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Rooks dermatology
Pg no 128.64 to 128.77
o Background
o Indications
o Methods
Background :
o Patch testing relies on antigen‐specific T
lymphocytes will be present throughout the body.
o Allergen in the patch test can be applied to normal
skin, usually on the upper back where the tests are
least likely to be disturbed.
 Active eczema because it may reduce
the threshold of activity and cause
non‐specific reactions
 Patch testing should be delayed for 4
weeks following sunbathing
 patches should not be exposed to the
sun or other sources of UV light
 Corticosteroids and other
immunosuppressive drugs should be
stopped .
 Pregnant patients
Methods
o The basis of testing is to elicit an immune response by
challenging already sensitized persons to defined amounts of
allergen and assessing the degree of response
oThe amount of allergen is defined by its concentration in the
vehicle and the amount applied
o By testing the same allergens in parallel, the technique has
been confirmed to be generally reproducible
oChambers or discs are used to ensure occluded contact with
the skin.
oThe fixing tape should be non‐occlusive, non‐allergenic and
non‐irritant.
o If the adhesive tapes peel off, the test should be repeated
o Test material
o Patch test vehicles
o Patch test concentration
o Patch test done
o Storage of allergens
o Test site
o Marking
 Allergens are obtained from
following manufacturers or from
their local distributors
1) TROLAB allergens (Smart
practice Europe)
2) Chemo technique Diagnostics
(Sweden)
3) allerg EAZE (Smart practice
Canada)
4) Epitest Ltd, Oy (Finland) finn
chamber on scanpor tape
Finn
chamber
on scanpor
tape
• chambers are
supplied in strips of
five or 10(two rows of
five),
• small, occlusive
aluminium discs
• mounted on
non‐occlusive tape
with an acrylic based
adhesive backing
chamber
Aluminium disc
Scanpor tape
o The older AL Test system (a filter
paper disc mounted on aluminized paper)
is now rarely used.
Other systems consist of:
o square plastic chambers (Van der Bend
chambers)
o oval plastic chambers (Epicheck).
o Systems continue to be developed (e.g.
IQ Ultra)
o to improve adhesion and comfort and
also to impart water resistance to enable
brief showering during the tests (e.g.
Curatest F).
 Few substances can be applied to the skin as they are. In
order to avoid an irritant effect, they must be mixed or
dissolved in a vehicle to achieve a suitable test
concentration
 Petrolatum is generally more reliable, and has the added
advantage of being occlusive
helps to prevent oxidation
prolongs shelf‐life
 substances can also be dissolved in water, alcohol,
acetone, methylethyl ketone or olive oil, as appropriate.
 Irritant solvents such as chloroform and benzene must
not be employed
 Choice of a suitable concentration is of fundamental
importance
 Excessive concentrations result in false positive reactions,
because of their irritant effect , may even sensitize
patients
 Insufficient concentrations produce false negative results
 The concentrations used for patch testing are usually
much higher than those encountered during the
development of dermatitis.
 An initial patch test concentration can often be selected
either by reference to standard texts or by contacting the
manufacturer for details of toxicological testing data
 nickel dermatitis produced by the minute amounts
dissolved from nickel‐plated objects, a 5% concentration
of nickel sulphate in petrolatum is necessary.
 Chromate 0.25–0.5% is required to prove sensitivity to
cement containing 0.0005–0.002% of chromate
 Neomycin should be tested at 20% despite only being at
0.5% concentrationin many topical medicaments
 Metal salts in particular are tested at the margins of
irritancy and may give false positive
 Other standard allergens such as fragrance mix, parabens
mix and wool alcohols may also be marginally irritant
 If petrolatum is used as the vehicle and disposable
syringes are the containers, a length of 5 mm of test
substance in a vehicle will suffice.
 For a Finn chamber, 20 mg of allergen as a
petrolatum dispersion has been shown to be the
optimum dose
 If the vehicle is a fluid, a digital pipette should be
used to deliver 15 μL to a filter paper in the chamber
 Dropper bottles supplied by the allergen
manufacturers tend to overfill the chambers.
 Shelf‐life’ is prolonged if test substances not in daily
use are stored in the dark in a refrigerator at 4°C.
