Allergy is an immune reaction causing local or systemic acute inflammation in susceptible individuals after repeated exposure to certain antigens (allergens).

Allergies may take many forms, from mild specific food intolerance, hay fever and allergic conjunctivitis to life-threatening anaphylaxis. It is essential to distinguish between allergy and other phenomena. Gastrointestinal (GI) intolerance of non-steroidal anti-inflammatory drugs (NSAIDs), lactose intolerance and simply not liking something are not allergies.

Approximately one-third of people will suffer from an allergy at some time in their life. Around 15% of people are affected by hay fever at some time in their lives and 1 in 6 children suffer from skin conditions associated with allergy, especially eczema. Asthma is the most common chronic disease of children, affecting about 11% of children in the UK. Food allergies, particularly to peanuts, are increasing, although they are still relatively uncommon, as is allergy to bee or wasp stings.

Theories as to the nature of allergy abound, recent studies suggesting a link between immune-related genes and environmental factors during infancy.¹
Atopy is a condition that is probably caused by immaturity of the T-cell system.² It tends to run in families and is associated with atopic eczema, asthma, urticaria and hay fever.

The term allergy was coined by Clemens von Pirquet in 1906.

Prevalence

In one study, around 20% of people thought they suffered from food allergy,³ but, on formal testing with the gold standard, double blind, placebo-controlled food challenge, only 1.4% of adults showed signs. In children, the overall prevalence of IgE-mediated food allergies is 5 to 7%.⁴ I One study found that about 2% of infants develop cow's milk protein allergy (CMPA) but as many as 15% of infants present with symptoms suggestive of an adverse reaction to CMP.⁵. The prevalence of food allergy appears to be increasing, particularly among adolescents and young adults.⁶ Allergy to occupational or environmental agents (e.g. house dust mite) is also extremely common and increasing.

Classification

It is important to distinguish between:

• IgE-mediated (Coombs and Gell classification type I). Timing is closely related to food intake and specific food triggers may be identified. There may be a personal or family history of atopy. Symptoms are typical and affect more than one organ or system. Non-anaphylactic reactions tend to affect single organ systems, e.g. peri-oral swelling or itching, gastroenterological symptoms (abdominal pain, nausea and D&V), urticaria, rhinitis and bronchospasm, angio-oedema and ultimately anaphylaxis. About a third of patients presenting with anaphylaxis have food allergy.
• Delayed hypersensitivity (type IV) reactions are also immunologically mediated (e.g. the aggravation of eczema by dairy products in susceptible individuals).
• Non allergic food intolerances (e.g. toxins and drugs, such as that due to monosodium glutamate causing Chinese Restaurant syndrome).
• Simple food aversion.

Presentation

Allergy can occur at any age. Neonates tend to suffer from atopic dermatitis and food allergies, young children tend to have house dust mite allergy and asthma, teenagers have hay fever while adults may have urticaria, angio-oedema (± aspirin sensitivity), allergy to bee and wasp stings and nasal polyps.⁷ Symptoms develop 1-10 hours after exposure in 25-50%, becoming more severe and rapid in onset as sensitivity increases.

Certain types of allergy are characteristic in the way they present. Contact dermatitis from cheap jewellery, especially if it contains nickel, is a type IV reaction. Some plants, especially Primula, may produce a delayed reaction. This can be aggravated by sunlight to produce a phyto-photosensitive reaction. Inhaled allergens such as pollens may cause asthma or hay fever. Asthma can also be triggered by chemical irritants rather than allergic sensitivity.

Allergy to medications, especially antibiotics, can be a great problem for patients and doctors.

