Transcription
Draft 6 compiledMay 11, 20221Drug Allergy: A 2022 Practice Parameter 2829303132333435363738394041424344Authors: David A. Khan, MD1, Aleena Banerji, MD2, Kimberly G. Blumenthal, MD3, Elizabeth J.Phillips, MD4, Roland Solensky, MD5, Andrew A. White, MD6, Jonathan A. Bernstein, MD7, DerekK. Chu, MD PhD8, Anne K. Ellis, MD9, David BK Golden, MD10, Matthew J. Greenhawt, MD11,Caroline C. Horner, MD12, Dennis Ledford, MD13, Jay A. Lieberman, MD14, John Oppenheimer,MD15, Matthew A. Rank, MD16, Marcus S. Shaker, MD, MSc17, David R. Stukus, MD18, DanaWallace19, MD, Julie Wang, MD20Chief Editor(s): David A. Khan, MD, David B.K. Golden, MD, Marcus Shaker, MD, MSc, and DavidR. Stukus, MDWorkgroup Contributors: David A. Khan, MD, Aleena Banerji, MD, Kimberly G. Blumenthal, MD,Elizabeth J. Phillips, MD, Roland Solensky, MD, Andrew A. White, MDJoint Task Force on Practice Parameters Reviewers: Jonathan A. Bernstein MD, Derek K. Chu,MD PhD, Anne K. Ellis MD, David BK Golden MD, Matthew J. Greenhawt MD, Caroline C. HornerMD, Dennis Ledford MD, Jay A. Lieberman MD, John Oppenheimer MD, Matthew A. Rank MD,Marcus S. Shaker MD Msc, David R. Stukus MD, Dana Wallace MD, Julie Wang, MD.Acknowledgement: The Workgroup and Joint Task Force on Practice Parameters would like torecognize Erin P. Scott, PhD, for providing administrative oversight and extensive editing andcoordination throughout the development and final editing process.1Departmentof Internal Medicine, Division of Allergy and Immunology, UT SouthwesternMedical Center, Dallas, Tx,2Department of Internal Medicine, Division of Rheumatology, Allergyand Immunology, Massachusetts General Hospital, Boston, MA, 3Department of InternalMedicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital,Boston, MA, 4Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch,WA, Australia; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN,5The Corvallis Clinic, Oregon State University/Oregon Health Science University College ofPharmacy, Corvallis, Ore, 6Department of Allergy, Asthma and Immunology, Scripps Clinic, SanDiego, CA, 7Department of Internal Medicine, Division of Immunology, Allergy Section,University of Cincinnati College of Medicine, Cincinnati, OH, 8Department of Health ResearchMethods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; Department ofMedicine, McMaster University, Hamilton, ON, Canada; The Research Institute of St Joe'sHamilton, Hamilton, ON, Canada,9Division of Allergy & Immunology, Department of Medicine,Queen’s University, Kingston, ON Canada,10Division of Allergy and Clinical Immunology, JohnsHopkins University School of Medicine, Baltimore, MD,11Food Challenge and Research UnitSection of Allergy and Immunology, Children’s Hospital Colorado University of Colorado Schoolof Medicine, Aurora, CO, 12Department of Pediatrics, Division of Allergy Pulmonary Medicine,Washington University School of Medicine, St. Louis, MO,13Division of Allergy and Immunology,Department of Medicine, University of South Florida Morsani College of Medicine and Jaems A.1
7071727374757677787980818283848586878889Draft 6 compiledMay 11, 2022Haley VA Hospital, Tampa, Fla,14Division of Allergy and Immunology, The University ofTennessee Health Science Center, Memphis, TN, 15Division of Allergy, Rutgers New JerseyMedical School, Rutgers, NJ, 16Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinicin Arizona, Scottsdale, AZ,17Dartmouth-Hitchcock Medical Center Department of PediatricsLebanon, NH, 18Division of Allergy and Immunology, Nationwide Children’s Hospital and TheOhio State University College of Medicine, Columbus, Ohio,19Nova Southeastern AllopathicMedical School, Fort Lauderdale, FL, 20Division of Allergy and Immunology, Department ofPediatrics, The Elliot and Roslyn Jaffe Food Allergy Institute, Icahn School of Medicine at MountSinai, New York, NY,Reprints: Joint Task Force on Practice Parameters (JTFPP) liaison: Rebecca Brandt (AmericanAcademy of Allergy, Asthma, and Immunology, 555 E. Wells Street, Suite 1100, Milwaukee, WI53202, rbrandt@aaaai.org); JTFPP.allergy@gmail.comPreviously published practice parameters and guidelines of the JTFPP are available athttp://www.allergyparameters.org.; http://www.AAAAI.org, and http://www.ACAAI.org.Disclosures: