f2 Cow's milk

Allergens within Food of Animal Origin

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  • Latin name: Bos spp.
  • Source material: Skimmed cow's milk
Cow's milk is a major cause of adverse reactions in infants and hidden exposure is common. Casein (cheese) is a heat-stable allergen while whey proteins are altered by boiling.

Allergen Exposure

Milk, cheese and other dairy products.
Bread and pastry.
Numerous dishes like pancakes, soups etc
 
Unexpected exposure
Candy.
Toppings.
Processed meat, like ham, sausages, patês,etc.
Hydrolyzed milk formulas.

Potential Cross-Reactivity

Milk from related animals.
Presence of shared allergens in milk, meat, and dander from cow has been demonstrated. Sensitivity to cow's milk does not usually presume sensitivity to beef or inhalation of cow dander. However, presence of common allergens in milk, meat and dander has been demonstrated (32, 33).

Clinical Experience

IgE-mediated reactions
Cow’s milk is a major cause of adverse reactions in infants. Prevalence of IgE-mediated reactions range from 0.5–7.5% in infants. Asthma has been noted in 7–29% of patients sensitive to milk. IgE-antibody measurement is sensitive and specific and may be  predictive of disease development, including sensitization to inhalant allergens.
 
Other reactions
Lactase deficiency (lactose intolerance).
Immune reactions without IgE antibody involvement.
 
Review
Cow's milk is a major cause of adverse reactions in infants. Cow’s milk-induced asthma is often observed in infants with food hypersensitivity. In fact, asthma has been noted in 7-29% of those sensitive to milk (1). Milk is often described as a cause of rhinoconjunctivitis in young children and a role for food allergy in serous otitis media has also been proposed (1). Cow's milk allergy in infants has a much better prognosis than in older children or adults (2). Olalde et al. (3) reported onset of IgE-mediated allergy in a patient aged 29.
 
Diversity in food processing
Milk and milk derivatives are used in a wide variety of confectionery products. Caramel flavor is best developed from sweetened condensed milk. Caseins help enhance moisture retention in candy. Hydrolyzed milk proteins are whipping agents for frappés and marshmallows. In baked goods milk improves the crust color, resilience, and the strength of cakes and cookie dough. Cases of allergic reactions to non-dairy or pareve products (no milk or meat) containing milk proteins either through contamination during processing or addition of sodium caseinate have been reported (4, 5).
 
Clinical experience
In a study in Japan using Pharmacia CAP System, the clinical sensitivity was 95% and specificity was 93% for milk (6). Businco et al. (7) found that cow's milk-allergic children developed IgE antibodies to milk before onset of clinical allergy, indicating in vitro measures can be good predictive tools. High levels of specific IgE antibodies against milk proteins were reported in 6 months old infants with cow’s milk allergy. The levels were further elevated in children with persistent problems at 12 months but fell in children on milk free diets (8). Milk protein specific IgE antibody levels correlate with development of tolerance to milk (9). IgE antibodies to milk proteins were rarely found in a Japanese normal population. IgG antibody levels to the same proteins were influenced by age and feeding habits, peaked at an age between 5 and 12 months and decreased to undetectable in normal adults (10).
 
Symptoms
The symptoms in infants are usually gastrointestinal (GI) and dermatological with dermatitis often appearing early. Foucard describes two different groups of infants; those who react immediately with GI symptoms and urticaria and who are often atopic with positive skin prick test and milk specific IgE antibodies; and, the late responders who may be governed by a non-IgE-mediated allergy (11). In children retaining milk allergy, cutaneous symptoms decrease while respiratory and GI symptoms increase with age (4-14 years) (12, 9). Infants with early sensitization to cow's milk proteins have an increased risk for later development of other food allergies and sensitization to inhalant allergens (13, 14).  A retrospective study on adults with milk- and cheese-allergy showed that the majority of the patients were women with symptoms from the respiratory tract or the skin. Many of them suffered their first symptoms in relation to pregnancy and most of them remained monosensitized to milk proteins, primarily casein (15). Inhaled milk proteins may cause occupational asthma in workers handling powdered proteins (16, 17) as well as in people milking animals (19). Gastrointestinal symptoms in adults after milk consumption are often caused by lactase deficency resulting in lactose intolerance but may also be immune reactions to the milk proteins, with or without involvement of IgE antibodies (18).
 
Prevalence
Reports of prevalence range from 0.5-7.5% in infants (2). Some patients retain the lifelong allergy (19). May et al. (20) found that children hypersensitive to another food were likely to have a greater antibody production to milk than those children who were not hypersensitive.
 