• Usually the response is a rash, sometimes called a fixed drug reaction but it can be more severe with erythema multiforme in Stevens-Johnson syndrome, exfoliative dermatitis, anaphylaxis and even death.
• Anaphylaxis tends to occur 5 minutes to 2 hours after taking the offending drug.
• Diarrhoea with antibiotics is due to upset of the gut flora and not to allergy.
• If antibiotics are used topically there is a much greater risk of allergy. Penicillins are a high risk. Aminoglycosides are less of a problem but still significant.
• Reactions to drugs taken systemically are sometimes typical, such as urticaria from aspirin or Stevens-Johnson syndrome from sulphonamides.
• Some reactions that are not allergic must be borne in mind, including the Jarisch Herxheimer reaction on starting to treat syphilis or the rash that frequently occurs if amoxicillin is given to a patient with glandular fever.
• Only 10% to 20% of patients who reported a history of penicillin allergy were truly allergic when assessed by skin reaction.⁸
• On the other hand, failure to note a reported allergy, giving the drug and producing a severe reaction, is medico-legally indefensible.
• Cross-reactivity between penicillin allergy and sensitivity to cephalosporins is probably no more than around 10%. The American Academy of Pediatrics' evidence-based guidelines endorse the use of cephalosporin antibiotics for patients with reported allergies to penicillin, for the treatment of acute bacterial sinusitis and acute otitis media.⁹

Gluten sensitivity occurs with allergy to gluten in wheat. It may present, usually in children, with coeliac disease in which there is subtotal villous atrophy in the small intestine. In adults it may appear as dermatitis herpetiformis in which there is little if any disturbance of the gut but the skin is the affected organ. Both respond to strict gluten avoidance.

History

• Ask about past allergies, personal and family history of asthma, hay fever, dermatitis and childhood eczema.
• Ask about the frequency, duration and severity of the symptoms.
• Do they occur in any particular season, or are there any known triggers?
• Have allergen avoidance and dietary exclusions had any effect?
• Are there any significant environmental factors at home or work?
• Finally, take a full drug history, with particular note of any antihistamine, steroid or adrenaline use.

Investigations

Skin prick test: this is the most widely used. It can be done in primary care or specialist clinics. Rarely, generalised allergic reactions can occur and measures to deal with such emergencies should always be available in facilities where such testing is provided.¹⁰

• The aqueous solutions of allergens are placed on the skin - including just diluent (control) and histamine solution (positive control).
• The skin is then pricked with a new orange needle (25 G) for each drop and excess allergen removed.
• Read after 15 minutes.
• If the wheal is larger than an arbitrary 2 mm greater than the negative control, the test is positive.

Remember that any antihistamines the patient is taking will suppress the reaction.

Food allergen solutions: although available, they are not well standardised and they are more often associated with anaphylactic reactions. Food tests should not be performed if the diagnosis is very obvious from the history as there is a risk of severe reaction and even fatal anaphylaxis. Dietary challenge in food allergy is time-consuming and requires "wash out" periods but recurrence of symptoms on re-exposure to the antigen may be the only available method of diagnosis.¹¹ Skin prick tests are a useful procedure for evaluating clinical reactivity to egg, milk, peanut and wheat but not to soy.¹²

Patch test: this is available for diagnosing allergic contact dermatitis, using either specific allergens or a "standard set". An eczematous reaction after 48-72 hours indicates a positive result. It can cause contact sensitisation and subsequent allergic contact dermatitis and may need specialist interpretation.

Radioallergosorbent test (RAST) or enzyme-linked immunosorbent assay (ELISA) test: these both measure allergen-specific IgE, so are unaffected by drug therapy, safe as they are in vitro and highly specific. They can be performed when there is extensive skin disease, making patch testing difficult, but they are expensive.

Drug provocation tests to investigate drug allergies can yield false positive and false negative results and can be clinically risky. They can be useful but need to be conducted in carefully controlled circumstances.¹³ The British Society for Allergy and Clinical Immunology (BSACI) has drawn up guidelines for investigation and management, emphasising that the selection of skin tests and drug provocation challenges needs to be based on an accurate history and on physical examination.¹⁴

Treatment

For emergency treatment see separate article Anaphylaxis and its Treatment.

With a history of anaphylaxis, absolute allergen avoidance is essential. Advise patients in the use of self-injectable adrenaline (epinephrine) and recommend that they wear MedicAlert® bracelets or necklaces.

