European Society of Contact Dermatitis
Practical guideline for diagnostic patch testing
Draft version 2: 16.Sep 2014
Background information for assessment
Agree guideline II requires:
1. The overall objective(s) of the guideline is (are) specifically described.
2. The health question(s) covered by the guideline is (are) specifically described
3. The population (patients, public, etc.) to whom the guideline is meant to apply is
specifically described.
Systematic methods were used to search for evidence.
1. The criteria for selecting the evidence are clearly described.
2. The strengths and limitations of the body of evidence are clearly described.
3. The methods for formulating the recommendations are clearly described.
4. There is an explicit link between the recommendations and the supporting evidence
1
Tabel of contents (overview)
Task: To update the paper on ‘terminology of contact dermatitis’ and make it consistent with current
knowledge.
Acta Dermatovener 1970: 287-292
Aim: a (short) paper giving a clear and short guidance and core references
Style according to authors instructions for Contact Dermatitis:
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1600-0536/homepage/ForAuthors.html
Extent: see table
Literature search: a pubmed search should be done for the relevant sections and the result accounted for.
References: put in all relevant references, but mark the 10 most important core references in red
Authors: See below. Those, who’s name are in red, are the main responsible for the section and should
contact the other authors of that chapter, co-ordinate the work and make sure deadlines are kept.
I.
Introduction
Definitions
Indication (typical vs. non-typical)
“When not to patch test” (misuse)
Information to patients prior to PTing
II.
Materials
Author
An, Alicia
Size (pages in word)
1000 words
Klaus A
Magnus B.
2000 words
Consider inclusion of a tabel
Magnus B,
Magnus L/
Mihály, Vera
3000 words
Alicia, Klaus A,
Andreas
Margarida
1000 words
1000 words
Tove, Mark,
Jørgen S.
1000 words
Martine, An,
Alicia and Radek
1000 words
Test systems (chambers sizes)
Patch test materials (sources, …)
- Allergens
- Vehicles
- Concentration
Storage/Stability
III.
Technique
Dosing of chambers
Anatomical site
Occlusion time
Modifying the system (tape stripping, increasing a
standard concentration, serial dilution)
Readings (morphology, times)
IV.
Other test techniques
Semi-open, open, ROATs
Photopatchtest ( other guideline)
V.
Individual factors
Medication, incl. immunosuppressing agents, also
addressing lacking evidence and possible re-test
Immunosuppression (acquired, ..)
UV-light/sun exposure
Atopic dermatitis
Active eczema
Skin types
VI.
Children
Special groups
2
Wolfgang,Carola,
Swen,
Margarida,
Andreas
2000 words
Kristiina,
Vera
2000 words
VIII.
Side effects
Pigmentation changes, PT-sensitisation, persistent
reactions, flare-up of clinical dermatitis, subjective
complaints
Ana, Thomas R.
1000 words
Rotating review: Ian White
IX.
Final evaluation
Diagnosis and Clinical Relevance
Interpretation also of negative PT results
Interpretation of doubtful PT reactions
Interpretation of late positive PT results
Jeanne, Ian
2000 words
Occupational
Drug eruptions
VII.
Testing of patients own materials
1000 words
Patients own materials ( COD-Textbook,
Occ.Handbook): present some general aspects
here
X.
Patients education (concerning
allergy)
Jacob T.
1000 words
XI.
Patch Test Training, Maintenance
of expertise
Mark, Vera
1000 words
XII.
Databases and surveillance (
refer to COD textbook chapter)
Wolfgang
1000 words
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I. Introduction
Authors
Prof. An Goossens, Contact Allergy Unit, Department of Dermatology, University Hospital K.U.Leuven
Kapucijnenvoer 33. B-3000 Leuven, Belgium. E-mail: an.goossens@uzleuven.be
Dr. Alicia Cannavó, 25 de Mayo 1617, (B1638ABD) Vicente López. Provincia Buenos Aires. República
Argentina. E-mail: acannavo4@gmail.com
COMMENTS BY WOLFGANG UTER INCLUDED 17TH JULY.
OVERALL OBJECTIVE
This guideline is intended for dermatologists involved in identifying the responsible contact
allergen(s) in patients (including children) suspected to suffer from allergic contact dermatitis or
other types of delayed hypersensitivity reactions. It represents an update of the paper on
‘terminology of contact dermatitis’ (Acta Dermatovener 1970: 287-292), with the aim of making it
consistent with current knowledge. The guideline includes information on patch testing materials,
techniques, test series, readings, final evaluation, individual factors that may influence the outcome
of the tests, potential side effects, as well as information to patients.
Process of developing the guideline
In October 2012 the European Society of Contact Dermatitis formed a working party to elaborate
an up-to-date patch test guideline. An open call for contributors experienced in the field was made
on the webpage of the society and an international group (see author list) collaborated in the
compilation of current information on the best practice in diagnostic patch testing.
An initiating meeting was held and sections were primarily drafted by 1 to 4 authors. In a rotating
review, sections were re-assigned and re-considered by a different team of authors. A pre-final
agreement on the resulting preliminary draft was achieved during a meeting; this draft was then
exposed to the comments of all members of the European Society of Contact Dermatitis and
Cutaneous Allergy (ESCD, www.escd.org). Amendments were accordingly made, provided (i) the
comment was substantiated – if possible, by scientific literature – and (ii) the guideline authors
found it acceptable. A pre-final draft was reviewed by two leading professors, who had not
participated in the work and based on their response a final version for acceptance by the authors
and members of ESCD was made.
Search of evidence and methodology
Care was taken to identify scientific literature pertinent to those aspects, where it was available by
performing searches in Medline, Web of Science and other bibliographic resources. Where
applicable search and search result are described in the sections. However, concerning many
topics no formal studies are available; hence, the statements are based on collective expert
judgement and consensus. If, exceptionally, no consensus on a certain topic was achieved,
phrasing such as “while most experts …, some advocate ...” makes the different alternatives clear.
PATCH TESTING
Definition
Patch testing is the gold standard to diagnose contact allergy. This test aims to reproduce the
biological reaction to a contact allergen, i.e. allergic contact dermatitis. It is the in vivo
demonstration in an individual of the elicitation phase of a type IV delayed hypersensitivity
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reaction. The patch test is performed by applying allergens under occlusion on the skin under
standardised conditions. Other epicutaneous tests will be briefly mentioned.
Indications
Diagnostic patch testing is an investigation undertaken on patients with a history of dermatitis
(eczema) in order to determine whether they have a contact allergy and then evaluate the relation
(if any) of the allergy to their dermatitis (see section IX).
Patch testing should be done in all patients in whom contact allergy is suspected or needs to be
excluded, regardless of e.g. age (see section VI Children) or anatomical site of eczema. This also
includes other conditions including erythema multiforme-like, lichen planus-like, or lymphomatoid
reactions.
Other presentations
PatAllergic contact reactions may also present as non-eczematous eruptions (3), such as, or may
also be a complicating factor of other skin conditions, such as stasis, atopic, or seborrheic
dermatitis, nummular eczema, or any other form of eczema. Moreover, patch testing may also be
very useful in pinpointing the culprit in T-lymphocyte mediated drug eruptions (4), and may also, in
special cases, identify contact allergic reactions in mucous membranes only such as, for example,
conjunctivitis and stomatitis (5), ***vulvar*** and those due to endogenous exposure, such as via
osteosynthesis or metal implants (6) - also stents- (7).
Immediate testing, namely prick testing or prick-prick testing, can be performed, in addition to
patch testing, in immediate contact reactions, namely in protein contact dermatitis or contact
urticaria and also in hand dermatitis where immediate reactions can contribute to the lesions.
Recommendations to patch test in patients with:
- Contact Dermatitis,
- Other types of eczema and skin eruptions for which contact allergy is suspected
- - - Dermatitis related to occupational exposures
- Chronic eczema not improving with treatment
Delayed-type drug eruptions
- Mucous membranes …
Postponing patch test
Postponing of patch test investigations should be
conditions:
-
considered in patients with the following
Severe or generalised active eczema
Systemic immunosuppressive treatment
Dermatitis on the upper back or other body areas chosen to apply patch tests
Test sites have been recently treated with topical corticosteroids
Recent UV exposure of the test area
5
-
Patch testing during pregnancy or lactation is not recommended for medico-legal (not
scientific) reasons)
These and several other factors, which may affect the out-come of patch testing, are reviewed in
section V.
Information to patients prior to patch testing
Patients should be told the purpose of patch testing, how patch testing is done and various
symptoms that may occur. It is valuable to inform about avoidance of showers, wetting the test
sites, irradiation and excessive exercise and about symptoms such as itch, loosening of patches
and late or severe reactions. Patients should get written information about the patch-test
procedure.
Contraindications or incorrect indications for patch testing
???
II. Materials
Klaus E. Andersen, Magnus Bruze
Comments from Vera, Misi and Magnus Lindberg from 29. August included.
Contact dermatitis textbooks and a literature search in July 2014 using combinations of the
following search terms: patch testing, contact dermatitis, contact allergy and technique revealed
numerous publications. A large number of those dealing with technical aspects (test systems, test
materials, allergens, vehicles, concentration, and stability) were reviewed and recent references
selected. The number of up-to-date controlled clinical experiments is limited and much of the
current standards in clinical use are based on old studies, which do not live-up to a high level of
evidence.
Patch testing is a biologic diagnostic assay with inherent pitfalls (Kligman, 1996).The technique
involves the cutaneous application under occlusion of a small amount of the suspected allergen in a
suitable concentration and vehicle. There is no “golden standard”. Development and improvement
of the assay is a constant challenge based on comparative clinical experiments using the “common”
techniques as comparator (Bousema et al 1991;Belsito et al 1992; Goh 1992; Ruhnek-Forsbeck et
al 1988; Jensen and Andersen 2005, Mørtz and Andersen 2010). The level of evidence for
recommendations is not satisfactory because of the inherent difficulty in standardization of all
aspects of the assay (technique, contact allergens, patients, environment, scoring and interpretation)
((Note on “commonly used test chamber system: FCS” ))
The commonest system used to occlude and apply the allergens is the Finn chamber® system on
Scanpor tape (supplied by SmartPractice, Phoenix, AZ, USA)(Fisher and Maibach 1984).
The chambers are supplied in strips of five or ten and consist of small aluminum disks mounted on
non-occlusive tape that has been chosen for its excellent adhesive properties and hypoallergenic
acrylic-based adhesive. ((Use plastic chambers in aluminium allergic patients))
6
Other systems consist of square polyethylene chambers on hypoallergenic tape (IQ chambers™. IQ
Ultima™ and IQ Ultra™, Chemotechnique, Vellinge, Sweden; van der Bend square chambers™,
Brielle, The Netherlands; and AllergEAZE® patch test chambers, SmartPractice, Phoenix, AZ.
USA).
Prepackaged tests (TRUE TESTS®)(SmartPractice Aps, Hillerød, Denmark), are also available –
but only for 35 allergens, and contain homogeneously dispersed allergens in a hydrophilic gel base
(hydroxypropylcellulose or povidone) mounted on an acrylic-based adhesive tape. TRUE TESTS®
are of pharmaceutical standard and registered as drugs. They are a portable and convenient method
for those wishing to test only a limited number of allergens. There is no documentation that proves
one test system superior to the others. The choice of patch test system in a clinic is based on
tradition and experience.
The critical factor for sensitization and elicitation of contact allergy is the “dose per unit area”
(Friedmann, 2006). Therefore, it is important that the dose of allergen is standardized for each type
of test chamber (see section III)(Frosch and Kligman 1979; Fisher and Maibach 1984, Svedman et
al 2012). For example, for small Finn Chambers® a small amount of each allergen in petrolatum
(approximately 20mg, 40 mg/cm2) is deposited from the syringe into the chamber such that it fills
the well of the disk but does not extrude when the patch is applied to the back (Bruze et al, 2007).
For aqueous-based allergens, small filter-papers are placed in the well and these will hold around 15
µl of liquid. The application of liquids is strongly recommended by means of a micropipette (FrickEngfeldt et al 2010).
The patch test material suppliers include AllergEAZE®, Calgary, Canada, Brial® Allergen Gmbh,
Greven, Germany; Chemotechnique™, Vellinge, Sweden; Trolab®, SmartPractice, Reinbek,
Germany, TRUE TEST®, SmartPractice, Hillerød, Denmark and van der Bend™, Brielle, Holland.
All companies supply catalogues and websites with lists of all commercially available allergens in
the European and international baseline series, additional series according to product groups or
professions, tables of allergen mixes, as well as general information on the occurrence of allergens
and cross-reactivity. A number of allergens, mainly fragrances and rubber compounds, are compiled
into mixes. The basic concept of using mixes of allergens instead of single allergens is to save time
and space. However, a positive reaction to a mix should normally prompt a subsequent break-down
test of its single ingredients. If this is not feasible, the patient is left with too general information.
