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Milk allergy: Clinical features and diagnosis

Kirsi M Jarvinen-Seppo, MD, PhD
Section Editor
Scott H Sicherer, MD, FAAAAI
Deputy Editor
Elizabeth TePas, MD, MS


Cow's milk allergy (CMA) is the most common food allergy in young children, but is uncommon in adults [1]. This food allergy presents with a wide range of clinical syndromes due to immunologic responses to cow's milk proteins that can be immunoglobulin E (IgE) mediated and/or non-IgE mediated [2-4] CMA does not include other adverse reactions to milk, such as lactose intolerance, which are nonimmune mediated [5]. (See "Lactose intolerance: Clinical manifestations, diagnosis, and management".)

The epidemiology, pathogenesis, clinical features, and diagnosis of CMA will be presented in this topic review. Cross-reactivity of cow's milk with other mammalian milks and management of milk allergy are discussed separately. General discussions of food allergy are presented separately in appropriate topic reviews. (See "Milk allergy: Management".)


General population — Cow's milk allergy (CMA) is the most common food allergy in young children, affecting approximately 2 percent of children under four years of age [1]. CMA is even more prevalent in infants. Two studies published in the 1990s reported a CMA prevalence of 2.2 and 2.8 percent at one year of age in general population birth cohorts [6,7], consistent with the rate found in another cohort of over 6000 newborns followed for 18 to 34 months [8]. In contrast, a lower rate of 0.6 percent in three-year-old children was reported [9].

The prevalence of CMA in adults is not as well reported [10]. The rate of CMA by patient report in a multinational survey of 17,280 adults (aged 20 to 44 years) from 15 countries that questioned participants about foods that "nearly always" caused "illness" or "trouble" was 4.3 percent. However, a much lower proportion of adults have confirmed CMA, ranging from 0.1 to 0.3 percent [1,9,11,12]. Allergy persists from childhood in a subgroup of adults with CMA, but two reports suggest that the majority of adults with CMA acquired the allergy in adulthood [13,14].

In two small series, over 80 percent of adults with CMA were female [13,14]. In contrast, childhood CMA is more prevalent in boys [15].


