Exploration of Asthma & Allergy

Table 6. Scenario 5: mixed IgE and non-IgE-mediated CMA.

EATERS-X abbreviation	Information from the history taking
E (Exposure)	7-month-old infant receiving cow’s milk formula for the first time.
A (Allergen)	Direct Cow’s milk protein (IgE) and also indirect through breast milk (non-IgE).
T (Timing)	Immediate perioral erythema and vomiting within 10 minutes of CM formula; eczema flare and increased vomiting and loose stools 12–48 hours later.
E (Environment)	Breastfed infant with generalised atopic dermatitis and chronic gut symptoms from 6 weeks old.
R (Reproducibility)	Immediate symptoms recurred with subsequent direct cow’s milk exposure.
S (Symptoms)	Acute urticaria and vomiting (IgE) followed by delayed eczema worsening and diarrhoea (non-IgE).
X (Extra/Rx)	The previous skin prick test was positive. Skin and gut symptoms cleared when the mother removed milk from her own diet (non-IgE).

Return to article view

CMA: cow’s milk allergy.

Supplementary materials

The supplementary table for this article is available at: https://www.explorationpub.com/uploads/Article/file/1009106_sup_1.pdf.

Declarations

Author contributions

MLQ: Data curation, Formal analysis, Methodology, Visualization, Writing—original draft, Writing—review & editing. IR, AMON, and SAD: Resources, Writing—review & editing. MG and RM: Writing—review & editing. MEL: Conceptualization, Supervision, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Luyt D, Ball H, Makwana N, Green MR, Bravin K, Nasser SM, et al.; Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). BSACI guideline for the diagnosis and management of cow’s milk allergy. Clin Exp Allergy. 2014;44:642–72. [DOI] [PubMed]

Grimshaw KEC, Bryant T, Oliver EM, Martin J, Maskell J, Kemp T, et al. Incidence and risk factors for food hypersensitivity in UK infants: results from a birth cohort study. Clin Transl Allergy. 2016;6:1. [DOI] [PubMed] [PMC]

Perkin MR, Logan K, Tseng A, Raji B, Ayis S, Peacock J, et al.; EAT Study Team. Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants. N Engl J Med. 2016;374:1733–43. [DOI]

Allen HI, Wing O, Milkova D, Jackson E, Li K, Bradshaw LE, et al. Prevalence and risk factors for milk allergy overdiagnosis in the BEEP trial cohort. Allergy. 2025;80:148–60. [DOI] [PubMed] [PMC]

Santos AF, Riggioni C, Agache I, Akdis CA, Akdis M, Alvarez-Perea A, et al. EAACI guidelines on the diagnosis of IgE-mediated food allergy. Allergy. 2023;78:3057–76. [DOI] [PubMed]

Erlewyn-Lajeunesse M, Weir T, Brown L, Howells H, Rowley J, Grainger-Allen E, et al. Fifteen-minute consultation: The EATERS method for the diagnosis of food allergies. Arch Dis Child Educ Pract Ed. 2019;104:286–91. [DOI] [PubMed]

Allen HI, Pendower U, Santer M, Groetch M, Cohen M, Murch SH, et al. Detection and management of milk allergy: Delphi consensus study. Clin Exp Allergy. 2022;52:848–58. [DOI] [PubMed]

Jutel M, Agache I, Zemelka-Wiacek M, Akdis M, Chivato T, Giacco SD, et al. Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper. Allergy. 2023;78:2851–74. [DOI] [PubMed]

Martorell-Aragonés A, Echeverría-Zudaire L, Alonso-Lebrero E, Boné-Calvo J, Martín-Muñoz MF, Nevot-Falcó S, et al. Position document: IgE-mediated cow’s milk allergy. Allergol Immunopathol (Madr). 2015;43:507–26. [DOI] [PubMed]

10.

Warren CM, Jhaveri S, Warrier MR, Smith B, Gupta RS. The epidemiology of milk allergy in US children. Ann Allergy Asthma Immunol. 2013;110:370–4. [DOI] [PubMed]

11.

Schoemaker AA, Sprikkelman AB, Grimshaw KE, Roberts G, Grabenhenrich L, Rosenfeld L, et al. Incidence and natural history of challenge-proven cow’s milk allergy in European children–EuroPrevall birth cohort. Allergy. 2015;70:963–72. [DOI] [PubMed]

12.

Cronin C, Ramesh Y, De Pieri C, Velasco R, Trujillo J. ‘Early Introduction' of Cow’s Milk for Children with IgE-Mediated Cow’s Milk Protein Allergy: A Review of Current and Emerging Approaches for CMPA Management. Nutrients. 2023;15:1397. [DOI] [PubMed] [PMC]

13.

