Diagnosing Allergy Introduction
• There is a wide array of diagnostic modalities available
• Skin tests are of paramount importance especially for IgE mediated and delayed allergy
• As immunologic diagnostic technology advances, in‐vitro tests have assumed greater significance
Introduction
• Lymphocyte functional assays are also recently being used for confirmation of humoral/cell‐
mediated conditions as well as delayed hypersensitivity reactions
• An increase in eosinophils and their products often occurs in the immediate‐ and late‐ phase responses
• Basophil activity can be assessed by the basophil activation test
But first……the basics
ATOPY
ALLERGY
?
HYPERSENSITIVITY
But first……the basics
ATOPY
ALLERGY
?
HYPERSENSITIVITY
Definitions
Hypersensitivity
• Objectively reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by normal persons
But first……the basics
ATOPY
ALLERGY
?
HYPERSENSITIVITY
Definitions
Allergy
• A hypersensitivity reaction that is mediated by the immune system
• The reaction can be antibody‐ or cell‐mediated
• Most often the antibody responsible for the reaction is IgE
But first……the basics
ATOPY
ALLERGY
?
HYPERSENSITIVITY
Definitions
Atopy
• A familial/personal tendency to become sensitised and produce IgE antibodies in response to ordinary exposure to allergens
• As a result, these individuals may develop the typical symptoms of asthma, allergic rhinitis or atopic eczema
Diagnosis
Principles
History
Physical examination
Special investigations
History
• In no other medical disease is history more important
• Without a thorough history one cannot appropriately investigate
History
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Main complaint
Age of onset
Seasonality
Time of onset
Aggravating factors
Relieving factors
Family history of allergies
Home/work/school environment
Medications
Dietary preferences
Occupation/hobbies
Physical examination
General – Shiners, Dennie’s lines, Nasal crease, Atopic eczema, Nutritional status
Systematic examination
Physical examination
Shiners
Physical examination
Dennie’s lines
Physical examination
Nasal crease
Special investigations
Why should allergy tests be done?
• To identify and avoid trigger allergens
• To be able to provide relevant and effective therapy
• To be able to choose effective immunotherapy/ desensitisation which is the only disease‐modifying therapy available for allergy
• To identify patients whose symptoms are not due to allergy and thus prevent unnecessary drug therapy/unnecessary allergen avoidance
Special investigations
Before ordering allergy tests, ask yourself…..
• Is the patient allergic?
• What are the clinically relevant allergens?
• Does the allergy contribute to the patient’s symptoms?
• What is the suspected mechanism of allergy?
Special investigations
• There are several different mechanisms of allergy
• As a result, there is a huge range of tests to diagnose these various mechanisms
• A negative test only excludes that particular mechanism of allergy, but not other types
Special investigations
• It is imperative to distinguish between allergic reactions that are mediated by the immune system vs non‐allergic reactions such as intolerances, toxic effects and side‐effects
• Obviously we cannot do allergy testing for these reactions as they are not mediated by the immune system
Hypersensitivity
Non Allergic
Allergic
IgE mediated
(side effect, toxic effect, intolerance)
Non IgE
Mediated
Mechanisms
• IgE mediated reactions usually occur within minutes, up to 2 hours after exposure to the allergen. Classic symptoms include :
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Skin: itch, erythema, urticaria, angioedema
Resp: rhinitis, cough, wheeze
GIT: diarrhoea, vomiting
Anaphylaxis Mechanisms
• Non‐IgE mediated reactions are mediated by other mechanisms that may include T‐cells, basophils and eosinophils
• Symptoms may be immediate but are generally more delayed Classic symptoms include:
eczema, urticaria, maculopapular rashes, GIT symptoms, rhinitis, respiratory and mucus membrane involvement
What tests are available?
In vivo
• Skin prick tests
• Patch tests
• Provocation tests
What tests are available?