Selection of patch test materials
The history and examination of a patient will usually give clues to the possible sensitizers and
should guide the choice of patch-test materials. Unfortunately, it is not sufficient to patch test with
only suspected sensitizers, for unsuspected ones frequently turn out to be relevant. An experienced
dermatologist will be able to guess correctly the clinically relevant contact allergens in some
patients, based on the history and the clinical appearance of the eczema. This guess is more likely to
be correct for common allergens, such as nickel (50-80%), and less likely to be correct for less
common allergens (<10%) (Cronin, 1972; Podmore et al, 1984).
However, this failure to guess correctly explains why a “baseline series” of test allergens should be
applied in the evaluation of all patients suspected of having a contact dermatitis. A sensitizer is
suggested for inclusion in the baseline series when routine (“consecutive”) patch testing of patients
with suspected contact dermatitis results in a contact allergy rate exceeding 0.5–1.0% (Bruynzeel et
al. 1995; Bruze et al. 1999; Isaksson et al. 2000) and in the same time this particular allergen is
7
ubiquitous and/or clinically highly relevant allergen. In particular cases (e.g. parabens) a contact
allergy rate much below 1% can justify routine testing as well.
The current European baseline series for adults, as recommended by the European Environmental
Contact Dermatitis Research Group (EECDRG), can be found in table 1 (Andersen et al, 2011;
Bruze et al. 2008; Bruze et al. 2013, 2014; Pontén et al, 2013). New allergens emerge and some are
phased out. However, in most cases application of additional patch test series must be considered.
__________________________________________________________________
Table 1. The current European baseline patch test series. The patch test concentrations are shown. (aq. water, pet.
petrolatum)
Trolab Hermal Chemotechnique
Potassium dichromate
0.5% pet.
Neomycin sulfate
20% pet.
Thiuram mix
1% pet.
p-phenylenediamine free base 1% pet.
Cobalt chloride
1% pet.
Benzocaine
5% pet.
Formaldehyde
1% aq.
Colophony (colophonium)
20% pet.
Clioquinol
5% pet.
Balsam of Peru (Myroxylon
pereirae)
25% pet.
N-Isopropyl-N-phenylparaphenylenediamine (IPPD) 0.1% pet.
Wool alcohols (lanolin alcohol) 30% pet.
1000µg/cm2
Mercapto mix
75 µg/cm2
Epoxy resin
50 µg/cm2
Paraben mix
1000µg/cm2
para-Tertiary-butylphenolformaldehyde resin (PTBP resin)
45 µg/cm2
Fragrance mix
430 µg/cm2
Quaternium-15
100 µg/cm2
TRUE Test
0.5% pet.
20% pet.
1% pet.
1% pet.
1% pet.
5% pet.
2% aq.
20% pet.
5% pet.
54 µg/cm2
600µg/cm2
27 µg/cm2
80µg/cm2
20 µg/cm2
25% pet.
800 µg/cm2
180 µg/cm2
1200µg/cm2
0.1% pet.
30% pet.
1% pet.
2% pet.
1% pet.
1% pet.
16% pet.
16% pet.
1% pet.
1% pet
8% pet.
8% pet.
1% pet.
1% pet.
8
Nickel sulfate
200 µg/cm2
Cl+Me-isothiazolinone
Mercaptobenzothiazole
75 µg/cm2
Primin
Sesquiterpene lactone mix
Parthenolide
3 µg/cm2
Budesonide
µg/cm2
Tixocortol pivalate
µg/cm2
Methyldibromo glutaronitrile 0.3% pet
µg/cm2
Dibromodicyanobutane/phenoxyphenol (1:4)
Hydroxyisohexyl 3-cyclohexene
carboxaldehyde
Fragrance mix II
Methylisothiazolinone
Caine mix
630 µg/cm2
Quinoline mix
190 µg/cm2
Black rubber mix
75 µg/cm2
Carba mix
250 µg/cm2
Thimerosal
7 µg/cm2
Ethylenediamine
50 µg/cm2
Hydrocortisone-17-butyrate
µg/cm2
Diazolidinyl urea
550 µg/cm2
Imidazolidinyl urea
600 µg/cm2
Gold Sodium Thiosulfate
75 µg/cm2
Bacitracin
600 µg/cm2
Disperse Blue 106
50 µg/cm2
2-Bromo-2-Nitropropane-1,3-diol
250 µg/cm2
5% pet.
5% pet.
0.01% aq.
2% pet.
0.01% aq.
4 µg/cm2
2% pet.
0.01% pet.
0.1% pet.
0.1% pet.
0.01% pet.
0.1% pet
0.01% pet.
1
1% pet
0.1% pet.
3
0.5% pet
5
1% pet
5% pet.
5% pet.
14% pet
14 %pet
0.2% pet
.
20
_______________________________________________________________________
The European baseline series is dynamic and subject to continual modification depending on
population exposures and prevalence of contact allergy. It can be complemented to include
allergens of local importance to specific dermatology departments. Allergens are obtainable from
the following manufacturers (although there may be local distributors in some countries):
9






AllergEAZE®, SmartPractice® Canada, 2150 29 Street NE, Unit 30, Calgary, AB T1Y 7G4, Canada
available at http://www.allergeaze.com/
Brial® Allergen GmbH, Bövemannstrasse 8, D-48268 Greven , Germany available at
http://www.brial.com/en/default_en.asp
Chemotechnique Diagnostics, Modemgatan 9, Vellinge S-235 39, Sweden; available at
http://www.chemotechnique.se/
Trolab®, SmartPractice, Scholtzstr. 3, D-21465 Reinbeck, Germany; available at
http://www.trolab.com/
TRUE TEST® Panels 1, 2 and 3 .SmartPractice, Hillerød, Denmark; available at
http://www.truetest.com/
van der Bend™, Klosterweg 34, Brielle, the Netherlands; available at
http://www.vanderbend.nl/producten.php?pr_id=6
Vehicles and concentrations
For the most part, allergens are dispersed in white soft paraffin (petrolatum) and are supplied in
labelled syringes with the name and concentration of the substance on the label, together with an
expiry date. Petrolatum is inexpensive, practical, gives good occlusion and can be mixed thoroughly
with most substances. However, choice of vehicle is important and some substances are better
tested in solution in water or ethanol. Test concentrations have been selected based on experience to
elicit an allergic response in those previously sensitized and to cause no positive reaction in those
who are not allergic. For these allergens patch test sensitisation is considered to be extremely rare.
For ease of clinical practice, groups of test allergens are arranged into test series or “batteries.”
Over 300 test allergens are available from suppliers, and others can be made up from the patient’s
own materials (see section VII). Supplementary test in individual cases may be performed with
patient´s own materials and working materials based on exposure evaluation (Jolanki et al 2000;
Frosch et al, 2011; Krautheim et al 2012) see section VII.
It is sometimes necessary to obtain constituent ingredients directly from the product manufacturer
in order to identify the causative allergen, if it is not explained by testing to selected test allergens.
In this way, new allergens may be identified for further evaluation. Constituent ingredients can be
made up for patch testing, but care should be taken to find the appropriate concentration and vehicle
(De Groot 2008). Moreover issues on purity, original concentration and reliability on this
manufacturer raise the question of extra cautiousness.
Storage and stability
Patch test materials should be stored at 4°C in the dark.
Some contact allergens with high vapor pressure as some fragrance chemicals, acrylates and
isocyanates are unstable and require more frequent renewal and strict storage conditions (Goon et
al 2011; Mose et al 2012). For some of the products (or patch test substances) storage in the freezer
is recommended. Glutaraldehyde in petrolatum and formaldehyde in aqueous solution are also
subject to instability and deterioration. It is important to respect expiration dates (Joy et al 2013;
Siegel et al 2014)
10
III. Technique
Magnus Bruze, Magnus Lindberg, Vera Mahler, Mihály Matura,
Comments from Andreas, Margarida included from 21.August
Dosing of chambers
The elicitation of a positive patch test reaction in a given individual depends upon
(i) the dose, i.e. the number of molecules of the allergen applied;
(ii) the patch test technique, i.e. the vehicle used and type of occlusion; and
(iii) the occlusion time (1-5).
The dose is determined by the concentration and volume/amount of test preparation applied. Thus,
if the same amount/volume of a test preparation is applied all the time with the same test technique
(same area of skin) and occlusion time, it is appropriate to use concentration as a dose parameter.
For most sensitizers, petrolatum (pet.) is an appropriate vehicle as it is stable and seems to
prevent/diminish degradation as well as oxidization and polymerization but not evaporation, of the
incorporated allergen (6-9). However, with pet. as the vehicle, it is impossible to repeatedly apply
an exact volume/amount. An experienced and trained person can, however, keep the variation
within a limited range (10,11).
Generally, petrolatum-based patch test substances should be prepared shortly before application of
the patches (no longer than a few hours), liquids and some volatile petrolatum-based substances
(e.g. acrylates) at the time of application. ((table of (critical) substances))  Magnus (to be
specified)
Until 2007 there was no amount of petrolatum preparation recommended to be applied on a small
Finn chamber (diameter 8 mm) or any other patch unit to be loaded before the application on the
skin. In 2005 and 2006 the Department of Occupational and Environmental Dermatology in Malmö
performed studies on the appropriate amount of petrolatum preparation to apply on a small Finn
chamber on behalf of the European Society of Contact Dermatitis. 20 mg petrolatum preparation
was the optimal dose for the Finn chamber (40 mg/cm2). Patch test courses held at the Department
of Occupational and Environmental Dermatology have shown that testing personnel can learn how
to apply a defined amount such as 20 mg petrolatum preparation with a minor variation of amount
applied (12). When other test chambers are used the same dose/unit area skin can be used.
<insert recommended doses for the most common test systems>
Besides petrolatum preparations, there are also aqueous test solutions in the European baseline
series (13). For liquid vehicles, i.e. solutions there have been generally accepted volumes to be
applied in each chamber when testing with the Finn chamber technique with internal diameter 8 mm
and van der Bend chamber technique, i.e. 15 µl and 20 µl, respectively (14,15). For solutions, as
opposed to petrolatum preparations, it is easy to apply the same amount/volume repeatedly if using
a micropipette. However, micropipettes are not used everywhere when applying test solutions to
patch test chambers. Besides the micro-pipette technique there are 2 other major ways to apply a
test solution onto a chamber. The drop technique means that a drop of solution is placed on the
chamber by squeezing the plastic bottle containing the test solution. The drop and wipe technique
means that a drop of test solution is placed on the filter paper of a test chamber by squeezing the
11
container. Before testing, the excess solution is wiped off with a soft tissue. A study comparing the
3 techniques using aqueous formaldehyde 1% and
methylchloroisothiazolinone/methylisothiazolinone 200 ppm aiming at the application of 15 µl of
the respective test solution showed that the micro-pipette technique had the best accuracy and
precision as well as the lowest variation between the 4 technicians participating in the study (ref).
Recommendation:
The optimal dose of petrolatum preparations in a 8 mm Finn Chamber is 20 mg (40 mg/cm2) and
15 µl of preparations in liquid vehicle
Liquids should be dosed with a micro pipette.
References
1. Upadhye M R, Maibach H I. Influence of area of application of allergen on sensitization in
contact dermatitis. Contact
Dermatitis 1992:27:281–6.
2. Bruze M. Patch testing with nickel sulphate under occlusion
for five hours. Acta Derm Venereol 1988: 68: 361–364.
3. Friedmann P S, Moss C, Shuster S, Simpson J M. Quantitative
relationships between sensitizing dose of DNCB and
reactivity in normal subjects. Clin Exp Immunol 1983:53:
709–15.
4. Bruze M, Conde-Salazar L, Goossens A, Kanerva L, White
I R. Thoughts on sensitizers in a standard patch test series.
The European Society of Contact Dermatitis. Contact
Dermatitis 1999:41:241–50.
5. Webster R C, Maibach H. Percutaneous absorption relative
to occupational dermatology. In: Occupational and Industrial
Dermatology, Maibach H (ed.): Chicago: Yearbook Medical
Publishers Inc., 1987:241–57.
6. Bruze M, Fregert S. Studies on purity and stability of
photopatch test substances. Contact Dermatitis 1983:9:33–9.
7. Isaksson M, Gruvberger B, Persson L, Bruze M. Stability of
corticosteroid patch test preparations. Contact Dermatitis
2000:42:144–8.