Prevention and elimination
There are many studies supporting avoidance of cow's milk and prolonged breastfeeding as preventive measures. In a report of a prevention program in Denmark, breastfeeding or a hypoallergenic formula and avoidance of other foods during the first six months of life had a protective effect (21). The authors reviewed 10 prospective studies almost all of which showed a reduction of atopic dermatitis and wheeze when preventive measures were taken (21). In a follow-up study of the effects of maternal antigen avoidance after four years, the authors found avoidance of cow’s milk, fish and egg during the first three months of lactation decreased both the current prevalence and the cumulative incidence of AD at age four in atopic children (22). High IgG antibody levels against b-lactoglobulin in atopic dermatitis were found to be predictive of positive response to a milk exclusion diet (23).
 
Allergen composition
There are many proteins in milk; six are of major interest. These include: bovine serum albumin, gamma globulin, a-lactalbumin, b-lactoglobulin, lactoferrin and casein. Reactions to separate proteins are uncommon (25). Ordinary industrial treatment of milk does not remove proteins and only partially reduces the allergenicity. Undegraded allergens are often present in hydrolyzed milk formulas and may cause symptoms in already sensitized subjects (26-28). Intact cow's milk proteins may pass from the gut into the circulation. High concentrations of a-lactalbumin were measured in sera of children with cow's milk allergy (29) and bovine IgG was found in breast milk from mothers on diets including cow’s milk (30).
 
Crossreactivity
There is crossreactivity between cow's milk and milk from related animals (31). Sensitivity to cow's milk does not usually presume sensitivity to beef or inhalation of cow dander. However, presence of common allergens in milk, meat and dander has been demonstrated (32, 33).

References:

