Cow's milk allergy T78.1

Allergic reactions to milk proteins casein (heat-resistant), β-lactoglobulin (heat-resistant), alpha-lactoglobulin (heat-labile), bovine serum albumin and bovine immunoglobulin, occurring mainly in infants and toddlers (frequency: about 0.5-1.0% (AA Schoenmaker 2015) of infants and toddlers).

Important allergens in cow's milk (modified according to I Rese 2015)

Bos d 2 Lipocalin

Bos d 3 S100 Calcium binding protein

Bos d 4 Alphalactalbumin

Bos d 5 Betalactoglobulin

Bos d 6 Serum albumin

Bos d 7 Immunoglobulin

Bos d 8 casein - total (breakdown for Bos d 9 -Bos d 12) - Heat stability

Bos d 9 alphaS1 casein

Bos d 10 alphaS2 casein

Bos d 11 beta-casein

Bos d 12 kappa -casein

The rate of proven cow's milk allergy was 0.4% in larger studies. However, there are differences between countries (Netherlands and United Kingdom: 1%). About 70% of those allergic to cow's milk were free of symptoms after 1 year! Only rarely do milk allergies persist in advanced age (anaphylactic reactions, exertion urticaria; hypotonic circulatory reactions)

Cow's milk consists of 80% casein fraction and 20% whey proteins.

People allergic to cow's milk are usually sensitised to several milk allergens at the same time. The main ones are caseins (Bos d8), beta-lactoglobulin (Bos d5), followed by alpha-lactoglobulin (Bos d4) and bovine serum albumin (Bos d9). The casein fraction is composed of various casein products (Bos d9 - Bos d12), which have different degrees of allergenicity. It is heat-stable.

There is a high sequential homology between molecule proteins and caseins between mammals and subsequent cross-reaction between cow, goat and sheep milk (Tomitz D et al. 2017).

Alpha-lactalbumin is species-specific. Only to goat lactalbumin there is a certain cross-reactivity. The molecular weight of the molecule consisting of a single chain is 14.2 kD. The amino acid sequence is known. Despite a 74% agreement with the analogous molecule of human milk, it belongs to the major allergens. The molecule contains up to 7 IgE-binding epitopes - currently linear. Probably the thermolability of the molecule indicates that the conformational epitopes play the dominant role.

Beta-lactalbumin consists of identical peptide chains. The amino acid sequence is known. An analogue molecule is found in human milk. It has the ability to bind retinol. The molecular weight is 18.6kD. Remarkably, this group also includes known inhalation allergens such as those of: mouse, rat, horse (Equ c1) and cockroach (Bla g4) (Jäger L 2001). Among the 5 genetic variants of beta-lactalbumin (A,B,C,D,Dr), A plays the dominant role in milk allergy. Up to 11 IgE-binding epitopes can be detected on the molecule.

The widest possible abstinence through the use of cow's milk substitutes. These should be tested before use, as an allergy to the substitute products may exist at the same time (20-30% of infants have a soy milk intolerance at the same time!). For infants, use only the hypoallergenic foods whose composition is in accordance with the recommendations for infant feeding (see Table 1). Infants with cow's milk allergy should be breastfed for at least 4-6 months. In order not to transfer allergens via breast milk, the mother should follow a cow's milk-free diet during this period (see Tab. 2). Over 80% of cow's milk allergy sufferers tolerate cow's milk again after the age of 3.

Basically, it can be stated that sheep's and goat's milk are rarely a suitable substitute because of the great similarity of their allergens.

Reports of tolerability of goat's milk in the presence of cow's milk allergy are attributed to a different composition of casein in goat's milk (Cap h 5) and a lack of cross-reactivity of beta-casein (bos d 11). This is despite a sequence homology of > 91% between the two casein fractions. Cross-reactivity to beef is rare in cow's milk allergic patients. Conversely, a large proportion of children with beef allergy also have a relevant cow's milk allergy at the same time. This is attributed to a relevant allergy to bovine serum albumin (Bos d 6). Alternatives for cow's milk allergy: rice drink, oat drink or almond drink. It is important to balance calcium!