In vitro
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Allergen specific IgE (ImmunoCAP®)
ISAC
Tryptase
Basophil activation tests (flow‐CAST)
T‐cell proliferation assays (MELISA)
Nasal eosinophils
Skin prick tests
• First described by Dr Charles Blackley in 1867
• Reliable, safe and cost effective in diagnosing IgE‐mediated allergy • Optimal results depend on quality of the extracts and proficiency of the tester
• Useful for : foods, aeroallergens, a few drugs and chemicals
Skin prick tests
Technique
• Allergen drops are placed on the skin
• A lancet, with a shoulder to prevent excess penetration into the dermis, is then passed through the droplet at 90° to the skin
• Each lancet must be discarded after a single use
Skin prick tests
• Various devices may be used
• No clear‐cut advantage
Skin prick tests
Drugs that may affect SPT results
• Antihistamines ‐ 1st gen stop for 3 days ‐ 2nd gen up to 7 days
• Doxepin/Imipramine – 6 days
• Ranitidine – 1 day
• Methotrexate – 5‐7 days
• Repetitive/prolonged application of high dose topical steroids – 3 weeks
Skin prick tests
• Use volar forearm or back
• Space droplets 2‐2.5cm apart
• Avoid 3cm from antecubital fossa and 5cm from wrist
• Avoid areas of active dermatitis
• Earlier study reported smaller wheal sizes in children <2yrs; a more recent study demonstrated good reliability in infants
Skin prick tests
• Extracts used should be of known composition and potency
• Standardised commercial extracts are available for most aeroallergens and some food allergens
• The quality of the extract is important
Skin prick tests
• Store extracts at <4° to maintain stability
• Always use a positive (histamine) and negative (glycerinated saline) control
• In some cases, SPTs done with fresh fruit/foods may be more helpful using the prick‐prick method
• Perform only where resuscitation equipment is available
• Small, but definite risk of systemic reactions
Skin prick tests
Reading the results wheal
flare
• Peak reactivity is 15‐20 minutes • Wheal and flare is recorded in millimetres
• Qualitative scoring (1+ ‐ 4+ is no longer used)
• A positive result is a mean wheal diameter ≥3mm than the negative control
Skin prick tests
Interpreting the result
• A positive test indicates the presence of specific IgE antibody
• It does not indicate clinical allergy
• The diagnostic value lies in comparing the results to the history of symptoms given by the patient
Skin prick tests
Interpreting the result for inhalant allergy
Comparing SPT to nasal provocation challenges
• Sensitivity 85‐87%
• Specificity 79‐86%
Skin prick tests
Interpreting the result for food allergy
Comparing SPT to food challenge
• Sensitivity and specificity depends on age of child and type of food
Skin prick tests
Interpreting the result for food allergy
Allergen
95% PPV <2yr
95% PPV >2 yr
Cow’s milk
6mm
>8mm
Egg
5mm
>7mm
Peanut
4mm
>8mm
PPV = positive predictive value Ref: Sporik et al
Skin prick tests
Common aeroallergens in South Africa
• House dust mite (Der p 1 and Der f 1)
• Rye and Bermuda grass
• Aspergillus, alternaria, cladosporium
• Cat
• Dog
Skin prick tests
Others to consider
• Farming areas – zea mayz pollen, horse, blomia tropicalis
• Health care worker – latex, chlorhexidine
• Grain industry – storage mites, wheat, rye
• Tree and weed pollens are regional
ImmunoCAP®
• First assay for specific IgE was reported in 1967 and was called the RAST
ImmunoCAP®
• Technical improvements have resulted in a uniform method of reporting IgE antibody results in quantitative kU/l
ImmunoCAP®
Interpreting the results
• As with SPT, a positive test indicates the presence of IgE antibody but not clinical allergy
• Interpretation requires correlation with history, physical examination and occasionally observation after exposure to the allergen concerned
ImmunoCAP®
Interpreting the results
• For inhalant allergens, a result of >0.35kU/l is considered positive
• Sensitivity 60‐80% and specificity 90%
