REVIEW ARTICLE World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines Alessandro Fiocchi, (Chair), Jan Brozek, Holger Schu¨nemann, (Chair), Sami L. Bahna, Andrea von Berg, Kirsten Beyer, Martin Bozzola, Julia Bradsher, Enrico Compalati, Motohiro Ebisawa, Maria Antonieta Guzman, Haiqi Li, Ralf G. Heine, Paul Keith, Gideon Lack, Massimo Landi, Alberto Martelli, Fabienne Rancé, Hugh Sampson, Airton Stein, Luigi Terracciano, and Stefan Vieths Keywords: Cow milk allergy; oral food challenge; epidemiology; Haiqi Li, MD, Professor of Pediatric Division, Department of DBPCFC; amino acid formula; hydrolyzed milk formula; Primary Child Care, Children’s Hospital, Chongqing Med- hydrolyzed rice formula; hydrolyzed soy formula; skin prick test; ical University, China, 400014. specific IgE; OIT; SOTI; GRADE Ralf G. Heine, MD, FRACP, Department of Allergy & Immunology, Royal Children’s Hospital, University of Authorship Melbourne, Murdoch Children’s Research Institute, Mel- bourne, Australia. Alessandro Fiocchi, MD, Pediatric Division, Department of Paul Keith, MD, Allergy and Clinical Immunology Division, Child and Maternal Medicine, University of Milan Medical Department of Medicine, McMaster University, Hamilton, School at the Melloni Hospital, Milan 20129, Italy. a Ontario, Canada. Holger Sch¨unemann, MD, Department of Clinical Epidemiology Gideon Lack, MD, King’s College London, Asthma-UK & Biostatistics, McMaster University Health Sciences Centre, Centre in Allergic Mechanisms of Asthma, Department of 1200 Main Street West Hamilton, ON L8N 3Z5, Canada. Pediatric Allergy, St Thomas’ Hospital, London SE1 7EH, Sami L. Bahna, MD, Pediatrics & Medicine, Allergy & United Kingdom. Immunology, Louisiana State University Health Sciences Massimo Landi, MD, National Pediatric Healthcare System, Center, Shreveport, LA 71130. Ј Italian Federation of Pediatric Medicine, Territorial Pediat- Andrea Von Berg, MD, Research Institute, Children s depart- ric Primary Care Group, Turin, Italy. ment , Marien-Hospital, Wesel, Germany. Alberto Martelli, MD, Pediatric Division, Department of Kirsten Beyer, MD, Charite´ Klinik fu¨r Pa¨diatrie m.S. Pneu- Child and Maternal Medicine, University of Milan Medical mologie und Immunologie, Augustenburger Platz 1, School at the Melloni Hospital, Milan 20129, Italy. D-13353 Berlin, Germany. Fabienne Rance´, MD, Allergologie, Hoˆpital des Enfants, Poˆle Martin Bozzola, MD, Department of Pediatrics, British Hos- Me´dicochirurgical de Pe´diatrie, 330 av. de Grande Bret- pital-Perdriel 74-CABA-Buenos Aires, Argentina. agne, TSA 70034, 31059 Toulouse CEDEX, France. Julia Bradsher, PhD, Food Allergy & Anaphylaxis Network, Hugh Sampson, MD, Jaffe Food Allergy Institute, Mount 11781 Lee Jackson Highway, Suite 160, Fairfax, VA 22033. a Sinai School of Medicine, One Gustave L. Levy Place, NY Jan Brozek, MD, Department of Clinical Epidemiology & 10029-6574. Biostatistics, McMaster University Health Sciences Centre, Airton Stein, MD, Conceicao Hospital, Porto Alegre, Brazil. 1200 Main Street West Hamilton, ON L8N 3Z5, Canada. a a Luigi Terracciano, MD, Pediatric Division, Department of Enrico Compalati, MD, Allergy & Respiratory Diseases Child and Maternal Medicine, University of Milan Medical Clinic, Department of Internal Medicine. University of School at the Melloni Hospital, Milan 20129, Italy. Genoa, 16132, Genoa, Italy. Stefan Vieths, MD, Division of Allergology, Paul-Ehrlich- Motohiro Ebisawa, MD, Department of Allergy, Clinical Institut, Federal Institute for Vaccines and Biomedicines, Research Center for Allergy and Rheumatology, Sagami- Paul-Ehrlich-Str. 51-59, D-63225 Langen, Germany. hara National Hospital, Kanagawa 228-8522, Japan. Maria Antonieta Guzman, MD, Immunology and Allergy aMember of the Grades of Recommendation, Assessment, Division, Clinical Hospital University of Chile, Santiago, Development and Evaluation (GRADE) Working Group Chile. Santos Dumont 999. Revision Panel Correspondence to: Alessandro Fiocchi, MD, Paediatric Division, Depart- Amal Assa’ad, MD, Division of Allergy and Immunology, ment of Child and Maternal Medicine, University of Milan Medical Cincinnati Children’s Hospital Medical Center, Cincinnati, School at the Melloni Hospital, Milan 20129 Italy. E-mail: [email protected]. This Review Article is co-published as a Supplement to the May 2010 issue Ohio, USA. of Pediatric Allergy and Immunology. Carlos Baena-Cagnani, MD, LIBRA foundation Argentina, Copyright © 2010 by World Allergy Organization Division of Immunology and Respiratory Medicine, De- WAO Journal ● April 2010 57 Fiocchi et al WAO Journal • April 2010 partment of Pediatric, Infantile Hospital Cordoba, Santa 17: Choosing the Appropriate Substitute Formula in Different Rosa 381, 5000 