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Diagnostic Techniques for Inhalant/Environmental Treatment George F. Kroker, MD FACAAI Tools of the Allergist--Inhalants 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 Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse Annals of Allergy 101:580-592, 2008 Copyright 2015 Allergy Associates of La Crosse 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, Asthama and Immunology. Dec 2008;101:580-592. Copyright 2015 Allergy Associates of La Crosse 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, Asthama and Immunology. Dec 2008;101:580-592. Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse History of the Skin Test Charles Blackley, MD 1820-1900 Copyright 2015 Allergy Associates of La Crosse Daily Pollen Counts May 28-Aug 1, 1866 Types of Skin Tests Epicutaneous Scratch Prick-puncture Modified prick Intradermal Single strength Intradermal Dilutional Titration (IDT) Copyright 2015 Allergy Associates of La Crosse Skin Testing: A Common Goal Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse Wait time for testing after med d/c First-generation H1 meds Second-generation H1 >24 hrs (hydroxyzine 72 hrs) >72 hrs H2 blockers <24 hrs Tricyclic antidepressants >7-14 days Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse 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 1second Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse Intradermal: Single-strength “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.” Allergy: Principles & Practice, 5th ed 1998 E. Middleton Ed. Copyright 2015 Allergy Associates of La Crosse Intradermal: Single-strength “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.” Joint Task Force on Practice Parameters for the Diagnosis and Treatment of Asthma. Annals of Allergy, Asthma and Immunology. 1995;75: 543-625. Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse Epicutaneous Skin Testing “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.” The skin prick test: “more than meets the eye”David Bernstein M. Annals of Allergy, Asthma and Immunology. June 2003;92: 587-588. (Editorial) Copyright 2015 Allergy Associates of La Crosse Epicutaneous Skin Testing 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?” What do allergy skin tests really mean? Portnory, JM. Annals of Allergy, Asthma and Immunology. 2002 Oct;89(4):335-6. Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse Leonard Noon MD 1878-1913 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 Copyright 2015 Allergy Associates of La Crosse Noon’s Quantified Results Copyright 2015 Allergy Associates of La Crosse 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.” Endpoint titration and immunotherapy. King HC. Otolaryngology Clinics of North America. 1985 Nov;18(4):703-17. Copyright 2015 Allergy Associates of La Crosse History of IDT French K. Hansel MD 1893-1981 Copyright 2015 Allergy Associates of La Crosse Herbert J. Rinkel MD 1896-1963 History of IDT (cont.) 1930: French Hansel was the first to perform skin tests using multiple-strength individual extracts instead of singleconcentration extracts He used intradermal injections of antigens in serial 1:10 ratios of varying strengths while measuring the response He demonstrated that each antigen has a unique response 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 Copyright 2015 Allergy Associates of La Crosse 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 quantitatively superior in measuring allergic skin reactivity. The response was constant through 3 or 4 dilutions in 72% of patients Copyright 2015 Allergy Associates of La Crosse 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 reactions (“Multi-antigen threshold therapy”) Copyright 2015 Allergy Associates of La Crosse 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 response is within a safe and therapeutic range Copyright 2015 Allergy Associates of La Crosse IDT: Standard Technique Allergenic extracts are prepared using 5-fold serial dilutions (Concentrate to a #6) Copyright 2015 Allergy Associates of La Crosse LCM Serial Dilutions Copyright 2015 Allergy Associates of La Crosse LCM Concentrates & No 1 dil Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse IDT: Technique Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse IDT: Typical Std Titration Results #6 #5 #4 #3 