• For food allergy, >0.35 is also the cutoff but clinical reactivity is age dependent and interpretation is guided more by history ImmunoCAP®
Interpreting the results for food allergy
IgE values at which there is a 95% chance of clinical reaction
Allergen
Child (kU/L)
<2yrs (kU/L)
Egg
7 2
Cow’s milk
15
5
Peanut
14
Fish
20
Soy
30
Wheat
26
Sampson JACI 2001 (107) 891‐896
SPT vs specific IgE
SPT
Specific IgE
Inexpensive
More expensive
Immediate results
Delayed results
Unable to perform if extensive Not influenced by skin disease skin disease/dermatographism or dermatographism
Affected by many drugs
Not affected by drugs
Small risk of anaphylaxis
No risk of anaphylaxis
Limited range of allergens
Wide range of allergens
Technique dependent
Not technique dependent
SPT vs specific IgE
SPT
Specific IgE
Inexpensive
More expensive
Immediate results
Delayed results
Unable to perform if extensive Not influenced by skin disease skin disease/dermatographism or dermatographism
Affected by many drugs
Not affected by drugs
Small risk of anaphylaxis
No risk of anaphylaxis
Limited range of allergens
Wide range of allergens
Technique dependent
Not technique dependent
SPT vs specific IgE
SPT
Specific IgE
Inexpensive
More expensive
Immediate results
Delayed results
Unable to perform if extensive Not influenced by skin disease skin disease/dermatographism or dermatographism
Affected by many drugs
Not affected by drugs
Small risk of anaphylaxis
No risk of anaphylaxis
Limited range of allergens
Wide range of allergens
Technique dependent
Not technique dependent
Multi‐allergen IgE antibody screening assays
Used to rule allergy in or out
• Phadiatop – screening test for inhalant allergy
• Fx5 – screening test for food allergy
Multi‐allergen IgE antibody screening assays
Phadiatop
• Reported as positive or negative
• Sensitivity 93% • Specificity 89%
• A positive test indicates that the patient may be sensitive to any of house dust mites, grass pollens, tree and weed pollens, moulds, cat or dog dander
• A negative test means it is highly unlikely that the symptoms are due to IgE‐mediated allergy
Multi‐allergen IgE antibody screening assays
Fx5
A positive test indicates that the patient may be sensitive to any of:
• egg white
• cow’s milk • peanut
• wheat • fish • soya
Component testing
• The identification of cross‐reacting allergens (pan allergens) has led to a new concept in allergy diagnosis Component‐resolved diagnostics
Component testing
• Natural allergen sources contain many different proteins
• Not all are allergenic
• Some occur in many different foods and pollens
Component testing
Component testing
Component testing
Panallergens include:
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CCD (cross‐reacting carbohydrate determinants)
Profilins
PR‐10 (Pathogenesis‐related protein) Lipid transfer protein (LTP) Storage proteins
Component testing
Provides additional diagnostic insight regarding • Prediction of risk of severe reactions (risk assessment)
• Heat‐stability/bio‐degradability of certain allergens
• Which patients will best respond to a course of immunotherapy
• Prediction of cross reactivity
Component testing
Risk assessment
• Certain components predict a higher risk of
developing anaphylaxis
• The protein AraH2, of peanut origin, is such a protein
• Those sensitised to LTP or storage proteins have a higher risk of reaction than those sensitised to CCD
• Obvious clinical implications – decreases the need for food challenges
Component testing
Heat stability/lability
• PR‐10 proteins and profilins are heat sensitive
• Implication is that some allergic patients may be able to tolerate these foods in a cooked form
Component testing
Selection of patients for immunotherapy
• Immunotherapy is more successful in patients who are sensitised to the specific components
found in each vaccine
Pan‐allergens
CCD
PROFILIN
PR‐10
LTP
STORAGE
PROTEIN
Stability to heat/digesti
on
Stable but still not usually
clinically relevant
Sensitive Sensitive Stable