• Soy milk: No cross reactivity to cow milk products.
• Mare milk or if available camel milk are suitable milk substitutes.
• Casein hydrolysate: Contains no longer-chain peptide moieties and is characterized by hypoallergenicity. Disadvantage: bad taste.
• Lactoglobulin hydrolysate: Contains mainly dipeptides and is well tolerated by all cow's milk allergic patients. Disadvantage: Bad taste.
• Meatbased formula: Cross-reactivity with proteins from cow's milk is not excluded.
• So-called hypoallergenic foods (NA) are usually not tolerated in manifest cow's milk allergy.

Milk substitute foods for infants

• Book K (2003) Food allergy. A guide for affected persons. Studien Verlag, ISBN 3-7065-1905-4, KNO-NR: 12 22 04 91
• Deilmann J, Zeltner J, Hummen B (1995) Low-allergen cooking for infants, toddlers and adults (available in pharmacies)
• Thiel C, Ilies A (1994) Cooking and baking for food allergies. Falken-Verlag, ISBN 3-8068-4745-2
• Lathia D, Lichte V (1989) A healthy diet without milk. Aids for milk allergy sufferers. Zenon Publishing House

Investigations on smaller collectives could prove the success of several years of oral hyposensitization therapy (protocol with slowly increasing amount of diluted cow's milk).

Cow's milk in baked form is tolerated by most cow's milk allergy sufferers! Baked products containing cow's milk (e.g. muffins) can be used to achieve hyposensitization in children who are allergic to cow's milk by increasing the milk content (Kim JS 2011).

1. Businco L et al (1993) Hydrolysed cow's milk formulae. Allergenicity and use in treatment and prevention. To ESPACI position paper. Pedriatr Allergy Immunol 4: 101-111
2. Fiocchi A et al (2003) Clinical tolerance to lactose in children with cow's milk allergy. Pediatrics 112: 359-362
3. Hazebrouck S et al (2014) Goat's milk allergy without cow's milk allergy: suppression of non-cross-reactive epitopes on caprine β-casein. Clin Exp Allergy 44:602-610
4. Jäger L et al (2001) Food allergens. In Jäger L et al (ed.) Food allergies and intolerances. Urban&Fischer publishing house S. 153-154
5. Jarvinen KM et al (2001) IgE and IgG binding epitopes on alpha-lactalbumin and beta-lactoglobulin in cow's milk allergy. Int Arch Allergy Immunol 126: 111-118

6. Kim JS et al (2011) Dietary baked milk accelerates the resolution of cow's milk allergy in children.
   J Allergy Clin Immunol 128:125-131.

7. Lehrnbecher T et al. (1994) Cow's milk protein induced colitis in fully breastfed young infants? Monthly paediatric cure 142: 446-448

8. Magazzu G et al (2002) Gastrointestinal manifestations of cow's milk allergy. Ann Allergy Asthma Immunol 89: 65-68
9. Patriarca G et al (2002) Oral desensitisation in cow milk allergy: immunological findings. Int J Immunopathol Pharmacol 15: 53-58
10. Reese I et al (2015) Allergy to cow's milk and hen's egg: what does molecular allergy diagnostics offer? Allergo J Int 24: 34-41
11. Recke A et al (2017) Four faces of a milk allergy. Allergo J Int 26: 56
12. Schoemaker AA et al(2015) Incidence and natural history of challenge-proven cow's milk allergy in European children--EuroPrevall birth cohort. Allergy70:963-972.
13. Tomitz D et al (2017) Isolated goat and sheep's milk allergy. Allergo J Int 26: 56-57
14. Worm M et al (2016) Guideline on the management of IgE-mediated food allergies. Allergology 39: 302-344
15. Zimmermann T (1994) The food-sensitive atopic eczema. Social pediatrics 16: 300-303