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Allergy Diagnosis in Primary Care A quick reference guide to allergy diagnosis for GPs in NHS Lothian Professor Aziz Sheikh

eAllergy www.allergyeducation.co.uk

Helpdesk

This guide provides information and advice on: • • • • • •

The different types of allergy commonly seen in primary care Clinical history taking Choosing which investigations to order Interpreting the results of these tests to make a diagnosis When to refer for a specialist opinion Useful local and national resources

Contents Key Definitions 04 ........................................................................................................................................... Introduction to Allergy 05 ........................................................................................................................................... Diagnosing Allergy: The Clinical History is the Key 06 ........................................................................................................................................... Diagnosing Allergy: Confirmatory Testing 07 ........................................................................................................................................... Patient History Template for Paediatric Food Allergy 08 ........................................................................................................................................... Patient History Template for Eczema 09 ........................................................................................................................................... Lothian Allergy Test Form 10 ........................................................................................................................................... Diagnosing Allergy: Interpreting the Results 11 ........................................................................................................................................... IgE Antibody Levels vs. Allergic Disease 11 ........................................................................................................................................... Worked Clinical Scenario 12 ........................................................................................................................................... When to Refer 14 ........................................................................................................................................... Local Allergy Clinics 14 ........................................................................................................................................... Other Local Contacts and Sources of Support 14 ........................................................................................................................................... Further Information 15 ...........................................................................................................................................

Further support... If you would like to learn more about the diagnosis and management of allergic problems in primary care then please visit: www.allergyeducation.co.uk where you can find a number of clinically important resources, free of charge. Specific clinical enquiries can be emailed to the eAllergy Helpdesk: www.allergyeducation.co.uk/hcp/helpdesk from where you can obtain free confidential advice and support with the investigation, diagnosis and management of allergic problems in primary care settings.

Key Definitions A good understanding of the terms and concepts below can prove very helpful in making an accurate diagnosis. Atopy: This is used to refer to those who have a tendency to produce excessive IgE in response to what should be harmless environmental stimuli - for example, grass pollen, pet dander and the house dust mite. This is normally detected by positive skin prick tests and/or raised specific-IgE to the allergens in question. Note however that atopy represents a predisposition - it does not necessarily mean that all who demonstrate IgE-hyper-responsiveness will actually develop allergic problems. Allergen: An allergen is any foreign protein to which the body mounts an allergic response. Commonly encountered allergens include cow’s milk, hen’s eggs, grass and tree pollens, and the house dust mite. Allergy: This is an inappropriate response of the immune system to an allergen, which results in the manifestation of clinical symptoms and signs - for example hay fever in response to grass pollen, and asthma in response to house dust mite. IgE and non-IgE-mediated allergy: There are two main types of allergic problems seen in primary care: • IgE-mediated reactions: These are often triggered by exposure to small amounts of allergen, have a rapid onset and may, in some cases, quickly progress to life-threatening reactions. These reactions typically display a clear temporal relationship between exposure to the allergen and the development of symptoms. These can be tested for by assessing measures of specific-IgE and/or skin prick testing to the likely allergens. This guide is primarily concerned with these reactions. • Non-IgE mediated reactions: These are typically less easy to recognise and diagnose as there is typically a less clear cut relationship between exposure to the allergen and the development of symptoms. Clinical features may develop over many hours or days. These reactions can be very troublesome, but will not prove life-threatening. In contrast to IgE-mediated reactions, there are no readily available diagnostic tests. 04

Introduction to Allergy Allergic problems are very common in Scotland. Recent estimates from The University of Edinburgh’s Allergy and Respiratory Research Group suggest that these problems now affect 1 in 3 of the general population at some point in their lives. The main allergic problems seen in primary care are listed in Box 1. These conditions can have a major adverse impact on individuals and family members, are responsible for considerable use of NHS resources, and a substantial wider impact on society. Taking a careful history and then, if appropriate, ordering relevant diagnostic tests can be very helpful in: • Making an accurate clinical diagnosis • Deciding whether the problems have an underlying allergic basis • Informing decisions on clinical management This guide aims to provide practical advice on the tests that are available, when they should be requested and how to appropriately interpret and act on the results of these investigations.

