Abstract
Keywords
Introduction

2010–2020: Open questions in diagnosis, therapy, and immunotherapy of CMA
Allergists respond to death of 3 year-old boy during oral food challenge.
- Nowak-Wegrzyn A.
- Chehade M.
- Groetch M.E.
- et al.

CMA guidelines published after DRACMA
Country/region | Issuing scientific society | Guideline identification | DRACMA based? | Main characteristics | Ref. |
---|---|---|---|---|---|
Europe | ESPGHAN | ESPGHAN CMPA guidelines | No | Focus on non-IgE CMA | 39 |
Europe | European Academy of Allergy and Clinical Immunology (EAACI) | EAACI food allergy guidelines | No | Not limited to CMA | 40 |
France | Société Française de Pédiatrie | Dietetic treatment of cow's milk protein allergy. | No | Limited to treatment | 41 |
Italy | Emilian Working Group on Pediatric Allergy and Gastroenterology | A practical guide | No | Focus on diagnosis and management in primary care | 42 |
Italy | Italian Society of Pediatric Allergy | DRACMA | Yes | Italian translation | 43 |
United Kingdom | National Institute for Health and Care Excellence (NICE) | MAP (Milk Allergy in Primary Care) | No | Focus on non IgE-CMA in primary care | 44 |
United Kingdom | NICE-derived | i-MAP (international MAP) | Partly | Focus on non IgE CMA in primary care | 45 |
United Kingdom | British Society for Allergy and Clinical Immunology (BSACI) | BSACI cow's milk allergy guideline | No | Comprehensive | 46 |
United Kingdom | NICE-derived | Updated i-MAP (international MAP) | Partly | Focus on CMA in primary care | 47 |
Finland | Finnish Allergy Programme 2008–2018 | Practical recommendations of the Finnish Allergy Programme 2008–2018 for prevention, diagnosis, and treatment | No | CMA as part of food allergy management in children | 48 |
Spain | Spanish Society of Pediatric Clinical Immunology and Allergology (SEICAP) | Spanish CM guideline | Partly | Comprehensive | 49 |
Spain | Spanish Society of Paediatric Gastroenterology, Hepatology, and Nutrition (SEGHNP), Spanish Association of Paediatric Primary Care (AEPAP), Spanish Society of Extra-hospital Paediatrics and Primary Health Care (SEPEAP), and the Spanish Society of Paediatric ClinicaL Immunology, Allergy, and Asthma (SEICAP) | Spanish CM guideline for non IgE-mediated CMA | No | Focus on non IgE CMA | 50
Non-IgE-mediated cow's milk allergy: consensus document of the Spanish Society of Paediatric Gastroenterology, Hepatology, and Nutrition (SEGHNP), the Spanish Association of Paediatric Primary Care (AEPAP), the Spanish Society of Extra-hospital Paediatrics and Primary Health Care (SEPEAP), and the Spanish Society of Paediatric ClinicaL Immunology, Allergy, and Asthma (SEICAP). An Pediatr (Barc). 2019; 90: 1-193 |
Turkey | Turkish Society of Pediatrics | Turkish Consensus | Partly | Focus on primary care | 51 |
Middle East | Independent group | Middle East consensus | Yes | Focus on primary care | 52 |
India | Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition | Indian Consensus | No | Focus on primary care | 17 |
China | World Allergy Organization (WAO) | DRACMA | Yes | Mandarin translation | 53 |
China | Independent group | Intensive DRACMA reading | Yes | Implementation in China | 54 |
Japan | Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI); Japanese Society of Allergology (JSA) | Japanese guidelines | Partly | Not limited to CMA | 55 |
Mexico | Independent group | GL-APLV | Partly | Comprehensive | 56 |
South America | World Allergy Organization (WAO) | DRACMA | Yes | Spanish translation | 57 Fiocchi A, Brozek J, Schunemann HJ, et al. Pautas de la Organización Mundial sobre Alergia para el Diagnóstico y Fundamento de la Acción Contra la Alergia a la Leche de Vaca. http://www.scp.com.co/ArchivosSCP/PDF/DRACMA.pdf, accessed May 5th, 2021. |
Methods applied in the 2021 DRACMA guidelines
General structure of the 2021 DRACMA guidelines
Topic | Method of preparation | |
---|---|---|
General | ||
1. | Overview and definitions | This paper |