Very stable Location
N/A
Throughout Mainly pulp
fruit
Severity of reaction
Usually no symptoms
None or mild localised
Symptoms
Usually none
None or oral OAS and allergy systemic
syndrome
symptoms
May May React to React to tolerate tolerate cooked food cooked food
cooked food cooked food
Usually
mild, may be severe
Mainly peel
Seed/nut/ke
rnel
Systemic and severe reactions
Severe
systemic reactions
Systemic
Severe
systemic, anaphylaxis
Pan‐allergens
CCD
PROFILIN
PR‐10
LTP
STORAGE
PROTEIN
Stability to heat/digesti
on
Stable but still not usually
clinically relevant
Sensitive Sensitive Stable
Very stable Location
N/A
Throughout Mainly pulp
fruit
Severity of reaction
Usually no symptoms
None or mild localised
Symptoms
Usually none
None or oral OAS and allergy systemic
syndrome
symptoms
May May React to React to tolerate tolerate cooked food cooked food
cooked food cooked food
Usually
mild, may be severe
Mainly peel
Seed/nut/ke
rnel
Systemic and severe reactions
Severe
systemic reactions
Systemic
Severe
systemic, anaphylaxis
Pan‐allergens
CCD
PROFILIN
PR‐10
LTP
STORAGE
PROTEIN
Stability to heat/digesti
on
Stable but still not usually
clinically relevant
Sensitive Sensitive Stable
Very stable Location
N/A
Throughout Mainly pulp
fruit
Severity of reaction
Usually no symptoms
None or mild localised
Symptoms
Usually none
None or oral OAS and allergy systemic
syndrome
symptoms
May May React to React to tolerate tolerate cooked food cooked food
cooked food cooked food
Usually
mild, may be severe
Mainly peel
Seed/nut/ke
rnel
Systemic and severe reactions
Severe
systemic reactions
Systemic
Severe
systemic, anaphylaxis
Pan‐allergens
CCD
PROFILIN
PR‐10
LTP
STORAGE
PROTEIN
Stability to heat/digesti
on
Stable but still not usually
clinically relevant
Sensitive Sensitive Stable
Very stable Location
N/A
Throughout Mainly pulp
fruit
Severity of reaction
Usually no symptoms
None or mild localised
Symptoms
Usually none
None or oral OAS and allergy systemic
syndrome
symptoms
May May React to React to tolerate tolerate cooked food cooked food
cooked food cooked food
Usually
mild, may be severe
Mainly peel
Seed/nut/ke
rnel
Systemic and severe reactions
Severe
systemic reactions
Systemic
Severe
systemic, anaphylaxis
Pan‐allergens
CCD
PROFILIN
PR‐10
LTP
STORAGE
PROTEIN
Stability to heat/digesti
on
Stable but still not usually
clinically relevant
Sensitive Sensitive Stable
Very stable Location
N/A
Throughout Mainly pulp
fruit
Severity of reaction
Usually no symptoms
None or mild localised
Symptoms
Usually none
None or oral OAS and allergy systemic
syndrome
symptoms
May May React to React to tolerate tolerate cooked food cooked food
cooked food cooked food
Usually
mild, may be severe
Mainly peel
Seed/nut/ke
rnel
Systemic and severe reactions
Severe
systemic reactions
Systemic
Severe
systemic, anaphylaxis
Pan‐allergens
CCD
PROFILIN
PR‐10
LTP
STORAGE
PROTEIN
Stability to heat/digesti
on
Stable but still not usually
clinically relevant
Sensitive Sensitive Stable
Very stable Location
N/A
Throughout Mainly pulp
fruit
Severity of reaction
Usually no symptoms
None or mild localised
Symptoms
Usually none
None or oral OAS and allergy systemic
syndrome
symptoms
May May React to React to tolerate tolerate cooked food cooked food
cooked food cooked food
Usually
mild, may be severe
Mainly peel
Seed/nut/ke
rnel
Systemic and severe reactions
Severe
systemic reactions
Systemic
Severe
systemic, anaphylaxis
Risk assessment
Component testing for foods
Cow’s milk
Casein
α lactalbumin Bovine serum β lactoglobulin albumin
Bos d 8
Bos d 4, 5
Bos d 6
Makes up 80% of milk protein
Whey proteins
Occurs in milk and beef
Heat stable Heat labile
Heat labile
Heat labile
May tolerate well cooked milk
Reacts to fresh milk
Severe and persistent allergy
Cross‐reacts with
other mammalian milks
Patients react more severely to fresh milk
May tolerate long‐
life milk, hard cheese
Cross reacts with other mammals
Lactoferrin
Component testing for foods
Cow’s milk
Casein
