Diagnosis of natural rubber latex allergy

Diagnosis of natural rubber latex allergy

28 CLINICAL MMUNOLOGY Newsletter fum a consistent,reproducible m&ion for thesetypes of symptoms?~p Vol. 16, No. l/2,1996 References 1. hderson JA...

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28 CLINICAL

MMUNOLOGY

Newsletter

fum a consistent,reproducible m&ion for thesetypes of symptoms?~p

Vol. 16, No. l/2,1996

References 1. hderson JA: Mikstem: marking the knowlCd@'Of8dVClXCrerctioartOfOOdhthC&C8dC

Contraindications to Oral Challenge Becauseof its potential risks, oral challenge should not be perfonued when a convincing history of life-threatening anaphylaxis exists and the causativefood is clearly knowa Similarly, becauseof the high risk for anaphylaxis, someinvestigators do not recommendoral challenge in infants under a year of age.951 Summary Oral provocation testing is useful in the evaluation of immunologic and non-immune mediatedadversefood reactions.Presumptive diagnosisbasedupon history and other testsis no longer satisfactory except for clear casesof severeanaphylaxis. Double-blind, placebocontrolled food challenge is now consideredto be the “gold standaS for the diagnosis of most cases of food hypersensitivity. This technique can be usedfor any food imaginable and ensuresobjective evaluation. Open ingestion of the food in question should always follow a negative challenge. The procedure should be pa-formed in a setting with medical personnelfamiliar with recognixing and treating anaphylaxis and appropriate emergencyequipment available. When properly performed,clinical reactions are similar to thosereported by history, but are less severe.A careful, unbiasedapproach to suspectedfood reactions improves diagnostic accuracyand avoids unnecessary dietary avoidancemeasures.

Diagnosis of Natural

of the 1980s.AM Allergy 72:143-154,1994. 2. Atkins FM, Steinberg SS. DD Metcalfe: Evaluationofimmed&advememactiomtofoodsin adult patienb. I. Correlation of demographic, kboratory. and prick skin test data with response to controlkd onI food challenge.J Allergy Clm Immmlol75:348-355.1985. 3. Atkins FM, SteinbergSS, Metcdfe DD: Evaluationofimtm&amadversemactionstofoodsin adult patkats. II. A detaikd analysis of reaction patterns during oral food challenge.J. Allergy Clin. Immtmol. 75:356-363.1985. 4. Beyer K, Niggemam B. Schulxe S, W&n U: Serum tryptase and urinaty 1-methylhistamineas parametersfor monitorht8 oral food dtalleuges in children. Int AmIt Allergy Immunol 104:348351,1994. 5. Bock SA, Lee W, Remigio LK, May CD: Studies of hyperseusitivity reactionsto foods in infants and children. J Allergy Clin Immunol62:327334.1978. 6. Bock SA, Atkins FM: Patternsof food hypenensitivity during sixteen years of double-blind, placebo-controlledfood challenges.J Pediatr 117:561-567,199O. 1. Bock SA, SampsonHA, Atkins FM, et al.: Double-blind, placebo-controlledfood challenge (DBPCFC) as an office procedure:a manual.J Allergy Clm Immunol82:986-997,1988. 8. Burks AW. SampsonHA: Diagnostic approaches to the patient with suspectedfood allergies. J Pediatr 121:%4-S71,1992. 9. Europa SocietyforPaediiccIastmeuterology andNuttition Working Croup for the Diagnostic Critetia for FoodAllergy: Diagnosticcriteria for food allergy withpmdominantly intestinalsymp units.J Ped GastroentemlNutr 14:108-l 12.1992. 10. JamesJJ. SampsonHA: An overview of food hypetsensitivity.Pediitr Allergy Immunol3%7-78. 1992. 11. JamesJJ. Bemhisel-BroadbentJ, SampsonHA:

