Specific Drugs Practical Guidance for the Evaluation and Management of Drug Hypersensitivity: Specific Drugs Chief Editors: Ana Dioun Broyles, MD, Aleena Banerji, MD, and Mariana Castells, MD, PhD Ana Dioun Broyles, MDa, Aleena Banerji, MDb, Sara Barmettler, MDc, Catherine M. Biggs, MDd, Kimberly Blumenthal, MDe, Patrick J. Brennan, MD, PhDf, Rebecca G. Breslow, MDg, Knut Brockow, MDh, Kathleen M. Buchheit, MDi, Katherine N. Cahill, MDj, Josefina Cernadas, MD, iPhDk, Anca Mirela Chiriac, MDl, Elena Crestani, MD, MSm, Pascal Demoly, MD, PhDn, Pascale Dewachter, MD, PhDo, Meredith Dilley, MDp, Jocelyn R. Farmer, MD, PhDq, Dinah Foer, MDr, Ari J. Fried, MDs, Sarah L. Garon, MDt, Matthew P. Giannetti, MDu, David L. Hepner, MD, MPHv, David I. Hong, MDw, Joyce T. Hsu, MDx, Parul H. Kothari, MDy, Timothy Kyin, MDz, Timothy Lax, MDaa, Min Jung Lee, MDbb, Kathleen Lee-Sarwar, MD, MScc, Anne Liu, MDdd, Stephanie Logsdon, MDee, Margee Louisias, MD, MPHff, Andrew MacGinnitie, MD, PhDgg, Michelle Maciag, MDhh, Samantha Minnicozzi, MDii, Allison E. Norton, MDjj, Iris M. Otani, MDkk, Miguel Park, MDll, Sarita Patil, MDmm, Elizabeth J. Phillips, MDnn, Matthieu Picard, MDoo, Craig D. Platt, MD, PhDpp, Rima Rachid, MDqq, Tito Rodriguez, MDrr, Antonino Romano, MDss, Cosby A. Stone, Jr., MD, MPHtt, Maria Jose Torres, MD, PhDuu, Miriam Verdú,MDvv, Alberta L. Wang, MDww, Paige Wickner, MDxx, Anna R. Wolfson, MDyy, Johnson T. Wong, MDzz, Christina Yee, MD, PhDaaa, Joseph Zhou, MD, PhDbbb, and Mariana Castells, MD, PhDccc Boston, Mass; Vancouver and Montreal, Canada; Munich, Germany; Nashville, Tenn; Porto, Portugal; Montpellier and Paris, France; Chicago, Ill; Charlottesville, Va; Newport Beach, Palo Alto, and San Francisco, Calif; Cincinnati, Ohio; Al-Kuwait, Kuwait; Catania, Italy; Málaga and Ceuta, Spain INTRODUCTION this is often required to maintain patients on first-line therapies, Allergists and clinical immunologists around the world are including antibiotics for those with cystic fibrosis, chemothera- increasingly faced with the task of addressing drug allergy and peutic agents for those with cancer, and mAbs for patients with hypersensitivity due to the increase in drug reactions. Furthermore, chronic inflammatory diseases. The endeavor assumes minor risks aDivision of Allergy/Immunology, Boston Children’s Hospital, Boston, Mass rDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, bDivision of Rheumatology, Allergy and Immunology, Massachusetts General Boston, Mass Hospital, Boston, Mass sDivision of Allergy/Immunology, Boston Children’s Hospital, Boston, Mass cDivision of Rheumatology, Allergy and Immunology, Massachusetts General tAssociated Allergists and Asthma Specialists, Chicago, Ill Hospital, Boston, Mass uDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, dDepartment of Pediatrics, British Columbia Children’s Hospital, University of Boston, Mass British Columbia, Vancouver, Canada vDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and eDivision of Rheumatology, Allergy and Immunology, Massachusetts General Women’s Hospital, Boston, Mass Hospital, Boston, Mass wDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, fDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Boston, Mass Boston, Mass xDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, gDivision of Sports Medicine, Brigham and Women’s Hospital, Boston, Mass Boston, Mass hDepartment of Dermatology and Allergy Biederstein, School of Medicine, Tech- yDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, nical University of Munich, Munich, Germany Boston, Mass iDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, zDivision of Asthma, Allergy & Immunology, University of Virginia, Charlottes- Boston, Mass ville, Va jDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medi- aaDivision of Allergy and Inflammation, Beth Israel Deaconess Medical Center, cine, Vanderbilt University Medical Center, Nashville, Tenn Boston, Mass kAllergology and Immunology Service, Centro Hospitalar Universitário de S.João bbAllergy and Immunology at Hoag Medical Group, Newport Beach, Calif Hospital, Porto, Portugal ccChanning Division of Network Medicine, Brigham and Women’s Hospital, Bos- lDivision of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, ton, Mass University Hospital of Montpellier, Montpellier, France ddDivision of Allergy / Immunology, Stanford University School of Medicine, Palo mDivision of Allergy/Immunology, Boston Children’s Hospital, Boston, Mass Alto, Calif nDivision of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, eeDivision of Allergy and Immunology, Department of Pediatrics, Cincinnati Chil- University Hospital of