α lactalbumin
β lactoglobulin
Bos d 8
Bos d 4, 5
Makes up 80% of milk protein
Whey proteins
Heat stable Heat labile
Severe and persistent allergy
Cross‐reacts with
other mammalian milks
Patients react more severely to fresh milk
May tolerate long‐
life milk, hard cheese
Component testing for foods
Cow’s milk
Casein
α lactalbumin
β lactoglobulin
Bos d 8
Bos d 4, 5
Makes up 80% of milk protein
Whey proteins
Heat stable Heat labile
Severe and persistent allergy
Cross‐reacts with
other mammalian milks
Patients react more severely to fresh milk
May tolerate long‐
life milk, hard cheese
Component testing for foods
Cow’s milk
Casein
α lactalbumin
β lactoglobulin
Bos d 8
Bos d 4, 5
Makes up 80% of milk protein
Whey proteins
Heat stable Heat labile
Severe and persistent allergy
Cross‐reacts with
other mammalian milks
Patients react more severely to fresh milk
May tolerate long‐
life milk, hard cheese
Component testing for foods Hen’s egg Ovomucoid
Ovalbumin
Egg serum albumin
Gal d 1
Heat stable
Gal d2
Heat labile
Gal d 5
Severe and persistent allergy
Often tolerates well Occurs in yolk, cooked egg (baked cross reacts with egg)
chicken serum albumin in chicken
meat and feathers
Most abundant protein
Component testing for foods
Hen’s egg Ovomucoid
Ovalbumin
Gal d 1
Heat stable
Gal d2
Heat labile
Severe and persistent allergy
Often tolerates well cooked egg (baked egg)
Most abundant protein
Component testing for foods
Hen’s egg Ovomucoid
Ovalbumin
Gal d 1
Heat stable
Gal d2
Heat labile
Severe and persistent allergy
Often tolerates well cooked egg (baked egg)
Most abundant protein
Component testing for foods
Hen’s egg Ovomucoid
Ovalbumin
Gal d 1
Heat stable
Gal d2
Heat labile
Severe and persistent allergy
Often tolerates well cooked egg (baked egg)
Most abundant protein
Component testing for foods
Peanut
Storage proteins
Ara h 1, 2, 3, 6
Profilin
PR‐10
LTP
Ara h 5
Ara h 8
Ara h 9
Heat stable
Heat labile
Risk of anaphylaxis
Marker of Marker of Systemic grass pollen grass pollen and local cross reactivity cross reactivity reactions incl OAS
Cross reacts with other nuts/seeds
Heat labile
Heat stable
Component testing for foods
Peanut
Storage proteins
Ara h 1, 2, 3, 6
Profilin
PR‐10
LTP
Ara h 5
Ara h 8
Ara h 9
Heat stable
Heat labile
Risk of anaphylaxis
Marker of Marker of Systemic grass pollen grass pollen and local cross reactivity cross reactivity reactions incl OAS
Cross reacts with other nuts/seeds
Heat labile
Heat stable
Component testing for foods
Peanut
Storage proteins
Ara h 2
Profilin
PR‐10
LTP
Ara h 5
Ara h 8
Ara h 9
Heat stable
Heat labile
Risk of anaphylaxis
Marker of Marker of Systemic grass pollen grass pollen and local cross reactivity cross reactivity reactions incl OAS
Cross reacts with other nuts/seeds
Heat labile
Heat stable
Component testing for foods
Soya
Storage proteins
PR‐10
Gly m 5, Gly m 6
Gly m 4
Heat stable
Heat labile
Severe systemic reactions
May cause OAS or severe reactions
Associated with birch pollen allergy
Component testing for foods
Soya
Storage proteins
PR‐10
Gly m 5, Gly m 6
Gly m 4
Heat stable
Heat labile
Severe systemic reactions
May cause OAS or severe reactions
Associated with birch pollen allergy
Component testing for foods
Soya
Storage proteins
PR‐10
Gly m 5, Gly m 6
Gly m 4
Heat stable
Heat labile
Severe systemic reactions
May cause OAS or severe reactions
Associated with birch pollen allergy
Component testing for foods
Wheat
Storage proteins
LTP
Omega 5 gliadin
Tri a 19
αβγW gliadins
Tri a 14
Systemic reactions
Severe reactions
Wheat dependent EIA
Persistence of allergy
Persistence of allergy
Wheat dependent EIA
Component testing for foods
Wheat
Storage proteins
LTP
Omega 5 gliadin
Tri a 19
αβγW gliadins
Tri a 14
Systemic reactions
Severe reactions
Wheat dependent EIA
Persistence of allergy
Persistence of allergy
Wheat dependent EIA
Component testing for foods
Wheat
Storage proteins
LTP
Omega 5 gliadin
Tri a 19
αβγW gliadins
Tri a 14
Systemic reactions
Severe reactions
Wheat dependent EIA