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Reqinkny readions provokedby do&k-blii food chaIlenger in children Am J Reapir Crit Care Med 149:59-64.1994. Lessof MH: The diagnosis of food intolerance. ClmExp Allergy 25:14-15.1995. May CD: Objective clinical and laboratory studies of immediate hyprsensitivity madions to food in asthmatic childmu. J Allergy Clin Immunol58:500-515.1976. Roy CC, Silverman A. Alagille D (ed.): Mdatt sorption syndrome,pp. 318-336. In: Pediatric Cliical Gastroenterokgy, 4th ed. Mosby-Year Book, Inc, St. Louis. SampsonHA: Immunologic mechanismsin adverse madions to foods. Immunol Allergy Clm N Am 11:701-716.1991. SampsonHA, Albergo R. Comparisonof msuIts of skin teats,RAST, and double-Mind,placebocontrolled food challengesin children with atopic dermatitis. J Allergy Clm Immunol74:2633,1984. SampsonHA, Broadbent RR, Bemhisel-Broadbent J. Spontaneousreleaseof histamine from basophils and histamine-releasingfactor in patients with atopic dermatitis and food hypersensitivity. N Engi J Med 321:228-232.1989. SampsonHA, Jolie PL: Increasedplasma histamine concentrationsafter food challengesin children with atopic dermatitis. N Engl J Med 311:372-376.1984. SampsonHA, McCaskill CC: Food hypenensitivity and atopic dermatitis: evahntion of 113patknta. J Pediatr 107:66%675,1985. Strobe1S: Mechanismsof tolerance and sensitixation in the intestine and other organsof the body. Allergy 50 (28 suppl.):lS-25.1995. Walker-Smith JA: Diagnostic criteria for gastm intestinal food allergy in childhood Clin Exp Allergy 25:u1-221995. Warner JO: Food and behavior. Clin Exp Allergy 2523-26.1995.

Rubber Latex Allergy

Robert G. Hamilton Division of Allergy and Clinical hnwaunology,Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School ofhfedcine. Baltimore, Maryland

Natural rubber latex (latex) is an organic substancethat is obtained in the form of milky sap from Heveu brusiliensis (rubkr) trees.Tbe unprocessedsapcollected directly from the tree is composedof 36% cis-1,4 polyisoprene long chain polymers, 0197-lS59/96/$c.O0+ 15.00

60% water, 1.6%carbohydrates,and 1.4% protein, the remainderbeing lipid and inorganic matter (Table l).’ The pulyisopmne is the primary ingredient usedin the manufaCtu.EOf such produCtS as latex ~bber gloves, dental dams,condoms,balloons, 0 1996Elsevier ScienceInc.

koosh ball toys, and other rubber-containing household and medical devices. Unfortunately, rubber proteins presentin the latex are conservedthrough the rubber manufacturing process.Their presencein high amounts in finished rubber products

CLINICAL IMMUNOLOGY NewsZerter 29

Vol. 16, No. l/2, 1996 TABLE 1. ~SI-IION

Latexeompwition

OF NATURAL

RUBBER LATM

PeIUY4l~

FROM

HEVEABRASILIENSIS Noturd

or additive

Cis-1.4 polyiroprene polymers

36%

NdUnl

Water

60%

NSltUral

Carbohydrates

1.6%

NatUral

Protein

1.4%

Natural

1%

NdUrsl

numberoflatexallergiccasesinthe United States.Roughprevalencee&mates may, however,be madefor two primary high-risk groups:adult healthcareworkers and children with myelomeningocelewho undergomultiple surgeries. Adult Healthcare Workers