Cordoba, Argentina. Presentations, p. 130. GR Bouygue, MSc, Pediatric Division, Department of Child 18: Grade Recommendations on Immunotherapy for CMA, p. 131. and Maternal Medicine, University of Milan Medical 19: Unmet Needs, Recommendations for Research, Implemen- School at the Melloni Hospital, Milan 20129, Italy. tation of DRACMA, p. 133. Walter Canonica, MD, Allergy & Respiratory Diseases Acknowledgements, p. 134 Clinic, Department of Internal Medicine. University of Appendix 1: Cow’s Milk Allergy Literature Search Algorithms, Genoa, 16132, Genoa, Italy. p. 135 Christophe Dupont, MD, Service de gastroente´rologie et Appendix 2: Evidence Profiles: Diagnosis of CMA, p. 144 nutrition, Hoˆpital Saint Vincent de Paul, 82, avenue Den- Appendix 3: Evidence Profiles: Treatment of CMA, p. 154 fert-Rochereau, 75674, Paris CEDEX 14, France. Appendix 4: Evidence Profiles: OIT for Treatment of CMA, Yehia El-Gamal, MD, Department of Pediatrics, Faculty of p. 160 Medicine, Ain Shams University, Cairo, Egypt. Matthew Fenton, MD, Asthma, Allergy and Inflammation SECTION 1: INTRODUCTION Branch, National Institute of Allergy and Infectious Dis- llergy and clinical immunology societies have issued eases, NIH, 6610 Rockledge Dr., Bethesda, MD 20892. Aguidance for the management of food allergy.1,2 Guide- Rosa Elena Huerta Hernandez, MD, Pediatric Allergy Clinic, lines are now regarded as translational research instruments, Mexico City, Mexico. designed to provide cutting-edge benchmarks for good prac- Manuel Martin-Esteban, MD, Allergy Department, Hospital tice and bedside evidence for clinicians to use in an interac- Universitario La Paz, Madrid, Spain. tive learning context with their national or international Anna Nowak-Wegrzyn, MD, Jaffe Food Allergy Institute, scientific communities. In the management of cow’s milk Mount Sinai School of Medicine, One Gustave L. Levy allergy (CMA), both diagnosis and treatment would benefit Place, NY 10029-6574. from a reappraisal of the more recent literature, for “current” Ruby Pawankar, MD, Department of Otolaryngology, Nip- guidelines summarize the achievements of the preceding pon Medical School, 1-1-5 Sendagi, Tokyo, 113 Japan. decade, deal mainly with prevention,3–6 do not always agree Susan Prescott, MD, School of Pediatrics and Child Health, on recommendations and date back to the turn of the centu- University of Western Australia, Princess Margaret Hos- ry.7,8 In 2008, the World Allergy Organization (WAO) Spe- pital for Children, Perth, Australia. cial Committee on Food Allergy identified CMA as an area in Patrizia Restani, PhD, Department of Pharmacological Sci- need of a rationale-based approach, informed by the consen- ences, Universita` degli Studi di Milano. sus reached through an expert review of the available clinical Teresita Sarratud, MD, Department of Pediatrics, University evidence, to make inroads against a burdensome, world-wide of Carabobo Medical School at the Carabobo Hospital, public health problem. It is in this context that the WAO Valencia, Venezuela. Diagnosis and Rationale for Action against Cow’s Milk Aline Sprikkelmann, MD, Department of Pediatric Respira- Allergy (DRACMA) Guidelines was planned to provide phy- tory Medicine and Allergy, Emma Children’s Hospital sicians everywhere with a management tool to deal with Academic Medical Centre, Amsterdam, The Netherlands. CMA from suspicion to treatment. Targeted (and tapped for their expertise), both on the DRACMA panel or as nonsitting reviewers, were allergists, pediatricians (allergists and gen- SECTIONS eralists), gastroenterologists, dermatologists, epidemiologists, methodologists, dieticians, food chemists, and representatives 1: Introduction, p. 58. of allergic patient organizations. Ultimately, DRACMA is 2: Methodology, p. 59. dedicated to our patients, especially the younger ones, whose 3: Epidemiology of CMA, p. 61. burden of issues we hope to relieve through an ongoing and 4: Allergens of Cow’s Milk, p. 65. collective effort of more interactive debate and integrated 5: Immunological Mechanisms of CMA, p. 71. learning. 6: Clinical History and Symptoms of CMA, p. 76. 7: Diagnosis of CMA According to Preceding Guidelines, p. 85. Definitions 8: The Elimination Diet in Work-Up of CMA, p. 88. Adverse reactions after the ingestion of cow’s milk can 9: Guidelines for Diagnosing CMA, p. 89. occur at any age from birth and even among infants fed 10: Oral Food Challenge Procedures in Diagnosis of CMA, exclusively at the breast, but not all such reactions are of an p. 100. allergic nature. A revision of the allergy nomenclature was 11: Natural History of CMA, p. 108. issued in Europe in 20019 and was later endorsed by the 12: Treatment of CMA According to Preceding Guidelines, p. 112. WAO10 under