    1. Bousquet, J; Chanez, P; Michel, F-B. The respiratory tract and food hypersensitivity. Food Allergy, Adverse Reactions to Foods and Food Additives. Metcalfe, DD; Sampson, HA; Simon, RA. Boston, MA, USA: Blackwell Scientific Publications; 1991: 139; ISBN: 0-86542-094-7.
    2. Bahna, SL. Milk allergy in infancy. Ann Allergy; 1987; 59 (5 pt 2): 131-136.
    3. Olalde, S; Bensabat, Z; Vives, R; Fernandez, L; Cabeza, N; Rodriguez, J. Allergy to cow's milk with onset in adult life. Ann Allergy; 1989; 62: 185a-185b.
    4. Gern, JE; Yang, E; Evrard, HM; Sampson, HA. Allergic reactions to milk-contaminated "nondairy" products. New Eng J Med; 1991; 324: 976-979.
    5. Jones, RT; Squillace, DL; Yunginger, JW. Anaphylaxis in a milk-allergic child after ingestion of milk-contaminated kosher-pareve-labeled "dairy-free" dessert. Ann Allergy; 1992; 68:223-227.
    6. Okudaira, H; Ito, K; Miyamoto, T ; Wagatsuma, Y; Matsuyama, R; Kobayashi, S; Nakazawa, T; Okuda, M; Otsuka, H; Baba, M; Iwasaki, E; Takahashi, T; Adachi, M; Kokubu, F; Nishima, S; Shibata, R, Yoshida, H; Maeda, K. Evaluation of new system for the detection of IgE antibodies (CAP) in atopic disease. Arerugi; 1991; 40(5): 544-545.
    7. Businco, L; Benincori, N; Cantani, A. Epidemiology, incidence and clinical aspects of food allergy. Ann Allergy; 1984; 53: 615-622.
    8. Host, A; Husby, S; Gjesing, B; Larsen, JN; Lowenstein, H; Prospective estimation of IgG, IgG subclass and IgE antibodies to dietary proteins in infants with cow milk allergy. Levels of antibodies to whole milk protein, BLG and ovalbumin in relation to repeated milk challenge and clinical course of cow milk allergy. Allergy;1992; 47:218-229.
    9. James, JM; Sampson, HA. Immunologic changes associated with the development of tolerance in children with cow milk allergy. J Pediatr; 1992; 121: 371-377.
    10. Ahmed, T; Sumazaki, R; Nagai, Y; Shibasaki, M; Takita, H. Immune response to food antigens: kinetics of food specific antibodies in the normal population. Acta Paediatr Jpn;1997; 39: 322-328.
    11. Foucard, T. Development of food allergies with special reference to cow's milk allergy. Pediatrics; 1985; 75(1 pt 2): 177-181.
    12. Amlot, PL; Kemeny, DM; Zachary, C; Parkes, P; Lessof, MH. Oral allergy syndrome (OAS): Symptoms of IgE-mediated hypersensitivity to food. Clin Allergy (Clin Exp Allergy); 1987; 17: 33-42.
    13. Businco, L; Benincori, N; Cantani A; Tacconi, L; Picarazzi, A. Chronic diarrhea due to cow's milk allergy. A 4- to 10- year follow-up study. Ann Allergy; 1985; 55(6): 844-847.
    14. Høst, A; Halken, S. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Allergy; 1990; 45: 587-596.
    15. Stöger, P; Wüthrich, B. Type I allergy to cow milk proteins in adults. Int Arch Allergy Immunol; 1993; 102:399-407.
    16. Joliat, TL; Weber, RW. Occupational asthma and rhinoconjunctivitis from inhalation of crystaline bovine serum albumin powder. Ann Allergy; 1991; 66: 301-304.
    17. Bernaola, G; Echechipia, S; Urrutia, I; Fernandez, E; Audicana, M; Fernandez de Corres, L. occupational asthma and rhinoconjunctivitis from inhalation of dried cow’s milk caused by sensitization to a-lactalbumin. Allergy; 1994; 49: 189-191.
    18. Pelto, L; Salminen, S; Lilius, EM; Nuutila, J; Isolauri, E. Milk hypersensitivity – key to poorly defined gastrointestinal symptoms in adults. Allergy; 1998; 53:307-310.
    19. Lee, EJ; Heiner, DC. Allergy to cow milk-1985. Pediatrics in review; 1986; 7(7): 195-203; ISSN: 0191-9601.
    20. May, CD; Remigio, L; Feldman, J; Bock, SA; Carr, RI. A study of serum antibodies to isolated milk proteins and ovalbumin in infants and children. Clin Allergy (Clin Exp Allergy); 1977; 7: 583-595.
    21. Halken, S; Høst, A; Hansen, LG; Østerballe, O. Effect of an allergy prevention programme on incidence of atopic symptoms in infancy. Allergy; 1992; 47: 545-553.
    22. Sigurs, N; Hattevig, G; Kjellman, B. Maternal avoidance of eggs, cow's milk, and fish during lactation. Pediatr; 1992; 89(4): 735-739.
    23. Casimir, GJ; Duchateau, J Gossard, B; Cuvelier, P; Vandaele, F. Atopic dermatitis: role of food and house dust mite allergens. Pediatrics; 1993; 92: 252-256.
    24. Agata, H; Kondo, N; Fukutomi, O; Shinoda, S; Orii, T. Effect of elimination diets on food-specific IgE antibodies and lymphocyte proliferative responses to food antigens in atopic dermatitis patients exhibiting sensitivity to food allergens. J Allergy Clin Immunol; 1993; 91(2): 668-679.
    25. .Savilahti, E; Kuitunen, M. Allergenicity of cow milk protein. J Pediatr, 1992; 121: S12-20.
    26. Chiancone, E; Gattoni, M; Giampietro, PG; Ragno, V; Businco, L. Detectoion of undegraded b-lactoglobulins and evaluation of the molecular weight of peptides in hydrolysate cow’s milk formula. J Investig Allergol Clin Immunol; 1995; 5: 228-233.
    27. Gortler, I; Urbanek, R; Forster, J. Characterization of antigens and allergens in hypo-allergenic infant formulae. Eur J Pediatr; 1995; 154:289-294.
    28. Ball, G; Shelton, MJ; Walsh, BJ; Hill, DJ Hoskings, CS; Howden, M. A major continuous epitope of bovine b-lactoglobulin recognized by human IgE binding. Clin Exp Allergy; 1994; 24: 758-764.
    29. Juvonen, P; Jakobsen, I; Lindberg,T. Macromolecular absorbtion and cow’s milk allergy. Arch Dis Child; 1991; 66: 300-303.
    30. Maeda, S; Morikawa, A; Tokuyama, K; Kuroume, T. The concentration of bovine IgG in human breast milk measured using different methods. Acta Pediatr; 1993; 82: 1012-1016.
    31. Spuergin, P; Walter, M; Schiltz, E; Deichman, K; Forster, J; Mueller. Allergenicity of a -caseins from cow, sheep, and goat. Allergy; 1997; 52: 293-298.
    32. Werfel, SJ; Cooke, SK; Sampson, HA. Clinical reactivity of beef in children allergic to cow’s milk.
    33. Szepfalusi, Z; Ebner, C; Urbanek, R; Ebner, H; Scheiner, O Boltz-Nitulescu, G; Kraft, D. Detection of IgE antibodies specific for allergens in cow milk and cow dander. Int Arch Allergy Immunol; 1993;102: 288-294.

1999



Further Reading