Persistence of allergy
Persistence of allergy
Wheat dependent EIA
Component testing for foods
Fish and shellfish
FISH
SHELLFISH
Parvalbumin
Cyp c 1 and Gad c 1
Tropomyosin
Heat stable
Broad cross‐reactivity
Heat stable muscle protein
Lower levels in various species
eg tuna
Crustaceans, molluscs, cockroach, mites – risk of cross reactivity
Component testing for foods
Fish and shellfish
FISH
SHELLFISH
Parvalbumin
Cyp c 1 and Gad c 1
Tropomyosin
Heat stable
Broad cross‐reactivity
Heat stable muscle protein
Lower levels in various species
eg tuna
Crustaceans, molluscs, cockroach, mites – risk of cross reactivity
Component testing for foods
Fish and shellfish
FISH
SHELLFISH
Parvalbumin
Cyp c 1 and Gad c 1
Tropomyosin
Heat stable
Broad cross‐reactivity
Heat stable muscle protein
Lower levels in various species
eg tuna
Crustaceans, molluscs, cockroach, mites – risk of cross reactivity
Component testing for animals
• Cross reactions can occur between animals • The primary sensitiser should be identified before starting immunotherapy
• Cat – Fel d 1
• Dog – Can f 1, 2 and 5
• Horse – Equ c 1
• Equ c 1 and Fel d 4 cross react (both are lipocalins) – important when deciding on horse immunotherapy
Component testing
• Should not be used for screening or first‐line tests
• Useful as a second‐line test in poly‐sensitized patients to distinguish genuine sensitivity from cross‐reactions
• Available as individual components or on multiplex platforms such as the ISAC test
ISAC
Immuno solid‐phase allergen chip
‐ A multiplex microchip array
‐ IgE is detected to multiple recombinant allergen components
‐ Requires only 20 µl serum to measure specific IgE
to 112 different allergens
ISAC
What is the difference between the ISAC and standard IgE tests?
• ImmunoCAP® test is based on allergen extracts prepared from biological raw materials
• Major and minor allergen components are not always standardised
• ISAC ‐ recombinant allergen components produced in a laboratory ISAC
Useful for
• Patients with multiple allergies
• Patients with combined food and inhalant allergies
• Patients with suspected allergen cross‐reactivity
• Patients who require a more in‐depth interpretation of their allergies
ISAC
Drawbacks:
• Not useful for drug and occupational allergy
• Does not contain every allergen, thus history is still the most important guide as to which test to request
• Expensive
ISAC
Tryptase
Tryptase is a sensitive and specific marker of mast cell degranulation
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Helpful in the context of anaphylaxis
Serum levels peak at 1 hour after a reaction and decline thereafter over 6 hours
Repeat samples taken at 0, 1 and 6 hours after the event may confirm anaphylaxis
CAST
• CAST= cellular antigen stimulation test
• Some patients have sensitivity to various foods, colourants, flavourants, preservatives or medications that are mediated by basophil activation
• The CAST test measures basophil activation markers by flow‐cytometry after exposure of the patients blood to the relevant allergen
• Useful for reactions to colourants and preservatives and drug allergies
MELISA
• Memory Lymphocyte Immunostimulation
assay
• Tests for T‐cell mediated reactions due to drugs, metals, latex and food
Patch test
• First used in 1896, the patch test has evolved as the definitive diagnostic technique for allergic contact dermatitis
• This is of particular importance as >3700 substances have been identified as contact allergens
Patch test
Common patch test techniques • Finn chambers – individual 8mm aluminium chambers, filled and applied
• TRUE test – preloaded template of 23 common contact allergens
Patch test
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Placed on the back
Keep on for 48 hrs
Read at 48 and 72 or 96hrs Occasionally as late as 7 days
Patch test
• 30% of relevant allergens are negative at 48 hrs but positive at 96hrs
• If positive reactions disappear by 96hrs, they may be due to irritants