4 4 5 7 Endpoint 5 5 7 Endpoint Copyright 2015 Allergy Associates of La Crosse 9 #2 9 #1 IDT: Std Titration Copyright 2015 Allergy Associates of La Crosse 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. Copyright 2015 Allergy Associates of La Crosse 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 Copyright 2015 Allergy Associates of La Crosse Optimized IDT Screening Dilutions Dog TCE Cladosporiu m Alternaria Aspergillus Penicillium AA Mold Mix 3 Cat Fall pollen 3 Oak Tree Birch 3 Bermuda Grass Mix Ragweed 3 Cockroach Mite 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 Normal Degree of Clinical Sensitivity 3 4 4 4 4 3 Moderate Degree of Clinical Sensitivity: DROP BACK 1 DILUTION 4 5 5 5 5 4 4 4 4 4 4 High Degree of Clinical Sensitivity DROP BACK 2 DILUTIONS Copyright 2015 Allergy Associates of La Crosse 4 4 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 Copyright 2015 Allergy Associates of La Crosse Modified Quantitative Testing (MQT) 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 Current in vivo and in vitro screens for inhalant allergy. KrouseJH, Stachler RJ, Shah A. Otolaryngology Clinics of North America. 2003 Oct;36(5):855-68. Copyright 2015 Allergy Associates of La Crosse Multi-Test Device allows consistent application of multiple tests to screen initial sensitivity Rapid, with minimum patient discomfort Copyright 2015 Allergy Associates of La Crosse Modified Quantitative Testing (MQT) 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 Current in vivo and in vitro screens for inhalant allergy. KrouseJH, Stachler RJ, Shah A. Otolaryngology Clinics of North America. 2003 Oct;36(5):855-68. Copyright 2015 Allergy Associates of La Crosse MQT Algorithm Summary SPT Wheal Size: > 9mm, No ID, Interpret as #6 EP SPT Wheal Size: 3-8 mm, Apply #5 ID ≤5mm, Interpret as #4 EP If 7-9mm, Interpret as #5 EP If ≥9mm, Interpret as #6 EP If SPT Wheal Size: <3mm, Apply #2 ID ≤6mm, Interpret as NEG If ≥ 7mm, Interpret as #3 EP If Current in vivo and in vitro screens for inhalant allergy. KrouseJH, Stachler RJ, Shah A. Otolaryngology Clinics of North America. 2003 Oct;36(5):855-68. Copyright 2015 Allergy Associates of La Crosse MQT Algorithm Copyright 2015 Allergy Associates of La Crosse Copyright 2015 Allergy Associates of La Crosse Testing Technique Summary Test Efficiency & Economy Specificity Sensitivity SPT only Yes Yes No IDT No Yes Yes Optimized IDT MQT (SPT+IDT) Yes Yes Yes Yes Yes Yes Copyright 2015 Allergy Associates of La Crosse Special considerations: Know your pollens Copyright 2015 Allergy Associates of La Crosse Special considerations Know your regional pollens! Copyright 2015 Allergy Associates of La Crosse Special considerations: Know your pollens Use of Allergen Mixes in testing Copyright 2015 Allergy Associates of La Crosse Use of Allergen Mixes: Testing & SLIT Considerations Testing with allergen mixes Reduces the number of tests Takes advantage of cross-reactivity or coseasonality For SLIT Inducement concern Copyright 2015 Allergy Associates of La Crosse of new sensitivities is not a Use of Mixes: Testing and SLIT Considerations Easy to describe “mixology” “Non Cross-reacting Mix”-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, AA Mold Mix). “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). Copyright 2015 Allergy Associates of La Crosse Use of Mixes: Testing & 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! Copyright 2015 Allergy Associates of La Crosse Special considerations: Know your pollens Use of Allergen Mixes in testing Recognizing atypical responses Copyright 2015 Allergy Associates of La Crosse IDT: Atypical Skin Test Responses #6 #5 4 4 5 7 #4 #3 5 7 7 Endpoint 21 7 9 Endpoint Copyright 2015 Allergy Associates of La Crosse #2 #1 11 Special considerations: Know your pollens Use of Allergen Mixes in testing Recognizing atypical responses Recognizing & recording delayed reactions Copyright 2015 Allergy Associates of La Crosse IDT: Atypical Skin Test Responses (cont.): Late Phase Reactions Endpoint 5 7 Endpoint Copyright 2015 Allergy Associates of La Crosse 7 7 8 “Delayed” IDT: Delayed Reactions Day of Testing Copyright 2015 Allergy Associates of La Crosse 24 hrs later 48 hrs later IDT: Delayed Reactions Pt. J.S. 2 weeks later Copyright 2015 Allergy Associates of La Crosse Dr. Keith Eaton LRCP LRCS 1936-2002 