Box 1: Main allergic problems seen in primary care • • • • • • • • •

Atopic dermatitis/eczema Food allergy Allergic rhinitis/hay fever Pollen food syndrome Asthma Drug allergy Venom Allergy Urticaria/angioedema Anaphylaxis

Diagnosing Allergy: The Clinical History is the Key... As with all other areas of medicine, taking a detailed history is the key to an accurate diagnosis. This is particularly important in the context of suspected allergic problems because the choice of investigations needs to be guided by the clinical history. It is important to note that blanket screening for possible allergens can result in a lot of false positive reactions and so this approach is not recommended for use in primary care settings. Boxes 2 and 3 provide pointers on some of the key areas that should be focused in on when faced with a patient with a suspected allergy. You can see a short video discussing how to take an allergy-focused patient history from: http://www.allergyeducation.co.uk/hcp/ An example history taking template can be downloaded from: http://www.allergyeducation.co.uk/docs/patient-history-form.pdf

Box 2: Key areas to concentrate on when taking a clinical history • Age of onset • Temporal relationship between exposure to allergen and development of symptoms • Route of exposure to the allergen(s): oral, inhaled or contact? • What symptoms were experienced? • Severity of symptoms • Have symptoms recurred on repeat exposure? • Frequency of occurrence • Setting of reaction: home, school or work? • Any previous reactions • Effects of any attempts at avoidance • Family history of allergic problems (e.g. eczema, hay fever or asthma)

Box 3: Characteristic features of an IgE-mediated reaction • • • • •

Family/personal history of atopic disorders Clear relationship between exposure to allergen and development of symptoms Maximum time elapsed between exposure and symptoms ~2 hours Reproducible reaction on subsequent exposure to the allergen Itch is a dominant feature

Diagnosing Allergy: ...Followed by, if Indicated, Confirmatory Testing If after taking a detailed history, IgE-mediated reactions are suspected, then this can be confirmed or refuted by allergy testing. There are two main types of tests available to primary care professionals: • Skin prick tests (SPT) • Blood tests measuring specific-IgE (formerly known as RAST tests) Skin prick testing can be very useful for confirming the diagnosis of, for example, food, pollen, dust and pet allergy. It has the advantage of offering an immediate result and providing visual reinforcement of the diagnosis, but should not be undertaken whilst on antihistamines and does run a small risk of triggering systemic reactions. It is therefore probably best undertaken in a hospital setting (see local resources at the end of this guide). Access to specific-IgE blood tests is available to all GPs in the Lothian area through the Pathology laboratories at Edinburgh Royal Infirmary. These tests are available to a whole host of allergens (see: http://www.phadia.com/en/Allergen-information/ImmunoCAP-Allergens/ and Figure 1) and a 1ml sample of blood is sufficient for up to 10 allergens. Please remember to also request a Total-IgE to aid with the interpretation of results.

Patient History Template for Paediatric Food Allergy Patient Name: 1. Is there a personal history of allergic problems?  Yes

 No

Details: _______________________________________

2. Is there a family history of allergic problems?  Yes

 No

Details: _______________________________________

3. What was the age of onset and relation to change in diet? Answer: __________________________________________________________ 4. What food or foods are causing concern?    

Cow’s milk Fish Egg Shellfish

   

Peanuts Soya Tree nuts Wheat

Other: ___________________________________________________________ 5. What symptoms are triggered? Skin? Gastrointestinal? Respiratory System? Cardiovascular?

_____________________________________________ _____________________________________________ _____________________________________________ _____________________________________________

6. What is the time course between exposure and the onset of symptoms?  More than 2 hours

 Less than 2 hours

7. What quantity of food is needed to trigger a reaction? Answer: __________________________________________________________

Please note that this form is a guide only and not an official test order form.

Patient History Template for Eczema Patient Name: 1. Is there a personal history of allergic disorders (e.g. hay fever/allergic rhinitis, asthma or food allergy)?  Yes

 No

Details: _______________________________________

2. Is there a family history of allergy (e.g. hay fever/allergic rhinitis, asthma or food allergy)?  Yes

 No

Details: _______________________________________

3. At what age did the eczema first manifest?

 <1

 1-2

4. How widespread is the eczema?

 Minimal

 >2 years

 Moderate

 Extensive

5. Assessing impact on quality of life: Is sleep regularly disturbed?  Yes  No Details: _______________________________________ Are activities of daily living affected?  Yes  No Details: _______________________________________ Any other social or psychological effects (including on family/carers)?  Yes  No Details: _______________________________________ 6. Can any triggers be identified? Skin irritants? (eg. bubble bath, soap, etc.)

