A recent position paper revised the nomenclature of adverse reactions to foods; this classification system categorises any food induced reaction that involves the immune system as ‘food allergy’.

In the medical world when we talk about food allergy, we are historically referring to reactions that involve IgE. The revised nomenclature now refers to these reactions as IgE-mediated food allergy.

All other food reactions that involve the immune system, but are not IgE mediated, are now referred to as non-IgE-mediated food allergy. Reactions to food that do not involve the immune system such as lactose intolerance are classified as non-allergic food hypersensitivity. There are currently no agreed figures as to the exact incidence of these conditions in infancy and one of the main reasons for this has been the lack of consensus on classification.

Figure 1: Classification of food hypersensitivity reactions

Johansson SG et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. JACI. 2004;113:832-6

This article focuses on both IgE mediated and non IgE mediated cows’ milk allergy. As we can see from Table 1.0 there is an overlap of symptoms and it should also be noted that many other conditions also share these symptoms. This includes lactose intolerance, colic, inflammatory bowel diseases, coeliac disease, pathogenic disease and malabsorption amongst others.

Confirmation of a diagnosis is therefore essential so that other disease entities do not remain undetected. To prevent unnecessary suffering and to truly liberate family life, an early and accurate diagnosis and clear consistent management advice is paramount.

TABLE 1.0: Definitions and presentation of different types of cows’ milk hypersensitivity

Type of cows’ milk hypersensitivity	Presenting Symptoms
IgE mediated Cows’ milk protein allergy	Usually immediate; Asthma Anaphylaxis Angioedema Itchy rash Hives Short of breath Rhinitis Urticaria GI symptoms including: Abdominal pains Diarrhoea Vomiting
Non IgE mediated Cows’ milk allergy	More likely to be a delayed reaction; Eczema GI symptoms including: Colic Abdominal pain Constipation Diarrhoea Reflux Vomiting
Lactose intolerance (LI) (a type of non-allergic hypersensitivity to the milk sugar lactose which can be a primary or secondary intolerance. Most common is the secondary type which is usually transient and often resolves after a couple of months.)	Abdominal pain Colic Bloating Diarrhoea Wind

Cows’ milk protein allergy – the facts

Both types of cows` milk protein allergy usually start in infancy when whole cows` milk formula or weaning foods containing cows` milk are introduced, such as baby cereals and fromage frais. Reactions are occasionally reported as occurring on the first exposure but it is more commonly on subsequent exposures that problems first occur.

An IgE mediated reaction cannot in theory actually occur on the first exposure, as immunological sensitisation is first required before a reaction can occur. (If the parent is adamant the reaction did occur on the first exposure then a likely explanation is that the mother consumed cows’ milk or foods containing it whilst breastfeeding or that inadvertent exposure had occurred). The mechanisms of non-IgE-mediated reactions are unclear.

It is comforting to know that the majority of children with cows’ milk allergy will outgrow it by the age of 5.

Diagnosis of cows’ milk allergy

Diagnosis of cows’ milk allergy is dependent on the type of immune mechanism involved. IgE mediated reactions are usually successfully diagnosed by a clear clinical history of an immediate reaction in conjunction with tests that measure for the presence of IgE. These include skin prick tests, and blood tests such as Specific Immunoglobulin-E (IgE). These can be done in primary care where resources are available or referred to a paediatric clinic or NHS Allergy Clinic specialising in the diagnosis and management of allergic disease. The latter is the preferred route but services can be scarce and under-funded with long waiting lists and geographically impractical.

For a list of British Society of Allergy and Clinical Immunology (BSACI) registered NHS Allergy Clinics refer to www.bsaci.org
For Department of Health July 2006 ‘Review of Allergy Services’ see http://www.dh.gov.uk/PublicationsAndStatistics/Publications/Publications

Non-IgE mediated allergic reactions to cows’ milk are usually more difficult to diagnose as they are usually delayed and if a mixed diet is being taken the culprit can be masked.

