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 lives. Around 20% of people are affected by hay fever at some time in their lives and 15-20% of children suffer from atopic eczema.[1, 2]Asthma is the most common chronic disease of children, affecting about 1 in 11 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 or even in utero.[4, 5]Atopy is a condition that is probably caused by immaturity of the T-cell system. 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.
The prevalence of food allergy varies according to age, geographical location and possibly ethnicity. The cumulative prevalence quoted in the literature is 3-6%.There has been an increase in food allergy in recent decades but this seems to be stabilising in developed countries.Some of this increase may have been due to reporting error and an increase in recognition of the condition, rather than a true increase in prevalence. 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.Allergy to occupational or environmental agents (eg, house dust mite) is also extremely common and increasing.
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 - eg, perioral swelling or itching, gastroenterological symptoms (abdominal pain, nausea and diarrhoea and vomiting), 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 (eg, the aggravation of eczema by dairy products in susceptible individuals).
- Non-allergic food intolerances (eg, toxins and drugs, such as that due to monosodium glutamate causing Chinese restaurant syndrome).
- Simple food aversion.
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.Unpredictably, some allergic episodes have a late phase reaction which can occur four to twelve hours after exposure.
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. However, it can be more severe with erythema multiforme in Stevens-Johnson syndrome, exfoliative dermatitis, anaphylaxis and even death.
- Anaphylaxis tends to occur five minutes to two 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 sulfonamides.
- 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.
- Fewer than 10% of patients who reported a history of penicillin allergy were truly allergic when assessed by skin reaction.
- 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 is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains. The use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy.
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.
- 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 (epinephrine) use.
Skin prick test: this is the most widely used. It is usually done in specialist clinics as, rarely, generalised allergic reactions can occur and measures to deal with such emergencies may be required.
- 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. Oral food challenges are the gold standard but are not without risk. Food allergies are most commonly diagnosed from the history confirmed by detection of serum-specific IgE or by skin prick test.
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 specialised 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. 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.
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 a medical emergency identification bracelet or similar.
Antihistamines, topical steroids (occasionally oral) and allergen avoidance are the mainstays of therapy. Intramuscular steroid injections (eg, Kenalog®) are not recommended for long-term conditions such as allergic rhinitis.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 the appropriate vacuum filter). Remove the 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 the 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. Indications for referral for specialised allergy advice are:
- For investigation and management of anaphylaxis.
- If the diagnosis is uncertain or to exclude allergy in 'nonspecific' illness.
- Food allergy - for specialised 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 of observation after each injection and longer if even mild hypersensitivity develops.
An oral preparation of grass pollen extract (Grazax®) is licensed in the UK for grass pollen-induced rhinitis and conjunctivitis.
Bee venom or wasp venom extract (Pharmalgen®) is available for selected patients with IgE-mediated bee and wasp venom allergy.
There are some reports in the literature supporting the use of sodium cromoglycate in food allergy but the evidence base is small.Despite apparent benefit in food intolerance causing irritable bowel syndrome, it has never been a popular treatment.[27, 28]
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.[14, 29]UK guidelines for the primary care management of cow's milk allergy were published in 2013.
Allergy to nuts and cod tends to stay for life.
Researchers at Addenbrooke's Hospital, Cambridge have reported promising results from a study of peanut immunotherapy. This involves the patient eating gradually increasing amounts of peanut allergy protein. Children who underwent the trial were able to eat up to five peanuts a day without ill effects. Anaphylaxis is a potential risk but only 0.01% (1 participant) required intramuscular adrenaline. This was a Phase 2 pre-marketing trial. The authors recommended further studies in wider populations.
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.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. Enquiry about perceived allergies and intolerances may help in the early identification of functional GI disorders. Cow's milk allergy can present as constipation in young children.