8. Andersen K E, Rastogi S C, Carlsen L. The Allergen Bank:
a source of extra contact allergens for the dermatologist in
practice. Acta Derm Venereol 1996:76:136–40.
9. Mowitz M, Zimerson E, Svedman C, Bruze M.
Stability of fragrance patch test preparations applied in test chambers.
Br J Dermatol. 2012 :167:822-7.
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10. MoffittD L, Sharp L A, Sansom J E. Audit of Finn Chamberpatch test preparation. Contact
Dermatitis 2002:47:334–6.
11. Bruze M, Frick-Engfeldt M, Gruvberger B, Isaksson M.
Variation in the amount of petrolatum preparation applied at patch testing.
Contact Dermatitis. 2007:56:38-42.
12. Bruze M, Isaksson M, Gruvberger B, Frick-Engfeldt M. Recommendation of appropriate
amounts of petrolatum preparation to be applied at patch testing. Contact Dermatitis 2007:56:281-5.
13. Bruze M, Goossens A, Isaksson M. Recommendation to increase the test concentration of
methylchloroisothiazolinone/methylisothiazolinone in the European baseline patch test series - on
behalf of the European Society of Contact Dermatitis and the European Environmental and Contact
Dermatitis Research Group.
Contact Dermatitis. 2014
14. Fischer T, Maibach H. Finn chamber patch test technique.
Contact Dermatitis 1984:11:137–40.
15. Isaksson M, Gruvberger B, Frick-Engfeldt M, Bruze M.
Which test chambers should be used for acetone, ethanol, and water solutions when patch testing?
Contact Dermatitis. 2007:57:134-6.
16. Frick-Engfeldt M, Gruvberger B, Isaksson M, Hauksson I, Pontén A, Bruze M.
Comparison of three different techniques for application of water solutions to Finn Chambers®.
Contact Dermatitis. 2010:63:284-8.
Anatomical site of patch test application
For practical reasons, the upper back is chosen. Reasons not to do so include …. Although in some
cases this area is not available or large enough for performing all tests planned. Sometimes the back
can not be used be it because of skin severe acne or scar formation or the nowadays more and more
popular giant tattoos covering the back. Some patients will not accept tests and potentially long
lasting reactions on their back because of cosmetic or medical reasons.
There are obvious variations in reactivity of the skin between different anatomical regions. For
example the forearm is less responsive to elicitation of contact allergy to nickel. (Memon ref) When
comparing sensitivity of various skin sites in repeated open application test Hannuksela (ref) found
that the lower arm was less sensitive than the upper arm and the skin of the back was most reactive.
13
In most countries the skin of the back is the preferred place of patch test application. Besides
practical aspects regarding testing on the back there is an important additional factor that one must
keep in mind, namely our goal for standardization. As outlined above the penetration is a crucial
factor for the effective dose of an allergen. As penetration of the skin has a big variation depending
on different anatomical sites using varying body sites for patch testing of the same substance might
result in varying grade of response. The back offers a flat surface for constant and sufficient
occlusion and large enough surface for application of up to 100 to XXX patch test substances. It is
less often affected by skin diseases, less exposed to sun and lies in comforting distance from
scratching hands. Some studies showed a higher reactivity of the upper back (especially when using
laser Doppler for evaluation Strien and Korstantje) compared to the lower back but later studies of
Simonetti et al and Memon and Friedman have not confirmed such a difference. Sometimes the
outer surface of the arms or similarly the thighs can also be used if the surface on the back of the
patients is not sufficient or can not be used for other reasons.
Recommendation
The upper back is the preferred site for patch testing. Outer surface of the arms or thighs can be
used if the back is not available for patch testing.
Occlusion time
Occlusion time is the duration of application of the patch test allergen to the skin. Exposure of the
outer surface of the horny layer to the haptens is obtained by an occlusive patch test chamber
system.The penetration is actually forced via occlusion and the quantitative aspects about this
process are not fully known. Penetration of substances and the process of enhanced penetration with
the help of occlusion (which among other factors increases the hydration of the skin and most likely
facilitates the penetration of less lipophilic or mainly hydrophilic substances) considerably varies
between different chemical substances. The currently used occlusion time established for patch
testing is a practical compromise, which makes it possible to patch test with many different
substances at the same time. Most handbooks and experts recommend an occlusion time of 48 hours
(2 days). A lower number of questionable and irritant patch test reactions as well as a lower
frequency of active sensitization to ?was observed after a 24h-exposure and first reading at day 1
[ 10,11].
In studies on PPD-allergic subjects it was shown that with longer occlusion time lower
concentrations of PPD were necessary to elicit a positive response (Hextall ref). In case of strong
contact allergy to PPD 30 minutes-application of PPD 1% in pet. was sufficient to elicit positive
responses. It was not the case for those patients that showed a lower reactivity. Even for some
contact allergens (in the particular case; photocontact allergen), e.g. ketoprofen (Marmgren) a much
shorter occlusion (1 hour) than 48 hours seems to be as effective as the traditional occlusion period.
On the contrary, it has been shown for nickel that 48 hours occlusion time reveals a higher
frequency of positive reactions compared to 24 hours occlusion (Kalimo 1984). However, it has
been also been shown for nickel that lowering the occlusion time can be compensated by a higher
test dose (Bruze 1988). Isaksson et al (ref) compared 5, 24 and 48 hours occlusion for several
dilutions of budesonide in allergic subjects and found that 48 h occlusion method revealed the
most positive responses. In contact allergy studies on DNCB (Friedman Moss Schuster DNCB)
longer duration of application at challenge evoked stronger responses because larger effective
dose has been reached the skin immune system.
14
Neither the literature study of Manuskiatti and Maibach, nor the data of Brasch et al revealed proof
for a general superiority of 24 versus 48 hours occlusion. Still, as no definite conclusion can be
drawn from studies of different methodology most handbooks and authors including the latest
recommendation by the ICDRG (Fregert 1981) recommend an occlusion time of 48h. For practical
purposes it is preferred to use days as denominators e.g day 2 , day 4 etc. Longer application
periods are not recommended
Recommendation
2 days occlusion are recommended.
References:
Brasch J, Geier J, Henseler T. Evaluation of patch test results by use of the reaction index-an
analysis of data recorded by the Information Network of Departments of Dermatology (IVDK).
Contact Dermatitis 1995;33: 375–80.
Bruze M. Patch testing with nickel sulphate under occlusion for five hours.
Acta Derm Venereol. 1988;68(4):361-4.
Fregert S. Manual of Contact Dermatitis. On behalf of the International Contact Dermatitis Group
and the North American Contact Dermatitis Group. Copenhagen: Munksgaard Publishers, 1981/2nd
edition.
Friedmann PS, Moss C, Shuster S, Simpson JM. Quantitative relationships between sensitizing dose
of DNCB and reactivity in normal subjects. Clin Exp Immunol. 1983 Sep;53(3):709-15.
Hannuksela M. Sensitivity of various skin sites in the repeated open application test. Am J Contact
Dermatitis. 1991; 2:102-104
Hextall JM, Alagaratnam NJ, Glendinning AK, Holloway DB, Blaikie L, Basketter DA, McFadden
JP. Dose-time relationships for elicitation of contact allergy to para-phenylenediamine. Contact
Dermatitis. 2002 Aug;47(2):96-9.
Isaksson M, Bruze M, Goossens A, Lepoittevin JP. Patch testing with budesonide in serial
dilutions: the significance of dose, occlusion time and reading time. Contact Dermatitis. 1999
Jan;40(1):24-31.
Kalimo K, Lammintausta K. 24 and 48 h allergen exposure in patch testing. Comparative study with
11 common contact allergens and NiCl2. Contact Dermatitis. 1984 Jan;10(1):25-9
Manuskiatti W, Maibach HI. 1- versus 2- and 3-day diagnostic patch testing. Contact Dermatitis.
1996 Oct;35(4):197-200
Marmgren V, Hindsén M, Zimerson E, Bruze M. Successful photopatch testing with ketoprofen
using one-hour occlusion. Acta Derm Venereol. 2011 Mar;91(2):131-6.
Memon AA, Friedmann PS. Studies on the reproducibility of allergic contact dermatitis. Br J
Dermatol. 1996 Feb;134(2):208-14.
Simonetti V, Manzini BM, Seidenari S. Patch testing with nickel sulfate: comparison between 2
nickel sulfate preparations and 2 different test sites on the back. Contact Dermatitis. 1998
Oct;39(4):187-91.
van Strien GA, Korstanje MJ. Site variations in patch test responses on the back. Contact
Dermatitis. 1994 Aug;31(2):95-6.
15
Schnuch A, Aberer W, Agathos M, Becker D, Brasch J, Elsner P, Frosch PJ, Fuchs T, Geier J,
Hillen U, Löffler H, Mahler V, Richter G, Szliska C. Patch testing with contact allergens. Guideline
of the German Dermatologic Society and the German Society for Allergy and Clinical Immunology.
J Dtsch Dermatol Ges 2008; 6: 770-5.
Reading times
After start of test application (day 0) and an allergen exposure for 24 (day 1) or 48h (day 2) the
patch test chambers are removed and after 15-60 minutes the test reaction is read for the first time
[1-3]. Internationally, most authors advocate an exposure time of two days and first reading at day 2
[1-8]. In some countries the first reading is on day 3 or day 4 after an exposure time of 2 days (48h)
in agreement with the latest recommendation from the ICDRG (9).
A second reading day 3 or day 4 is obligatory [1, 5,10]. Further readings (day 5-10) may be
necessary. In a study where patch-tested individuals were read several times in the range day 2 –
day 9, the single day which traced most contact allergy was day 4 but to trace all contact allergy 2
readings on day 4 and day 7 were required (12). Depending on the allergen (e.g. corticosteroids,
aminoglycoside antibiotics) 7-30% of contact sensitizations will be missed unless not reading
around day 7 in addition to the reading on day3 or 4 (12-14).
Due to geographic or organizational circumstances the reading times may vary.
Recommendation:
At least 2 readings of the patch test reactions are recommended; ideally at day 3 or 4 and around
day 7. If only one reading is possible, day 4 (96 hours after start of allergen application) is
recommended.
Morphology
The reading of patch test reactions is based on inspection and palpation of the morphology
(erythema, infiltrate, papules, vesicles). The globally acknowledged reading criteria of the ICDRG
[1, 9] include:
Symbol
Morphology
Assessment
16
-
No reaction
negative reaction
?+
faint erythema only
doubtful reaction
+
erythema, infiltration, possibly papules
weak positive reaction
++
erythema, infiltration, papules, vesicles
strong positive reaction
+++
Intense
erythema,
infiltrate,
confluescing extreme positve reaction
vesicles
IR
various morphologies, e.g. soap effect, bulla, irritant reaction
necrosis
Positive patch test reactions ("+", "++" or "+++") at the 72h- or at a later reading-time are usually
assessed as allergic. An allergic versus irritant aetiology of weak reactions (erythema only or few
follicular papules, sometimes even of “+”-reactions) cannot be distinguished based on morphology
alone [18]. Questionable reactions (?+) may be clinically relevant and important for the individual
patient and may need further work-up (e.g. repetition of the patch test with several
concentrations/serial dilutions, use test) [18].
Substances in a liquid vehicle may lead to a ring-shaped test reaction. Sharp-edged margins and fine
wrinkling of the surface of the test area point towards irritant reactions.
The assessment of patch test reactions also includes reaction dynamics between first and second
reading: A crescendo- or plateau-pattern is indicative for an allergic, a decrescendo for an irritant
reaction.
Over the years, different patch test traditions and reading systems have evolved, and are used
unequally in different countries [19]. Recently, an interindividual inhomogeneity has been
identified in discriminating between doubtful and irritant reactions and in the grading between
doubtful and weak positive allergic + reactions [18, 19]. Further standardization and reading
training is advisable [19].
After the reading of patch test reactions a conclusive interpretation is mandatory concerning the
relevance of the test reactions in the respective case with regard to the patient’s history, exposure
and clinical course (see section IX)..
For the interpretation it is necessary to keep in mind, that besides their properties as a patch test
allergen, most patch test chemicals also have an irritant potential to a certain degree [20], which is
more predominant for some allergens (e.g. benzoylperoxide, phenyl mercuric acetate, propylene
glycol, benzalkonium chloride, octyl gallate, cocamidopropyl betaine, 1,3-diphenyl-guanidine)
17
resulting frequently in weak erythematous (questionable) test reactions [21-23]. A relevant factor
for the assessment of patch test results is the individual skin sensitivity and irritability of the
individual tested at the time of patch testing. At times of individually increased skin irritability more
nonspecific questionable test reactions may occur. An irritant control patch test is done in some
centres (e.g. SLS 0.25% aq., e.g. [24]) where it is considered to help in the interpretation of weak
reactions to allergens. The value of such “control” has not been unequivocally proven. .