 Yes

 No

Details: _____________

Skin infections?

 Yes

 No

Details: _____________

Contact allergens? (eg. nickel, hair products, etc.)

 Yes

 No

Details: _____________

Food

 Yes

 No

Details: _____________

Aeroallergens (eg. dust, pollen, pet dander, etc.)

 Yes

 No

Details: _____________

7. How responsive is the eczema to standard topical treatments (e.g. emollients & weak steroids)?  Complete response

 Partial response

Please note that this form is a guide only and not an official test order form.

 Poor response

Lothian Allergy Test Form Common allergen panels (Please indicate as appropriate) Nasal and Bronchial Symptoms d1 house dust mite ex1 mixed animal (cat, dog, horse and cow dander) gx3 mixed grass pollen (sweet vernal, rye, timothy cultivated rye, velvet grass) Urticarial, Gastrointestinal Symptoms and Eczema f1 egg white f2 cow’s milk

f4

wheat

f4 f9 f17 f25 f36 f47 f83 f93 f203

wheat rice hazel nut tomato coconut garlic chicken cocoa pistachio

Individual allergen (Please indicate as appropriate) Foods f1 f6 f12 f20 f27 f41 f49 f87 f95 f235 fx1 fx2

egg white f2 cow’s milk f3 cod barley f7 oat f8 maize pea f13 peanut f14 soya almond f23 crab f24 shrimp beef f33 orange f35 potato salmon f44 strawberry f45 yeast apple f79 gluten f81 hard cheese melon f88 mutton f92 banana peach f201 pecan nut f202 cashew nut lentil f256 walnut f284 turnkey mixed nuts (peanut, hazelnut, brazil nut, almond, coconut) mixes fish (cod, shrimp, blue mussel, tuna, salmon)

f5 f10 f18 f26 f40 f48 f84 f94 f210

rye sesame brazil nut pork tuna onion kiwi pear pineapple

Animals and Insects d1 house dust mite i1 honey bee venom i3 common wasp venom f5 rye e3 horse dander e5 dog dander e1 cat dander ex1 mixed animal (cat, dog, horse and cow dander) ex70 mixed rodent (guinea pig, rabbit, hamster, epithelium, rat, mouse) ex71 mixed feathers (goose, chicken, duck, turkey feathers) Pollens Rw203 tx1

rape seed pollen gx3 mixed grass pollen (sweet vernal, rye, timothy cultivated rye, velvet grass) mixed tree pollen (box-elder, silver birch, oak, elm, walnut)

Drugs c1 c6

Penicilloyl G Amoxicilloyl

Occupational k82 latex e73 rat epithelium Moulds m3 mx1

c2 Rc202

Penicilloyl V Suxamethonium

c5

Ampicilloyl

e71 e74

mouse epithelium rat urine

e72

mouse urine

Aspergillus mixed moulds (Penicillium notatum, Cladosporium herbarum, Aspergillus fumigatus, Alternaria alterata)

Other allergens may be available. Please contact laboratory for further details.

Diagnosing Allergy: Interpreting the Results Figure 2 can be used to help interpret the results of these investigations. In essence, it demonstrates that the higher the level the more likely it is that the individual is to experience clinical symptoms on exposure to the allergen. A reading of <0.35ku/L is commonly used as a cut-off level below which it is unlikely that clinical problems are likely to be associated with the particular allergen in question. It is important to note that whilst levels of >0.35ku/L incrementally suggest a greater risk of clinical problems manifesting, these levels give no indication of the likely severity of the reaction. The risk of severe reactions therefore needs to be assessed from the clinical picture. In summary: • A positive history + raised specific-IgE = Allergy • A negative history + normal specific-IgE = No allergy

IgE Antibody Levels vs. Allergic Desease: 100 -

Inhalant allergens

Proportion with symptomatic allergy [Probability %]

Food allergens 80 -

60 -

40 -

The curves are generated with data obtained from 7 clinics in Europe and the US (5147 and 1882 test results for inhalant and food allergens respectively).

