New classifications in food allergy

Allergy is not only increasing in incidence, cases of allergic disease appear to be also increasing in severity and complexity. For example, severe and potentially life-threatening disorders such as peanut allergy, which was previously rare, is now more common¹. Allergic disorders may also affect more than one body system making them more complex to manage.

Children are particularly vulnerable to allergy, with 39% of children being diagnosed with one or more atopic symptoms according to a recent survey². Food allergy appears to be increasingly common and is the most common cause of anaphylaxis in children¹. Peanut allergy has trebled in incidence over 4 years and now affects one in 70 children in the UK¹.

With such a high incidence it is not surprising that treatments for asthma and other allergic disorders currently account for 10% of primary care prescribing costs with direct costs to the NHS for managing allergic problems being estimated at over one billion pounds per annum².

Food allergy is however, the cause of much controversy as the popular practice of calling all adverse reactions to food as `allergies` is inaccurate and has created confusion amongst health care professionals and the public. To help provide a correct diagnosis and appropriate management of food allergy it is important to understand the broader classification and different mechanisms by which foods can cause a reaction.

Classification
Classifications for food allergy have been developed based on the proposed mechanisms by which they are caused. The most recent classification system has been developed by the World Allergy Organization (WAO) and the European Academy for Allergology and Clinical Immunology (EAACI) and aims to clarify the differences between true allergic responses and those that have been previously described as `intolerances`^3,4. The term `hypersensitivity`, should be used as an umbrella term to cover all of these reactions and should be defined as follows:

`Hypersensitivity causes objectively reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by normal subjects`
Other methods of classification exist such as those developed by the Committee on Toxicity⁵ and the British Nutrition Foundation⁶. The classification for food hypersensitivity as defined by the WAO and the EAACI is outlined in Figure 1.

Figure 1: Classification of food hypersensitivity^3,4.


The classification begins by describing food hypersensitivity as either `food allergy` or `non-allergic food hypersensitivity`:

Food allergy is immune mediated, dose dependent and is usually induced by proteins. There are two types of food allergy:

• IgE mediated- these reactions are very rapidly induced and are mediated by IgE antibody, causing degranulation of mast cells and the release of histamine and other pro-inflammatory substances which cause the allergic symptoms such as rhinitis, asthma, eczema, swelling (e.g. of the lips) and difficulty in breathing.
• Non-IgE mediated – these reactions take longer to develop and are mediated by other immune cells and are associated with direct damage to cells or the deposition of immune complexes. Non IgE mediated allergy can also be mediated by T lymphocytes, for example, in coeliac disease. Most allergic reactions to food are IgE mediated but there is evidence that non-IgE mediated reactions are involved in delayed responses to certain foods.

Non-allergic food hypersensitivity is a reproducible adverse reaction to food caused by a non-immunological mechanism. This category has also been defined as `food intolerance` and this term is still commonly in use in the UK. Examples include lactose intolerance and reactions to vasoactive amines such as histamine and tyromine found in certain foods.

The term food hypersensitivity does not cover reactions to toxic substances found in foods such as sea food toxins or fungal toxins. Food allergy is more clearly defined than non-allergic food hypersensitivity with IgE mediated reactions being the best understood and perhaps easiest to diagnose. Non- IgE mediated food allergy is less well understood and for many reactions the mechanism is unclear.

Clinical features
True allergic reactions to foods and food ingredients can give rise to many clinical features which may be confined to a single organ system such as the skin or respiratory system or affect multiple organ systems. Occasionally, systemic reactions such as anaphylaxis may occur which can be fatal. Table 1 provides an overview of the clinical features that may be caused by allergic responses to foods. However, due to the diverse nature of clinical symptoms diagnosis of the condition can be difficult. A good clinical history combined with appropriate diagnostic tests is vital to establish a true diagnosis of food allergy.

Table1: Clinical features of food allergy

Body system affected	Clinical features
Skin	Urticaria Eczema Angio-oedema
Gastrointestinal tract	Oral allergy syndrome: burning, itching of the lips and mouth and sometimes the larynx and pharynx Pain, colic Diarrhoea Vomiting Gastro-oesophageal reflux Constipation
Respiratory tract	Asthma Rhinitis Laryngeal oedema
Eyes	Conjunctivitis
Cardiovascular system	Hypotension
Generalised systemic	Anaphylaxis

Common foods responsible
The majority of immunological reactions to foods and food ingredients (i.e. those defined as food allergy) are caused by a limited number of foods. In children, 90% of reactions are caused by cows` milk, eggs, wheat, peanuts, tree nuts (walnuts, brazil nuts, hazel nuts) and soya protein⁵.

In adults, most allergic reactions are caused by peanuts, tree nuts, fish and shellfish ⁵. Patients can react to more than one food and cross reactions to related allergens can occur, making management of the condition more complex. For example, around 10% of children with cows` milk protein allergy may also become sensitised to soya⁷. Infants and children are particularly vulnerable to the nutritional consequences of food allergy as exclusion of the offending foods can easily result in nutritional inadequacies without appropriate dietetic supervision.

Children will often outgrow allergies to some foods and studies have shown that the majority of infants diagnosed with cows` milk protein allergy will be tolerant to milk by the age of 5 years⁸. Peanut allergy is, however, a life-long condition in the majority of cases.

