Guidance

2 Clinical need and practice

2 Clinical need and practice

The problem addressed

2.1 The risk of an allergic reaction to an allergen varies between people. Multiplex allergen testing allows a clinician to test for multiple allergens at the same time and may help to determine a person's sensitisation profile. The resulting allergen profile may help clinicians to recognise genuine sensitisation, predict the risk of a local or systemic allergic reaction, help with avoidance advice, and identify allergy‑triggering components before starting immunotherapy. Multiplex allergen testing may be most appropriate for helping to diagnose more complex allergy cases, such as those where a trigger cannot be identified based on patient history or with conventional testing (such as in idiopathic anaphylaxis), or where polysensitisation makes it difficult to interpret conventional allergen testing results.

2.2 The purpose of this assessment is to assess the clinical and cost effectiveness of using ImmunoCAP ISAC 112 and Microtest to help diagnose allergy and predict the risk of an allergic reaction in people with allergy that is difficult to diagnose.

The condition

2.3 Allergy is a form of exaggerated sensitivity (hypersensitivity) to a 'foreign' substance, called an allergen, that is either inhaled, swallowed, injected, or comes into contact with the skin, eyes or mucosa. Examples of allergens include: pollen from grass, weeds and trees; proteins excreted by house dust mite; food proteins; and insect venoms. Immunoglobulin E (IgE) is a type of antibody that is normally present in very small amounts in the blood but may be increased in allergy. Exposure to an allergen starts a complex set of cellular events leading to the production of a specific IgE antibody to a specific allergen, but no clinical reaction – a process known as sensitisation. Upon re‑exposure, the allergen binds to the specific antibody and the immune system starts a more aggressive and rapid reaction resulting in an inflammatory response with clinical symptoms. When a person is sensitised to 2 or more allergens (polysensitisation), the cause of allergy can be difficult to diagnose because of cross‑reactivity, that is, the immune system reacts to other allergens because they are similar in molecular shape and structure to the causal allergen.

2.4 Hypersensitivity reactions are divided into 2 categories: IgE‑mediated reactions and non‑IgE‑mediated reactions. IgE‑mediated reactions are usually rapid in onset, and cause symptoms ranging from mild to moderate reactions (such as hives), to severe systemic reactions (anaphylaxis). Non‑IgE‑mediated reactions are less well understood and are mediated by other parts of the immune system. They usually have a delayed onset, and can happen up to 72 hours after exposure to an allergen.

2.5 In severe cases of allergy, a person may have anaphylaxis: an acute, potentially fatal, multi‑organ system, allergic reaction. It is characterised by rapidly developing life‑threatening airway, breathing and circulation problems. Certain foods, insect venoms, drugs and latex are common causes of IgE‑mediated allergic anaphylaxis. Co‑factors such as exercise can also contribute to triggering an anaphylactic event. Food is a very common trigger in children, whereas medicines are much more common triggers in adults. If the cause of anaphylaxis cannot be identified, this is known as idiopathic anaphylaxis.

2.6 Multiple and complex allergies are becoming more common (Allergy UK). In 2008, it was estimated that 16.1% of children in the UK have 2 diagnosed allergies and 2.5% have 3 diagnosed allergies (Punekar and Sheikh 2009). Often these are eczema, asthma and rhinitis. The younger the child is when the first allergic condition appears, the more likely they are to develop multiple allergic conditions (the Parliamentary Office of Science and Technology 2014). Food allergy, one of the most common allergic disorders and a major paediatric health problem in western countries, may be confused with food intolerance. NICE's guideline on food allergy in under 19s notes that only 25–40% of self‑reported food allergy is confirmed as true clinical food allergy by an oral food challenge.

2.7 The frequency of anaphylaxis from all causes in the UK is unknown, and because people with anaphylaxis present mainly in emergency departments and outpatient settings, few estimates of prevalence are available from NHS sources. Anaphylaxis may not be recorded, or may be misdiagnosed as another condition, for example, asthma. One study in the UK suggested that about 1 in 1,333 people in England have had anaphylaxis (Stewart and Ewan 1996). About 20 deaths from anaphylaxis are reported each year in the UK (Pumphrey 2000).