 Many substances are unstable if exposed to light
 Commercially available allergens are labelled with
an expiry date
 For some materials such as isocyanates, freezing is
essential to prevent the loss of allergen
 Storage in small jars has the drawbacks of
oxidation, drying and evaporation of volatile test
substances
o Rubber pipette caps contaminate
o The solutions and may cause false positive reactions in
persons sensitive to rubber.
o Homogeneity of patch test allergens may be lost,
especially in hot climates, if they are not refrigerated
o Many centres prepare their allergens prior to
application
o It is preferable to prepare on the day and apply
immediately to avoid consequent false negative reactions
 both allergic and irritant reactions are most easily
provoked on the upper back
 lateral aspect of the upper arm
 Abdomen
 Thighs
 Test sites must be marked with indelible ink or stratum
corneum stains
 fluorescent markers used on dark skins
 Marking materials can be obtained from allergen suppliers
 It is necessary to repeat marking before removal of the
patches (because their positions cannot be distinguished once
the pressure effects have subsided)
 The patient should be instructed not to bathe or shower for the
duration of the tests, and to avoid exercise or other activity
likely.
o A typical regimen is a 48 h application
time , with readings taken 1 h after removal
and again 48 h later (that is day 2 and day 4)
o If only 1 patch test reading_ day 4.
o 3rd reading on day 5–7 day.
o Others have suggested that a second
reading on day 5 is better
Patch test result at Day 4
reading
o Immediately after removal of the patch tests, there may be
erythema
o From the stripping action of the tape, especially in dermographic
subjects, and this must be allowed to settle
o some reactions may take up to 1 h to develop once the pressure
of the strips has been released, and the infiltration allowed to swell
the dermis.
Patch
tests
with
neomycin
20%
in
petrolatum:
positive
reaction
times
after
application
A
positive
allergic
(++)
patch
test
response
in
a
patient
sensitive
to
neomycin
It is important
that patch test
readings are
scored
according to the
reactions seen
o It is important to establish relevance by carefully re‐examining
the patient‘s history
o Distribution of the rash and materials with which there has
been contact
o If relevance can be clearly established and avoidance advice
can be given.
o Measurements of changes in skin surface
o Epidermal hydration
o water barrier function
o Parameters of inflammation
o Replica techniques
o Transepidermal water loss
o Skin reflectance
o Laser doppler flowmetry
o Thermography and
o High‐frequency ultrasound
o False positive reactions : something is true
when it actually is false
o False negative reactions : something is false
when its actually true
Compound allergy occurs when a positive allergic patch test
reaction is seen to a finished product but tests with the ingredients
are negative.
For example: Hirudoid cream, where a new allergen was formed
as a reaction product of two preservatives in the medicament
o The product and the constituents should be patch tested when
allergy is suspected.
o A constituent allergen may be an undeclared ingredient or there
may be batch/source differences between the original compound
and the subsequently provided components.
For example : The allergen may be in the container, a rubber
stopper, and not in the product
o A combination of chemicals may lead to a quenching effect there
may be potentiation of allergic and irritant responses.
e.g: fragrance material aldehydes
o Quenching effects may be due to one of the compounds having
anti‐inflammatory properties.
Such as triclosan having a ‘quenching’ effect on nickel allergic
contact dermatitis.
o The presence or absence of impurities or degradation products
o Hidden additives
o Batch differences
o Some chemicals may undergo reactive metabolic changes in the skin.
o Natural products vary according to source, season and method of
extraction.
o Storage or ‘ageing’ of a product may also affect its allergenicity and
irritancy, e.G : d‐limonene has been shown to be allergenic only in its old
and oxidized state.
o Patients should therefore always be tested with their own product.
o Season may also influence patch test results
o Baseline series
o Additional series
o Other materials
 EECDRG contains 28 allergens
(European environmental and contact dermatitis research group)
 BSCA has 39 allergens
(British society for cutaneous allergy )
 NACDG includes 65 allergens
(North american contact dermatitis group)
 Additional series of allergens are useful in certain situations
For example in the investigation of dermatitis occurring
In certain sites liable to medicament allergy (eyes, ears, perineum
and venous ulcers/eczema)
sensitization from components of shoes or clothing .
Some occupational groups, for example hairdressers , florists,
dentists and metal machinists , are exposed at work to a variety of
potential allergens not found in the standard series
Others may handle a specific group of allergenic chemicals
For example : epoxy or acrylic resins
 Commercially produced patch test allergens, either singly or in
small numbers, may be applied where relevant.
 Patients may bring a wide variety of materials from their own
from home or work for testing
 these must be thoroughly assessed and diluted appropriately
before being tested.
