ALLERGY TESTING USER GUIDE Allergy testing by Specific IgE QUEEN’S & KING GEORGE HOSPITALS Q Pulse record: Pathology3552 Revision: 3 Page 1 of 8 Approved / Authorised by: Zahra Khatami Last updated May 2017 These pathways do not apply to diagnosis of anaphylaxis, where referral for expert advice is always recommended Clinical Diagnosis of Allergy Clinical Diagnosis of Allergy No clear History for target allergen Clear and Consistent History for target allergen Suspect Chronic Spontaneous Urticaria Angioedema and treat with non-drowsy antihistamines up to 4x normal doses/day If no response 1.Avoidance e.g. HDM/Pets 2.Topical therapies 3.Systemic therapies Refractory Asthma or Respiratory Symptoms GI symptoms Consider contact sensitivity & nonIgE mediated food intolerance Routine advice: Avoid Soaps, Emollients +/Topical steroids Rule out IBS Test for Coeliac Consider exclusion of non-staple foods Symptom Control? YES Childhood Eczema Rhinits Sinusitis Conjuncitivitis 1.Topical therapies 2.Systemic therapies NO Symptom Control? Consider specialist referral to consider immunotherapy NO YES Review History: Consistent triggers Yes Refer to specialist No SPT to Confirm sensitization ?Skin Test available. If not, sIgE Specific IgE an alternative in selected cases SPT – Skin Prick Test sIgE – Specific Immunoglobulin-E HDM – House Dust Mite IBS – Irritable Bowel Syndrome Common Diagnostic Pathway Perennial; HDM Cat Dog Seasonal; Tree Grass Mould Food Mix Food Mix HDM Alternative Diagnostic Pathway Q Pulse record: Pathology3552 Revision: 3 Page 2 of 8 Approved / Authorised by: Zahra Khatami Last updated May 2017 Perennial; HDM Cat Dog Seasonal; Tree Grass Mould Allergies are increasing rapidly; in the UK, 1 in 4 people suffers from an allergy at some time in their life. It is estimated that allergic conditions are increasing at roughly 5 per cent a year. Asthma, eczema, hay fever and allergic rhinitis are all atopic conditions. Allergy may contribute to the pathology in these conditions but this is varied in different subtypes of these1 diseases to the point that in some individuals allergy to specific allergens does not play any role in the pathology. Total Serum IgE was the original screening test for allergy, but it has been superseded by newer more specific tests. Total IgE levels are associated with having an atopic condition. However it may be raised in parasitic infections, immune diseases, in cigarette smokers, with high levels of alcohol consumption and in certain cancers. Levels increase from infancy to adolescence when they plateau and then slowly decrease with old age. Setting a cut-off that accounts for age, sex and racial or ethnic origin is not always reliably achieved. The sum total of allergen specific IgE results in an individual does not add up to the measured total IgE. When should I consider allergy testing? Testing for allergic sensitisation by skin testing or specific IgE should as with all diagnostic tests aim to enhance diagnostic probability, modify or target therapy or act as a guide to an individual’s response to treatment. NICE guidelines state that all patients with a history of anaphylaxis have to be referred to a specialist to be investigated. A large proportion of patients presenting with allergic-type symptoms do not have an allergy to specific allergens. For these patients the symptoms are recurrent and do not seem to be linked to specific and consistent triggers. These patients commonly have chronic urticaria angioedema (CUA), 95% of whom have the spontaneous or idiopathic variety. The British Society for Allergy and Clinical Immunology guidelines on CUA recommend using up to 4x normal doses of a non-drowsy anti-histamine. The length of treatment should be based on the severity of the disease. The antihistamines can be discontinued after a one week period of being asymptomatic but may need to be restarted if they have not been used for long enough. In 5% of patients, the cause for the recurrent presentation of CUA could be another underlying condition. Hence, the history, examination and investigations should focus on ruling out connective tissue disease, lymphoproliferative disease, autoimmune thyroid disease, infections, colonisation with H. Pylori and in particular in patients with a history of travel and raised eosinophils a parasitic infection needs to be ruled out. Raised eosinophils in association with urticaria could also be a sign of systemic mastocytosis or eosinophilia . If patients fail to respond