• Weak sensitizers may need to be read at 7 dys
Patch tests
Common • Health professions
• Beauticians
• Machinists
• Food processors
• Construction workers
Atopy patch test
• The Atopy patch test is a modification of the traditional patch test
• Evaluated in patients with atopic eczema and eosinophilic esophagitis as an adjunct for the diagnosis of food allergy
• Also used for drugs that cause mixed cutaneous reactions
Atopy patch test
• Food placed in 12mm Finn chambers on patients back
• 2g of food in 2ml saline (or single ingredient commercially prepared food)
• Keep on for 48hrs
• Read results at 72hrs
• For drugs, read at 48, 96hrs and 7dys if negative
Atopy patch test
• Clinical relevance still evolving
• Not yet standardized, nor reproducible
Nasal eosinophils
• Helpful to distinguish between allergic and non‐allergic rhinitis
• Sensitivity ~ 50%
• Specificity ~ 88%
Clinical relevance
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Asthma/AR/AC
Food allergy
Atopic eczema
Contact dermatitis
Anaphylaxis
Drug allergy
Acute urticaria
Chronic urticaria
Insect venom allergy
Asthma/rhinitis/conjunctivitis
• Consider seasonality and geography
• Seasonal – do tree pollens via SPT or specific IgE
• Perennial – do Phadiatop
‐ if positive, do individual IgE or do SPTs for inhalants
• If negative, consider another mechanism: do CAST or nasal mucous for eosinophils
Asthma/rhinitis/conjunctivitis
Commonest perennial inhalant allergens in SA
• Bermuda grass and rye grass (cross reacts with most SA grasses)
• D pteronyssinus (cross reacts with D farinae)
• B tropicalis
• Alternaria
• Cladosporium
• Aspergillus
• Cat
• Dog
Food allergy
• History and examination
• Immediate reactions – food mixes, specific IgE, SPT, components, oral food challenge
• Delayed reactions – CAST, MELISA, scope/biopsy, coeliac tests, reducing substances, H breath test, exclusion/reintroduction
• Oral allergy syndrome – do pollens and cross‐
reactive components (profilin, PR‐10, LTP and CCD)
Atopic eczema
• History and examination
• Most children with AE do not have food allergy
• 30‐40% with moderate to severe AE may have a food allergy
• May have multiple false positives
• Test only for foods implicated on history
Atopic eczema
• Specific IgE (or Fx5 screen followed by specific IgE if +) • SPTs for foods, house dust mite and animal dander sensitisation • (flow‐CAST and APT)
• Elimination and reintroduction under supervision of a dietician
• Oral food challenge
Contact dermatitis
• History
• Examination
• Patch test – True test, European baseline series (a mix of 26 different allergens), hairdressing, cosmetic and sunscreen series etc
• MELISA – nickel, latex, gold, aluminium, platinum
Anaphylaxis
• History
• Examination
• Tryptase
• Specific IgE or flow‐CAST based on clinical history (beware SPTs)
• EIA – omega 5 gliadin
Drug allergy
• History
• Examination
• Immediate reactions – Specific IgE, SPT, CAST, drug provocation test
• Delayed reactions – C3, C4, skin biopsy, CAST, MELISA, Patch test, drug provocation
Urticaria
Chronic
Acute
IgE mediated
Non IgE
mediated
Food
Viral
Drugs
Drugs
Latex
Additives/preservatives
Insect venom
Direct histamine release
Animal dander
Scombroid
Contact
Urticaria
Chronic
Acute
Spontaneous
Inducible
no obvious trigger
specific trigger
FBC & ESR
Cold
Avoid suspected drugs
Delayed pressure
Solar
TFT and antibodies
ASST, SPT, dipstix
Autoantibodies
Skin biopsy, Tryptase
Pseudoallergen free diet
Infectious diseases
Dermographic
Vibratory
Cholinergic Heat Aquagenic
Specific provocation tests
Insect venom
• History • Examination
• Specific IgE
• (SPT)
• Component testing to identify primary sensitisation and cross‐reactivity new!
• Bee ‐ Api m 1 and Api m 10
• Wasp ‐ Ves v 1 and Ves v 5 • Paper wasp ‐ Pol d 5
• CCD South African Allergic rhinitis guidelines 2014
EAACI/GA2LEN/EDF/WAO urticaria guideline 2014
Chronic urticaria guideline
JACI May 2014: 133(5)
Acute urticaria guideline
JACI May 2014: 133(5)
the end