Recommendation: The patch test is read according to morphology. A positive patch test reaction is
defined as a reaction which fulfils the criteria of at least a 1 + reaction.
18
References
1. Magnusson B, Blohm SG, Fregert S, Hjorth N, Hovding G, Pirilä V, Skog E. Routine patch
testing. II. Proposed basic series of test substances for Scandinavian countries and general remarks
on testing technique. Acta Derm Venereol 1966; 46: 153-8.
2. Schnuch A, Aberer W, Agathos M, Becker D, Brasch J, Elsner P, Frosch PJ, Fuchs T, Geier J,
Hillen U, Löffler H, Mahler V, Richter G, Szliska C. Patch testing with contact allergens. Guideline
of the German Dermatologic Society and the German Society for Allergy and Clinical Immunology.
J Dtsch Dermatol Ges 2008; 6: 770-5.
3. Lindberg M, Matura Mihaly. Patch testing. In:Johansen JD; Frosch PJ, Lepoittevin, JP (Eds.).
Contact Dermatitis. Springer Berlin Heidelberg, Fifth edition, 2011, pp.439-464.
4. Lachapelle J-M, Maibach HI. Patch Testing, Prick Testing. A Practical
Guide. Springer Berlin Heidelberg, 2003.
5. Bourke J, Coulson I, English J; British Association of Dermatologists Therapy Guidelines and
Audit Subcommittee.Guidelines for the management of contact dermatitis: an update. Br J Dermatol
2009; 160: 946-54.
6. Uter W, Rämsch C, Aberer W, Ayala F, Balato A, Beliauskiene A, Fortina AB, Bircher A,
Brasch J, Chowdhury MM, Coenraads PJ, Schuttelaar ML, Cooper S, Corradin MT, Elsner P,
English JS, Fartasch M, Mahler V, Frosch PJ, Fuchs T, Gawkrodger DJ, Gimènez-Arnau AM,
Green CM, Horne HL, Jolanki R, King CM, Krêcisz B, Kiec-Swierczynska M, Ormerod AD, Orton
DI, Peserico A, Rantanen T, Rustemeyer T, Sansom JE, Simon D, Statham BN, Wilkinson M,
Schnuch A. The European baseline series in 10 European Countries, 2005/2006--results of the
European Surveillance System on Contact Allergies (ESSCA). Contact Dermatitis 2009; 61:31-8.
7. Johansen JD, Menné T, Christophersen J, Kaaber K, Veien N. Changes in the pattern of
sensitization to common contact allergens in denmark between 1985-86 and 1997-98, with a special
view to the effect of preventive strategies. Br J Dermatol 2000; 142:490-5.
19
8. Svedman C, Andersen KE, Brandão FM, Bruynzeel DP, Diepgen TL, Frosch PJ, Rustemeyer T,
Giménez-Arnau A, Gonçalo M, Goossens A, Johansen JD, Lahti A, Menné T, Seidenari S, Tosti A,
Wahlberg JE, White IR, Wilkinson JD, Mowitz M, Bruze M. Follow-up of the monitored levels of
preservative sensitivity in Europe: overview of the years 2001-2008. Contact Dermatitis 2012;
67:312-4.
9. Brasch J, Geier J, Henseler T. Evaluation of patch test results by use of the reaction index. An
analysis of data recorded by the Information Network of Departments of Dermatology (IVDK).
Contact Dermatitis 1995; 33:375-80.
10. Hillen U, Jappe U, Frosch PJ, Becker D, Brasch J, Lilie M, Fuchs T, Kreft B, Pirker C, Geier J;
German Contact Dermatitis Research Group. Late reactions to the patch-test preparations paraphenylenediamine and epoxy resin: a prospective multicentre investigation of the German Contact
Dermatitis Research Group. Br J Dermatol 2006; 154: 665-70.
11. de Waard-van der Spek FB, Oranje AP. Patch tests in children with suspected allergic contact
dermatitis: a prospective study and review of the literature. Dermatology 2009; 218:119-25.
12. Simonsen AB, Deleuran M, Mortz CG, Johansen JD, Sommerlund M.Allergic contact
dermatitis in Danish children referred for patch testing - a nationwide multicentre study. Contact
Dermatitis 2014; 70:104-11.
13. Worm M, Aberer W, Agathos M, Becker D, Brasch J, Fuchs T, Hillen U, Höger P, Mahler V,
Schnuch A, Szliska C; German Contact Dermatitis Research Group (DKG).
Patch testing in children--recommendations of the German Contact Dermatitis Research Group
(DKG). J Dtsch Dermatol Ges 2007; 5: 107-9.
14. Fregert S. Manual of Contact Dermatitis. On behalf of the International Contact Dermatitis
Research Group and the North American Contact Dermatitis Group. Copenhagen: Munksgaard
Publishers,1981/2nd edition.
20
15. Andersen KE, Andersen F. The reaction index and positivity ratio revisited. Contact Dermatitis
2008: 58: 28–31.
16. Svedman C, Isaksson M, Björk J, Mowitz M, Bruze M 'Calibration' of our patch test reading
technique is necessary. Contact Dermatitis 2012; 66:180-187.
17. Nosbaum A, Vocanson M, Rozieres A, Hennino A, Nicolas JF. Allergic and irritant contact
dermatitis. Eur J Dermatol 2009; 19: 325-32.
18. Geier J, Uter W, Lessmann H, Schnuch A. The positivity ratio –another parameter to assess the
diagnostic quality of a patch test preparation Contact Dermatitis. 2003; 48: 280-282.
19. Brasch J, Henseler T. The reaction index – a parameter to assess the quality
of patch test preparations. Contact Dermatitis 1992: 27: 203–204.
20. Brasch J, Geier J. How to use the reaction index and positivity ratio. Contact Dermatitis 2008:
59: 63–65.
21. Löffler H, Becker D, Brasch J, Geier J. Simultaneous sodium lauryl sulphate testing improves
the diagnostic validity of allergic patch tests. Results from a prospective multicentre study of the
German Contact Dermatitis Research Group (DKG). Br J Dermatol 2005; 152: 709-19.
Factors of the patch test system
To modify is defined as to change some parts of (something) while not changing other parts
(www.merriam-webster.com/dictionary).
The patch test technique is constantly developing and all points mentioned below (a-g) can be
modified. During the past years much focus has been on standardization of the different parts of the
test system, especially the European base line series and various national baseline series. By
changing one or several parts (a-g) of the system there is a need for standardization of this (these)
changes and also a validation of the whole test system for each change. (1, 9, 13)
The system for patch testing can be defined as consisting of the following parts (13):
a. The test preparation which in turn is composed of a substance, mix of substances or a
product used as is or dissolved in a vehicle.
21
b. The applied amount of the test preparation.
The application technique used.
c. Time of application (time of occlusion).
d. Reading time (-s)).
Evaluation of patch test morphology.
e. The status of the skin where the test is applied.
Selected references
1
2
3
4
5
6
7
8
9
10
11
Svedman C, Isaksson M, Bjork J, Mowitz M, Bruze M. 'Calibration' of our patch test
reading technique is necessary. Contact dermatitis 2012: 66: 180-7.
Mowitz M, Zimerson E, Svedman C, Bruze M. Stability of fragrance patch test preparations
applied in test chambers. The British journal of dermatology 2012: 167: 822-7.
Isaksson M, Moller H, Bruze M. The reliability of visual scoring of patch test reactions
revisited. Contact dermatitis 2012: 66: 163.
Goon A T, Bruze M, Zimerson E, Sorensen O, Goh C L, Koh D S, Isaksson M. Variation in
allergen content over time of acrylates/methacrylates in patch test preparations. The British
journal of dermatology 2011: 164: 116-24.
Frick-Engfeldt M, Gruvberger B, Isaksson M, Hauksson I, Ponten A, Bruze M. Comparison
of three different techniques for application of water solutions to Finn Chambers(R).
Contact dermatitis 2010: 63: 284-8.
Isaksson M, Gruvberger B, Frick-Engfeldt M, Bruze M. Which test chambers should be
used for acetone, ethanol, and water solutions when patch testing? Contact dermatitis 2007:
57: 134-6.
Bruze M, Isaksson M, Gruvberger B, Frick-Engfeldt M. Recommendation of appropriate
amounts of petrolatum preparation to be applied at patch testing. Contact dermatitis 2007:
56: 281-5.
Dickel H, Kreft B, Kuss O, Worm M, Soost S, Brasch J, Pfutzner W, Grabbe J, AngelovaFischer I, Elsner P, Fluhr J, Altmeyer P, Geier J. Increased sensitivity of patch testing by
standardized tape stripping beforehand: a multicentre diagnostic accuracy study. Contact
dermatitis 2010: 62: 294-302.
Wolf R, Orion E, Ruocco V, Baroni A, Ruocco E. Patch testing: facts and controversies.
Clinics in dermatology 2013: 31: 479-86.
Uter W, Frosch P J, Becker D, Schnuch A, Pfahlberg A, Gefeller O. Are we biased when
reading a doubtful patch test reaction to a 'clear-cut' allergen such as the thiuram mix?
Contact dermatitis 2009: 60: 234-5.
Uter W, Frosch P J, Becker D, Schnuch A, Pfahlberg A, Gefeller O. The importance of
context information in the diagnostic rating of digital images of patch test reactions. The
British journal of dermatology 2009: 161: 554-9.
22
12
13
14.
15.
Uter W, Becker D, Schnuch A, Gefeller O, Frosch P J. The validity of rating patch test
reactions based on digital images. Contact dermatitis 2007: 57: 337-42.
Lindberg M, Mihaly M. Patch testing. In Eds. Johansen JD, Frosch PJ, Lepoittevin J-P,
Contact Dermatitis 5:th edition, pp 439-464, Springer Verlag, 2010.
Niinimäki A. Scratch-chamber tests in food handler dermatitis. Contact Dermatitis
1987:16:11-20.
Hannuksela M. Epicutaneous testing. Allergy 1979:34:5-10.
IV. Other techniques
Comments from Tove, Mark and Jørgen 2. Sep 2014 included
Alicia Cannavó and Klaus E. Andersen
REPEATED OPEN APLICATION TEST (ROAT)
The repeated open application test (ROAT) was developed by Hannuksela and Salo. It is
today a standardised exposure test mimicking a user situation, where it is possible over
few weeks in cooperative sensitive patients to study hypersensitivity by repeated
applications to the volar forearm of the suspected product containing the allergen in
question. It aims at eliciting allergic contact dermatitis in the test area. By using this
method it is possible to clarify the clinical importance of selected patch test reactions. The
ROAT may be useful both in experimental studies and in the daily clinic.
Indication for ROAT:
- clarify the relevance of selected positive and doubtful patch test positive reactions.
- testing of leave-on cosmetics, topical drugs and other suitable formulations
METHODOLOGY
Test substances, either commercial products or special test substances (e.g allergens)
applied twice daily usually for 2 weeks and up to four weeks on the flexor aspect of the
forearm near the ante-cubital fossa. The size of the test area is usually 3x3 to 5x5 cm, and
the amount of test substance should cover the test area. The applications continue until a
reaction develops or until the end of the selected trial period.
23
READING AND EVALUATION
A positive response in the form of eczematous dermatitis may appear after a few days or
later depending on dose/area, matrix effects and individual elicitation thresholds. However,
a negative ROAT after 1-2 weeks does not exclude a relevant allergic sensitivity.
Therefore extended application periods of 3-4 weeks may be relevant order not to miss
late appearing reactions. Johansen and co-workers developed a scale for evaluation of
ROAT responses. It is noteworthy that positive reactions often start with follicular papules
in the application area. It is advisable in selected cases to include control substance on the
contralateral arm, and ROAT may also be performed in a double blind fashion for research
purposes.
< consider inclusion of an illustration of a positive ROAT> insert scale
SEMIOPEN TEST
In 1995 Goossens suggested the use of semi-open test mainly for testing patient supplied
products with suspected irritant properties, e.g., shampoos, detergents, paints, resins,
varnishes, cooling fluids, pharmaceuticals and cosmetics. A small amount (about 15ul) of
the product is applied with a cotton swab on an area (1cm)2 of the skin, allowed to dry
completely, checked for signs of contact urticaria, then covered with acrylic tape. Readings
are performed the same way as for patch testing. Immediate reactions may appear after
20-30 minutes as a sign of contact urticaria, and eczematous reactions may develop at
days 2 to 4.