There are no reliable tests available, and diagnosis will therefore depend on a clear clinical history often requiring confirmation by an exclusion and reintroduction diet. This should always be done under the supervision of a Paediatric Dietitian who can be hospital or community based and will usually see an infant at short notice if required.

It is very important that reintroduction of cows’ milk should happen in a supervised hospital setting if there is a history of an immediate IgE mediated cows’ milk allergy.

Specialised formula milks can then be prescribed and trialled until a suitable one is tolerated.

The infant can also be monitored to ensure that nutritional requirements are met for the infants changing growth and development needs.

TABLE 2.0: Summary of the diagnosis and management of cow’s milk protein allergy

Mechanism	How diagnosed?
IgE mediated	Clinical history Skin prick test Specific IgE blood test
Non-IgE mediated	Clinical history Exclusion & reintroduction diagnostic diet to determine tolerance levels may be indicated

The Management of cows` milk allergy

The management of cows` milk allergy in infants who are formula fed, or part formula fed always involves finding a suitable formula milk that is tolerated by the infant. The latest guidance is to use an extensively hydrolysed formula (EHF) which although still based on cows` milk, the proteins contained in them have been broken down leading to a reduction in potential allergenicity. If none of the EHF are suitable or tolerated then other options are available as shown in table 4.0

Once a suitable one is tolerated this can then be used as a drink, on cereal and in cooking.A recently published booklet ‘Meal Appeal’ contains easy to make family meals using specialised formula milks. It is available free of charge from Cow & Gate (subject to availability). For more details call the careline on 08457623 624.

If the baby is breastfed (or part breastfed) the mother may be required to avoid cows’ milk and dairy products. This is only necessary if the infant’s symptoms clear up when they are removed from the mother’s diet and reappear on reintroduction. This can be monitored by keeping a detailed food and symptom diary. Furthermore, reintroduction trials for the mother should be done at intervals to see if the infant’s tolerance has increased or that cows’ milk was taken out in error.

Cessation of breastfeeding should never occur if the mother wishes to continue, instead she should be supported to consume a diet free from cows’ milk protein if indicated.Modifying the mother’s diet should not be encouraged without reliable information as it may become unbalanced and affect both her and the baby’s health. Any dietary changes will require close and regular supervision.

The management of IgE mediated reactions usually involves the total avoidance of cows’ milk protein. This includes foods containing cows’ milk, dairy products and manufactured foods containing milk derivatives. Great care usually has to be taken to ensure these foods do not contaminate suitable foods. In some instances traces are enough to elicit a reaction. The management of non-IgE-mediated reactions to cows’ milk varies from total avoidance to tolerating significant amounts. Each case requires individual assessment and evaluation and will depend on the amount tolerated at the time. Reassessment is very important as this tolerance level can change or the allergy is outgrown altogether (Approx 90% outgrow by the age of 5).

It should be noted that avoidance of cows’ milk usually requires the avoidance of all other animal milks although occasionally they may be tolerated.

TABLE 3.0: Summary of the Management of cows’ milk protein allergy

Mechanism	How managed?
IgE mediated	Total avoidance of whole cows` milk protein. Use of EHF or other suitable formula if not breastfeeding. Usually includes avoiding even traces of milk protein. Usually applies to all animal milks.
Non-IgE mediated	Management can be anywhere along the spectrum of total avoidance of cows’ milk to consuming to tolerance depending on the symptoms. Each case requires individual assessment and reassessment over time.

Formula milks

There are various specialised formula milks available that could be suitable for both types of cows’ milk allergy. In practice what is prescribed is often dependent on the person prescribing it and the infants` requirements. Finding a suitable milk can be trial and error and the most important factor is to ensure that various ones are trialled until one is found that is tolerated. Table 4.0 summarises the specialised formulas available for use in infants with cows’ milk allergy. Ensuring that the infant’s nutritional requirements are met whilst remaining symptom free is essential.

Parents should be reassured that all formula milks have to comply with government legislation. They should also be warned that ‘off the shelf’ soya milks (not including soya formula milks) oat and rice milks are not usually suitable for an infant under 24 months (and sometimes up to aged 5 or more) as the main milk drink. They are inferior to formula milks nutritionally, and suitability will depend upon an individual’s diet, nutritional intake, and growth.