Antihistamines, topical steroids (occasionally oral) and allergen avoidance are the mainstays of therapy. Intramuscular steroid injections (e.g. Kenalog®) are not recommended. They are extremely effective but the risk of adverse effects is not justified. If house dust mite allergy is detected, arrange for mite-proof allergen covers for all bedding and ensure the room is well ventilated and vacuumed (obtain appropriate vacuum filter). Remove bedroom carpet if possible and keep soft toys to a minimum. In the case of pet allergy, the animal should be excluded from the home if possible, although confining the animal to kitchen and outside may be all that can reasonably be expected.

Psychological intervention may be helpful even if the allergy is organic in nature, as this can help with coping strategies.¹⁵
Indications for referral for specialist allergy advice:

• For investigation and management of anaphylaxis
• If diagnosis is uncertain or to exclude allergy in "non-specific" illness
• Food allergy - for specialist dietetic advice
• If occupational allergy is suspected
• Persistent allergic urticaria
• Severe sting allergy or severe hay fever for possible immunotherapy

Allergen injection immunotherapy (hyposensitisation) should only take place in hospital outpatient departments where there is immediate access to resuscitation equipment. It is generally only considered for patients with severe hay fever, inadequately controlled by anti-allergic drugs or in the case of wasp or bee sting anaphylaxis. Patients need at least 60 minutes' observation after each injection and longer if even mild hypersensitivity develops. The place of oral cromoglycate for food allergy is disputed. Despite apparent benefit in food intolerance¹⁶ causing irritable bowel syndrome, it has never been a popular treatment.

About 90% of babies allergic to cow's milk will have grown out of it by age 3 as will 50% of those with allergy to eggs.¹⁷ International guidelines for the management of cow's milk allergy (CMA) have been produced but have yet to be adapted to be more relevant to the UK.⁵

Allergy to nuts and cod tends to stay for life.

Allergy and somatisation

One reason for the discrepancy between perceived and true prevalence may be that the self-reporting of allergy is a manifestation of somatisation and that declaring an allergy is more acceptable than "admitting" to psychological problems.¹⁸ It is known that 65% of those who think they are suffering from the total allergy syndrome fulfil criteria for past or current anxiety or a somatoform disorder, compared with 28% of peers.¹⁹ The label allergy covers a vast range of human suffering and a complaint of allergy should prompt explicit questions to uncover (and treat) all the psychological and psychiatric unhappiness with which this label is associated. Patients with GI symptoms who report drug or food allergies or worsening of symptoms with various foods, are more likely to have functional than organic illness.²⁰ Enquiry about perceived allergies and intolerances may help in the early identification of functional GI disorders. CMA can present as constipation in young children.²¹

The withdrawal of a food, especially in young children, should not be undertaken lightly. There is evidence that allergy to CMPs or bovine proteins may aggravate atopic eczema²² but enthusiasm for this is limited.²³ Cow's milk can be replaced with goat's milk. If soya milk is used or dairy products simply avoided in young children, other sources of calcium must be sought.

In the 1980s there was much enthusiasm for linking hyperactivity in children to artificial colouring in food, especially tartrazine. This seems less fashionable nowadays and the evidence was never strong²⁴ but it is difficult to distinguish between the effect of removing the colouring and the associated parental attention.