 In those units with access to thin layer chromatography there is
the opportunity to patch test with extracted components of
textiles
plastics
plants and other materials
koebnerization of vitiligo
o Specific chemicals
o Chemical groups
o Specific substances
o Finished products
have been collated in a number of standard contact dermatitis
references given in the resources
o Before patch testing with any unfamiliar material, the
appropriate vehicle and concentration should be sought from one
or more of these databases
o A reaction appearing 7 or more days after the application
may indicate either delayed expression of a pre‐existing
sensitivity or sensitization from the patch test.
o Late reactions, occurring up to 14 days after the application
of patch tests, are weak sensitivities from poorly penetrating
allergens.
o Active sensitization usually presents as a strong positive
patch test occurring at around 3 weeks.
1 Non‐specific hyper reactivity.
2 Multiple primary hypersensitivities.
3 Cross‐reactions (true and false).
 The threshold at which a false positive irritant reaction develops.
 During active dermatitis, uninvolved skin, even at distant bodysites,
exhibits increased susceptibility to irritant reactions.
 ‘status eczematicus’ may lead to false positive patch test results
 ‘eczema creates eczema’ and that a strongly positive patch test
reaction may induce other non‐specific false positive patch test
reactions
 Such reactions occur more readily with marginally irritant
chemicals. When this affects adjacent patch test sites it is often
referred to as spillover, excited skin or angry back.
Some patients develop multiple sensitivities
 Patients with a long history of dermatitis
 Patients with leg ulcers
 Patients with chronic actinic dermatitis
 Sensitization is facilitated if an allergen is applied on
injured(e.g. eczematous) skin
 In dermatitis of the feet, concomitant sensitivity to chromate,
rubber and dyes in shoes or stockings.
 Cross‐sensitization is defined as the phenomenon where
sensitization engendered by one compound,
the primary allergen, extends to one or more other compounds
the secondary allergens, as a result of structural similarity
 The proposal is that the primary and secondary allergens are
so closely related that sensitized T cells
 Aromatic compounds with a ‘para’group, for example PPD,
benzocaine,procaine,sulphonamides,mesalazine,diaminodiphe
nylmethane and PABA UV filters, may all cross‐sensitize
o Open tests
o Usage tests
o Repeat open application tests
o Intra dermal tests
o In vitro tests
o Migration inhibition tests
o Lymphocyte transformation tests
o Leukocyte pro coagulant activity
o Spot tests
o Dimethylglyoxime (DMG) test for nickel
o Acetylacetone method for formaldehyde
o Other analyses
GENERAL PRINCIPLES
o Avoidance advice
o Active treatment
o Hypo sensitization
PREVENTION
o Allergen containment and replacement
o Legal and other regulatory measures
o Corporate responsibility
o Work
o Domestic
o Education
Investigations of allergic contact dermatitis by dr maria

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Investigations of allergic contact dermatitis by dr maria

  • 1. Rooks dermatology Pg no 128.64 to 128.77
  • 3. Background : o Patch testing relies on antigen‐specific T lymphocytes will be present throughout the body. o Allergen in the patch test can be applied to normal skin, usually on the upper back where the tests are least likely to be disturbed.
  • 4.
  • 5.  Active eczema because it may reduce the threshold of activity and cause non‐specific reactions  Patch testing should be delayed for 4 weeks following sunbathing  patches should not be exposed to the sun or other sources of UV light  Corticosteroids and other immunosuppressive drugs should be stopped .  Pregnant patients
  • 6. Methods o The basis of testing is to elicit an immune response by challenging already sensitized persons to defined amounts of allergen and assessing the degree of response oThe amount of allergen is defined by its concentration in the vehicle and the amount applied o By testing the same allergens in parallel, the technique has been confirmed to be generally reproducible oChambers or discs are used to ensure occluded contact with the skin. oThe fixing tape should be non‐occlusive, non‐allergenic and non‐irritant. o If the adhesive tapes peel off, the test should be repeated
  • 7. o Test material o Patch test vehicles o Patch test concentration o Patch test done o Storage of allergens o Test site o Marking
  • 8.  Allergens are obtained from following manufacturers or from their local distributors 1) TROLAB allergens (Smart practice Europe) 2) Chemo technique Diagnostics (Sweden) 3) allerg EAZE (Smart practice Canada) 4) Epitest Ltd, Oy (Finland) finn chamber on scanpor tape
  • 9. Finn chamber on scanpor tape • chambers are supplied in strips of five or 10(two rows of five), • small, occlusive aluminium discs • mounted on non‐occlusive tape with an acrylic based adhesive backing chamber Aluminium disc Scanpor tape
  • 10. o The older AL Test system (a filter paper disc mounted on aluminized paper) is now rarely used. Other systems consist of: o square plastic chambers (Van der Bend chambers) o oval plastic chambers (Epicheck). o Systems continue to be developed (e.g. IQ Ultra) o to improve adhesion and comfort and also to impart water resistance to enable brief showering during the tests (e.g. Curatest F).