Montpellier, Montpellier, France dren’s Hospital Medical Center, Cincinnati, Ohio oDepartment of Anesthesiology and Intensive Care Medicine, Groupe Hospitalier ffDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Paris-Seine-Saint-Denis, Assistance Publique-Hôpitaux de Paris, Paris, France Boston, Mass pDivision of Allergy/Immunology, Boston Children’s Hospital, Boston, Mass ggDivision of Allergy/Immunology, Boston Children’s Hospital, Boston, Mass qDivision of Rheumatology, Allergy and Immunology, Massachusetts General hhDivision of Allergy/Immunology, Boston Children’s Hospital, Boston, Mass Hospital, Boston, Mass S16 J ALLERGY CLIN IMMUNOL PRACT BROYLES ET AL S17 VOLUME 8, NUMBER 9S such as urticaria and major risks that include anaphylaxis and to this section of the supplement have provided the most current Stevens-Johnson syndrome. Most of the time these must be information on and the standards for in vitro and in vivo testing and addressed without navigation tools or clear algorithms for the desensitization procedures when these exist. Their efforts have mechanisms of reactions. There are few standardized skin tests/in resulted in an accurate compilation of drug hypersensitivity pro- vitro tests for diagnosis and rare validated desensitization protocols. cedures data that can be applied in a personalized fashion to each Drug testing and desensitization should be considered on the basis drug-allergic patient. of consensus reports (International Consensus [ICON], Interna- The hope is that this supplement will provide a user-friendly in- tional Collaboration in Asthma, Allergy and Immunology strument that will be used in clinics, hospitals, wards, and the [ICALL], Practical Allergy [PRACTALL]) as well as practice pa- emergency department on a daily basis, and that its principles will rameters. However, new and targeted drugs that better address guide and increase allergist immunologists’ skills and level of comfort diseases in a precise and personalized fashion are emerging rapidly, with a practical approach to drug hypersensitivity. The application of and they induce new, unpredictable, and poorly understood re- thestandardsdescribedhereshouldhelpstreamlinetheclinical actions. This publication was born out of a grassroots need to practice of drug hypersensitivity and provide the most updated and provide the seeds of a new discipline: the understanding, diagnosis, safe care to all patients with drug hypersensitivity. It is also hoped that management, and treatment of drug allergy and hypersensitivity as his resource will be updated every 2 to 3 years with new developments a practical clinical endeavor. that arise in the diagnosis and management of drug hypersensitivity Dr Thomas Fleisher embraced this as his presidential theme, as so as to continue to improve the quality and safety of care. mentioned in the Introduction section of this supplement. In the General Concepts article in this supplement, Drs Ana Dioun ANTIMICROBIAL AGENTS Broyles, Aleena Banerji, and Mariana Castells provided the foun- dational steps in describing the phenotypes, endotypes, and bio- Penicillins (by Timothy Lax, MD, and Antonino markers of drug reactions, amplifying the Gell and Coombs Romano, MD) classification and providing practical algorithms for the diagnosis General. Penicillins are commonly used to treat infections caused and management.1 The lead authors next consulted drug hyper- by both gram-negative and gram-positive organisms. Penicillin al- sensitivity experts from around the world to precisely define specific lergy is one of the most commonly reported drug allergies, with a drugs and/or drug classes regarding the phenotypic presentations of prevalence of 5% to 10%.2,3 The reported prevalence is higher reactions, diagnostic tools such as skin testing, in vitro testing, and among hospitalized patients, at 11% to 15%.4,5 Individuals with a challenges, and the best management and treatment approaches history of penicillin hypersensitivity are more likely to receive including desensitization. The numerous authors who contributed alternative antibiotic therapy, which can lead to added expense, ii Division of Allergy and Clinical Immunology, Respiratory Medicine, Department Conflicts of interest: K. Blumenthal reports grants from the National Institutes of of Pediatrics, University of Virginia, Charlottesville, Va Health (NIH), CRICO, American Academy of Allergy, Asthma, and Immunology jj Division of Allergy, Immunology and Pulmonology, Monroe Carell Jr. Children’s (AAAAI) Foundation, and Massachusetts General Hospital; and a beta-lactam Hospital at Vanderbilt, Nashville, Tenn allergy clinical decision support tool licensed to