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Literature review current through: Sep 2016. | This topic last updated: Sep 30, 2015.
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  1. Rona RJ, Keil T, Summers C, et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol 2007; 120:638.
  2. Høst A. Cow's milk protein allergy and intolerance in infancy. Some clinical, epidemiological and immunological aspects. Pediatr Allergy Immunol 1994; 5:1.
  3. Heine RG, Elsayed S, Hosking CS, Hill DJ. Cow's milk allergy in infancy. Curr Opin Allergy Clin Immunol 2002; 2:217.
  4. Järvinen KM, Chatchatee P. Mammalian milk allergy: clinical suspicion, cross-reactivities and diagnosis. Curr Opin Allergy Clin Immunol 2009; 9:251.
  5. Bahna SL. Cow's milk allergy versus cow milk intolerance. Ann Allergy Asthma Immunol 2002; 89:56.
  6. Høst A, Halken S. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy 1990; 45:587.
  7. Schrander JJ, van den Bogart JP, Forget PP, et al. Cow's milk protein intolerance in infants under 1 year of age: a prospective epidemiological study. Eur J Pediatr 1993; 152:640.
  8. Saarinen KM, Juntunen-Backman K, Järvenpää AL, et al. Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants. J Allergy Clin Immunol 1999; 104:457.
  9. Osterballe M, Hansen TK, Mortz CG, et al. The prevalence of food hypersensitivity in an unselected population of children and adults. Pediatr Allergy Immunol 2005; 16:567.
  10. Woods RK, Abramson M, Bailey M, Walters EH. International prevalences of reported food allergies and intolerances. Comparisons arising from the European Community Respiratory Health Survey (ECRHS) 1991-1994. Eur J Clin Nutr 2001; 55:298.
  11. Osterballe M, Mortz CG, Hansen TK, et al. The prevalence of food hypersensitivity in young adults. Pediatr Allergy Immunol 2009; 20:686.
  12. Jansen JJ, Kardinaal AF, Huijbers G, et al. Prevalence of food allergy and intolerance in the adult Dutch population. J Allergy Clin Immunol 1994; 93:446.
  13. Stöger P, Wüthrich B. Type I allergy to cow milk proteins in adults. A retrospective study of 34 adult milk- and cheese-allergic patients. Int Arch Allergy Immunol 1993; 102:399.
  14. Lam HY, van Hoffen E, Michelsen A, et al. Cow's milk allergy in adults is rare but severe: both casein and whey proteins are involved. Clin Exp Allergy 2008; 38:995.
  15. Ngamphaiboon J, Chatchatee P, Thongkaew T. Cow's milk allergy in Thai children. Asian Pac J Allergy Immunol 2008; 26:199.
  16. Järvinen KM, Sicherer SH, Sampson HA, Nowak-Wegrzyn A. Use of multiple doses of epinephrine in food-induced anaphylaxis in children. J Allergy Clin Immunol 2008; 122:133.
  17. Colver AF, Nevantaus H, Macdougall CF, Cant AJ. Severe food-allergic reactions in children across the UK and Ireland, 1998-2000. Acta Paediatr 2005; 94:689.
  18. Uguz A, Lack G, Pumphrey R, et al. Allergic reactions in the community: a questionnaire survey of members of the anaphylaxis campaign. Clin Exp Allergy 2005; 35:746.
  19. Bock SA, Muñoz-Furlong A, Sampson HA. Further fatalities caused by anaphylactic reactions to food, 2001-2006. J Allergy Clin Immunol 2007; 119:1016.
  20. Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 1992; 327:380.
  21. Pumphrey RS. Fatal anaphylaxis in the UK, 1992-2001. Novartis Found Symp 2004; 257:116.
  22. Pumphrey RS, Gowland MH. Further fatal allergic reactions to food in the United Kingdom, 1999-2006. J Allergy Clin Immunol 2007; 119:1018.
  23. Eigenmann PA, Sicherer SH, Borkowski TA, et al. Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics 1998; 101:E8.
  24. Wal JM. Bovine milk allergenicity. Ann Allergy Asthma Immunol 2004; 93:S2.
  25. Docena GH, Fernandez R, Chirdo FG, Fossati CA. Identification of casein as the major allergenic and antigenic protein of cow's milk. Allergy 1996; 51:412.
  26. Natale M, Bisson C, Monti G, et al. Cow's milk allergens identification by two-dimensional immunoblotting and mass spectrometry. Mol Nutr Food Res 2004; 48:363.
  27. Gaudin JC, Rabesona H, Choiset Y, et al. Assessment of the immunoglobulin E-mediated immune response to milk-specific proteins in allergic patients using microarrays. Clin Exp Allergy 2008; 38:686.
  28. Chen WL, Hwang MT, Liau CY, et al. Beta-lactoglobulin is a thermal marker in processed milk as studied by electrophoresis and circular dichroic spectra. J Dairy Sci 2005; 88:1618.
  29. Ehn BM, Ekstrand B, Bengtsson U, Ahlstedt S. Modification of IgE binding during heat processing of the cow's milk allergen beta-lactoglobulin. J Agric Food Chem 2004; 52:1398.
  30. Nowak-Wegrzyn A, Bloom KA, Sicherer SH, et al. Tolerance to extensively heated milk in children with cow's milk allergy. J Allergy Clin Immunol 2008; 122:342.
  31. Fiocchi A, Schünemann HJ, Brozek J, et al. Diagnosis and Rationale for Action Against Cow's Milk Allergy (DRACMA): a summary report. J Allergy Clin Immunol 2010; 126:1119.
  32. Sicherer SH, Sampson HA. Food hypersensitivity and atopic dermatitis: pathophysiology, epidemiology, diagnosis, and management. J Allergy Clin Immunol 1999; 104:S114.
  33. Ellman LK, Chatchatee P, Sicherer SH, Sampson HA. Food hypersensitivity in two groups of children and young adults with atopic dermatitis evaluated a decade apart. Pediatr Allergy Immunol 2002; 13:295.
  34. Niggemann B, Sielaff B, Beyer K, et al. Outcome of double-blind, placebo-controlled food challenge tests in 107 children with atopic dermatitis. Clin Exp Allergy 1999; 29:91.
  35. Sicherer SH, Teuber S, Adverse Reactions to Foods Committee. Current approach to the diagnosis and management of adverse reactions to foods. J Allergy Clin Immunol 2004; 114:1146.
  36. Moissidis I, Chaidaroon D, Vichyanond P, Bahna SL. Milk-induced pulmonary disease in infants (Heiner syndrome). Pediatr Allergy Immunol 2005; 16:545.
  37. Skripak JM, Matsui EC, Mudd K, Wood RA. The natural history of IgE-mediated cow's milk allergy. J Allergy Clin Immunol 2007; 120:1172.
  38. Shek LP, Soderstrom L, Ahlstedt S, et al. Determination of food specific IgE levels over time can predict the development of tolerance in cow's milk and hen's egg allergy. J Allergy Clin Immunol 2004; 114:387.
  39. Levy Y, Segal N, Garty B, Danon YL. Lessons from the clinical course of IgE-mediated cow milk allergy in Israel. Pediatr Allergy Immunol 2007; 18:589.
  40. Fiocchi A, Brozek J, Schünemann H, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. Pediatr Allergy Immunol 2010; 21 Suppl 21:1.
  41. NIAID-Sponsored Expert Panel, Boyce JA, Assa'ad A, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol 2010; 126:S1.
  42. Luyt D, Ball H, Makwana N, et al. BSACI guideline for the diagnosis and management of cow's milk allergy. Clin Exp Allergy 2014; 44:642.
  43. Food Allergy - A Practice Parameter Update - 2014. http://www.allergyparameters.org/published-practice-parameters/alphabetical-listing/food-allergy-download/.
  44. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 2001; 107:891.
  45. García-Ara C, Boyano-Martínez T, Díaz-Pena JM, et al. Specific IgE levels in the diagnosis of immediate hypersensitivity to cows' milk protein in the infant. J Allergy Clin Immunol 2001; 107:185.
  46. Wang J, Godbold JH, Sampson HA. Correlation of serum allergy (IgE) tests performed by different assay systems. J Allergy Clin Immunol 2008; 121:1219.
  47. Perry TT, Matsui EC, Kay Conover-Walker M, Wood RA. The relationship of allergen-specific IgE levels and oral food challenge outcome. J Allergy Clin Immunol 2004; 114:144.
  48. Hill DJ, Heine RG, Hosking CS. The diagnostic value of skin prick testing in children with food allergy. Pediatr Allergy Immunol 2004; 15:435.
  49. Vandenplas Y, Koletzko S, Isolauri E, et al. Guidelines for the diagnosis and management of cow's milk protein allergy in infants. Arch Dis Child 2007; 92:902.