The JTFPP members and work group members’ conflict of interest disclosure formscan be found at www.allergyparameters.org. David Khan has received financial support fromUpToDate and Aimmune; serves on the Board of Directors of the AAAAI, ACAAI Chair ofLiterature Review, Co-Chair of Conjoint Board Review, Texas Allergy, Asthma, and ImmunologySociety Chair of Meetings Committee, and is Associate Editor of the Journal of Allergy andClinical Immunology In Practice. Aleena Banerji has received financial support from Kalvista,Pharvaris, CSL, Takeda, Biocryst. Jonathan Bernstein has received financial support fromTeledoc/Advanced Medical, Inspirotec, PulmOne, Medpace, Sanofi Regeneron, AstraZeneca,Merck, Optinose, Takeda, CSL Behring, Biocryst, Pharming, Kalvista, Ionis, Novartis, Genentech,the National Institutes of Health (NIH), Taylor Francis, INEOS; is Editor in Chief of the Journal ofAsthma, INEOS Medical Immunosurveillance Director, Vice Chair and Lectureship Chair of theAmerican Academy of Allergy, Asthma, and Immunology (AAAAI) Foundation, Chairman of AFI,American College of Asthma, Allergy, and Immunology (ACAAI) Asthma Chair, Scientific Chair,and Young Investigator Award Chair, and serves of the Board of Directors and ScientificCommittee of Interasma as well as the Board of Directors for the AAAAI and World AllergyOrganization. Kimberly Blumenthal has received financial support through UpToDate andresearch grants through NIH. Derek Chu has received research grants through the CanadianAllergy, Asthma and Immunology Foundation and AAAAI Foundation. Anne Ellis has receivedfinancial support from Mylan, Bausch Health, Pfizer, ALK, Medexus, Aralez, Novartis,AstraZeneca, Bayer LLC, Regeneron; serves on the Board of Directors of the Canadian AllergySociety of Allergy and Clinical Immunology. Dennis Ledford has received financial support fromALK, Boehringer Ingelheim, AstraZeneca, BioCryst, AAAAI, Informa, UpToDate, Genentech, GSK,SanofiRegeneron. David Golden has received financial support from Aquestive, ALK-Abello,Genentech, Novartis, ThermoFisher, Allergy Therapeutics, Regeneron, and UpToDate; serves onthe Editorial Boards for The Journal of Allergy and Clinical Immunology In Practice and Annals ofAllergy, Asthma and Immunology. Matthew Greenhawt has received financial support fromAllergy Therapeutics, Allergenis, Sanofi Regeneron, Pfizer, US World Meds, Prota, Aquestive,Novartis, ACAAI, DBV, Intrommune, and is supported by the Agency of Healthcare Research and2
6127128129130131132133Draft 6 compiledMay 11, 2022Quality; has served on the advisory board of International FPIES Association, the Asthma andAllergy Foundation of America, and the National Peanut Board; is Associate Editor of the Annalsof Allergy, Asthma, and Immunology. Caroline Horner has served as committee chair for theAAAAI Asthma Diagnosis and Treatment Interest Section, Interest Section CoordinatingCommittee, and In-Training Exam Coordinating Committee. Jay Lieberman has receivedfinancial support from the ACAAI, DBV Technologies, Novartis, Genentech, Aimmune,Regneron, ALK Abello; is Associate Editor of the Annals of Allergy, Asthma, and Immunology,Chair for the ACAAI Food Allergy Committee, Vice Chair for the ACAAI Annual Meeting ProgramCommittee, Board Member for the American Board of Allergy and Immunology, and MedicalDirector for Food Allergy Alliance of the MidSouth. John Oppenheimer has received financialsupport from Aquestive, Aimmune, GSK, Amgen, AstraZeneca, Regeneron, UpToDate, receivedgrant support from NIH, and serves as an Executive Editor for Annals of Allergy, Asthma, andImmunology. Elizabeth Phillips has received financial support from Biocryst, Regeneron, Vertex,UpToDate, Janssen; research grant support from NIH, NHMRC Australia. Matthew Rank hasreceived financial support from the ACAAI, NIH, Flinn Foundation, and Levin Family Foundation;has served as Chair of the AAAAI HEDQ Interest Section, and is Research Director of the PhoenixChildren’s Hospital Breathmobile. Marcus Shaker is Associate Editor for Annals of Allergy,Asthma and Immunology and Editorial Board Member for the Journal of Allergy and ClinicalImmunology In Practice; has participated in research that has received funding from DBV.Roland Solensky has received