2. | CMA epidemiology and natural history | Narrative review |
3. | CM allergens and immunologic mechanisms | Narrative review |
4. | Clinical presentations: IgE-mediated | Narrative review |
5. | Clinical presentations: non IgE-mediated | Narrative review |
6. | Comparison among different guidelines | Systematic review |
7. | DRACMA methodology | Synthesis of methods |
CMA diagnosis | ||
8. | Diagnosis of CMA | Systematic review |
9. | Recommendations on CMA diagnosis | Guideline |
Treatment options | ||
10. | Breastfeeding a baby with CMA | Narrative review |
11. | Substitutive formulae | Systematic review |
12. | Recommendations on substitutive treatment | Guideline |
13. | Oral Immunotherapy for CMA | Systematic review |
14. | Recommendations on CMA OIT | Guideline |
15. | Other milks (goat's, ewe's, mare's, donkey's, camel's, and substitutes from non-animal sources) | Narrative review |
16. | Nutritional considerations in CMA infants | Narrative review |
Conclusions | ||
17. | Which is the 1st choice formula case by case? | Synthesis of recommendations |
18. | Unmet needs. Recommendations for research. Recommendation for the implementation of the DRACMA guidelines. Periodical update of DRACMA. | Synthesis of recommendations |
Glossary of CMA
- -Cow's milk hypersensitivity indicates non-allergic hypersensitivity (traditionally termed “cow's milk intolerance”) and allergic milk hypersensitivity
- -Cow's milk allergy (CMA) indicates “a hypersensitivity reaction initiated by specific immunological mechanisms”62
- -IgE-mediated CMA (IgE-CMA) indicates a hypersensitivity reaction to cow's milk proteins initiated by specific Immunoglobulin E binding to Fcε receptors on effector cells as mast cells and basophils. This causes release of histamine and other preformed mediators, and rapid symptom onset.63
- -Non IgE-mediated CMA (non-IgE-CMA) indicates a hypersensitivity reaction to cow's milk proteins initiated by non-IgE mediated (mainly cell-mediated) mechanisms. Non-IgE-mediated milk reactions are typically delayed in onset
- -Anaphylaxis is defined according to the amended WAO criteria for the diagnosis of anaphylaxis.64
What is next
Mario Sánchez-Borges

Consent to publish
Ethics statement
Author contributions
Funding
Declaration of competing interest
Acknowledgement
Appendix A. Supplementary data
- Multimedia component 1
References
- World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines.World Allergy Organ J. 2010; 3: 57-161
- How guideline can shape clinical practice globally: the diagnosis and rationale for action against cow's milk allergy experience.Curr Opin Allergy Clin Immunol. 2019; 19: 185-191
- Oral immunotherapy for IgE-mediated cow's milk allergy: a systematic review and meta-analysis.Clin Exp Allergy. 2012; 42: 363-374
- Cow's milk allergy guidelines: a quality appraisal with the AGREE II instrument.Clin Exp Allergy. 2016; 46: 1236-1241
- Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention, and management.J Allergy Clin Immunol. 2018; 141: 41-58
- Epidemiology of cow's milk allergy.Nutrients. 2019; 11: 1051
- Global patterns in anaphylaxis due to specific foods: a systematic review.J Allergy Clin Immunol. 2021; (Epub ahead of print)
- Prediction of the severity of allergic reactions to foods.Allergy. 2018; 73: 1532-1540
- Addressing risk management difficulties in children with food allergies.Pediatr Allergy Immunol. 2021; 32: 658-666
- Biomarkers of severity and threshold of allergic reactions during oral peanut challenges.J Allergy Clin Immunol. 2020; 146: 344-355
- Risk prediction of severe reaction to oral challenge test of cow's milk.Eur J Pediatr. 2019; 178: 181-188
- Making the most of in vitro tests to diagnose food allergy.J Allergy Clin Immunol Pract. 2017; 5: 237-248
- Allergists respond to death of 3 year-old boy during oral food challenge.2017 (Available from:)https://acaai.org/allergists-respond-death-3-year-old-boy-during-oral-food-challengeDate accessed: October 7, 2021