Early prevalencestudiesbasedtheir estimatesof latexallergy on questionnaires, Additive 2oo4oomM Ammonie clinical history,andpoorly controlled Additive 1% w/v Pwaphenylenediamine glove usage(provocation)tests.Between Additive 1% wtv Merapcobenzothiazole 2.2% and 7.5% of hospitalpersonnel(surgeons, nurses,dentists,radiologists)and Additive 1% wtv Carbrunate mixture l%and2%oflaboratorypersonnelarebe Additive 1% w/v Mempto mixtme lieved to be sensitizedto naturalrubberlaAdditive 0.25% wfv Tbham mixture tex.27*8*‘0-*2 More recently,the FDA has examinedthe prevalenceof latex-specific IgE antibodiesamongemergencyroom workersat ninereferencehospitalsdistrib1991regardingtype I hypersensitivityreac- uted throughoutthe United States.Of the hasled to the wide-spreadsensitixationof tions to naturalrubberlatex+Xnaining extensivelyexposed“high-risk” individu507 individualsstudied,21 or 4.1% were als?This sensitizationhasraisedconcerns products.By the fmt internationalsympo- found to be serologicallypositivefor latexaboutlife&teateGng allergicreactionsfol- siumon rubberlatexallergy in November specificIgE antibocly.*3In this study,latex1992,therehadbeen 1,133reportsto the lowing re-exposureto latexrubberallerspecificIgE was moreprevalentin CDC of latexreactionsassociatedwith 30 gen.This report focuseson the issueof participantswho reportedtachycardia,paldiagnosisanddescribesrecentlydeveloped typesof rubberdevices.Most of the reacpitations,flushing,or wheezingassociated diagnosticskintestingreage4ltsthatareun- tions involvedthe useof rubberlatex-con- with latex glovesin a codedquestion&e dergoingfinal clinical validation. taininggloves,condoms,adhesivetape, (oddsratio = 10.2,95%C = 3.7-28.6).Usintravascularcatheter, toy balloons,and ing a HealthIndustry Manu&ctumr’sAsso Adverse Reactions to Rubber Products dentaldams.Presently,typeI hypersensi- ciation @LA)-generated estimateof 5.5 tivity readionsareknown to be causedby million healthcamworkersin the United The earliestreportedclinical reactionto exposure to allergenic proteins in the latex States,one may estimatethat as manyas naturaIN~latexwasadelay~(lypeIv products.The cornstarchdonningpowder, 420,CNlO healthcareworkershavebecome cell-mediated)hypersensitivityinvolving which wasoncethoughtto be an allergen, sensitizedto latex rubberproteins.These contactdermatitisto a rubber glovethat is now known to bind allergeniclatexpro- individualsareexpectedto experiencea wasassociatedwith the oxidizing CbeNiteinsand transporttheminto the air when spectrumof symptomsrangingfrom localc&ad&dtothelatexpriortoglovemanua powderedlatex gloveis removed?Com- ized hives,itching, and u&aria (distinct -iI CraMe1).WwtIbody-mediated starchparticlesate of u@rable sizeand hypenie&tivitytonattualrubberlatexprofrom contactdermatitis)at the siteof the they remainahimne for extendedperiods. glovecontactto rhinitis and asthmarelated teinswas6rstmpa&din19n,howeveir,it The inductionof allergicrespiratorysymp to inhalationof aemsolixedallergenon was52 yearslater,following the adventof tans in hospitalenvironmentshasbeendi- cornstarch.A minority of casesareexUniversalRecautious,that latex allergy rectly attributedto allergensthat become wasrecognizedasa emergingseriousprobpectedto experienceseveresystemicalleraeNsolized following the removalof pow- gic reactionsinvolving anaphylztic shock leminEumpeandNorthAn&ca.~Since then,therehasbeenanappcuentprogres- dered latex rubber gloves.SomeAmerianddeath.At present,the only treatment can hospitalshave installed laminar flow siveincmaseinthenumberofrepo&d for theselatexsensitivehealthcareworkers hoodsand establishedglove removal arcasesof latex allergy amongtwo primary is strict avoidanceof latexexposure,which easin surgery suitesand nursing stahigh-riskgroups:healthcareworkersand involveseitherleavingtheir jobs or elimipatieutsreceivingmultiple surgeries(e.g., tions; however, this appearsto havedone natingrubberproduct usein their environlittle to minimize the risk of sensitization ments. childlwl with spinabifida).=’ In 1989 for their employees. alone,400 latex-asclociated allergicreacChildren With Spina Bij’ida tionsand15deathsduetolatexenemabal Prevalence of Latex Allergy The prevalenceof allergic reactionsto ~b1oonexposurewere~totheCenters Due to the laclrof FDA-approveddiagnos- ber latexamongchildrenwith myelomenfor DiseaseControl (CDC). This led the tic skin testingreagents,it hasnot been ingocclehasbeenestimatedat 28% and FoodandDrugAdmi&Wiion(FDA)and 34% of the total spinabifida groupsstudpossibleto preciselydeterminethe total CDCtoissuemedicalalertsinMarch Lipid and inorganic matter