research grant support from ALK, Staller-Greer. David Stukus hasreceived financial support from Before Brands, DBV Technologies, Novartis, Kaleo, Integrity CE,the American Academy of Pediatrics (AAP), ACAAI; has served as Committee Chair for theAAAAI and ACAAI, is an advisor for the Asthma and Allergy Foundation of America, Co-Chair forNorth American Pediatric Asthma and Allergy Conference Annual Meeting Planning Committee,Associate Editor for Annals of Allergy, Asthma and Immunology, serves on the Board of Regentsfor ACAAI and is the Social Media Editor for AAAAI. Julie Wang has received financial supportfrom ALK Abello, Regeneron, DBV, Aimmune, Jubilant HollisterStier; is an UpToDate author;serves on the Executive Committee of the American Academy of Pediatrics Section on Allergyand Immunology; serves as Chair of the AAAAI Anaphylaxis, Dermatitis, Drug Allergy InterestSection; serves as Vice Chair of the AAAAI Annual Meeting Program Committee. Dana Wallacehas no conflicts of interest to declare. Andrew White has received financial support throughGenentech, GSK, Blueprint Pharmaceuticals, Optinose, Sanofi Regeneron, AstraZeneca; servesas a Board Member for the Western Society of Allergy, Asthma and Immunology.Resolving conflict of interest:The Joint Task Force on Practice Parameters (JTFPP) is committed to ensuring that all guidelinesare based on the best scientific evidence at the time of publication, and that such evidence isfree of commercial bias to the greatest extent possible. Before confirming the selection of theworkgroup chairpersons and members, the JTFPP discusses and resolves all relevant potentialconflicts of interest (COI) of each potential workgroup member. The JTFPP recognizes thatexperts in a field are likely to have interests that could come into conflict with the developmentof a completely unbiased and objective guideline. Therefore, a process has been developed toacknowledge potential COI when making specific recommendations. To preserve the greatesttransparency regarding potential COI, all members of the JTFPP and workgroup complete a COI3
67168169170171172173174175176177178Draft 6 compiledMay 11, 2022disclosure form prior to beginning work on practice parameter and again prior to the guidelinesubmission for publication. These disclosure forms are published on the JTFPP website.During the review process there are additional measures to avoid bias. At the workgroup level,all the recommendations and discussion sections are reviewed by all workgroup members toensure that content is appropriate and without apparent bias. If any recommendation orsection is deemed to have apparent bias, it is appropriately revised, without the sectionauthor’s involvement, in an attempt to remove potential bias. In addition, the entire documentis also reviewed by the JTFPP and any apparent bias is acknowledged and removed at that level.For each and every recommendation, a vote is required by the workgroup and JTFPP, and anymember with any perceived COI is recused from that vote (and so explained in the document).Any dissenting votes that cannot be resolved are described and explained in the document.In a final stage of review, the practice parameter is sent to invited expert reviewers, selected bythe American Academy of Allergy, Asthma, and Immunology (AAAAI) and the American Collegeof Allergy, Asthma, and Immunology (ACAAI). The document is also posted on the AAAAI andACAAI websites for general membership and the public-at-large to review and offer comment.All reviewers must provide statements of potential COI. Although the JTFPP has the finalresponsibility for the content of the documents submitted for publication, each reviewer’scomments will be discussed and reviewers will receive written responses to comments whenappropriate.The JTFPP members and workgroup members’ conflict of interest disclosure forms can be foundat www.allergyparameters.org.Disclaimer: The American Academy of Allergy, Asthma, and Immunology and the AmericanCollege of Allergy, Asthma, and Immunology have jointly accepted responsibility for developingthe Drug Allergy 2022: A Practice Parameter Update. The medical environment is rapidlychanging, and not all recommendations will be appropriate or applicable to all patients and