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 The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology AAAAI or ACAAI interpretation of these practice parameters. Any (ACAAI) have jointly accepted responsibility for establishing the request for information about or an interpretation of these practice Allergy Diagnostic Testing: An Updated Practice Parameter. This is a parameters by the AAAAI or ACAAI should be directed to the complete and comprehensive document at the current time. The medical Executive Offices of the AAAAI, the ACAAI, and the Joint Council of environment is a changing environment and not all recommendations Allergy, Asthma and Immunology. These parameters are not designed will be appropriate for all patients. Because this document incorporated for use by pharmaceutical companies in drug promotion. the efforts of many participants, no single individual, including those Received for publication October 27, 2007; Accepted for publication who served on the Joint Task Force, is authorized to provide an official November 16, 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. Parameters for Allergy Diagnostic Testing is focused on how 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 mentarium of allergists/clinical immunologists and how their appropriate to the mission of the parameter. The broad range optimal use enables confirmation of human clinical sensitiv- of diagnostic techniques for varying purposes could not pos- ity. The term allergy in this Practice Parameter denotes major 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- immunology. enced narrative discussions on each subject. The Practice The impetus for Practice Parameters for Allergy Diagnos- Parameter is divided into 2 parts: part 1 is a detailed descrip- tic Testing originally stemmed from a consensus conference tion of diagnostic modalities currently available to allergists/ sponsored by the National Institute of Allergy and Infectious clinical immunologists. It encompasses both IgE and cell- Diseases and published as a supplement to the Journal of mediated in vivo (skin and patch) and in vitro tests for a wide Allergy and Clinical Immunology in September 1988. One of spectrum of inhalant, food, and contactant allergens. Organ the major conclusions of that workshop was that periodic challenge tests are discussed in greater detail in this revised reassessment of diagnostic techniques should be mandatory, Practice Parameter because controlled challenges or super- and in keeping with that recommendation, the 1995 Practice vised exposure ultimately serve as the appropriate gold stan- Parameters for Allergy Diagnostic Tests further reviewed and dard for assessing whether clinical sensitivity is present. considered new developments up to that time. In the 13-year Consonant with their recent emergence as diagnostic ad- juncts, the section concerning current status of cytokines and interval since that publication, there has been an exponential chemokines has been expanded. A new section on “Other progression of basic and translational immunologic research, Immunologic Tests” has been added in recognition that many 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- overhaul of the 1995 Allergy Diagnostic Parameter commen- 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 The working draft of the Parameter on Allergy Diagnostic particular problems. Tests update was based on an outline jointly conceived by Part 2 considers optimal utilization and integration of ev- James T. Li and I. Leonard Bernstein and realized by a work 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- ments in diagnostic technology could render specific past and 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 Asthma and Immunology (ACAAI), and the Joint Council of intervals. Nevertheless, whatever the update interim period Allergy, Asthma and Immunology and a number of experts may be, the allergy/clinical immunology community should on in vivo and in vitro diagnostic immunology selected by the be prepared to accept novel new diagnostic techniques, pro- supporting organizations. Comments were also solicited from vided that they are validated by scientifically accepted ap- the general membership of these societies via their Web sites. proaches. This document