- The fascinating world of molecular diagnosis in the management of food allergy: nondum matura est.Curr Opin Allergy Clin Immunol. 2011; 11: 200-203
- Improving diagnostic accuracy in food allergy.J Allergy Clin Immunol Pract. 2021; 9: 71-80
- Dietary baked milk accelerates the resolution of cow's milk allergy in children.J Allergy Clin Immunol. 2011; 128: 125-131
- Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition; Pediatric Gastroenterology Chapter of Indian Academy of Pediatrics. Guidelines on Diagnosis and Management of Cow's Milk Protein Allergy.Indian Pediatr. 2020; 57: 723-729
- International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: executive summary-workgroup report of the adverse reactions to foods committee, American Academy of Allergy, Asthma & Immunology.J Allergy Clin Immunol. 2017; 139: 1111-1126
- What's next for DRACMA?.Expert Rev Clin Immunol. 2018; 14: 649-651
- Assessment of evidence about common infant symptoms and cow's milk allergy.JAMA Pediatr. 2020 Jun 1; 174: 599-608
- Efficacy and safety of hydrolyzed formulas for cow's milk allergy management: a systematic review of randomized controlled trials.Clin Exp Allergy. 2020; 50: 766-779
- Safety and tolerance of a new extensively hydrolyzed rice protein-based formula in the management of infants with cow's milk protein allergy.Eur J Pediatr. 2014; 173: 1209-1216
- A well-tolerated new amino acid-based formula for cow's milk allergy.Immun Inflamm Dis. 2020; 8: 140-149
- Comparison of the Allergenicity and Immunogenicity of Camel and Cow's Milk-A Study in Brown Norway Rats.Nutrients. 2018; 10: 1903
- Donkey's Milk in the Management of Children with Cow's Milk protein allergy: nutritional and hygienic aspects.Ital J Pediatr. 2019; 45: 102
- Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial.J Allergy Clin Immunol. 2017; 139: 1906-1913
- Long-term safety assessment in children who received hydrolyzed protein formulas with Lactobacillus rhamnosus GG: a 5-year follow-up.Eur J Pediatr. 2017; 176: 217-224
- A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants.Pediatr Res. 2018; 83: 677-686
- A specific synbiotic-containing amino acid-based formula in dietary management of cow's milk allergy: a randomized controlled trial.Clin Transl Allergy. 2019; 9: 5
- Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study.Ann Allergy Asthma Immunol. 2010; 105: 376-381
- Efficacy of the slow dose-up method for specific oral tolerance induction in children with cow's milk allergy: comparison with reported protocols.J Investig Allergol Clin Immunol. 2010; 20: 538-539
- Rapid oral desensitization in combination with omalizumab therapy in patients with cow's milk allergy.J Allergy Clin Immunol. 2011; 127: 1622-1624
- Comparison between two maintenance feeding regimens after successful cow's milk oral desensitization.Pediatr Allergy Immunol. 2013; 24: 376-381
- Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic patients.J Allergy Clin Immunol. 2015; 136: 1601-1606
- Dietary baked milk accelerates the resolution of cow's milk allergy in children.J Allergy Clin Immunol. 2011; 128: 125-131
- Debates in allergy medicine: baked egg and milk do not accelerate tolerance to egg and milk.World Allergy Organ J. 2016; 9: 2
- Oral immunotherapy for milk allergy.Cochrane Database Syst Rev. 2012; 11: CD009542
- Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.Allergy. 2017; 72: 1133-1147
- European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines.J Pediatr Gastroenterol Nutr. 2012; 55: 221-229
- EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy.Allergy. 2014; 69: 1008-1025
- Comité de nutrition de la Société française de pédiatrie. Prise en charge diététique de l'allergie aux protéines du lait de vache [Dietetic treatment of cow's milk protein allergy].Arch Pediatr. 2011; 18: 79-94
- Emilian Working Group on Pediatric Allergy and Gastroenterology. Cow's milk protein allergy in children: a practical guide.Ital J Pediatr. 2010; 36: 5