The withdrawal of a food, especially in young children, should not be undertaken lightly. Current UK recommendations are that infants with moderate-to-severe atopic eczema should be given extensively hydrolysed formula (eHF). Babies over the age of 6 months may be given soya milk if they do not tolerate eHF. If soya milk is used or dairy products simply avoided in young children, other sources of calcium must be sought.Goat's milk has no clear nutritional advantage over cow's milk and is not less allergenic.
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 strong but it is difficult to distinguish between the effect of removing the colouring and the associated parental attention.
Further reading and references
Molloy J, Allen K, Collier F, et al; The Potential Link between Gut Microbiota and IgE-Mediated Food Allergy in Early Life. Int J Environ Res Public Health. 2013 Dec 1610(12):7235-56. doi: 10.3390/ijerph10127235.
Eiwegger T, Gruber S, Szepfalusi Z, et al; Novel developments in the mechanisms of immune tolerance to allergens. Hum Vaccin Immunother. 2012 Oct8(10):1485-91. doi: 10.4161/hv.20903. Epub 2012 Oct 1.
Kalpaklioglu AF, Kalkan IK, Akcay A, et al; (Un)Awareness of allergy. World Allergy Organ J. 2011 Nov4(11):170-8. doi: 10.1097/WOX.0b013e31823842bc. Epub 2011 Nov 18.
Allergic rhinitis; NICE CKS, September 2012
Eczema - atopic; NICE CKS, last revised March 2013 (UK access only)
Asthma facts and statistics; Asthma UK
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 Mar64(3):348-53. Epub 2009 Feb 6.
de Planell-Saguer M, Lovinsky-Desir S, Miller RL; Epigenetic regulation: The interface between prenatal and early-life exposure and asthma susceptibility. Environ Mol Mutagen. 2013 Dec 9. doi: 10.1002/em.21836.
Loza MJ, Peters SP, Penn RB; Atopy, asthma, and experimental approaches based on the linear model of T cell maturation. Clin Exp Allergy. 2005 Jan35(1):8-17.
Clemens von Pirquet; US National Library of Medicine/Science Photo Library
Sicherer SH; Epidemiology of food allergy. J Allergy Clin Immunol. 2011 Mar127(3):594-602. doi: 10.1016/j.jaci.2010.11.044. Epub 2011 Jan 13.
Ben-Shoshan M, Turnbull E, Clarke A; Food allergy: temporal trends and determinants. Curr Allergy Asthma Rep. 2012 Aug12(4):346-72. doi: 10.1007/s11882-012-0274-3.
Meyer R; New guidelines for managing cow's milk allergy in infants. J Fam Health Care. 200818(1):27-30.
Valero A, Justicia JL, Vidal C, et al; Diagnosis and treatment of allergic rhinitis due to house-dust mites in Spain. Am J Rhinol Allergy. 2012 Jan-Feb26(1):23-6. doi: 10.2500/ajra.2012.26.3695.
Beatty R; Hypersensitivity
Williams AN, Woessner KM; Monosodium glutamate 'allergy': menace or myth? Clin Exp Allergy. 2009 May39(5):640-6. doi: 10.1111/j.1365-2222.2009.03221.x. Epub 2009 Apr 6.
White Book on Allergy; World Allergy Organization, 2011
Glacy J et al; Treatments for Seasonal Allergic Rhinitis, Comparative Effectiveness Reviews, No. 120, 2013.
Raja AS, Lindsell CJ, Bernstein JA, et al; The use of penicillin skin testing to assess the prevalence of penicillin allergy in an emergency department setting. Ann Emerg Med. 2009 Jul54(1):72-7. doi: 10.1016/j.annemergmed.2008.12.034. Epub 2009 Feb 13.
Campagna JD, Bond MC, Schabelman E, et al; The use of cephalosporins in penicillin-allergic patients: a literature review. J Emerg Med. 2012 May42(5):612-20. doi: 10.1016/j.jemermed.2011.05.035. Epub 2011 Jul 13.
Norrman G, Falth-Magnusson K; Adverse reactions to skin prick testing in children - prevalence and possible risk factors. Pediatr Allergy Immunol. 2009 May20(3):273-8. Epub 2009 Feb 10.