This is a practical tool which requires some experience for interpretation
OPEN TEST
The open test means that a product, as is or dissolved in water or some organic solvent
(e.g. ethanol, acetone, either products), is dropped onto the skin and allowed to dry. No
occlusion is used. The usual test site is the volar forearm, but it is less reactive than the
upper back or the upper arm. An open test is recommended as the first step, when testing
poorly defined substances or products such as those brought by the patient (section VII).
Readings are made at regular intervals during the first 30 – 60 minutes after application in
order to detect immediate reactions or urticaria. A second reading should be done at 3 – 4
days. A negative open test can be explained by insufficient penetration, but indicates that
one may proceed with an occlusive patch test.
WARNING:
These types of tests should only be undertaken by clinicians experienced in patch testing
who fully understand the hazards of the applied substances / products.
Photo patch testing
Comments from Tove, Mark and Jørgen 2. Sep 2014 included
24
Margarida Gonçalo, Andreas Bircher
Photopatch testing is mainly indicated in the study of photoallergic contact dermatitis, where
ultraviolet exposure is necessary to induce the hypersensitivity reaction, but it can be helpful also
in the study of any dermatitis of the photoexposed areas or in systemic drug photosensitivity
(Bruynzeel et al., 2004).
For performing photopatch- testing a duplicate set of allergens is prepared and applied on two
different areas of the back. ((insert a sentence from Margarida))After 24 or 48h of occlusion one
set of tests is irradiated with 5J/cm2 of UVA while the other is completely shielded from light and
should be kept protected until further reading. Readings should be performed before and
immediately after irradiation and at least 48h thereafter. Grading of the reactions should obey the
general rules of patch tests reading but for result interpretation it is necessary to compare reactions
in the irradiated and non-irradiated sites. A positive photopatch tests occurs when there is no
reaction at the non-irradiated site and a positive (1+ to 3+) on the irradiated one. Positive reactions
on both sets of tests represent a contact allergy, with photoaggravation if the irradiated test is at
least 1+ more intense than the non-irradiated, or with photo-inhibition if the irradiation reaction is
less intense.
Non
irradiated
Irradiated
Final diagnosis
neg.
pos.
PhCA
pos.
pos.
CA
At present the recommended European baseline series for photopatch testing includes mostly UV
filters of the different chemical families, non-steroidal anti-inflammatory drugs and a few older
photosensitizers (Gonçalo et al., 2013). A more extended photopatch test series may be used, or
any product suspected to be implicated in the reaction can also be photopatch tested.
In highly suspected cases UVB can additionally be used to irradiate one set of allergens. In the
photosensitive patient, it is recommended to determine first their reactivity to UV light (phototests
performed on the day of application of the patches) and, the UV dose for irradiation of the test site
will be only 75% of their MED.
References
ROAT, semiopen, open.
Hannuksela M, Salo H. The repeated open application test (ROAT) in Contact Dermatitis 1986 14
(4): 221-7
Lachapelle, J.M; Maibach H.I in Patch Testing. Prick Testing. A practical guide
25
Chapter 5, p95-100, Chapter 7, 111-120, Chapter 11, 149-162, Springer-Verlag Berlin Heidelberg,
Germany, 2003
Johansen JD, Bruze M, Andersen KE, Frosch PJ, Dreier B, White IR, Rstogj S, Lepoittevin JP,
Menné T. The repeated open applied test: suggestions for a scale of evaluation. Contact
Dermatitis 1998 Aug; 39(2): 95-6
Fischer LA, Voelund A, Andersen KE, Menné T, Johansen JD. The dose response relationship
between the patch test and ROAT and the potencial use for regualtory purpose. Contact
Dermatitis 2009 Oct:61 (4): 201-8
Goossens A. Alternatives to patch tests. Ann Dermatol Venereol 2009 Aug-Sep, 136 (8-9): 623-5
Heratizadeh A, Killig C, Worm M, Soost S, Simon D, Bauer A, Mahler V, Schuster C, Szliska C,
Frambach Y, Eben R, Werfel T, Uter W, Schnuk A. Quantitative repeated open applicaation
testing with a rinse off product in methyldibromo glutaronitrile-sensitive patients: results of the
IVDK. Contact Dermatitis. 2010 Jun, 62(6):330-7
Bruze M, Johansen JD, Andersen KE, Frosch P, Goossens A, Lepoittevin JP, Rastogi SC, White I,
Menné T. Deodorants: an experimental provocation study with isoeugenol Contact Dermatitis.
2005 May, 52(5) :260-7
Frosch P, Rastogi SC, Pirker C, BrinkmeierT, Andersen KE, Bruze M, Svedman C, Goossens A,
White IR, Uter W, Arnau EG, Lepoittevin JP, Menne T. Patch testing with a new fragante mixreactivity to the individua constituents and Chemicals detection in relevant cosmetic products.
Contact Dermatitis. 2005 Apr, 52 (4): 216-25.
Gruvberger B, Andersen KE, Brandao FM, Bruynzeel DP, Bruze M, Frosch PJ, Goosens A, Lahti
A, Maibach HI, Menné T, Orton D, Seidenari S. Repeated open application test with
methyldibromo glutaronitrile, a multicentre study within the EECDRG. Cntact Dermatitis 2005 Jan,
5281): 19-23
Johansen JD, Andersen KE, Menné T. Quantitavie aspects of isougenol contact allergy assessed
by use and patch tests. Contact Dermatitis 1996 Jun, 34 (6): 414-8
Svedman C, Engfeldt M, Api AM, Politano VT, Belsito DV, Isaksson M, Bruze M. A pilot study
aimed at finding a suitable eugenol concentration for a leave –on product for use in a repeated
open application test. Ann Dermatol Venereol 2009 Aug-Sep, 136 (8-9):596-9
Fischer LA, Johansen JD, Menné T. Nickel allergy: relationship between patch test and repeated
open application test thresholds. Br J Dermatol. 2007 Oct, 157(4):723-9
Svedman C, Bruze M, Johansen JD, Andersen KE, Goossens A, Frosch P, Lepoittevin JP,
Rastogi SC, White I, Menné T. Deodorants: an experimental provocation study with
ihydroxycitronellal. Contact Dermatitis. 2003 Apr,,48(4):217-223.
Jeanne Duus Johansen, Peter J. Frosch and Jean – Piere Lepoittevin
Contact dermatitis
Fifth Edition
Chapter 24, p 439-464
Chapter 29, p 519-531
Chapter 28, p511-517
26
Springer-Verlag Berlin Heidelberg
Germany, 2011
Guin J.D
Practical Contact Dermatitis
Capter 9, 93-96
1995, Mc Graw-Hill. New York United States of America
Luis Conde-Salazar Gómez y Armando Ancona Alayon
Dermatología Profesional.
Chapter 6, p 51 – 67.
Editorial Signament, Madrid, España, 2004
Giménez Camarasa José María
Dermatitis de Contacto
Chapter 7, p 77 - 87
Editorial Aula Médica
1999, Madrid. España
Kanerva L; Elsner P; Wahlberg J.E & Maibach H.I
Handbook of Occupational Dermatology
Chapter 46, p371 - 374
Springer, 2004
Fischer LA, Menné T,Johansen JD. Dose per unit area – a study of elicitation of nickel allergy.
Contact Dermatitis 2007 May, 56(5): 255-61
Zachariae C, Hall B, Cupferman S, Andersen KE, Menné T. ROAT: morphology of ROATon arm,
neck and face in formaldehyde and diazolidinyl urea sensitive individuals. Contact Dermatitis 2006
Ja, 54(1): 21-4
Zachariae C, Lerbaek A, McNamee PM, Gray JE, Wooder M, Menne T. An evaluation of
dose/unita rea and time as key factors influencing the elicitation capacity of
methylchloroisothiazolinone/methylisothiasolinone (MCI/MI) in MCI/MI allergic patients. Contact
Dermatitis 2006 Sep,55(3):160-6.
Weber F, Barbaud A, Reichert-Penetrat S, Danchin A, Schmutz JL. Unusual presentation in a
case of contact dermatitis due to corticosteroids diagnosed by ROAT. Contact Dermatitis 2001
Feb; 44(2):105-6
Photopatch testing
Bruynzeel, D., Ferguson, J., Andersen, K., Gonçalo, M., English, J., Goossens, A., … Tanew, A.
(2004). Photopatch testing: a consensus methodology for Europe. JEADV, 18, 679–682.
27
Gonçalo, M., Ferguson, J., Bonevalle, A., Bruynzeel, D. P., Giménez-Arnau, A., Goossens, A., …
Wilkinson, M. (2013). Photopatch testing: recommendations for a European photopatch test
baseline series. Contact Dermatitis, 68(4), 239–43. doi:10.1111/cod.12037
V. Influence of individual factors
Comments from Martine, An and Alicia 29th August included
1Tove
Agner, 1Jørgen Serup, 2 S Mark Wilkinson.
1Department
of Dermatology, University of Copenhagen, Bispebjerg Hospital, 2400 Copenhagen,
Denmark, 2 Spire Hospital, Leeds LS8 1NT, UK
Search strategy:
Historic data was reviewed by reference to relevant chapters in Burns DA, Breathnach S, Cox N,
Griffiths CEM. Rook’s Textbook of Dermatology 8th edition Blackwell (Oxford) 2010 and Johansen,
JD, Frosch, PJ, Lepoittevin, JP. Contact Dermatitis. 5th edition Springer (Berlin) 2011. This was
supplemented by searching PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) using relevant
search terms and a hand search of the indices of the journals Contact Dermatitis and Dermatitis
from 2008.
When patch testing is used for identifying type IV sensitization as the trigger of allergic contact
dermatitis it is important, among other factors, to consider the responsiveness of the patient.
Many factors may theoretically weaken the patch test response, including medication,
immunosuppression, UV-light and tanning resulting in false negative reactions, whilst other factors
may increase the response, such as active eczematous disease. Much evidence within this area is
based on clinical experience, and limited controlled data are available.
Medication
Little data is in the literature about of the effect of immunosuppressive agents and allergic patch
test reactions. . In practice it may be difficult or impossible for patients to be removed from their
immunosuppressive drugs. In such circumstances patch testing may be undertaken, but the
clinician must be aware that false-negative reactions may occur. However, positive reactions may
occur despite immunosuppressive therapy. Whilst strong (++ and +++) responses may remain
unchanged, weak reactions may become negative. With respect to how many days an oral
treatment should be stopped to avoid a theoretical influence on patch testing, 5 half-lives of the
particular drug seems reasonable from a clinical point of view.
28
Antihistamines and disodium cromoglycate are not reported to influence the allergic contact
dermatitis reaction1, and the same is the case for non-steroidal anti-inflammatory drugs. Retinoids
(alitretinoin) are used in the treatment of hand dermatitis and whilst they are not thought to
influence the outcome of patch testing there is no data in the literature. Topical corticosteroids
have been reported to weaken the patch test response, although dependent on the potency ,and
not in all studies 6-8.
Immunosuppressive diseases
Some patients with severe generalised disease or certain cancer diseases may have an impaired
capacity for contact sensitization9-11.
UV-light/sun exposure
Exposure to UVB may reduce risk of sensitization and temporarily diminish the ability to elicit
allergic reactions in sensitized individuals. Whilst this seems not to be the case for UVA12;13, PUVA
is reported to cause a reduction in patch test reactions14. UV-irradiation resulted in a reduction in
epidermal LC numbers [Br J Dermatol. 2003 Feb;148(2):291-9. Alterations in human epidermal
Langerhans cells by ultraviolet radiation: quantitative and morphological study.
Seité S1, Zucchi H, Moyal D, Tison S, Compan D, Christiaens F, Gueniche A, Fourtanier A.].
.
Recommendation: If allergic contact dermatitis is suspected in patients under
immunosuppresionit is recommended not to restrain from patch testing, but to keep in mind that
false negative reactions may occur, and if possible, to repeat patch testing on a later stage.
Atopic dermatitis and concomitant active eczematous disease
In most studies the frequency of positive patch tests in atopic subjects is the same as in other
dermatitis patients, and therefore,- patch testing is encouraged at the same indication as other
patients, albeit that the interpretation may be difficult due to their generally hyper-reactive skin
with risk of false positive reactions. ((mention FLG – one referenceFilaggrin mutations are strongly
associated with contact sensitization in individuals with dermatitis.Thyssen JP, Linneberg A, Ross-Hansen K,
Carlsen BC, Meldgaard M, Szecsi PB, Stender S, Menné T, Johansen JD. Contact Dermatitis. 2013
May;68(5):273-6. doi: 10.1111/cod.12021. Epub 2013 Jan 24 ))
29
Box: Recommendation: Patients with atopic dermatitis should be patch tested … ((keep the Cronin
reference)) ((in the indication section))
.
VI. Special groups
1. Children
Including comments from Andreas B, Margarida 21. August 2014; WU, Vera, Carola and Swen 25.