Copyright 2015 Allergy Associates of La Crosse Moulds, Yeasts, Ascospores, Basidiospores, Algae and Lichens: Toxic and Allergic Reactions “…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.” Eaton, K . J Nutr Environ Med. 2002;12:321-335 Copyright 2015 Allergy Associates of La Crosse IDT: Delayed Reactions 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 Copyright 2015 Allergy Associates of La Crosse IDT: Delayed Reaction Report Card Copyright 2015 Allergy Associates of La Crosse Special considerations: Know your pollens Use of Allergen Mixes in testing Recognizing atypical responses Recognizing & recording delayed reactions Special testing considerations Copyright 2015 Allergy Associates of La Crosse IDT: Special Testing Situations 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 Copyright 2015 Allergy Associates of La Crosse Skin Testing: Histamine Control 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 Copyright 2015 Allergy Associates of La Crosse IDT: Special Testing Situations: 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):112936, 2004. AAOA sponsored study 2003-2008 : safety of allergy IDT 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 Copyright 2015 Allergy Associates of La Crosse IDT: Special Testing Situations; 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.” Copyright 2015 Allergy Associates of La Crosse Causes for INCREASED ID reactions 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 Copyright 2015 Allergy Associates of La Crosse False negative inhalant tests Localized IgE production can exist! Remember the skin test is a “surrogate marker” for reaction in other parts of the body Some patients (allergic conjunctivitis) may have minimal skin test reactivity but still react in the eyes Copyright 2015 Allergy Associates of La Crosse Skin test “memory” Remember skin test sites have a “memory” (skin resident memory t cells) An allergenic exposure may trigger a reaction at prior skin test sites Most often caused by molds Example: A boy who mows the lawn Copyright 2015 Allergy Associates of La Crosse 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) Phadia diagnostic component testing Total IgE, other tests Copyright 2015 Allergy Associates of La Crosse In Vitro Tests Types of tests Principles & mechanisms Advantages/disadvantages Indications Scoring Sample panel & hints Copyright 2015 Allergy Associates of La Crosse Discovery of IgE Kimishige & Teruko Ishizaka,1967 Copyright 2015 Allergy Associates of La Crosse Types of In Vitro Tests 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 Copyright 2015 Allergy Associates of La Crosse ELISA test 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 Copyright 2015 Allergy Associates of La Crosse ELISA measures unbound IgE in the allergic Cascade Copyright 2015 Allergy Associates of La Crosse ELISA Testing: Summary Copyright 2015 Allergy Associates of La Crosse ELISA Testing: Technique Copyright 2015 Allergy Associates of La Crosse In Vitro Tests: Advantages 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 IgEmediated food allergy Copyright 2015 Allergy Associates of La Crosse In Vitro Tests: Disadvantages 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” Copyright 2015 Allergy Associates of La Crosse In Vitro Tests: Diseases with high yield Atopic Dermatitis Chronic Respiratory/sinus congestion Asthma Recurrent infections Chronic gastrointestinal symptoms Chronic urticaria Anaphylaxis Copyright 2015 Allergy Associates of La Crosse In Vitro Tests: Indications 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 Copyright 2015 Allergy Associates of La Crosse Typical IgE Modified Class System Specific IgE Class Conc in IU/ml Neg 1/0 1 2 <0.05 0.05-0.08 0.08-0.15 0.15-0.50 3 4 5 6 0.50-2.50 2.50-12.50 12.50-62.50 >62.60 Copyright 2015 Allergy Associates of La Crosse Interpretation Absent Equivocal Low Increasing Levels In Vitro Test Interpretation: Clinical Considerations (Cont) “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. Annals of Allergy, Asthama and Immunology. Dec 2008;101:580-592. Copyright 2015 Allergy Associates of La Crosse Thank you Next: Break followed by La Crosse Method Practice Protocol Dosing Guidelines for Inhalant Allergies Mary Morris MD Copyright 2015 Allergy Associates of La Crosse Thank You Copyright 2015 Allergy Associates of La Crosse