Document references

1. Vuillermin PJ, Ponsonby AL, Saffery R, et al; Microbial exposure, interferon gamma gene demethylation in naive T-cells, and the risk of allergic disease. Allergy. 2009 Mar;64(3):348-53. Epub 2009 Feb 6. [abstract]
2. Loza MJ, Peters SP, Penn RB; Atopy, asthma, and experimental approaches based on the linear model of T cell maturation. Clin Exp Allergy. 2005 Jan;35(1):8-17. [abstract]
3. Young E, Stoneham MD, Petruckevitch A, et al; A population study of food intolerance. Lancet. 1994 May 7;343(8906):1127-30. [abstract]
4. Bindslev-Jensen C; Food allergy. BMJ. 1998 Apr 25;316(7140):1299-302.
5. Meyer R; New guidelines for managing cow's milk allergy in infants. J Fam Health Care. 2008;18(1):27-30. [abstract]
6. Wrobel JP, O'Hehir RE, Douglass JA; Food allergy in adults. Aust Fam Physician. 2008 Apr;37(4):222-6. [abstract]
7. Bindslev-Jensen C; ABC of allergies: Food allergy. BMJ 1998 316:1299-1302.
8. Salkind AR, Cuddy PG, Foxworth JW; The rational clinical examination. Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy. JAMA. 2001 May 16;285(19):2498-505. [abstract]
9. Pichichero ME; A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics. 2005 Apr;115(4):1048-57. [abstract]
10. Norrman G, Falth-Magnusson K; Adverse reactions to skin prick testing in children - prevalence and possible risk factors. Pediatr Allergy Immunol. 2009 May;20(3):273-8. Epub 2009 Feb 10. [abstract]
11. Eigenmann PA, Beyer K, Wesley Burks A, et al; New visions for food allergy: an iPAC summary and future trends. Pediatr Allergy Immunol. 2008 Aug;19 Suppl 19:26-39. [abstract]
12. Eigenmann PA, Sampson HA; Interpreting skin prick tests in the evaluation of food allergy in children. Pediatr Allergy Immunol. 1998 Nov;9(4):186-91. [abstract]
13. Aberer W, Kranke B; Provocation tests in drug hypersensitivity. Immunol Allergy Clin North Am. 2009 Aug;29(3):567-84. [abstract]
14. Mirakian R, Ewan PW, Durham SR, et al; BSACI guidelines for the management of drug allergy. Clin Exp Allergy. 2009 Jan;39(1):43-61. [abstract]
15. Knibb RC, Horton SL; Can illness perceptions and coping predict psychological distress amongst allergy sufferers? Br J Health Psychol. 2008 Feb;13(Pt 1):103-19. [abstract]
16. Lunardi C, Bambara LM, Biasi D, et al; Double-blind cross-over trial of oral sodium cromoglycate in patients with irritable bowel syndrome due to food intolerance. Clin Exp Allergy. 1991 Sep;21(5):569-72. [abstract]
17. Rusznak C, Davies RJ; ABC of allergies. Diagnosing allergy. BMJ. 1998 Feb 28;316(7132):686-9.
18. Howard LM, Wessely S; The psychology of multiple allergy. BMJ. 1993 Sep 25;307(6907):747-8.
19. Black DW, Rathe A, Goldstein RB; Environmental illness. A controlled study of 26 subjects with '20th century disease'. JAMA. 1990 Dec 26;264(24):3166-70. [abstract]
20. Bhat K, Harper A, Gorard DA; Perceived food and drug allergies in functional and organic gastrointestinal disorders. Aliment Pharmacol Ther. 2002 May;16(5):969-73. [abstract]
21. Iacono G, Carroccio A, Cavataio F, et al; Chronic constipation as a symptom of cow milk allergy. J Pediatr. 1995 Jan;126(1):34-9. [abstract]
22. Oranje AP, Wolkerstorfer A, de Waard-van der Spek FB; Natural course of cow's milk allergy in childhood atopic eczema/dermatitis syndrome. Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):52-5. [abstract]
23. Werfel T, Breuer K; Role of food allergy in atopic dermatitis. Curr Opin Allergy Clin Immunol. 2004 Oct;4(5):379-85. [abstract]
24. Wender EH; The food additive-free diet in the treatment of behavior disorders: a review. J Dev Behav Pediatr. 1986 Feb;7(1):35-42. [abstract]

Internet and further reading

• Cross S, Buck S, Hubbard J; ABC of allergies: Allergy in general practice; BMJ 1998 316:1584-1587.
• Kay AB; Clinical review: ABC of allergies: Good allergy practice; BMJ 1998 316:535-537.
• Sicherer S, Food Allergy, eMedicine. (Sept 2009)

Acknowledgements