July; Spiewak
Authors : Martine Vigan Department of Dermatology CHRU Besançon 3 boulevard Fleming 25030
Besançon Cedex tel : +33381218108. E-mail : martine.vigan@gmail.com
Prof. An Goossens, Contact Allergy Unit, Department of Dermatology, University Hospital
K.U.Leuven
Kapucijnenvoer 33. B-3000 Leuven, Belgium. E-mail: an.goossens@uzleuven.be
Dra. Alicia Cannavó, 25 de Mayo 1617, (B1638ABD) Vicente López. Provincia Buenos Aires.
República Argentina. E-mail: acannavo4@gmail.com
Prof. Radoslaw Spiewak, Department of Experimental Dermatology and Cosmetology, Jagiellonian
University Medical College, Krakow, Poland, email: spiewak.eu@gmail.com
INTRODUCTION
Allergic contact dermatitis (ACD) in children does occur, but has been under recognized and only
recently more extensively studied. Most physicians consider atopic dermatitis as the only diagnosis
when babies or toddlers suffer from eczema, while all children, whether atopic or not, may become
sensitized to environmental chemicals. Moreover, there are practical problems involved with patch
testing, particularly in very young children (1).
METHOD
The literature search was done using PubMed; key words used in various combinations were
“allergic contact dermatitis”, “children”, “baseline series”, “active sensitization”, “patch testing”. We
30
have selected the recent articles about epidemiologic data, adverse effects associated with an
allergen as well as papers discussing concentrations of allergens or abbreviated baseline series
PREVALENCE
Contact allergy in children of all ages is well documented (refs.)) Data on the prevalence of contact
allergy in healthy children are scarce and studies in children suspected to suffer from ACD are
difficult to compare because of differences in age groups, exposures to environmental agents,
indications for patch testing, selection of allergens tested, and atopic condition.
In a review of data obtained during the last decade (2) contact sensitization rates varying from 26.6
to 95.6% were observed in selected groups of children.
Atopic diathesis and atopic eczema seem relevant risk factors for contact sensitization (x,xx).
Infants and children may be prone to react to topical pharmaceuticals and skin-care products
(iatrogenic contact sensitization), to topical products used by their caregivers (dermatitis by proxy,
connubial dermatitis), or to any other material in prolonged contact with the skin. Adolescents are
more likely to become sensitized to similar allergens as adults, including initial contacts with
occupational sensitizers.
PATCH TESTING IN CHILDREN
Indications
Patch testing in children is considered to be safe and is recommended when allergic contact
dermatitis is suspected or needs to be excluded, as in adults (5).
Technique and allergens
The patch-testing technique is exactly the same as in adults, but certain factors need to be taken
into consideration, such as the smaller test area on the back and greater mobility of younger
children, therefore, with a need to use a stronger adhesive tape.
In case of contact dermatitis after a 'henna tattoo', even much lower concentrations of PPD or
shorter exposure times or open testing may be advisable to avoid unneccessarily strong patch test
reactions (11).
Patch testing with the products the children actually are exposed to, such as topical products,
antiseptics, toys, etc., along with their potential ingredients, is crucial (section VII). In young
children, in particular, they may sometimes be the only allergens to be tested. For guidance on
patch testing own products see section VII.
Recommendation
Patch testing in children is safe and indications are the same as in adults.
31
2. Occupational contact dermatitis
Including comments from Andreas and Margarida
Wolfgang Uter, Vera Mahler, Swen Malte John, Carola Lidén
Patients presenting with possibly work-related contact dermatitis require a number of special
considerations outlined in the following section.
Patient history
In addition to a standard history, present and previous (¿) employments, occupational exposures,
work tasks and other relevant aspects need to be documented in detail, also in view of their use in
a later medico-legal procedure (Fig. x). Some more common occupations may be familiar to the
physician, depending on his or her experience. Nevertheless, check lists may help to cover all
relevant aspects and, at the same time, aid documentation (e.g. “EVA Hair” available at
http://safehair.loungemedia.de/fileadmin/user_upload/documents/Documents/EVA_Hair_all_langua
ges_all_languages/Final_Agreement_Evaluation_questionnaireEN.pdf, last accessed 14-02-07).
Other occupations usually require consultation of textbooks (e.g. (1, 2)) or information resources
on the Internet (section XII) to get an idea of the array of relevant exposures. It has recently been
pointed out that sketches (3) or photographs (enabled by the increasingly used smart or mobile
phones) provided by the patient can be very helpful in identifying an exposure-related problem. It is
strongly recommended that a visit to the patient’s workplace is organized, because it may add
crucial information concerning the exposure.
Exposure analysis
After the collection of basic information from the patient’s history, it is often be necessary to
proceed to in-depth analyses of occupational exposures of the patient (Fig. x). Depending on the
national and regulatory framework, these can either be done e.g. by the treating physician,
occupational healthcare or occupational hygiene specialist, or by experts from the involved health
insurance. Exposure analysis includes two levels: (i) Collection of products and materials handled
by the patient along with information on their ingredients, e.g. in terms of material safety data
Sheets (MSDS) which often, however, lack sufficient degree of detail, or may even be misleading
or incorrect. (ii) Actual chemical analysis of working materials deemed possibly relevant by suitable
laboratory ((2) chapter 27). Spot tests, such as those available for nickel (dimethylglyoxime (DMG)
test) (5), cobalt (6, 7), diphenylcarbazide test for chromium (VI) and the chromotropic acid test for
formaldehyde ((2), chapter 27) are useful to screen the (working) environment for the presence of
these allergens.
Exposure analysis should ideally include also assessment of how much of the allergen is deposited
onto the skin ((2), chapter 27). Such information may be used when assessing the occupational
relevance of patch test reactions and planning exposure reduction (8). Only a few methods for
assessment of skin exposure to common allergens, such as metals (9), some hair dyes, epoxy and
acrylates, are available today ((2), chapter 27). The most simple, which easily can be applied in the
clinic or workplace, is to use the DMG test on the skin for qualitative assessment of nickel
exposure (10).
32
Patch testing with commercial preparations of occupational allergens
General recommendations outlined in this text should be considered. In addition, guided by the
patient’s occupation and individual exposures, special test series covering allergens to which the
patient may be exposed should be applied (Fig. x). Some textbooks or journal articles have offered
guidance on the selection of allergens and test series, respectively (e.g. (1, 2)). Moreover,
allergens offered by the patch test manufacturers are arranged in ‘test series’ indicatively covering
certain, e.g., occupational, exposure areas, in some cases following the recommendations of
(inter-) national contact dermatitis research groups. A case-by-case extension of these common
standards requires sufficient knowledge of the patient’s exposure; referral to specialised institutions
is advised. A missed allergen or allergens, besides other problems, must be suspected in case of
persisting skin problems.
Patch testing with work materials
Recommendations found in section VII of this text should be followed. In practice, it may be difficult
to obtain (i) a list of ingredients and (ii) the set of actual chemicals, to prepare allergens from these
for patch testing. Difficulties may be due to company secrets, unwillingness by employers, retailers
or manufacturers to respond, lack of information of downstream manufacturers or importers, lack of
time, dedication or knowledge by the physician, and unwillingness to undergo further testing from
the side of the patient. If successful, however, such detailed work-up can profoundly aid patient
management and may prompt preventive measures in the work place.
Relevance assessment and final diagnosis
Assessment of the clinical relevance of the patch test result is another difficult task, and particularly
so concerning occupational exposure in environments and to chemicals the dermatologist has little
experience with. The assessment may also have direct impact on the prognosis of the patient’s
dermatitis and future work career, on medico-legal decisions including compensation or re-training,
and on preventive measures in the workplace.
After the final reading of the patch test, best done at day 6 or 7 to reliably avoid false-negative
results (section III), the test result will either be entirely negative, or one or several contact allergies
will have been diagnosed. In case of a negative test, contact sensitisation as a cause of the
patient’s contact dermatitis has likely been ruled out regarding the set of allergens tested, which
should thus be sufficiently comprehensive. The patient needs to be made aware of the fact that this
is an important finding, and not a disappointment, and that other reasons of occupational contact
dermatitis, namely irritation and skin sensitivity, need to be addressed.
In case of one or more positive patch test reactions, the significance of each of these in terms of
“explaining” the episode of (occupational) contact dermatitis the patients is presenting with, i.e.,
“clinical relevance”, needs to be evaluated carefully. Regarding occupational relevance, the
association between onset and course of dermatitis (improvement or healing off work, relapse after
return to work?) and affected anatomical site (hand, face, other sites directly or indirectly exposed
by airborne dust or liquid aerosol, gas, by drips or spills or other contamination) on the one hand
and exposures to work materials containing the allergen on the other hand needs to be elucidated.
Occasionally, allergens may be relevant both occupationally and in a non-occupational context,
and it may be difficult to estimate the relative contribution of the 2 exposure arenas. A statement on
relevance should also include a reference to time, i.e., whether relevance is current or previous.
For a more complete discussion of this important and difficult topic see section IX.
Finally, one diagnosis, or several diagnoses, need to be made, each with a statement concerning
the role of occupational exposure, which can be the sole, the predominant or a contributing cause.
Ideally, each diagnosis should give information on the affected anatomical site, the causative
33
exposure/work material, and the actual allergen(s) (if ACD or CU) or irritant(s) (if ICD) involved,
and, moreover, whether any pre-existing disease or disposition (mainly atopic dermatitis) or
exogenous co-factors such as occlusion, friction etc. are involved.
Recommendation
Systematic evaluation of occupational dermatitis patients needs to address diagnoses
affected site, offending work material, causative allergen or irritant. for optimal patient
counselling and exposure reduction.
Acknowledgement
This section has been discussed by members of the working group “Surveillance, risk assessment
and allergens” of the COST action StanDerm (TD1206) on its meeting on March, 11th, 2014 in
Erlangen; in alphabetical order: K. Aalto-Korte, J. Bakker, D. Chomiczewska Skora, J.D. Johansen,
B. Krecisz, S. Ljubojevic, M. Matura, C. Schuster, C. Svedman, M. Wilkinson.
3. PATCH TESTING IN DRUG ERUPTIONS
Including comments from Kristiina and Vera 3. July 2014, sent back to Authors and revision
returned.
3.1. Indications
Although less standardised in this context, patch testing may also be indicated in the study of
delayed cutaneous adverse drug reactions (CADR), namely in maculopapular exanthema, DRESS
(drug reaction with eosinophilia and systemic symptoms), AGEP (acute generalized
exanthematous pustulosis), Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN)
(Santiago, Gonçalo, Vieira, Coelho, & Figueiredo, 2010),(Annick Barbaud, 2014).
3.2. Technique
Patch testing should be optimally performed at least 4-6 weeks after complete resolution of the
CADR or eventually later in DRESS (Annick Barbaud, 2014). All possible culprit drugs should be
tested, that means all drugs taken within the possible chronological period. The approach and
technique for performing patch testing in CADR is the same as reported for the study of allergic
contact dermatitis (ACD), except for fixed drug eruption, where lesional patch testing is advised. In
this case, apart from applying the allergen on the uninvolved back skin (control test), the
allergen(s) is applied also in a residual pigmented lesion for 6-24 hours, usually under occlusion
with a patch test chamber. The readings are performed at 24 and 48h (eventually at 6h), as the
reaction usually is accelerated due to the retention of drug specific T cells in the residual patch of
fixed drug eruption. Results are compared with the normal control skin, which is usually nonreactive (Andrade, Brinca, & Gonçalo, 2011).
In all other CADR, patch test readings should be performed at D2 or D3 and D5 to D7 as in ACD,
but apart from erythema and papules, possibly vesicles, different reaction patterns (pustular,
lymphomatoid or bullous) that simulate the acute CADR may occur (Gonçalo, Serra, Cabral, Reis,
& Tellechea, 2011),(Serra, Ramos, Brinca, & Gonçalo, 2012).
3.3. Allergens for patch testing in CADR
34
There are only a few drug allergens commercially available for patch testing, like some antibiotics,
NSAID and anticonvulsants, usually at 10% in petrolatum. Therefore, in most cases patch test
material has to be prepared in-house from the drugs used by the patients. The powder for i.v.
preparation or from capsules is preferred over tablets for preparing material for patch testing. After
grinding to a fine powder, the material should be incorporated in petrolatum, whenever possible to
have the active principle in a final 10% concentration. When the concentration of the active drug is
too low in the patient’s drug the whole powder should be diluted in petrolatum at 30% (A Barbaud,
Gonçalo, Bircher, & Bruynzeel, 2001), (Brockow et al., 2013). Positive patch test results obtained
with these in house made preparations should be validated with controls, as some drugs or their
excipients may have irritating properties, as shown for instance for colchicine and desloratadine (A
Barbaud et al., 2013). For commercially available drug allergens no further controls are needed.