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30 CLINICAL IMMUNOLOGY Newsletter ied.8*“‘-‘2 Dr. GodfreyP. Oakley,Jr., M.D., MPH, directorof the Birth Defectsand DevelopmentalDisabilitiesBranchat the CDC, hasestimatedthe total numberof neuraltubedefectsperyearat1in1000 live births.Approximately50% of these defects(0.05%of all live births) may be classifiedasspinabifida that requiremultiple surgeries.Accordingto Dr. Oakley, therearean estimated4 million live births per yearin the United States.Thus,640 childrenper yearis a best-estimateof spinabifida childrenwho becomesensitized to latexasa resultof repeatedsurgeries.It appearsthat at leastfour surgeries maybe requiredwith high allergen-containingpowderedlatexglovesfor a predisposedatopicchild with spinabifida to producedetectablelatexspecificIgE antiMY.

Vol. 16, No. l/2,1996

of thesemethodshavein commonthe requirementfor a well-characterizedallergen reagentthatcontainsall the majorproteinaceousallergeniccomponentspresentin theallergensource.We andothershave performedimmunochemicalstudieswith serumti-omlatex-sensitizedchildrenand adultsto identify theseallergeniclatexpm teins.A detailedsummaryof the allergen profilesin variouslatexsourcematerialsis beyondthe scopeof this reportand is presentedelsewhere.iCi8

preservativesuchasglycerin. AL hasthe advantagethat it representsthe actualmaterial usedin the manufacturingprocessof glovesandotherrubberproducts.However,ammoniawith its resultanthigh pH producesprogressivedegradationof allergeniclatexprotein and thusits stability andreproducibilityappearto be inferior to the non-ammo&ted form of latex.The ammoniaalsoappearsto causelossof resolution in Westernblot analysis,which is usedin routinequality control.

Lg~~twgen

Extracts of Rubber Devices

ReagentSource

Threegeneralsourcesof naturalrubberlatex maybe consideredsuitablefor develop mentinto in vitro (allergosorbent)and in

General Public

D

It hasnot beenpossibleto get an accurate estimateof the prevalenceof latex allergy amongthe generalpublic. It is known that someatopicindividualswho are not in the high-riskgroupshavebecomesensitized following exposureto latexrubbercontaining consumerproducts(toy balloons,condoms,kooshballs, hot waterbottles,baby pacifiers,diving masks,showercurtains, air mattresses,stampadhesives,rubber handleson canesandrackets).Oneestimatehassuggestedthat up to 0.8% of their total populationmay havebecomesensitizedto rubberlatex.‘OThe accuracyand relevanceof thesenumbershavebeenextensivelydebated.A moreaccurateestimateof latexallergy amongnon-high-risk individualsin the generalpopulationwill await the availabilityof an FDA-approved skin testingreagent.

Ammoniated and Non-ammoniated L4ltex

Diiostic Reagentsand Methods Historically,the skin testand the immunoassayfor mastcell-boundand serum IgE antibody,respectively,havebeenthe two primaryassaysthat areusedto sup ptt the clinical history in the definitivediagnosisof humanallergic disea~e.‘~*” The in vitro basophilhistaminereleaseassay andin vivo provocationprocedures(bronchial, nasal,and handprovocation)have beenconsideredsecondarydiagnostictests thatam usefulin clarifying equivocalskin testsandIgE antibodymeasurements. All

Becauselatex is collectedalmostexclusivelyin tropicalzonesof the world (e.g., SoutheastAsia), it is drippedfrom the tree into bucketscontainingammonia.A final ammoniaconcentrationof 200-400 mM is usedto preventspoilagedue to microbial growth. Ammoniatedlatexis thendeliveredto largetanksresidingat factories whereit is storedfor daysto monthsand ultimatelyusedto manufacturedippedand moldedrubberproducts.Alternatively, NAL is a form of the latex sapthat is collectedBorn the treeinto a non-ammonia

or97-1859/96/!$0.00+ 15.00

I resently, type I hypersensitivity reactions are known to be caused by exposure to allergenic proteins in the latex products.

vivo (skin test)allergenreagents:ammoniatedlatex (AL), non-ammoniatedlatex (NAL), andan extractof a latexrubberde vice suchasa rubberglove.