- Organizzazione mondiale dell’allergia: le line-guida DRACMA (diagnosi e terapia della allergia alle proteine del latte vaccino).Rivista di Immunologia ed Allergologia Pediatrica. 2011; 26: 1-104
- Diagnosis and management of non-IgE-mediated cow's milk allergy in infancy – a UK primary care practical guide.Clin Transl Allergy. 2013; 3: 23
- Better recognition, diagnosis and management of non-IgE-mediated cow's milk allergy in infancy: iMAP-an international interpretation of the MAP (Milk Allergy in Primary Care) guideline.Clin Transl Allergy. 2017; 7: 26
- British Society for Allergy and Clinical Immunology (BSACI) guideline for the diagnosis and management of cow's milk allergy.Clin Exp Allergy. 2014; 44: 642-672
- An update to the Milk Allergy in Primary Care guideline.Clin Transl Allergy. 2019; 9: 40
- Allergy in children: practical recommendations of the Finnish Allergy Programme 2008-2018 for prevention, diagnosis, and treatment.Pediatr Allergy Immunol. 2012; 23: 103-116
- Food allergy committee of SEICAP (Spanish Society of Pediatric Allergy, Asthma and Clinical Immunology). Position document: IgE-mediated cow's milk allergy.Allergol Immunopathol (Madr). 2015; 43: 507-526
- Non-IgE-mediated cow's milk allergy: consensus document of the Spanish Society of Paediatric Gastroenterology, Hepatology, and Nutrition (SEGHNP), the Spanish Association of Paediatric Primary Care (AEPAP), the Spanish Society of Extra-hospital Paediatrics and Primary Health Care (SEPEAP), and the Spanish Society of Paediatric ClinicaL Immunology, Allergy, and Asthma (SEICAP).An Pediatr (Barc). 2019; 90: 1-193
- Consensus statement on diagnosis, treatment and follow-up of cow's milk protein allergy among infants and children in Turkey.Turk J Pediatr. 2016; 58: 1-11
- Middle East consensus statement on the prevention, diagnosis, and management of cow's milk protein allergy.Pediatr Gastroenterol Hepatol Nutr. 2014; 17: 61-67
- The outline of World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines.Zhonghua Er Ke Za Zhi. 2012; 50: 510-515
- Intensive reading of World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline.Zhonghua Er Ke Za Zhi. 2012; 50: 516-518
- Japanese guidelines for food allergy 2020.Allergol Int. 2020; 69: 370-386
- Guía latinoamericana para el diagnóstico y tratamiento de alergia a las proteínas de la leche de vaca (GL-APLV).Rev Invest Clin. 2014; 66: S9-S72
Fiocchi A, Brozek J, Schunemann HJ, et al. Pautas de la Organización Mundial sobre Alergia para el Diagnóstico y Fundamento de la Acción Contra la Alergia a la Leche de Vaca. http://www.scp.com.co/ArchivosSCP/PDF/DRACMA.pdf, accessed May 5th, 2021.
- Cow’s Milk Allergy Prescribing is influenced by Regional and National Guidance.J Pediatr Gastroenterol Nutr. 2016; 62: 688-693
- Interpreting the results of guideline implementation: a long and winding road.J Pediatr Gastroenterol Nutr. 2016; 62: 665-666
- Cow's milk allergy guidelines: a quality appraisal with the AGREE II instrument.Clin Exp Allergy. 2016; 46: 1236-1241https://doi.org/10.1111/cea.12784
- Methods for development of the European Commission initiative on breast Cancer guidelines: recommendations in the era of guideline transparency.Ann Intern Med. 2019; 171: 273-280
- Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization, 2003.J Allergy Clin Immunol. 2004; 113: 832-836
- IgE-mediated food allergy.Clin Rev Allergy Immunol. 2019; 57: 244-260
- World allergy organization anaphylaxis guidance 2020.World Allergy Organ J. 2020; 13: 100472
Article info
Publication history
Footnotes
Full list of author information is available at the end of the article
Identification
Copyright
User license
Creative Commons Attribution (CC BY 4.0) |
Permitted
- Read, print & download
- Redistribute or republish the final article
- Text & data mine
- Translate the article
- Reuse portions or extracts from the article in other works
- Sell or re-use for commercial purposes
Elsevier's open access license policy