ACD is frequently IgG antibodies in the test system, and high total serum IgE
caused by unsuspected substances, up to 65 patch tests may ((cid:5)20,000 IU). (E)
be required for diagnosis. (B) Summary Statement 120. A multiallergen (up to 15 aller-
Summary Statement 110. Total serum IgE concentrations gensboundtoalinearsolid-phasesystem)testcanscreenfor
arereportedininternationalunitsornanogramspermilliliter atopic status, following which allergen specific tests are re-
(1 IU/mL (cid:3) 2.44 ng/mL). (A) quired for more definitive evaluation. (C)
Summary Statement 111. Total IgE is cross-standardized Summary Statement 121. Specific IgE immunoassays are
withtheWHO75/502humanreferenceIgEserumverifiedby
notrecommendedasadefinitiveconfirmatorytestforseveral
periodic proficiency surveys. (B)
specific clinical conditions. They provide neither diagnostic
Summary Statement 112. The clinical applications of total
norprognosticinformationwhenmeasuredinthecordblood
serum IgE are of modest value. High serum IgE concentra-
ofnewborninfants.Theydonothavesufficientsensitivityfor
tions occur in allergic bronchopulmonary Aspergillosis
foolproofpredictionofanaphylacticsensitivitytovenomsor
(ABPA), the therapeutic response of which is evaluated by
penicillins. (B)
serial IgE values. (B)
SummaryStatement 122.SpecificIgEimmunoassaysmay
Summary Statement 113. Total serum IgE is required for
bepreferabletoskintestingunderspecialclinicalconditions,
assessing the suitability of a patient for omalizumab therapy
such as widespread skin disease, patients receiving skin test
and determining the initial dose. (B)
suppressivetherapy,uncooperativepatients,orwhenthehis-
Summary Statement 114. As with total IgE, commercial
tory suggests an unusually greater risk of anaphylaxis from
specific IgE antibody assays are calibrated using heterolo-
skin testing. (B)
gous interpolation against the WHO 75/502 human IgE ref-
Summary Statement 123. Determination of allergen speci-
erence serum, thereby enabling a uniform system of report-
ficity by inhibition of specific IgE binding is a unique at-
ing. (E)
tribute of specific IgE testing. (E)
Summary Statement 115. In addition to WHO 75/502 cal-
Summary Statement 124. Automated systems using multi-
ibration, an earlier specific IgE classification system was
plexed allergen assays are being rapidly developed. One of
based on internal positive calibration curves from a positive
these is cleared by the FDA for the simultaneous measure-
control heterologous serum containing specific IgE antibod-
ment of 10 allergens. (E)
ies, which in the original RAST was white birch specific.
Summary Statement 125. Allergen specific IgG may be
However, FDA clearance for modified specific IgE tests
measured by immunodiffusion or immunoabsorption. (E)
requires use of homologous internal control allergic sera
Summary Statement 126. Immunodiffusion antibodies to
whenever this is possible to obtain. (E)
cow’s milk are associated with Heiner’s disease, a non-IgE
Summary Statement 116. The precise sensitivity of these
disorder that presents in infants with pulmonary infiltrates.
immunoassays compared with prick/puncture skin tests has
(B)
beenreportedtorangefromlessthan50%tomorethan90%,
with the average being approximately 70% to 75% for most Summary Statement 127. IgG and IgG subclass antibody
studies; similar sensitivity ranges pertain when immunoas- tests for food allergy do not have clinical relevance, are not
says are compared with symptoms induced after natural or validated, lack sufficient quality control, and should not be
controlled organ challenge tests. (C) performed. (B)
Summary Statement 117. As with skin tests, the interpre- SummaryStatement128.Althoughanumberofinvestiga-
tation of specific IgE results requires correlation with the tors have reported modest increases of IgG4 during venom
history,physicalexamination,and,insomecases,symptoms immunotherapy,confirmationandvalidationofthepredictive
directly observed after natural or laboratory exposure to al- valueofIgG4fortherapeuticefficacyofvenomimmunother-
lergens.Thiscannotbeaccomplishedbycommercialremote apy are not yet proven. (C)
practice laboratories, which base recommendations for im- Summary Statement 129. The probability distribution of
munotherapy on a history form submitted by the patient and specificIgEforseveralanaphylactogenicfoods(peanuts,egg
specific IgE results. (B) white,cow’smilk,andcodfish)candefineclinicalsensitivity
Summary Statement 118. Because the constitutive allerge- as verified by double-blind oral challenge tests; similar rela-
nicity, potency, and stability are variable among commercial tionshipshavebeendefinedforseveralrespiratoryallergens.
allergen extract reagents, sensitivity and the positive predic- (A)
S10 ANNALSOFALLERGY,ASTHMA&IMMUNOLOGY