Edwards CW, Younus MA. Cow Milk Allergy. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. [PubMed]

14.

Meyer R, Chebar Lozinsky A, Fleischer DM, Vieira MC, Du Toit G, Vandenplas Y, et al. Diagnosis and management of Non-IgE gastrointestinal allergies in breastfed infants—An EAACI Position Paper. Allergy. 2020;75:14–32. [DOI] [PubMed]

15.

Chebar-Lozinsky A, De Koker C, Dziubak R, Rolnik DL, Godwin H, Dominguez-Ortega G, et al. Assessing Feeding Difficulties in Children Presenting with Non-IgE-Mediated Gastrointestinal Food Allergies-A Commonly Reported Problem. Nutrients. 2024;16:1563. [DOI] [PubMed] [PMC]

16.

Meyer R, Cianferoni A, Vazquez-Ortiz M. An update on the diagnosis and management of non-IgE-mediated food allergies in children. Pediatr Allergy Immunol. 2025;36:e70060. [DOI] [PubMed]

17.

Mathew M, Leeds S, Nowak-Węgrzyn A. Recent Update in Food Protein-Induced Enterocolitis Syndrome: Pathophysiology, Diagnosis, and Management. Allergy Asthma Immunol Res. 2022;14:587–603. [DOI] [PubMed] [PMC]

18.

Stiefel G, Alviani C, Afzal NA, Byrne A, du Toit G, DunnGalvin A, et al. Food protein-induced enterocolitis syndrome in the British Isles. Arch Dis Child. 2022;107:123–7. [DOI] [PubMed]

19.

Ludman S, Harmon M, Whiting D, du Toit G. Clinical presentation and referral characteristics of food protein-induced enterocolitis syndrome in the United Kingdom. Ann Allergy Asthma Immunol. 2014;113:290–4. [DOI] [PubMed]

20.

Lozinsky AC, Meyer R, Anagnostou K, Dziubak R, Reeve K, Godwin H, et al. Cow’s Milk Protein Allergy from Diagnosis to Management: A Very Different Journey for General Practitioners and Parents. Children (Basel). 2015;2:317–29. [DOI] [PubMed] [PMC]

21.

Jensen SA, Fiocchi A, Baars T, Jordakieva G, Nowak-Wegrzyn A, Pali-Schöll I, et al. Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines update-III—Cow’s milk allergens and mechanisms triggering immune activation. World Allergy Organ J. 2022;15:100668. [DOI] [PubMed] [PMC]

22.

Kessel A, Dalal I. The pendulum between food protein-induced enterocolitis syndrome and IgE-mediated milk allergy. Acta Paediatr. 2011;100:e183–5. [DOI] [PubMed]

23.

Zhang S, Sicherer S, Berin MC, Agyemang A. Pathophysiology of Non-IgE-Mediated Food Allergy. Immunotargets Ther. 2021;10:431–46. [DOI] [PubMed] [PMC]

24.

Dantzer JA, Lewis SA, Psoter KJ, Sutherland A, Frazier A, Richardson E, et al. Clinical and immunological outcomes after randomized trial of baked milk oral immunotherapy for milk allergy. JCI Insight. 2025;10:e184301. [DOI] [PubMed] [PMC]

25.

Barni S, Mori F, Bianchi A, Pucci N, Novembre E. Shift from IgE-mediated cow’s milk allergy to food protein-induced enterocolitis syndrome in 2 infants. Pediatr Allergy Immunol. 2018;29:446–7. [DOI] [PubMed]

26.

Carroccio A, Montalto G, Custro N, Notarbartolo A, Cavataio F, D’Amico D, et al. Evidence of very delayed clinical reactions to cow's milk in cow’s milk-intolerant patients. Allergy. 2000;55:574–9. [DOI] [PubMed]

27.

Hill DJ, Firer MA, Shelton MJ, Hosking CS. Manifestations of milk allergy in infancy: Clinical and immunologic findings. J Pediatr. 1986;109:270–6. [DOI] [PubMed]

28.

Eichenfield LF, Stripling S, Fung S, Cha A, O’Brien A, Schachner LA. Recent Developments and Advances in Atopic Dermatitis: A Focus on Epidemiology, Pathophysiology, and Treatment in the Pediatric Setting. Paediatr Drugs. 2022;24:293–305. [DOI] [PubMed] [PMC]

29.

Helseth S, Misvær N, Småstuen M, Andenæs R, Valla L. Infant colic, young children’s temperament and sleep in a population based longitudinal cohort study. BMC Pediatr. 2022;22:163. [DOI] [PubMed] [PMC]