to treatment or there are features of these underlying causes, treat the underlying cause or consider referral to immunologists or allergists instead of performing allergy tests. For the individuals with allergic symptoms, that recur only after specific triggers (eg. everytime within 1-2 hours of eating the same food), the candidate allergen(s) can be determined by taking a full history, and either avoidance strategies implemented (e.g. house dust mite avoidance), or targeted therapy initiated. Allergen testing by skin prick test or specific IgE may be warranted where avoidance is not possible (e.g. wheat which is in many foods and is hard to exclude), where symptoms are severe (e.g. anaphylaxis to peanut) or if objective confirmation is required (e.g. occupational allergy). Q Pulse record: Pathology3552 Revision: 3 Page 3 of 8 Approved / Authorised by: Zahra Khatami Last updated May 2017 How should I test? The results of in-vitro immunoassays for allergen-specific IgE usually correlate well with invivo test such as skin tests, bronchial provocation or conjunctival challenge, however, for some allergens up to 40% of skin test positive individuals will not be identified by blood tests. When the allergen of interest has been associated with a severe or life threatening reaction (e.g. anaphylaxis to penicillin), in-vivo confirmation should always be sought if the specific IgE is not detectable. (Please note that as mentioned above, if there is a history of anaphylaxis the NICE guidelines state that the patient should be seen by a specialist) Considerations for Performing Skin Prick Testing Indications for Measuring Specific IgE 1. 1. 2. 3. 4. Greater sensitivity than sIgE Immediate results Cheaper than sIgE determination Determination of cross-reactivity 2. 3. 4. 5. Avoiding risk of anaphylaxis in suggestive history Multiple allergen candidates (Unclear history) Patient taken antihistamine or corticosteroids Non-co-operative patient (including unconscious) High total IgE (Parasitic infection) Given the above, clinicians are encouraged to use skin testing where available as a more sensitive and immediate/cost effective method for diagnosing allergic sensitisation. What should I test for? Take a full history focussing on timing of symptoms (day, night, seasonal or perennial), site affected (skin, gut, eyes),. What does the patient think is causative (in the majority of the cases of true allergy the patient will have identified the allergen). Has exclusion or avoidance been attempted? If the history identifies the allergen, testing is not usually required. Testing can be performed to support the history or for specialists to determine the type of allergy. i.e. some allergen components or patterns of sensitisation are associated with a more severe outcome. Patients who have recurrent symptoms without an obvious seasonal or temporal pattern to a potential allergen should not be tested as there is a high rate of false positives with both SPT and sIgE methods which could lead to giving unnecessary avoidance advice. It is important to mention here that SPT and sIgE test can only be used for immediate type hypersensitivity reactions (type I). Therefore, to suspect a temporal relationship a trigger needs to have occurred within few hours, not longer, except for allergy to meats (Beef, Pork, chicken, lamb) where there could be a delay of up to 4-6 hours. Where there is a high index of suspicion, the pre-test probability is raised which would mean that a positive result is more reliable as the positive predictive value of a test is raised. Q Pulse record: Pathology3552 Revision: 3 Page 4 of 8 Approved / Authorised by: Zahra Khatami Last updated May 2017 When testing is indicated, panels have been set-up which measure multiple allergens in one test. Wherever possible please request the specific allergen that has been implicated in the patient’s history, since this reduces the number of tests. This not only reduces cost, but avoids the difficulty of interpreting sensitisation that does not correlate with clinical symptoms. 1. Respiratory panels For direct confirmatory testing please request the specific implicated allergen. Where there is a history of wheeze and no-specific identifiable allergen, consider testing for house dust mite alone. If seasonal exacerbations choose either tree or grass panels, since the seasons for these allergens peak at separate times of year. Patients who are sensitised to multiple allergens may have responses to both, please specify. Where moulds are a candidate please specify. Pet related symptoms; please specify the animal and symptoms. If Allergic Bronchopulmonary Aspergillosis (ABPA) is suspected request sIgE and precipitins (IgG) to Aspergillus. Where this is specified, other allergen panels will not normally be performed unless specific clinical grounds are given. 