Turner PJ, Campbell DE; What's new in the diagnosis and management of food allergy in children? Asia Pac Allergy. 2013 Apr3(2):88-95. doi: 10.5415/apallergy.2013.3.2.88. Epub 2013 Apr 26.
Aberer W, Kranke B; Provocation tests in drug hypersensitivity. Immunol Allergy Clin North Am. 2009 Aug29(3):567-84.
Mirakian R, Ewan PW, Durham SR, et al; BSACI guidelines for the management of drug allergy. Clin Exp Allergy. 2009 Jan39(1):43-61.
Knibb RC, Horton SL; Can illness perceptions and coping predict psychological distress amongst allergy sufferers? Br J Health Psychol. 2008 Feb13(Pt 1):103-19.
Immunotherapy for allergic rhinitis; British Society for Allergy and Clinical Immunology (2011)
Nasser S, Vestenbaek U, Beriot-Mathiot A, et al; Cost-effectiveness of specific immunotherapy with Grazax in allergic rhinitis co-existing with asthma. Allergy. 2008 Dec63(12):1624-9. doi: 10.1111/j.1398-9995.2008.01743.x.
Venom anaphylaxis - immunotherapy pharmalgen; NICE Technology Appraisal Guidance, February 2012
Weangsripanaval T, Murota K, Murakami Y, et al; Sodium cromoglycate inhibits absorption of the major soybean allergen, Gly m Bd 30K, in mice and human intestinal Caco-2 cells. J Nutr. 2006 Nov136(11):2874-80.
Wang GD, Wang XY, Zou F, et al; Mast cell expression of the serotonin1A receptor in guinea pig and human intestine. Am J Physiol Gastrointest Liver Physiol. 2013 May 15304(10):G855-63. doi: 10.1152/ajpgi.00421.2012. Epub 2013 Mar 21.
Philpott H, Gibson P, Thien F; Irritable bowel syndrome - An inflammatory disease involving mast cells. Asia Pac Allergy. 2011 Apr1(1):36-42. doi: 10.5415/apallergy.2011.1.1.36. Epub 2011 Apr 26.
Fiocchi A, Brozek J, Schunemann H, et al; World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. World Allergy Organ J. 2010 Apr3(4):57-161. doi: 10.1097/WOX.0b013e3181defeb9. Epub 2010 Apr 23.
Venter C, Brown T, Shah N, et al; Diagnosis and management of non-IgE-mediated cow's milk allergy in infancy - a UK primary care practical guide. Clin Transl Allergy. 2013 Jul 83(1):23. doi: 10.1186/2045-7022-3-23.
Anagnostou K, Islam S, King Y, et al; Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial. Lancet. 2014 Jan 29. pii: S0140-6736(13)62301-6. doi: 10.1016/S0140-6736(13)62301-6.
Hassel JC, Danner D, Hassel AJ; Psychosomatic or allergic symptoms? High levels for somatization in patients with drug intolerance. J Dermatol. 2011 Oct38(10):959-65. doi: 10.1111/j.1346-8138.2011.01249.x. Epub 2011 Jul 18.
Bhat K, Harper A, Gorard DA; Perceived food and drug allergies in functional and organic gastrointestinal disorders. Aliment Pharmacol Ther. 2002 May16(5):969-73.
Dehghani SM, Ahmadpour B, Haghighat M, et al; The Role of Cow's Milk Allergy in Pediatric Chronic Constipation: A Randomized Clinical Trial. Iran J Pediatr. 2012 Dec22(4):468-74.
Turck D; Cow's milk and goat's milk. World Rev Nutr Diet. 2013108:56-62. doi: 10.1159/000351485. Epub 2013 Sep 6.
Kanarek RB; Artificial food dyes and attention deficit hyperactivity disorder. Nutr Rev. 2011 Jul69(7):385-91. doi: 10.1111/j.1753-4887.2011.00385.x. Epub 2011 Jun 30.
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