0 1996Elsevier ScienceInc.

Dippedrubberproductssuchassurgical and examinationgloves,condoms,andballoons areproducedon calciumcarbonatecoatedceramicmoldsof the right sizeand shapethat areattachedto a long conveyer belt. As the moldsmovethroughthe plant, they arephysically dippedinto vatsof AL (alsocalledcream),which producesa thin layer of rubberon the mold’s surface. Highly irritating chemicals(Table 1) are addedto the crudelatex beforedipping to increaseits durability, elasticity,and strengthand to facilitatevulcanization,a processof sulfur cross-linkingthat occurs in thepresenceof heat.Finally, the solidified rubbercoatedmoldsare dippedin water tanksfor minutesto hoursto leach excesschemicalsandproteins.Among the latter stepsof the process,the gloveis mistedwith a fine layer of cornstarchdonning powder or dippedin a chlorination tank if a non-powderedglove is being produced.The fmishedgloveis peeledoff the mold insideout by hand,packaged,and,in the caseof surgicalgloves,sterilized.The dippedrubberproductsin the form of examinationand surgicalglovesrepresent the largestsourceof latexallergen(protein) exposureto the healthcareworker andultimatelyto the generalpublic. The yearly useof latexrubbersurgicalandexaminationglovesin the United Stateshas beenestimatedby the HILA GloveTask Forceat 3.6 billion pairs.This numberis only expectedto increasewith the continued observanceof UniversalPrecautions. Extractsof latex gloveshavebeenconsideredfor usein diagnosticallergosorbentsand as skin testingreagents. Typically, a buffered-physiologicalsaline is pipettedinto a glove in a ratio of 5 ml per gramof rubberproduct.While aller-

Vol. 16, No. l/2, 1996 genicpu&insappearintheextmctwithin minutes,sbve exkm are UsmY asiw overnightbefotethey ate centrifuged,sterile filtered,tested,and froxenfor long-term storage.Sincethe gloveextmctshouldin theorycontainall the relevantallergenspf+ cificities to which sensitizedindividuals havemadeIgE antibody,it hasbeenconsideredan attractivelatexallergensource for teagentdevelopment.However,variationin the levelsof allergenicproteinsbetweenglovelots and differentbrandshas ledtoconcemsaboutthelong-termreproducibility Ofsuchextractsfor useaSa diagnosticreagent. Identification of the Optimal Latex Allergen Source

In 1994,we begana study to determine which of the threepotentialsourcesof latex allergen(NAL, AL, and glove extract) representsthebestsotucefor diagnosticin vivo and in vitro reagentdevelopment.Our working hypothesisenteringinto this studywastbat all threelatex sourcematerials would exhibit a differentdiagnosticsensitivity andspecificityas skin testing reagentsbasedon the fact that immunochemicalstudieshaveclearly shownlarge qualitativeand quantitativedifferencesin their proteinand allergencontent.We obtainedfreshNALandALfiomclone6OO of Hevea brasiliensis &es in Malaysia andultracentrifugedthe materialwitbin 1 weekof collection.Theprotein-containing middIefluid layer was sterilefiltered, aliquou and frozen.We alsoprepamdan extmctof powderedlatex surgeongloves thathadbeenman~fromthesame Hevea latex clone.All threepreparations wereshownby FDA-requiredteststo be sterileandbiologically safe.They were thennormalizedto 1 mg/ml of total protein,which also normalixedtheir allergen potenciesasassessedby radioallegosorbenttest(RAST) inhibition.‘9 In our initial safetyand diagnosticspeciOcitystudies,24 non-latexallergicsubjectswererecruited.Following informed consent,blood was takenfor IgE anti-latex analysisand both pick pwcture and intra&xmalskin testswereperfomxl with the NAL, AL, and gloveextractsusinga skin teattitration procedurz?to maximize safety.Basedon thesestudies,we identif& 100erg/ml(punctureskin test)and 1