maychange over time. Because this document incorporates the efforts of many participants, nosingle individual, including members serving on the JTFPP, is authorized to provide an officialAAAAI or ACAAI interpretation of this practice parameter. Any request for information orinterpretation of this practice parameter by the AAAAI or ACAAI should be directed to theexecutive offices of the AAAAI and the ACAAI. Practice parameters and guidelines are notdesigned for use by the pharmaceutical industry in drug development or promotion. The JTFPPunderstands that the cost of diagnostic tests and therapeutic interventions is an importantconcern that may appropriately influence the evaluation and treatment selected for a givenpatient. The JTFPP recognizes that the emphasis of our primary recommendations regarding amedication may vary, for example, depending on third-party payer issues and product patentexpiration dates. However, because a given test or a therapeutic intervention’s cost is so widelyvariable, and there is a relative paucity of pharmacoeconomic data, the JTFPP is not always ableto consider cost when formulating recommendations. In extraordinary circumstances, when thecost benefit of an intervention is prohibitive as supported by pharmacoeconomic data,commentary may be provided.4
Draft 6 compiledMay 11, 2022179180181182Table of Contents183Abbreviations . 7184Preface . 8185Glossary . 9186What’s New and What’s Different . 10187Executive Summary. 13188Classification of Drug Allergies . 14189Diagnostic Tests . 15190Antibiotic Allergy. 17191Penicillin . 17192Cephalosporins . 19193Beta-lactam Cross-Reactivity . 19194Sulfonamides. 21195Fluoroquinolones . 21196Macrolides . 21197NSAID Hypersensitivity . 22198Cancer Chemotherapeutics . 24199Platins . 24200Taxanes . 25201Tyrosine Kinase Inhibitors . 25202Immune checkpoint inhibitors . 26203Biologics . 26204Rituximab . 27205Cetuximab . 28206Infliximab . 28207Omalizumab . 29208Excipients . 29209Methods and overview of the practice parameter development process. 30210List of Consensus Based Statements . 33211MAIN TEXT . 39Drug Allergy: A 2022 Practice Parameter Update . 15
212Draft 6 compiledMay 11, 2022Diagnostic Testing Updates . 39213Drug Challenges . 39214Testing for Delayed Hypersensitivity Reactions . 48215Overview . 48216Testing for Delayed HSRs . 48217In vivo testing (PT and dIDT) . 49218Ex vivo and In vitro testing . 57219Pharmacogenomics . 57220Pharmacogenomics of Drug Allergy. 57221Immediate and Accelerated Reactions . 58222Delayed Reactions. 60223Summary of Pharmacogenomics . 64224Antibiotic Allergy Updates . 64225Beta-Lactams. 64226Penicillin . 64227Cephalosporins . 76228Carbapenems . 87229Monobactams (Aztreonam) . 88230Drug allergy history-based beta-lactam allergy pathways . 89231Sulfonamides. 90232Fluoroquinolones and Macrolides . 94233Fluoroquinolones . 94234Macrolides . 96235NSAID Hypersensitivity Updates . 97236Aspirin/NSAID Hypersensitivity Phenotypes . 97237Aspirin-Exacerbated Respiratory Disease (AERD) . 99238Management of AERD – challenge and desensitization . 103239Management of AERD – aspirin as therapy . 107240NSAID-Exacerbated Cutaneous Disease . 108241Management of NSAID-exacerbated cutaneous disease . 108242Multiple NSAID-Induced Urticaria and Angioedema . 109243Management of NSAID-induced urticaria and angioedema. 110244Single NSAID Induced Urticaria, Angioedema, and Anaphylaxis . 110245Management of single NSAID reactors . 1116
246Draft 6 compiledMay 11, 2022Other NSAID Hypersensitivity Subtypes . 112247Common NSAID hypersensitivity clinical scenarios . 113248Urgent requirement for aspirin in a patient with an acute coronary syndrome . 114249A patient requiring NSAID use for pain . 116250NSAID Hypersensitivity in Children . 116251Clopidogrel Hypersensitivity . 117252Cancer Chemotherapeutic Hypersensitivity . 117253Platins . 122254Taxanes . 128255Asparaginase . 131256Tyrosine Kinase Inhibitors . 132257Adverse Reactions to Immune Checkpoint Inhibitors . 134258Biologic Hypersensitivity . 137259Rituximab . 139260Cetuximab . 144261Infliximab . 144262Tocilizumab . 146263Omalizumab . 146264Excipients Allergy . 147265References . 