3.4. Sensitivity and specificity of patch testing in CADR
Patch test specificity is usually high, with drug specific T cells isolated from positive patch tests.
Patch test sensitivity in CADR is lower than in ACD (30-70%) and depends on the culprit drug and
the clinical pattern of CADR (Annick Barbaud, 2014).
Drugs like carbamazepine, tetrazepam, pristinamycin induce positive reaction in about 60% of
cases (Santiago et al., 2010),(Pirker, Misic, Brinkmeier, & Frosch, 2002),(A Barbaud et al., 2004),
whereas for other drugs, like betalactam antibiotics and clindamycin, a low percentage of reactivity
is expected (20-30%) (Romano & Caubet, 2014),(Pereira, Canelas, Santiago, Brites, & Gonçalo,
2011) reflecting probably reduced absorption, the role of metabolites or the need for concomitant
factors for inducing the CADR. E. g. allopurinol patch tests are usually negative (Santiago et al.,
2010),(Annick Barbaud, 2014). Patch tests are more frequently positive in maculopapular
exanthema, DRESS and AGEP, whereas very seldom in SJS/TEN.
Prick and intracutaneous (i.c.) tests, with immediate and late readings can add an additional value
in CADR, but they are out of the scope of these guidelines (A Barbaud et al., 2013),(Romano &
Caubet, 2014).
Patch testing is a safe procedure, even in severe CADR, with exceptional cases of reactivation of
the CADR (Annick Barbaud, 2014).((add COD reference))
Recommendation
Although with variable sensitivity, patch testing should be considered in delayed CADR. A positive
patch test can help confirm a possible culprit drug, therefore avoiding an oral provocation. A
negative patch test, on the other hand, cannot exclude the contribution of a possible culprit drug,
determined on clincal grounds.
VI: special groups: children
1. Morren M-A. Goossens A. Contact Allergy in Children. In Chapter 48: Contact Dermatitis, 5 th ed.
Duus Johansen J, Frosch PJ, Lepoittevin JP. Springer-Verlag Berlin Heidelberg, Germany 2011: pp. 937-61
2. Simonsen AB, Deleuran M, Duus Johansen J and Sommerlund M.
Contact allergy and allergic contact dermatitis in children- a review of current data
Contact Dermatitis, 2011, 65: 254-65.
3 Simonsen AB, Deleuran M, Mortz CG, Duus Johansen J, Sommerlund M. Contact Dermatitis. 2013; 70:104-11
4 Bonitsis NG, Tatsoni A, Bassioukas K, Ioannidis JPA. Allergens responsible for allergic contact dermatitis among childr
systematic review and meta-analysis. Contact Dermatitis. 2011, 64: 245-57.
35
5 Moustafa M, Holden C.R, Athavale P, Cork MJ, Messenger AG and Gawkrodger DJ.
Patch testing is a useful investigation in children with eczema
Contact Dermatitis.2011, 65: 208-12.
6 Wahlberg JE, Goossens A (2001) Use of patch test concentration for adults in children and their influence
on test reactivity. Occup Environ Dermatol. 2001; 49: 97-101
7 Pratt MD, Belsito DV, DeLeo VA et al. North American Contact Dermatitis Group Patch-Test results, 2001-2002 study p
Dermatitis 2004; 15:176-83.
8 Vigan M Peculiarities of patch testing in children. Ann Dermatol Venereol. 2009; 136: 617-20
9 Worm M, , Aberer W, Agathos M, Becker D, Brasch J, Fuchs T, Hillen U, Hoger P, Mahler V, Schmuch A,
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Dermatitis Research Group. Acta Derm Venereol. 2011; 91:295-8
11 Spornraft-Ragaller P, Schnuch A, Uter W. Extreme patch test reactivity to p-phenylenediamine but not to
other allergens in children. Contact Dermatitis. 2011 Oct;65(4):220-6. doi: 10.1111/j.16000536.2011.01930.x. Epub 2011 May 19.
X. Mailhol C, Lauwers-Cances V, Rance F, Paul C, Giordano-Labadie F. Prevalence and risk factors for allergic c
dermatitis to topical treatment in atopic dermatitis: a study in 641 children. Allergy. 2009;64(5):801-6.
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dermatitis. J Eur Acad Dermatol Venereol. 2011;25(9):1104-7.
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VI special groups : occupational
1.
2.
3.
4.
5.
Rustemeyer T, Elsner P, John S M, Maibach H I. Kanerva's Occupational Dermatology.
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Friis U F, Menné T, Thyssen J P, Johansen J D. A patient's drawing helped the physician to
make the correct diagnosis: occupational contact allergy to isothiazolinone. Contact
Dermatitis 2012: 67: 174-176.
Isaksson M, Zimerson E. Risks and possibilities in patch testing with contaminated personal
objects: usefulness of thin-layer chromatograms in a patient with acrylate contact allergy
from a chemical burn. Contact Dermatitis 2007: 57: 84-88.
Thyssen J P, Skare L, Lundgren L, Menne T, Johansen J D, Maibach H I, Liden C.
Sensitivity and specificity of the nickel spot (dimethylglyoxime) test. Contact Dermatitis
2010: 62: 279-288.
36
6.
7.
8.
9.
10.
Midander K, Julander A, Skare L, Thyssen J P, Liden C. The cobalt spot test--further
insights into its performance and use. Contact Dermatitis 2013: 69: 280-287.
Kettelarij J A, Lidén C, Axén E, Julander A. Cobalt, nickel and chromium release from
dental tools and alloys. Contact Dermatitis 2014: 70: 3-10.
Jensen P, Thyssen J P, Johansen J D, Skare L, Menné T, Lidén C. Occupational hand
eczema caused by nickel and evaluated by quantitative exposure assessment. Contact
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skin in some occupations - assessment by acid wipe sampling. Contact Dermatitis 2008: 58:
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DMG test. Contact Dermatitis 2011: 64: 151-157.
VI: special groups drug eruptions
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review. Contact Dermatitis, 65(4), 195–201. doi:10.1111/j.1600-0536.2011.01946.x
Barbaud, A. (2014). Skin testing and patch testing in non-IgE-mediated drug allergy. Curr Allergy
Asthma Rep, 14(6), 442. doi:10.1007/s11882-014-0442-8
Barbaud, A., Collet, E., Milpied, B., Assier, H., Staumont, D., Avenel-Audran, M., … Waton, J.
(2013). A multicenter study to determine the value and safety of drug patch tests for the three
main classes of severe cutaneous adverse drug reactions. Br J Dermatol, 168(3), 555–62.
Barbaud, A., Gonçalo, M., Bircher, A., & Bruynzeel, D. (2001). Guidelines for performing skin tests
with drugs in the investigation of cutaneous adverse drug reactions. Contact Dermatitis, 45,
321–8.
Barbaud, A., Trechot, P., Weber-Muller, F., Ulrich, G., Commun, N., & Schmutz, J. L. (2004). Drug
skin tests in cutaneous adverse drug reactions to pristinamycin: 29 cases with a study of
cross-reactions between synergistins. Contact Dermatitis, 50(1), 22–6.
Brockow, K., Garvey, L. H., Aberer, W., Atanaskovic-Markovic, M., Barbaud, A., Bilo, M. B., …
Terreehorst, I. (2013). Skin test concentrations for systemically administered drugs -an
ENDA/EAACI Drug Allergy Interest Group position paper. Allergy, 68(6), 702–12.
doi:10.1111/all.12142
Gonçalo, M., Serra, D., Cabral, A., Reis, J., & Tellechea, O. (2011). Histopathology of positive skin
tests in different drug eruptions. J Invest Dermatol, S33, 131.
Pereira, N., Canelas, M. M., Santiago, F., Brites, M. M., & Gonçalo, M. (2011). Value of patch tests
in clindamycin-related drug eruptions. Contact Dermatitis, 65(4), 202–7.
Pirker, C., Misic, A., Brinkmeier, T., & Frosch, P. (2002). Tetrazepam drug sensitivity - usefulness
of the patch test. Contact Dermatitis, 47, 135–8.
37
Romano, A., & Caubet, J.-C. (2014). Antibiotic allergies in children and adults: from clinical
symptoms to skin testing diagnosis. J Allergy Clin Immunol, 2(1), 3–12.
doi:10.1016/j.jaip.2013.11.006
Santiago, F., Gonçalo, M., Vieira, R., Coelho, S., & Figueiredo, A. (2010). Epicutaneous patch
testing in drug hypersensitivity syndrome (DRESS). Contact Dermatitis, 62(1), 47–53.
Serra, D., Ramos, L., Brinca, A., & Gonçalo, M. (2012). Acute generalized exanthematous
pustulosis associated with acyclovir, confirmed by patch testing. Dermatitis, 23(2), 99–100.
doi:10.1097/DER.0b013e31824a603d
VII. Patch Testing of patients’ own materials
Including comments by Ana and Thomas R. 5. July 2014
Kristiina Aalto-Korte
Occupational Medicine, Finnish Institute of Occupational Health
Helsinki, Finland
Vera Mahler
Allergy Unit, Department of Dermatology University Hospital Erlangen
Erlangen, Germany
The textbook chapters in the references provide more detailed information on this subject (1,2,3,4).
Information in this section is based on practical observations and empirical evidence as no
experimental data exists in this area.
According to European legislation, (5) patch test substances are drugs and must be licenced as
drugs. However, a treating physician can patch test patients’ own materials, although, according to
current national directives, it may be mandatory in some countries (e.g. in Germany) to declare this
to the supervisory authorities (6). A patch testing dermatologist must be aware of the national legal
requirements in the respective country.
Patch testing patients' own products is especially important in occupational dermatology, because
standardized commercial patch test substances of many occupationally used chemical compounds
are lacking. About 4000 contact allergens are known, but only about 600 commercially available
allergen preparations exist. The number of allergens in an ordinary test laboratory is usually much
lower. Thus all possible problems cannot be solved with commercial allergens, and testing
patients' own products is necessary. Moreover, our environment is constantly changing, and
workers and consumers are exposed to new chemicals, some of which are sensitizers. Routine
test substances never cover new allergens. Testing patients' own products is the only way of
finding new allergens. Previously known allergens can be found in new types of products i.e.
testing patients’ own materials may reveal previously unknown sources of sensitization. In addition,
38
patch testing patients’ own materials often helps assess the clinical relevance of an allergic
reaction to standard allergens: for example when a cosmetic product induces an allergic reaction
and the patient also reacts to some of the ingredients labelled on the product, the allergen is
probably the cause of the patient’s problems. It must be remembered that a negative result to a
patient’s own product does not exclude contact allergy to some of its components.
Wide-ranging, efficient testing of patients’ own substances requires experience and a sufficient
number of staff. The concentration of an allergen in the product may be too low to provoke an
allergic reaction i.e. a false negative reaction. Many products need to be diluted due to their irritant
components, which may lead to a falsely negative test result. If the product is not sufficiently
diluted, the irritant components can induce false positive reactions. Concentrations that are too
high may also lead to active sensitisation. Testing individual allergenic components separately may
be the only solution to these problems. Many cosmetic companies provide the separate ingredients
of a cosmetic product at adequate concentrations for patch testing. However, some companies
send the ingredients diluted to a concentration that is used in the product, which may in turn be too
low, and lead to a false negative reaction. Dermatological clinics with experience in non-standard
materials prefer to decide on test concentrations themselves. Many European companies selling
industrial products also provide the components of their product for patch testing, but co-operation
with non-European countries is more rarely successful.
Centres that test patients’ own materials on a regular basis ask patients to bring samples and all
possible information of the products they suspect: safety data sheets, lists of ingredients on the
packages (e.g. INCI lists), or the products’ information leaflets. Similar information can be found on
the internet and requested from manufacturers. A general impression of the composition of the
product should be formed before testing. Safety data sheets provide only basic information, and all
sensitizing components may not be listed. Totally unknown substances should never be tested,
because necrosis, scarring, pigmentation/depigmentation, and systemic effects due to
percutaneous absorption may appear. Extremely hazardous chemicals (strong acids, alkalis, very
poisonous chemicals) and products without sufficient information should not be tested.
Patch test concentrations
The choice of test concentration is based on the characteristics of the product (skin irritant
components, sensitizing components, pH etc.). Components available as commercial test
substances should be tested separately at the same time. The test concentration of an individual
allergen in the product should not exceed the recommended test concentration for this allergen (4).
