Allergic phenomena

What are allergies?

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.

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.

Approximately one third of people will have an allergy at some time in their lives. A population-based survey found the prevalence of hay fever in adults was 26% in the UK, and 10-30% of children have atopic eczema.^{1 2} Asthma is a common chronic disease, affecting about 3.53 million people in the UK, and only 20% of those feel their asthma is well controlled.³ Food allergies, particularly to peanuts, are increasing, although they are still relatively uncommon, as is allergy to bee or wasp stings.

A genome-wide association study (n = 360,838) of a broad allergic disease phenotype identified 132 genes in allergic disease pathophysiology.⁴

How common are allergies? (Prevalence)

The prevalence of food allergy varies according to age, geographical location and possibly ethnicity. The lifetime prevalence of immediate hypersensitivity reactions is around 15% and European data suggest 0.3% of the population will experience anaphylaxis at some point in their life.⁵ 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.

Cow's milk protein allergy is one of the most common childhood food allergies in the developed world, second to egg allergy. It affects about 7% of formula- or mixed-fed infants, with the highest prevalence during the first year of life.⁶ Allergy to occupational or environmental agents (eg, house dust mite) is also extremely common and increasing.⁷

Classification of allergies

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.

Presentation of allergies

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.⁸ 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.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 (epinephrine) use.

Investigations

Skin prick test:¹⁰ 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.¹¹

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 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.¹⁰

Management of allergies

For emergency treatment see the separate Anaphylaxis and its Treatment article.

With a history of anaphylaxis, absolute allergen avoidance is essential.¹² 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.¹ They are extremely effective but the risk of adverse effects is not justified.

The efficacy of house dust mite avoidance has been widely questioned.¹³ Although an intuitive strategy, avoidance is not supported by robust evidence of efficacy. Despite this, avoidance is still widely recommended to reduce the severity of symptoms.

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.¹⁴ 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.

Developments in immunotherapy are continuing to build on the successful demonstration of the safety and efficacy of both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in both reducing symptom burden and use of pharmacotherapeutic medication.¹³ Both SCIT and SLIT require treatment over several years, and SCIT must be given under medical supervision. It 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.

GRAZAX® is a grass pollen allergen extract available as a sublingual tablet. It is cost-effective, efficacious and has a good safety profile.¹⁵ Its association with an easy and safe route of administration improves patient compliance.

Bee venom or wasp venom extract (Pharmalgen®) is available for selected patients with IgE-mediated bee and wasp venom allergy.¹⁶

There are some reports in the literature supporting the use of sodium cromoglycate in food allergy but the evidence base is small and 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 years, as will 50% of those with allergy to eggs.⁸ There are UK guidelines for the management of cow's milk protein allergy.^{17 6} .

Allergy to nuts and to cod tends to stay for life, but immunotherapy has improved the outlook for nut allergy. Omalizumab allows subjects with peanut allergy to be rapidly desensitised over as little as eight weeks of oral immunotherapy.¹⁸ In the majority of subjects, this desensitisation is sustained after omalizumab is discontinued.

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.¹⁹ People with allergies have been found to have distinct psychological profiles. ²⁰ 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.

The withdrawal of a food, especially in young children, should not be undertaken lightly. Expert opinion in guidelines and review articles on atopic eczema is that any dietary exclusion or elimination diets should be implemented and monitored by a specialist.² In the UK infants with moderate-to-severe atopic eczema may be prescribed extensively hydrolysed formula (eHF).²¹ 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.²² Goat's milk has no clear nutritional advantage over cow's milk and is not less allergenic, but has kinetics of protein digestion that are closer to human milk than cow's milk.²³