The diagnostic and care pathways

Diagnosis

2.8 The first step if an allergy is suspected should be an allergy‑focused clinical history. Getting a clinical history and asking specific allergy‑focused questions is extremely important for diagnosis. NICE's guideline on food allergy in under 19s states that this can be done by GPs or other primary healthcare professionals with the appropriate competencies, and indicates what should be included when taking a clinical history.

2.9 The Royal College of Paediatrics and Child Health's Allergy Care Pathways Project includes a set of specific questions for taking an allergy‑focused clinical history. It recommends several questions grouped into themes. The first set contains 3 screening questions used to identify a person who might need more detailed allergy questioning. If allergy is suspected, a further set of questions is recommended. If the expertise needed to take an allergy‑focused clinical history is not available in primary care, a referral to secondary care is recommended. Further history taking is presented across 6 areas; questioning will partly depend on the responses of the child, young person, or parent or carer.

2.10 NICE's guideline on atopic eczema in under 12s recommends that healthcare professionals should try to identify potential triggers during clinical assessment, including irritants, skin infections, contact allergens and inhalant allergens. The guideline also provides guidance on considering a diagnosis of food or inhalant allergy, or allergic contact dermatitis in children with atopic eczema.

2.11 Based on the results of the allergy‑focused clinical history, if IgE‑mediated allergy is suspected, NICE's guideline on food allergy in under 19s recommends that the child or young person should be offered a skin prick test or blood tests for specific IgE antibodies to the suspected foods and likely co‑allergens. It recommends that these tests should only be carried out by healthcare professionals with the appropriate competencies to select, perform and interpret the results and should only be done where there are facilities to deal with an anaphylactic reaction. The choice between a skin prick test and a specific IgE‑antibody blood test should be based on:

  • the results of the allergy‑focused clinical history

  • whether the test is suitable for, safe for and acceptable to the child or young person and

  • the available competencies of the healthcare professionals doing the test and interpreting the results.

    It is recommended that information from the allergy‑focused clinical history is used to interpret the results of the tests.

2.12 An allergen challenge or provocation test is done by giving a person a suspected allergen to see if they react to it. This is considered the gold standard in allergy diagnosis because it shows a clinical response to the allergen. Oral food challenges are done either because a diagnosis of food allergy is not supported by the clinical history or there is a discrepancy between history and test results. NICE's guideline on food allergy in under 19s states that information should be given to the child or young person and their parent or carer on when, where and how an oral food challenge or food reintroduction procedure may be done. However, they should not be done in primary care, and should only be done in a setting that is fully equipped for emergency treatment if anaphylaxis occurs.

Management and treatment

2.13 Management depends on the type and severity of the allergy. Mild allergies can be managed in primary care, more severe allergies and more complex allergies may need additional management and referral to specialist services. NICE's guideline on food allergy in under 19s gives guidance on when to refer to secondary or specialist care. NICE's guideline on atopic eczema in under 12s and NICE's quality standard on atopic eczema in under 12s recommend that children with a suspected food allergy should be referred for specialist investigation and management by a paediatric allergist or paediatric dermatologist.

2.14 Mild allergies can be treated using over‑the‑counter medications such as antihistamines and simple avoidance of the allergen. NICE's guideline on food allergy in under 19s recommends that once an allergy is suspected based on clinical history, information and support should be given, particularly on eliminating the food from their diet.

2.15 NICE's guideline on anaphylaxis recommends that after emergency treatment for suspected anaphylaxis, people should be offered an appropriate adrenaline injector as an interim measure before the specialist allergy service appointment.

2.16 NICE's guideline on atopic eczema in under 12s recommends that healthcare professionals should use a stepped approach for managing atopic eczema in children and should adapt the treatment to the severity of the atopic eczema.

2.17 Some people may need allergen‑specific immunotherapy, in which allergen extracts are repeatedly given subcutaneously or sublingually for desensitisation so that the response to the allergen decreases. The British Society for Allergy and Clinical Immunology's guidelines on immunotherapy for allergic rhinitis (Walker et al. 2011) recommend that allergy specialists supervise the start and monitoring of all immunotherapy. Immunotherapy should only be given by physicians and nurses with specialist knowledge of allergy and specific immunotherapies.