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Milk Allergy

In most cultures cow’s milk is the most commonly consumed milk. Therefore, when speaking of milk allergy in general we mean allergy to cow’s milk. This does not mean that milk from other animals like goat or sheep does not cause allergy (see section on Related foods).

Adverse reactions to cow’s milk may be explained by different mechanisms. At this place we only deal with the most common adverse reaction, so-called IgE-mediated or type I allergy. IgE is the allergy antibody. Other adverse reactions to milk are classified as cow’s milk hypersensitivity and include reactions such as lactose-intolerance due to lactase-deficiency, pharmacological reactions and some undefined reactions.

Allergy to milk is caused by proteins in milk. Milk contains 30-35 gram of protein per litre. The proteins in milk can be divided into the so called caseins (80%) and a group of proteins called the whey proteins (20%). Beta-lactoglobulin (BLG), alpha-lactalbumin, proteose-peptones and the blood proteins serum albumin and immunoglobulins belong to the whey proteins. Caseins and beta-lactoglobulin are regarded as the most important allergens in milk.

Related foods (cross-reactions)
In general, individuals with cow’s milk allergy will not tolerate milk from other animals like goat’s milk or sheep’s milk. This can be explained by the similarity of the allergenic proteins, like caseins or beta-lactoglobulin, in milk from different dairy animals. Allergic reactions to other milk varieties based on such similarity are called cross reactions.

The blood proteins present in cow’s milk are also present in meat (beef). These proteins are not the most important allergens of milk, but for around 10% of milk allergic patients, allergy to milk goes together with allergy to beef. Some of them may tolerate well cooked beef.

In breastfed infants clinical reactions to human milk have been reported, but these are related to the presence of cow’s milk proteins in the mother's milk. The cow’s milk protein beta-lactoglobulin has been detected in breast milk of 95% of breast feeding women.

Processed and compound foods
In many countries, cow’s milk proteins in cow’s milk infant formula are the first foreign proteins given as a substitute for human breast milk. Later on a variety of commercial cow’s milk products are consumed by children and adults, e.g. different forms of milk, yoghurts, cheeses, and butter. Milk proteins are also contained in a large variety of prepared foods like pastries, cookies, candies, sauces, salty biscuits, pretzels, pizzas, sausages, soups, cold and hot drinks, puddings, ice cream, bread, cereals, pasta and vitamin and mineral supplements. Production of milk products and compound foods often involves heat treatment. Low heat treatment like pasteurisation at 75° C for 15 seconds ensures the bacteriological safety of milk. It does not cause significant reduction in the allergenicity. Strong heat treatment (121° C for 20 minutes) largely destroys the allergenicity of the whey proteins, but it only reduces that of the caseins. The allergenicity of milk proteins is unaffected by homogenisation. Therefore, processed dairy products and compound food products with milk or milk-derived protein as an ingredient will contain milk allergens. According to the latest legislation of the European Union, all products containing milk or milk-derived ingredients must be clearly labelled as such.

Non-food products
Milk proteins are frequently used as ingredients in cosmetics and carriers for medicines. These products can also cause allergic responses in milk-sensitive patients.

At what age does the allergy develop and how frequently does it occur (epidemiology)?
Symptoms suggestive of cow’s milk allergy may be encountered in around 5-15% of infants, but the diagnosis can only be confirmed in about 2-3%. Part of this three- to five-fold overestimation is explained by lactose intolerance. Lactose intolerance is caused by a defect in the digestion of lactose and causes symptoms of the gut that can be mistaken for milk allergy. Geographic differences in the frequency of milk allergy are influenced by eating habits, particularly the timing of the introduction of cow’s milk-based formula. Most infants develop symptoms before one month of age, often within one week after introduction of cow’s milk based formula. Onset of the disease after 12 months is rare. The prognosis to out grow it is good with a remission rate around 45-50% at one year, 60-75% at two years, and 85-90% at three years. Around 50% of all children with milk allergy also develop allergies to other foods. In addition, milk allergy can be seen as a risk factor for the development of inhalant allergies like hay fever or asthma. Around 50-80% of milk allergic infants develop inhalant allergies before puberty, in particular when their family has a history of allergic diseases.

Symptoms
The majority of milk allergic children demonstrate two or more types of symptoms in at least two different organs. About 50-70% have skin symptoms (atopic dermatitis/flexural fold eczema, urticaria/nettle rash), 50-60% have symptoms of the stomach/gut (vomiting, diarrhoea, constipation, abdominal pain) and about 20-30% have symptoms of the airways (hay fever- like symptoms from the nose and eyes, recurrent wheezing). Systemic symptoms such as anaphylactic shock may occur in up to 10% of subjects. In exclusively breastfed infants with cow’s milk allergy severe atopic eczema is the predominant symptom.

Symptoms may occur within a few minutes up to an hour after milk exposure. These reactions are called immediate reactions. Reactions occurring after 1 h are called delayed reactions. In some cases symptoms occur only after days. These so-called late reactions are usually restricted to atopic eczema and gastrointestinal disorders like constipation.

The lowest dose of milk protein provoking an allergic reaction during challenge studies has been reported to range from 0.6 mg to 180 mg.

Diagnosis
It is not always possible to differentiate between IgE-mediated milk allergy and hypersensitivities on the basis of observed or reported clinical symptoms. Further support for IgE-mediated milk allergy can be obtained from skin prick testing and from serum IgE testing. The presence of a positive skin prick test or of milk protein-specific IgE-antibody in serum is indicative of an IgE-mediated cow’s milk allergy, but both tests may be false-positive or false-negative. Therefore, a definitive diagnosis has to be based on strict, well-defined elimination and re-introduction protocols or on controlled milk challenge procedures. Milk allergy is confirmed if symptoms disappear after elimination and re-appear upon re-introduction.

Due to the good prognosis to grow out of cow’s milk allergy in the first years of life, re-challenges or clinical and immunological examination are recommended at intervals of 6-12 months until 3 years of age and there after at intervals of 1-2 years until tolerance has developed.

Dietary precautions
The basic treatment of milk allergy is complete avoidance of cow’s milk protein. Other forms of treatment are not (yet) available. In infancy a documented hypoallergenic formula, i.e. extensively hydrolysed formula, is needed. Hydrolysis degrades milk proteins into small fragments that have lost their allergenicity. In rare cases an aminoacid-based formula may be needed. Proteins are chains of amino acids, their building blocks. Hydrolysis generates small chains of amino acids. Aminoacid-based formulas contain only these single building blocks. Partially hydrolysed formulas are not tolerated because large fragments may still be allergenic. In older children soy milk or soy-milk formula may be tolerated. The advice from a clinical dietician is often needed in order to ensure an adequate diet and in order to avoid “hidden” cow’s milk proteins in commercial foods with insufficient labelling of cow’s milk proteins such as caseins, whey protein, and beta-lactoglobulin. According to the latest EU labelling directive (2000/13/EC) any cow’s milk-derived protein must be labelled in commercial foods.