The proteins in extensively hydrolysed formulas are broken down into tiny peptides allowing them to be tolerated by the majority of sufferers. Occasionally they may not be tolerated and an alternative is required.

Issues that must be considered when prescribing a formula include the age of the infant; the more hydrolysed the formula is, the less likely an older infant will accept it due to taste changes. The severity of the symptoms, the effect on the bowels, any other pertinent dietary restrictions, acceptance from a cultural or religious perspective, cariogenicity, cost and whether or not medium chain triglycerides (MCT’s) are required.

TABLE 4.0: Summary of the Management of cows’ milk protein allergy

Type of formula	Indications/comments	Examples
Extensively hydrolysed Whey formula	Less hydrolysed than casein hydrolysates; peptides are 3000-5000 daltons which offers a superior taste to the casein hydrolysates.	Pepti (Cow & Gate) When MCT’s required: Pepti junior (Cow & Gate) (50% MCT clinically nil lactose)
Extensively hydrolysed Casein formula	The peptides are less than 1200 daltons with 50% less than 50 daltons. This allows them to be tolerated in some very sensitive infants.	Nutramigen 1 (Mead Johnson) (up to 6 months) Nutramigen 2 (Mead Johnson) (over 6 months) Prejestimil (Mead Johnson) (54% MCT)
Soya formula’s (non hydrolysed protein)	Not recommended for infants under 6 months. Not recommended as the first choice of formula for 6-12 months. Protein supplied by soya; so no cows` milk protein or lactose present. Not recommended as the first choice formula. May be given to those refusing extensively hydrolysed formulas or vegans."	Infasoy (Cow & Gate) Farley’s soya formula (Heinz) Isomil (Abbott) Prosobee (Mead Johnson) Wysoy (SMA)
Non-Milk based extensively hydrolysed formulas	Not suitable for some cultures, religions or vegetarians (because contains meat derivatives).	Prejomin (Milupa) Pepdite (SHS) (under 1 year) Pepdite 1+ (SHS) (over 1 year) MCT Pepdite (SHS) (75% MCT)
Elemental amino acid based formula	Suitable for multiple food allergies when other formulas are unsuitable. For persisting symptoms in a milk allergic child not tolerating or refusing EHF. Not always accepted on grounds of taste for older infants. Used for extremely severe milk allergic infants where there is a history of or risk of anaphylaxis.	Neocate (SHS) (up to 1 year) Neocate Advance (SHS) (1-10 years)

Support for the parents/carers

Once the diagnosis is clear, the infant will require assessment & reassessment; of their symptoms, growth & development and nutritional requirements and changing status of the allergy. The parents/carers will require information and support whilst establishing a diet that is tolerated including help with understanding food labelling issues. For details of the 2005 EU food allergen labelling laws see Locating suitable products such as dairy free yogurts, cheeses and margarines for the older infant is another consideration including their availability and accessibility. Adapting recipes, cookbooks and using replacement products in cooking should also be discussed.Issues that will require more support if the allergy is not outgrown include eating out, holidays and keeping to the diet when in childcare. Two useful resources are www.allergyinschools.org.uk, www.allergyaction.org.uk

The impact of food allergy can affect all the family. For severe milk allergic infants the Anaphylaxis Campaign can be extremely informative and supportive www.anaphylaxis.org.uk

Finally, the issue of treating a reaction should it occur needs careful assessment and a management plan written by experienced healthcare professionals in liaison with the parents and any carers.
Call us on 08457 623 634 to get copies of the milk free recipe booklet (subject to availability) and find out more about the products Cow & Gate have for cows’ milk allergy.

About the author

Tanya Wright is a Specialist Dietitian & Clinical Services Allergy Coordinator, Department of Dermatology, Amersham Hospital. Tanya also writes and conducts the food challenge service and is an advisor to the food industry, and for the Anaphylaxis Campaign.