2. ENT (Rhinitis) panels Seasonal rhinitis: For direct confirmatory testing please request the specific implicated allergen. Where there is a history of perennial rhinitis and no-specific identifiable allergen, consider testing for house dust mite alone. If seasonal exacerbations choose either tree or grass panels, since the seasons for these allergens peak at separate times of year. Patients who are sensitised to multiple allergens may have responses to both, please specify. If there are pet related symptoms please specify the animal and symptoms. 3. Food Related Symptoms Food intolerance and food allergy can usually be distinguished on clinical history, however, in paediatric practice when this is less clear the food panels which contain; egg, milk, fish, wheat, peanut, soybean are usually sufficient. Where gluten containing foods are considered to be causative, please specify if IgA TTG to rule out Coeliac disease is also required. 4. Atopic Dermatitis As with gastrointestinal investigation the investigation of atopic dermatitis particularly in younger children may require the investigation of several allergens, the commonest are grouped in the food panel with the addition of HDM testing. It is now thought that eczema specially in adults in on the whole not associated with food allergy. Interpretation of Results Positive Results In general the lower grade (<2) results to food allergens or moulds are significant. This means that the patient may be sensitised to a food allergen but whether this sensitisation has a clinical implication depends on the history. i.e. positive specific IgE to apples could be because of sensitisation to a heat resistant or a heat sensitive component of apple. The former may result in an anaphylactic reaction whereas the latter could cause oral allergy syndrome or have no clinical manifestation. On the other hand for inhaled allergens they are usually not so pertinent. If the total IgE is high (>1000 kU/L) low grade (< grade 2 or <0.7 Ku/L) specific allergens are of limited significance. As with skin prick testing, a positive RAST indicates sensitisation, not that allergy exists, which takes us back to the necessity for a good history. Q Pulse record: Pathology3552 Revision: 3 Page 5 of 8 Approved / Authorised by: Zahra Khatami Last updated May 2017 GRADE 0 1 2 3 4 5 6 UNITS KU/L <0.35 0.36-0.7 0.7-3.5 3.5-17.5 17.5-50 50-100 >100 INTERPRETATION Negative Weak Positive Positive Positive Strong Positive Strong Positive Strong Positive Negative results Shortly after anaphylaxis the specific IgE may become negative in serum for days and sometimes weeks. Patients with suspected anaphylaxis should have mast cell tryptase sent 1-2 hours and 24 hours after the attack to confirm the diagnosis and specific IgE should be tested 1 month later. Not all hypersensitivity is Type I mediated and so, when patients (adults or children) present with eczema (which may be Type IV hypersensitivity) apparently related to food, negative skin tests or specific IgE do not represent a useful diagnostic test. Allergen Information House Dust Mite Avoidance is key. Most patients report symptom improvement on holiday to hot climates with low humidity or at high altitude (no HDM found at these locations). Exclusion by avoiding dusty household items, damp dusting and using vacuum cleaners with HEPA filter, no carpets (hard flooring), no curtains (Blinds kept dusted), keep mattress aired and covered (same for pillows and duvets). Dog/Cat Mild symptoms can be managed by restricting the animal to non-sleeping part of the house, decrease dander by someone grooming dogs outside, wash pet bedding regularly, use a HEPA filtered vacuum cleaner. More severe symptoms especially significant worsening of asthma requires complete avoidance. It may take months for all dander traces to go after removing a pet from a house. Desensitisation is rarely successful but may be considered to delay time to onset of symptoms following unavoidable exposure. Tree, Grass, Weed and Mould The allergen can be identified by the seasonal timing of symptoms. Tree season is March/April when they flower, Grasses is longest from