CLINICAL IMMUNOLOGY Newsletter 31 ug/ml (intradenna skin test)as the highest concentratitmof all threeallergenextits thatcould be appliedwhile alsomaximixing specificity(e.g.,not producea falsepositiveskin test). In the diagnosticsensitivityphaseof the study,59 clinicalIy Iatexallergic subjects wereevaluatedwith the sameprotocol,using extractconcentrationsidentifiedin the first phaseto not inducefalse+positive reactions.Fifty of thesehadstronglypositive skin tests(ST) andIgE anti-latex(IgE Ab) asmeasutedby RAST.” Of the nine l&+/ST+@ AL sub&ts, ftve wem availablefor the two-stagelatexglove provocationtest.In this test,a high-allergenpowderedlatexgloveis put on one handand a control (vinyl) gloveon the otherhand.The subjectis thenobserved for 30 minutesfor any allergic symptoms. If no symptomsattributableto the glove occd, it wasremoved,blown up like a balloon,and its contents(allergen/powder) werereleasedinto the subject’sface.After a second3Ominuteobservationperiod, noneof the five subjectshadany allergic symptoms,indicatinga negativeprovocation test.We thereforeclassifiedthesesubject8with a negativeskintest,IgE antibody level,andgloveprovocationtestasnot allergic to latex(falsepositivehistory). Theresultsof our studydemonstrated thatall threeallergenextractsources (NAL, AL, andglove)canperformequivalently well in termsof their ability to detfxt IatexspecificIgE antibodyin the skin whenthey arenormalizedbasedon total proteinandallergencontent.The NAL extract wasthereforeselectedas thecandidatesourcematerialof choicedue to factorsotherthandiagnosticperformance thatrelatedto its superiorinter-lot reproducibility andeaseof quality control with immunochemicalassays.Whenusedin punctureskin testingat 100ug/ml, the candidatenon-ammonia&llatexdisplayeda diagnosticsensitivityof 95% and specificity of 100%.Moreover,excellentconcordancewasobservedbetweenthe presence of IgEiantibodydetectedin the skin by puncttueskin testingand in the blood with the IgE anti-latexRAST (i=O.98; P
negativeskin testand negativeIgEantibodyRAST,mtulethemca&&b&aforthe gloveprovocationtest.Furtherdetailson the comparativeperformanceofthe three soulcesoflatexininvivoandinvitrodiagnmtic methodsatepresentedelse~hete.~*-~ Concluding Comments

At the time of this writing, thecandidate non-ammoniatedlatex skin testingmatelialthatwasselectedfromourcIinical studiesis enteringinto a multi-centervalidation study.We expectthe test&sof this study to lead to its approvalby FDA for usea8a diagnosticskin testingreagent. Moreover,thereis currentlyone (the Alastat) and shouldsoonbe other serological assayreagentsthat are approvedby the FDA for the measurement of IgH anti-latex in serum.With thesewell-characterixedreagentsand serologicalassays,we will be able to providehigh quality diagnostic teststo aid in confhming suspectedincreasing trendsin the prevalenceof latexallergy in the United States. Acknowledgments This work hasbeensuppottedin part by NIH grantUOl-AI-31867. References 1. D’Auxac J, JacobJL. Cmstio H (cds.):Physioiogy of the Rubts~ Tree Latex. CRC Pmss.Boca Raton. FL, 1989. 2. Chamus BL, Hamilton RG. Yuaginger Jw: Ckcupational latex exp0surc: charac&stia 0f contact and systemic reactionsin 47 woken. J Allergy Clin Immunol94:12-18.1994.