  • 11.  Few substances can be applied to the skin as they are. In order to avoid an irritant effect, they must be mixed or dissolved in a vehicle to achieve a suitable test concentration  Petrolatum is generally more reliable, and has the added advantage of being occlusive helps to prevent oxidation prolongs shelf‐life  substances can also be dissolved in water, alcohol, acetone, methylethyl ketone or olive oil, as appropriate.  Irritant solvents such as chloroform and benzene must not be employed
  • 12.  Choice of a suitable concentration is of fundamental importance  Excessive concentrations result in false positive reactions, because of their irritant effect , may even sensitize patients  Insufficient concentrations produce false negative results  The concentrations used for patch testing are usually much higher than those encountered during the development of dermatitis.  An initial patch test concentration can often be selected either by reference to standard texts or by contacting the manufacturer for details of toxicological testing data
  • 13.  nickel dermatitis produced by the minute amounts dissolved from nickel‐plated objects, a 5% concentration of nickel sulphate in petrolatum is necessary.  Chromate 0.25–0.5% is required to prove sensitivity to cement containing 0.0005–0.002% of chromate  Neomycin should be tested at 20% despite only being at 0.5% concentrationin many topical medicaments  Metal salts in particular are tested at the margins of irritancy and may give false positive  Other standard allergens such as fragrance mix, parabens mix and wool alcohols may also be marginally irritant
  • 14.  If petrolatum is used as the vehicle and disposable syringes are the containers, a length of 5 mm of test substance in a vehicle will suffice.  For a Finn chamber, 20 mg of allergen as a petrolatum dispersion has been shown to be the optimum dose  If the vehicle is a fluid, a digital pipette should be used to deliver 15 μL to a filter paper in the chamber  Dropper bottles supplied by the allergen manufacturers tend to overfill the chambers.
  • 15.  Shelf‐life’ is prolonged if test substances not in daily use are stored in the dark in a refrigerator at 4°C.  Many substances are unstable if exposed to light  Commercially available allergens are labelled with an expiry date  For some materials such as isocyanates, freezing is essential to prevent the loss of allergen  Storage in small jars has the drawbacks of oxidation, drying and evaporation of volatile test substances
  • 16. o Rubber pipette caps contaminate o The solutions and may cause false positive reactions in persons sensitive to rubber. o Homogeneity of patch test allergens may be lost, especially in hot climates, if they are not refrigerated o Many centres prepare their allergens prior to application o It is preferable to prepare on the day and apply immediately to avoid consequent false negative reactions
  • 17.  both allergic and irritant reactions are most easily provoked on the upper back  lateral aspect of the upper arm  Abdomen  Thighs
  • 18.
  • 19.  Test sites must be marked with indelible ink or stratum corneum stains  fluorescent markers used on dark skins  Marking materials can be obtained from allergen suppliers  It is necessary to repeat marking before removal of the patches (because their positions cannot be distinguished once the pressure effects have subsided)  The patient should be instructed not to bathe or shower for the duration of the tests, and to avoid exercise or other activity likely.
  • 20. o A typical regimen is a 48 h application time , with readings taken 1 h after removal and again 48 h later (that is day 2 and day 4) o If only 1 patch test reading_ day 4. o 3rd reading on day 5–7 day. o Others have suggested that a second reading on day 5 is better Patch test result at Day 4 reading
  • 21. o Immediately after removal of the patch tests, there may be erythema o From the stripping action of the tape, especially in dermographic subjects, and this must be allowed to settle o some reactions may take up to 1 h to develop once the pressure of the strips has been released, and the infiltration allowed to swell the dermis.
  • 23. It is important that patch test readings are scored according to the reactions seen
  • 24.
  • 25.
  • 26. o It is important to establish relevance by carefully re‐examining the patient‘s history o Distribution of the rash and materials with which there has been contact o If relevance can be clearly established and avoidance advice can be given.
  • 27. o Measurements of changes in skin surface o Epidermal hydration o water barrier function o Parameters of inflammation o Replica techniques o Transepidermal water loss o Skin reflectance o Laser doppler flowmetry o Thermography and o High‐frequency ultrasound
  • 28. o False positive reactions : something is true when it actually is false o False negative reactions : something is false when its actually true
  • 29.
  • 30.