April to September. Weeds flower in the Autumn. Moulds are often on house plants and may give rise to perennial symptoms. Peanut Whilst all food allergy is relatively rare compared to aero-allergen related symptoms, anaphylaxis is often encountered in cases of true allergy. Avoidance is difficult and requires careful reading of labels, avoidance of processed foods and awareness that all that purports Q Pulse record: Pathology3552 Revision: 3 Page 6 of 8 Approved / Authorised by: Zahra Khatami Last updated May 2017 to be cashew or walnut may actually be pressed peanut (it’s a cheap filler food). allergies with anaphylaxis require Epipen assessment. All food Fish and Shellfish Anaphylaxis again common and very quick onset. The allergen seen in Cod is found in most fish Wheat When a candidate should always prompt testing for Coeliac, remembering that the serological test for this is an IgA test and IgA deficiency is common in individuals with Coeliac. Wheat is another cheap filler and difficult to avoid. May exacerbate eczema in children or cause severe GI symptoms. Some tablets contain wheat and may cause intolerance to multiple drugs. Latex Less of a problem occupationally now that latex free gloves are largely used in healthcare and other commercial settings. Symptoms may be contact hypersensitivity with dermatitis or urticaria, rhinoconjunctivitis, asthma or anaphylaxis. In the case of contact hypersensitivity, the specific IgE and SPT may be negative, in which case patch testing by a dermatologist may confirm the diagnosis. A negative specific IgE or SPT needs to be validated by skin and mucosal latex challenge which should be done in a dedicated challenge clinic. Avoid gloves, shoes, condoms, balloons, car tyres, bottle teats. In occupational settings use latex free, powder free gloves and note that some individuals develop a subsequent sensitivity to the vulcanizing agent and will still react to vinyl gloves. Cross reactivity occurs to a number of foods notably banana, avocado, melon, kiwi, spinach and chestnut. Special surgical preparation for a latex free theatre is required for the highly sensitised patient. Indication for referral from Primary Care Where symptoms are significant, severe or do not respond to basic therapy, specialist referral should be sought. Usually this is for patients who have received topical corticosteroids +/sodium cromoglycate and systemic antihistamine, but are still symptomatic. Patients who require frequent systemic corticosteroids to control symptoms should be referred or advice sought re: additional steroid sparing agents. All patients with anaphylaxis or suspected anaphylaxis should be assessed by a physician with relevant allergy expertise. Contact Dermatitis and Delayed Type Hypersensitivity Patients who complain of a delayed or non-urticarial rash following cutaneous exposure to compounds, including metals (e.g. nickel), usually have a type IV or delayed type hypersensitivity. Since this is not specific IgE mediated, the estimation of specific IgE is not of utility in such cases. Diagnosis of sensitization is usually achieved by patch testing with the relevant material and appropriate controls. Investigation of Suspected Anaphylaxis All patients with suspected anaphylaxis should have a serum sample for mast cell tryptase taken as soon as possible after the event and then 2-4 hours later. If possible a further sample at 12- 24 hours should be taken (baseline). Patients should be given advice regarding delayed/relapsed symptoms and given a pair of adrenaline autoinjectors (NICE Guidance) and followed up in an allergy clinic. Definitive diagnosis by specific allergy testing should be made Q Pulse record: Pathology3552 Revision: 3 Page 7 of 8 Approved / Authorised by: Zahra Khatami Last updated May 2017 where possible, with avoidance of possible precipitants in the meantime. Full anaesthetic records should accompany all per-operative related reactions following the BSACI guidelines. Note that specific IgE testing is insensitive for up to 6 weeks following an acute drug reaction and from 6 months after a drug reaction. Useful Websites For clinicians and Patients British Society Allergy & Clinical Immunology http://www.bsaci.org/ For Patients The anaphylaxis campaign http://www.anaphylaxis.org.uk/ Allergy UK http://www.allergyuk.org/ Q Pulse record: Pathology3552 Revision: 3 Page 8 of 8 Approved / Authorised by: Zahra Khatami Last updated May 2017
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