Biochemistry / Immunology allergy testing user guide

ALLERGY TESTING
USER GUIDE
Allergy testing by
Specific IgE
QUEEN’S & KING GEORGE HOSPITALS
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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
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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been superseded by newer more specific tests.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).
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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.
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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.
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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
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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
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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/
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