Prevalence
The lack of definition of some of the mechanisms, differences in classification and difficulties in diagnosis make it difficult to define the overall prevalence of food allergy. This is highlighted by the fact that, in the adult population, as many as 20-30% believe that they have some form of `food allergy`, whereas studies have shown the prevalence to be significantly lower⁵.

The prevalence of food allergy amongst children is greater than in adults (reaching approximately 5%) reflecting the fact that some types of childhood food allergies are relatively transient, resolving over time⁵. It is also important to consider the statistics for food allergy against the backdrop of allergic diseases generally as it is likely that cases of food allergy are undiagnosed or diagnosed according to the symptoms they produce i.e. eczema, asthma (Table 2).

The prevalence of food allergy appears to be increasing and has been highlighted in several reports^1,5. This is supported by statistics from research relating to peanut allergy in children born on the Isle of Wight which showed a strong trend of increased peanut allergy over a four year period⁹.

Table 2: Prevalence of some allergic disorders in adults and children in the UK and other EU countries¹⁰.

	Children prevalence %	Adults prevalence %
Asthma
Wheeze in past year	32	19
Ever wheezed	49	32
Allergic rhinitis
Rhino-conjunctivitis in past year	19	19
Hay fever ever	35	19
Eczema
Eczema ever	24	16
Food
Peanut and/or tree nut	2	Not known
Peanut	1.4	Not known
Egg	1.6	Not known
Milk	1.1-3	Not known

Allergic disease is one of the major causes of illness in developed countries and its prevalence is steadily increasing. Rising trends in food allergy appear to contribute to this general increase in allergic disease. There is also considerable interest in the area of food allergy which is fuelled by the fact that a significant proportion of the population consider themselves to suffer from such reactions. In order to facilitate identification and onward referral it is important for Healthcare Professionals to have an understanding background of these conditions. The diagnosis and management of food allergy is a specialist field and will be discussed in a future article.

Food allergy focus- cows` milk protein allergy

• Cows` milk protein allergy is an allergic response to the protein found in cows` milk. It should not be confused with lactose intolerance which is a type of non-allergic food hypersensitivity caused by an inability to digest lactose, a carbohydrate, found in cows` milk.
• The allergic response can be either an immediate reaction facilitated by IgE or a non- IgE mediated reaction in which symptoms may take longer to appear.
• Symptoms may be diverse including vomiting, diarrhoea, failure to thrive, eczema, asthma or occasionally anaphylaxis.
• Cows` milk protein allergy is the commonest food allergy in infants and young children.
• Prevalence has been estimated at around 1.1-3 % of children.
• The majority of infants diagnosed with cows` milk protein allergy will outgrow their allergy by the age of 5 years.

Key Terminology

Allergen	A substance, which is usually a protein, that is capable of inducing an allergic response
Anaphylaxis	An acute allergic response which is characterised by urticaria, shortness of breath, rapid fall in blood pressure and swelling of the throat and lips. Anaphylaxis requires immediate treatment as it can be fatal
Antibodies	Antibodies are also known as immunoglobulins. They are specific to an antigen or allergen and facilitate the allergic response
Antigen	A substance recognised by the immune system
Atopic	A predisposition to an allergic response to common allergens facilitated by IgE production
Food allergy	An adverse reaction to food which is mediated by an immunological mechanism
Histamine	An important inflammatory mediator in the allergic response
Hypersensitivity	Hypersensitivity causes objectively reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by normal subjects
IgE	A type of human immunoglobulin involved in the allergic response. Most allergic reactions to food are IgE mediated
IgG	A type of human immunoglobulin
Mast cells	Cells found in connective tissue and mucosal sites (e.g. the gut) which, upon degranulation, can release mediators of inflammation such as histamine
Non-allergic food hypersensitivity	An adverse reaction to food which is mediated by a non-immunological mechanism
T lymphocytes	A type of lymphocyte (white blood cell) which is produced in the thymus which help other lymphocytes during immunological responses
Vasoactive amines	Nitrogen containing substances that can affect the tone of blood vessel walls

References

1. Royal College of Physicians working party on the provision of allergy services in the UK (2003). Allergy; the unmet need. A blueprint for better patient care. Royal College of Physicians, London.
2. Gupta R et al. (2004). Burden of allergic disease in the UK; secondary analyses of national databases. Clin Exp Allergy; 34: 520-526.
3. Johansson SGO et al. (2004). Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organisation, October 2003. J Allergy Clin Immunol; 113: 832-6.
4. Johansson SGO et al. (2001). A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy; 56: 813-824.
5. Foods Standards Agency (2000). Adverse reactions to Food and Food Ingredients. Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. TSO, London
6. Buttriss J (2002). Adverse reactions to Food. The Report of the British Nutrition Foundation Task Force. Blackwell Science, London.
7. Klemola T et al. (2002). Allergy to soy formula and to extensively hydrolysed whey formula in infants with cows` milk allergy: a prospective, randomised study with a follow-up to the age of 2 years. J Pediatr; 140: 219-224.
8. Hill DJ et al. (1995). Challenge confirmation of late onset reactions to extensively hydrolysed formulas in infants with multiple food protein intolerance. Journal of Allergy and Clinical Immunology; 96(3): 386-394.
9. Grundy J et al. (2002). Rising prevalence of allergy to peanut in children: data from 2 sequential cohorts. J Allergy Clin Immunol; 110: 784-9.
10. House of Commons Health Committee (2004). The provision of allergy services. Sixth report of the session 2003-04; volume 1. The Stationary Office, London.