3. Stem G: Ubemnpfiiichkeit gegenksutschuk als umschevon Urticdria md q~drcrchna odem. Klin Wochenschrifi 6:1O96-1097.1927. 4. Nutter AF: Contad u&aria to rubber. Br J Dermat01101:587-588.1979. 5. Slatcr JE: Rubber anaphykxis. N Engl J Med 320:1126-1130.1979. 6. SpannerD, Dolovich J, Tarlo S. et al.: Hypersensitivity to natual latex. J Allergy Clin Immunol 83:1135-1137.1989. 7. Ownby DR. Tomknovich M, SammonsN. McCullough J: Anaphylaxir associatedwith Iatex allergy during barium enemaexuninations. Am J Radio1lS6.9O3-9O8.1991. 8. Slater JB: Latex alkrgy IReview]. J Allergy Clin Immuno14:139-149.1994. 9. Tomah VJ, Shampa& EL, Lamam A, et al.: Cornstanzhpowderon latex pmductsis an alkrgen car&r. J AUcrgy Clin Xmmunol93:751-758.1994. 10. TujnnmaaKReudaT.RumrL:Com@son 0fdii~stiCmeth0dsin&cxmrgialglovec0n‘act luticalia. conlau kmmtith 9:241-247, 1988. 0197-185!J19615o.OO + 15.00

32 CLINICAL IMMUNOLOGY Newsletter 11. JugcrD,Klei&uD.&ulqnmAB,BaurX: Latcx-qc45filprotcinrc8luing--typo cutueulI. Msal, bmnchkl and 1ymnic restions. J Allergy Uin Immurml g9:759-76g. 1992 12 Kelly KJ, Kun~ VP, Rcijuk KE, Fir& JN: ‘Ihe diignosis of natuml mbht latex alkrgy. J AIletgy Clin hnmol93:813-816.1994. 13. Kaanarek, RG. Silvemmn BG, Gmsr ‘IP, et al.: Rubber latex-rpccifk IgB antibodks lll~hs cmergmcy mom workers: lesti of 8 multi-antcr pmvdcncc study. AM Allergy Aatbma Inununol76~5156.19%. 14. BernsteinIL: hceedioga d tbc ta& force m guidclincr for atah&& old sod new tinologier usedfor the di8gnoaiauld tlvatmau of dkrgic diMMu. J Akgy an IImlMo182:487515.1988. 15. Htihon RG, A&km NF Jr.: Mawnun& of

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Vol. 16, No. l/2,1996 total amnn IgB and alkrgaqecifk IgB aruibody.In:RoscHR,dcMaarioBC,FaheyJL, Frk&un H, bM GM (41): hhud of Cliicd Laboratory Immunology. America Society for Miuobiology. Washbgm, D.C.. pp 689-701. 1992. ToanazicVI. Withrow TJ. Hamilton RGzChractciizati~ of the rlkrgcn(s) in latex proteh extracts.J Allergy Clii Imm~ol%:635-642,1995. Akasawa A. Hsicb LS, Lii Y: Saum ructivitkr to latex pro&~ (Hevea bacilirnris): J Alkrgy Clin IMlnun019s:1196-1205,1995. Sktcr JB, ChhabmSK: Latex antigens.J Allergy Clii Immunol89z673478.1992 Brolr~rt CX. Wisauuer JA, A&son NF, HamiltonRG:Quantitatianofktcxaikqeaiarubbcr gloves. 1. All-y Clin Immmol93:306A, 1994. Turk&aubPC.RastogiRS,BaaH,ctrl.:A

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st8adatdizedquantitative ti test uuy of alkrgcn potency and stability: atudkr 00 the allaga~ dou-rupoluc curve uld effect ofwhul. crytkm&uldpatklaul~onuMy results. J Allergy Clii Immunol70:343-352.1982. 21. Hamilton RG. Chous BL, Xmginger JW, Adkinson NF Jr.: Serological m&ads ia the kbomtoty dirgnosir of hex rubber 8lkrgy: study of non-ammoanmoniatal8nd glove extracts as allergen rcagea sourcea.J Lab Clii Mcd 123594404.1994. 22. Hamilton RG. Adkinaon NF Jr.: N&ml r&her latex kin testing rcqcnts: safety and diagnostic a&Talaq of wn-ramari8tcd latex. munmiated kdcx and latex rub&r glove extmctt. J Alkrgy Clin Immu101(in prur).