  • 31. Compound allergy occurs when a positive allergic patch test reaction is seen to a finished product but tests with the ingredients are negative. For example: Hirudoid cream, where a new allergen was formed as a reaction product of two preservatives in the medicament
  • 32. o The product and the constituents should be patch tested when allergy is suspected. o A constituent allergen may be an undeclared ingredient or there may be batch/source differences between the original compound and the subsequently provided components. For example : The allergen may be in the container, a rubber stopper, and not in the product
  • 33. o A combination of chemicals may lead to a quenching effect there may be potentiation of allergic and irritant responses. e.g: fragrance material aldehydes o Quenching effects may be due to one of the compounds having anti‐inflammatory properties. Such as triclosan having a ‘quenching’ effect on nickel allergic contact dermatitis.
  • 34. o The presence or absence of impurities or degradation products o Hidden additives o Batch differences o Some chemicals may undergo reactive metabolic changes in the skin. o Natural products vary according to source, season and method of extraction. o Storage or ‘ageing’ of a product may also affect its allergenicity and irritancy, e.G : d‐limonene has been shown to be allergenic only in its old and oxidized state. o Patients should therefore always be tested with their own product. o Season may also influence patch test results
  • 35. o Baseline series o Additional series o Other materials
  • 36.  EECDRG contains 28 allergens (European environmental and contact dermatitis research group)  BSCA has 39 allergens (British society for cutaneous allergy )  NACDG includes 65 allergens (North american contact dermatitis group)
  • 37.
  • 38.
  • 39.
  • 40.  Additional series of allergens are useful in certain situations For example in the investigation of dermatitis occurring In certain sites liable to medicament allergy (eyes, ears, perineum and venous ulcers/eczema) sensitization from components of shoes or clothing . Some occupational groups, for example hairdressers , florists, dentists and metal machinists , are exposed at work to a variety of potential allergens not found in the standard series Others may handle a specific group of allergenic chemicals For example : epoxy or acrylic resins
  • 41.  Commercially produced patch test allergens, either singly or in small numbers, may be applied where relevant.  Patients may bring a wide variety of materials from their own from home or work for testing  these must be thoroughly assessed and diluted appropriately before being tested.  In those units with access to thin layer chromatography there is the opportunity to patch test with extracted components of textiles plastics plants and other materials
  • 42.
  • 44. o Specific chemicals o Chemical groups o Specific substances o Finished products have been collated in a number of standard contact dermatitis references given in the resources o Before patch testing with any unfamiliar material, the appropriate vehicle and concentration should be sought from one or more of these databases
  • 45. o A reaction appearing 7 or more days after the application may indicate either delayed expression of a pre‐existing sensitivity or sensitization from the patch test. o Late reactions, occurring up to 14 days after the application of patch tests, are weak sensitivities from poorly penetrating allergens. o Active sensitization usually presents as a strong positive patch test occurring at around 3 weeks.
  • 46. 1 Non‐specific hyper reactivity. 2 Multiple primary hypersensitivities. 3 Cross‐reactions (true and false).
  • 47.  The threshold at which a false positive irritant reaction develops.  During active dermatitis, uninvolved skin, even at distant bodysites, exhibits increased susceptibility to irritant reactions.  ‘status eczematicus’ may lead to false positive patch test results  ‘eczema creates eczema’ and that a strongly positive patch test reaction may induce other non‐specific false positive patch test reactions  Such reactions occur more readily with marginally irritant chemicals. When this affects adjacent patch test sites it is often referred to as spillover, excited skin or angry back.
  • 48. Some patients develop multiple sensitivities  Patients with a long history of dermatitis  Patients with leg ulcers  Patients with chronic actinic dermatitis  Sensitization is facilitated if an allergen is applied on injured(e.g. eczematous) skin  In dermatitis of the feet, concomitant sensitivity to chromate, rubber and dyes in shoes or stockings.
  • 49.  Cross‐sensitization is defined as the phenomenon where sensitization engendered by one compound, the primary allergen, extends to one or more other compounds the secondary allergens, as a result of structural similarity  The proposal is that the primary and secondary allergens are so closely related that sensitized T cells  Aromatic compounds with a ‘para’group, for example PPD, benzocaine,procaine,sulphonamides,mesalazine,diaminodiphe nylmethane and PABA UV filters, may all cross‐sensitize
  • 50. o Open tests o Usage tests o Repeat open application tests o Intra dermal tests o In vitro tests o Migration inhibition tests o Lymphocyte transformation tests o Leukocyte pro coagulant activity o Spot tests o Dimethylglyoxime (DMG) test for nickel o Acetylacetone method for formaldehyde o Other analyses
  • 51. GENERAL PRINCIPLES o Avoidance advice o Active treatment o Hypo sensitization PREVENTION o Allergen containment and replacement o Legal and other regulatory measures o Corporate responsibility o Work o Domestic o Education