20 -

0.3

100

IgE antibody concentration [kUA/I]

Worked Clinical Scenario The following clinical case from a typical general practice consultation aims to illustrate how the above approach can be employed in everyday practice. Presenting complaint: • 4 year old Tom had what Mum describes as “an allergic reaction on biting a cookie”. Mum is keen to know what he is allergic to so as to avoid the allergen in the future. Allergy-focused history: • On closer questioning, Mum reports that Tom was not quite right almost immediately following his first bite. He spat out the cookie, but still developed swelling of his lips, a widespread urticarial rash and vomiting. • He was rushed to the local A&E, but by the time they got there the reaction was already subsiding; he was treated with oral antihistamines and observed for a few hours before being discharged. • He has a past medical history of eczema, but nil else of note. • There is a family history of allergic problems: Mum had eczema as a child and now has asthma; Tom’s older brother has hay fever. • Further enquiries reveal that the cookie contained three possible common food allergens: milk; eggs; and pecan nuts. He has subsequently had both milk and eggs with no problems, but has not been re-exposed to pecan nuts. Investigations: • A specific-IgE is ordered to pecan nuts and an accompanying total IgE. These show that specific-IgE is moderately raised with a near normal total IgE.

Diagnosis: • The combination of a positive clinical history and raised specific-IgE to the likely allergen confirm that this is a case of IgE-mediated food allergy. Management: • Mum was advised of the importance of avoiding pecan nuts and given detailed advice of the foods that are liable to contain pecan nuts. • It was also explained that all tree nuts and peanuts should also be avoided because of the risk of cross-reactivity and cross-contamination during food processing. • She was given a supply of antihistamines for use in the context of accidental re-exposure. • Reactions to tree nuts can be very severe and given the immediate onset of symptoms with minimal exposure Tom was judged to be at high risk of anaphylaxis. • It was therefore explained that in the context of any further reactions, should breathing difficulties ensue or there are any signs of cardiovascular compromise (e.g. fainting) then medical help should urgently be sought. • He was also referred to the Paediatric Allergy Clinic, The Royal Hospital for Sick Children for an assessment of whether he should be issued an adrenaline auto-injector.

When to Refer The following are examples of contexts in which you may wish to seek a specialist assessment: • Discordance between the clinical history and the test results. In particular, if there is a history clearly indicative of an IgE-mediated reaction, but a negative test; in such cases, challenge tests may need to be performed. • Food allergy in those with asthma as the risk of life-threatening reactions is high. • Poor response to standard treatments. • Severe allergic reaction with cardiovascular and/or respiratory involvement i.e. anaphylaxis.

Local Allergy Clinics • Paediatric Allergy Clinic, The Royal Hospital for Sick Children, Edinburgh. • Paediatric Dietetics, The Royal Hospital for Sick Children, Edinburgh. • Paediatric Allergy Clinic, St John’s Hospital, Livingston. • Dermatology Clinic, Royal Infirmary, Edinburgh (will see adult allergy patients and perform skin prick tests and patch testing).

Other Local Contacts and Sources of Support • Allergy and Respiratory Research Group, The University of Edinburgh, Teviot Place, Edinburgh, EH8 9DX. • National Network, Children’s and Young People’s Allergy Network Scotland (CYANS) www.cyans.org.uk/

Further Information The following are selected useful sources of additional information and support: Allergy Academy: www.allergyacademy.org Allergy care pathways for children - information for health professionals: http://www.rcpch.ac.uk/child-health/researchprojects/carepathways-children-allergies/information-health-professionals/all Allergy Identification and Management (AIM) resources for healthcare professionals: http://www.allergyeducation.co.uk/hcp/ Allergy UK: http://www.allergyuk.org/ Anaphylaxis Campaign: http://www.anaphylaxis.org.uk/ Asthma UK: http://www.asthma.org.uk/ National Eczema Society: http://www.eczema.org/ NICE Guidelines on Atopic eczema in children: http://publications.nice.org.uk/atopic-eczema-in-children-cg57 NICE Guidelines on Food allergy in children and young people: http://guidance.nice.org.uk/CG116 UK Resuscitation Council, Anaphylaxis Guidelines: http://www.resus.org.uk/pages/reaction.pdf

Visit the eAllergy Helpdesk for practical help with the diagnosis and management of allergic problems in primary care: www.allergyeducation.co.uk/hcp/helpdesk 15

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Led by Professor Aziz Sheikh