1Abbreviations95% CI, 95% confidence interval; 95% Crl, 95% credible interval; AERD, aspirin exacerbatedrespiratory disease; AGEP, acute generalized exanthematous pustulosis; ALOX5, arachidonate5-lipoxygenase; CBS, consensus-based statement; CTLA-4, cytotoxic T-lymphocyte-associatedprotein 4; COX-1, cyclooxygenase 1; COX-2, cyclooxygenase 2; CYSLTR1, cysteinyl leukotrienereceptor 1; dIDT, delayed intradermal test; DIHS, drug-induced hypersensitivity syndrome;DRESS, drug reaction with eosinophilia and systemic symptoms; EGFR, epidermal growth factorreceptor; FDA, Food and Drug Administration; FDE, fixed drug eruption; HLA, human leukocyteantigen; HSR, hypersensitivity reaction; ICI, immune checkpoint inhibitors; irAEs, immunerelated adverse events; mAb, monoclonal antibody; MRGPRX2, Mas-related G-protein coupledreceptor membrane X2; MPE, maculopapular exanthem; NPV, negative predictive value; NSAID,non-steroidal anti-inflammatory drug; OR, odds ratio; PD-1, programmed cell death protein 1;PD-L1, programmed death-ligand 1; PEG, polyethylene glycol; PPL, penicilloyl-polylysine; PPV,positive predictive value; PT, patch test; SCARs, severe cutaneous adverse reactions; SJS,7
282283284Draft 6 compiledMay 11, 2022Stevens-Johnson syndrome; SPT, skin prick test; SSLR, serum sickness-like reactions; TEN, toxicepidermal necrolysis; TKI, tyrosine kinase inhibitors; TMP-SMX, trimethoprimsulfamethoxazole; U.S., United States285286Preface287This practice parameter provides an updated approach to the diagnosis and management of288various drug allergy reactions. Evidence has evolved since the previous Drug Allergy practice289parameter1 and currently supports the ability to risk stratify each patient based upon reaction290phenotype. Evaluation of suspected drug allergy focuses on preferential utilization of drug291challenges as opposed to skin testing in many circumstances. Clarification of drug allergy history292is a valuable resource that allergists and immunologists provide to patients with shared293decision making regarding testing and management options central to each evaluation. These294parameters will help clinicians better understand how and when to utilize drug challenges,295including consideration for 1-, 2-, or multi-step challenges. A proactive approach to delabeling296penicillin allergy as well as unnecessary avoidance of safe antibiotic alternatives for patients297with proven penicillin allergy is emphasized. Approaches to diagnosis and management of non-298penicillin drug reactions are discussed in updated sections on cephalosporins, sulfonamides,299fluroquinolones, macrolides, aspirin, chemotherapeutic agents, and biologics. This300comprehensive resource provides consensus-based statements (CBS) throughout, as well as301detailed background and discussion to assist implementation into clinical practice.3028
Draft 6 compiledMay 11, 2022303304305306Glossary1. Delayed hypersensitivity reaction: Immunologic mediated reaction occurring at least 6 hoursafter dosing, with majority occurring 1-2 weeks after drug initiation2. Delayed intradermal testing (dIDT): Intradermal injection of non-irritating drug concentration307on the volar aspect of the forearm followed by evaluation for induration 24 hours after308application3093. Desensitization: A form of induction of drug tolerance typically for IgE-mediated reactions310through administration of multiple gradually increasing doses of a drug to allow for311treatment. Ongoing consistent exposure to the drug is required to maintain desensitization3124. Direct challenge: Performing drug challenge without prior skin testing3135. Drug challenge: Procedure whereby drug is administered to determine tolerance. Preferred314nomenclature compared with “drug provocation tests” or “test doses”, which imply intent to315provoke a reaction3163173183193203216. Drug challenge; 1-step: One treatment dose of the drug is administered, followed byobservation for objective symptoms of reaction7. Drug challenge;
Draft 6 compiled May 11, 2022 2 45 Haley VA Hospital, Tampa, Fla,14Division of Allergy and Immunology, The University of 46 Tennessee Health Science Center, Memphis, TN, 15Division of Allergy, Rutgers New Jersey 47 Medical School, Rutgers, NJ, 16Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic 48 in Arizona, Scottsdale, AZ,17Dartmouth-Hitchcock Medical Center Department of .