This may lead to insufficient concentrations of other ingredients in the test preparation (false
negative results). Contact dermatitis/occupational dermatology textbooks contain
recommendations on test concentrations (1,2,3,4). When the number of suspected materials is
low, and the level of suspicion is high, using a concentration dilution series of the suspected
material is recommended. When investigating possible new allergens, retesting with a dilution
series down to negative concentrations is of utmost importance. Allergic-looking reactions that
extend to very low concentrations strongly support the allergic nature of the reaction. The strength
of allergic reactions gradually diminishes along with decreasing concentration, while a falsepositive irritant reaction vanishes abruptly when the concentration is lowered. Identification of a
new allergen often requires serial testing because products are usually composed of many
different chemical substances. The components of the product are tested in the second phase,
preferably with a dilution series down to negative concentrations (often ppm level). Very low
concentrations can usually be increased, and the concentration should not exceed the recommend
test concentrations for the type of product or chemical group (e.g. acrylates 0.1%, methacrylates
1%). It is quite common that the first patient diagnosed with contact allergy to a previously
unknown allergen is strongly sensitized to the substance and displays allergic reactions to very low
concentrations, about 10 ppm, of the substance. In such a case, the low threshold concentration
39
itself strongly supports the allergic nature of the reactions, as irritant reactions to such low
concentrations are rare.
Leave-on cosmetic preparations, protective creams and topical medicaments can usually be tested
as they are, because they are intended to be applied to the skin. A negative test does not exclude
contact allergy to the product for various reasons (the concentration in the products may be too
low, corticosteroids may have an anti-inflammatory effect etc.).
Rinse-off skin care products such as liquid soap, shampoos and shower gels can be tested at
concentrations of 1–10% in water, depending on the ingredients.
Many cleaning products and metal-working fluids are diluted at the workplace before use. Used
products can be dirty and the concentration is not necessarily exactly in accordance with the use
recommendations. The most significant allergens in metal working fluids are biocides,
rust preventives, emulsifiers, and tall oil derivatives. Although it is safer to use unused undiluted
products and prepare the test dilutions at the test laboratory, some important impurities may be
missed, especially preservatives and perfumes added as odour masks to the metal working fluid in
the circulatory system. Therefore, it may be advisable to test the metal-working fluid taken from the
machine as well as a fresh dilution prepared from the concentrate. Oil-based fresh and used metalworking fluids are tested at a concentration of 50% in olive oil. Water-based fresh metal working
fluids are tested at a 5% concentration in fresh tap water. . The workplace concentration of waterbased metal working fluids is usually 4% to 8% in the circulatory system. After testing, and if
necessary, adjusting the pH, the used water-based 4% to 8% metal working fluids taken from the
circulatory system can be tested as they are. If the use concentration is ≥ 8%, further dilution with
water is necessary to obtain a 5% concentration. Further possible sources of impurities can be
evaluated separately, for example, the composition of tooled materials and the leakage of guideway oil into the metal-working fluid system.
Textbooks contain detailed information regarding dilutions and vehicles, depending on the
composition of the products (1,2,3). As regards acrylic compounds, epoxy diacrylates, for example,
should be tested at a concentration of 0.5% in pet., products based on dimethacrylates, such as
dental composite resins should be tested at a 1–2% concentration, cyanoacrylate-based instant
glues should be at a 1–10% in pet. concentration or allowed to dry in the test chamber,
methacrylates such as prosthesis materials should be tested at a concentration of 2% in pet., but
the suitable concentration for UV-curable inks and lacquers or other acrylate-containing products is
only 0.01–0.1% in pet.
Many solid materials (paper, textile, plastic, rubber, metal specimens of suitable shape, wood dust
etc.) can usually be tested as they are. Powdery materials, ground dust, scrapings or small cut
pieces can be tested in chambers (first moistened with water or organic solvents). Larger pieces
(glove material, textiles etc.) can be tested semi-open, covered with surgical test tape without a
chamber. Tests can be falsely negative if not enough of the allergen is released onto the skin.
Pressure effects and mechanical traumas due to sharp particles must be differentiated from
allergic reactions.
Patch testing plants is problematic. Irritant reactions are frequent, and their allergen content may
vary. Active sensitization may occur. Plant extracts can also be irritating. Commercially available
standardized test materials (sesquiterpene lactones, primin, Tulipaline A etc.) are safer and identify
most cases. Tropical woods can also be strongly irritating and sensitize.
Vehicle
The choice of vehicle depends on the characteristics of the product, solubility and pH. When watersoluble chemicals are tested, it is important to check the pH before testing. Neutral products (pH
40
4–9) can be diluted with distilled water. For testing more alkaline or acidic substances, the use of
buffer solutions are recommended, to reduce irritability and to allow higher concentrations. Acid
buffer is used for alkaline products (pH > 9) and alkaline buffer for acid products (pH < 4) while
monitoring pH. Water-insoluble chemicals are usually diluted in petrolatum, but acetone, ethanol,
olive oil and methyl ethyl ketone (MEK) are other alternatives (4).
Extracts and chromatograms
The use of ultrasonic bath extracts is an alternative to testing solid materials. Small pieces of the
material are put in water or organic solvent (ethanol, acetone, ether) and then extracted in an
ultrasonic cleaner device, and finally filtered (8). Patch testing with thin-layer chromatograms can
be valuable for products such as textiles, plastics, food, plants, perfumes, drugs and grease (9).
Preparation of the test material
It is advisable to use disposable containers, syringes, stirrers and spatulas for preparing the test
substances. Solid materials in crystal or powder form can be ground with a pestle and mortar.
Liquids are diluted by using pipettes and syringes, and the percentage is given by volume
(volume/volume). When electronic scales are used, the percentage is given by weight
(weight/weight). Thorough mixing is important for a homogenous distribution of the allergen in the
vehicle. Serial dilutions can be prepared from these preparations. The test substances should be
stored in a fridge in tightly closed containers or syringes.
General recommendations
 Asess the products’ composition by reading safety data sheets, ingredient lists,
information from the manufacturerer and other data
 Test individual components of patients’ own products separately if possible
 Check pH and adjust it with buffers if necessary
 The test concentration of an individual allergen should not exceed the recommended
test concentration for this allergen
 Remember that a negative result does not exclude contact allergy to some of the
product’s components
 Leave-on cosmetic preparations, protective creams and topical medicaments can
usually be tested as they are
 Rinse-off skin care products such as liquid soap, shampoos and shower gels can be
tested at concentrations of 1–10% in water
 Many solid materials can usually be tested as they are.
References
VII: Own materials
1
Jolanki R, Estlander T, Alanko K, Kanerva L. Patch Testing With a Patient's Own Materials
Handled at Work. In: Handbook of Occupational Dermatology 1st edn, L Kanerva, P Elsner,
J E Wahlberg and H I Maibach (eds): Berlin, Springer, 2000: 375-384.
2
Frosch P J, Geier J, Uter W, Goossens A. Patch Testing with the Patients' Own Chemicals.
In: Contact Dermatitis 5th edn, P J Frosch, T Menné and J-P Lepoittevin (eds): Berlin,
Springer, 2011: 1107-1119.
41
3
4
5
6
7
8
9
Krautheim A, Lessmann H, Geier J. Patch Testing with Patient's Own Materials Handled at
Work. In: Kanerva's Occupational Dermatology 2nd edn, T Rustemayer, P Elsner, S M
John and H I Maibach (eds): Heidelberg, Springer, 2012: 919-933.
De Groot AC. Patch Testing 3rd Edition. Wapserveen, The Netherlands, 2008.
DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
of 6 November 2001 on the Community code relating to medicinal products for human use
OJ L 311, 28.11.2001, p. 67ff
Zweites Gesetz zur Änderung arzneimittelrechtlicher und anderer Vorschriften vom
19.10.2012. Bundesgesetzblatt 2012; 50: 2192-227.
Fregert S. Publication of allergens. Contact Dermatitis 1985: 12: 123-4.
Bruze M, Trulsson, L., Bendsöe, N. Patch testing with ultra-sonic bath extracts. Am J
Contact Dermat 1992: 3: 133-137.
Bruze M, Frick M, Persson L. Patch testing with thin-layer chromatograms. Contact
Dermatitis 2003: 48: 278-9.
VIII. Potential side effects of Patch Testing
Include comments/corrections by Ian White from 1. Sept 2014
Ana Giménez Arnau
Department of Dermatology. Hospital del Mar. Universitat Autònoma . Barcelona
Thomas Rustemeyer
Department of Dermatology, VU University Medical Centre, De Boelelaan 1117, 1081 HV
Amsterdam, The Netherlands
Dr. Eman A. Al-Haqan MD, MRCP, SCE (Derm)
Specialist Dermatologist Al-Adan Hospital - Kuwait
Introduction:
Patch Test Adverse Reactions
1. Irritant reaction
Minor irritant reactions are commonly seen to some standard allergens and e.g. when testing the
atopic skin. Unexpected irritant reactions may be seen when non-standard allergens or products
are tested, sometimes brought by the patient, and applied without appropriate dilution (see section
VII).
Different types of irritant reactions have been described. Well demarcated erythematous reactions
are often seen with fragrance mix, and thiuram mix. Purpuric reactions are commonly caused by
metal salts, e.g. cobalt chloride. Pustular reactions are seen mainly with non-noble metals like
chromium, cobalt, and nickel. Necrotic reactions which are the most severe type, occur with
substances as sodium hydroxide or kerosene among others, are incorrectly patch tested.
42
Testing should not be performed with undiluted solvents, gasoline, soaps, or detergents. Serious
irritation can be avoided by using standard procedures which include pretesting substances of
unknown composition in several volunteers (including the investigator) 2.
, which include pretesting substances of unknown composition in several volunteers (including the
investigator) 2.
3. Patch test sensitization
Although active sensitisation is now uncommon, it is an important potential complication of patch
testing. It is defined as a positive patch test reaction generally beyond 2 weeksafter an initially
negative response. In practice, it may be difficult to differentiate between induction of sensitization
due to allergen exposure from the patch test and a delayed patch test elicitation reaction4. To
confirm the diagnosis of active sensitization, repeat patch testing can be performed. A positive
reaction, with ‘normal’ latency of elicitation (one to a few days) supports iatrogenic sensitization,
although a boosting of a pre-existing, but weak sensitization cannot be ruled out. Several allergens
are known to carry some risk of active sensitization, examples include: para-phenylenediamine 1,
primula extracts, isothiazolinones, acrylates3 and para-tertiary-butylcatechol 4. Compositae mix
was also reported to cause active sensitization in four patients out of 576 after patch testing 5. It
was concluded by Gawkrodger and English that the risk of active sensitization is very low when
using standardized allergens and concentrations (1-1.5%)7.
Despite the minor risk of active sensitization, the benefit of patch testing is agreed to outweigh the
risk.
4. Pigmentation changes
A patch test reaction may rarely result in localised either transient hyper- or hypopigmentation5.
Flare up of clinical dermatitis
Flare of an existing, or sometimes a previous dermatitis, mayoccur in the course of a mostly strong
positive reaction. Such flare-up reactions usually indicates that the responsible allergen is the
culprit for the current dermatitis. 9.
6. Persistent reaction
A positive patch test reaction can sometimes persist up to several weeks Uchida et al reported a
case with positive patch test reaction to p-phenylenediamine that persisted for more than one
month 10. Gold chloride 0.5% aqueous solution is notorious for causing persistent reactions 1, 13.
7. Subjective complaints
Itching at the site of applying the patches is commonly observed, it can either be due to a positive
patch test reaction or as a result of tape irritation. However, some patients feel more itching
immediately after removal of the tape 9,11.
Various unrelated subjective complaints of patch tested patients have been reported in the
literature. Among these: fatigue, fever, headache, vomiting, and dizziness are common 2. There is
no evidence of a cause-effect relationship.
8. Scarring and necrosis:
Exceptionally, secondary scarring may occur after strong (allergic and especially irritant) patch test
reactions, in particular, if superinfection occurs or scratching.
43
Although very rare, it has been reported that testing with strong irritants may cause skin necrosis
and scarring at the test site. Testing with strong irritants should not be performed (cf. testing of own
materials and selection of allergens).
10. Generalised immediate reactions
There are very rare reports that some biological materials or drugs have been suspected to have
caused anaphylactic reactions in patients with strong immediate type hypersensitivity.
References
VIII: side effects
1. Lachapelle Jean-Marie, Maibach H. Patch Testing and Prick Testing. Second edition. 2009.
Springer.
2. Rietschel R, Fowler J. Fisher's Contact Dermatitis. Sixth edition. 2008.
3. Johansen J, Frosch P, Lepoittevin J. Contact dermatitis. Fifth Edition. 2011.
4. Hillen U et al. Patch test sensitization caused by para-tertiary-butylcatechol. Contact Dermatitis,
2001; 45, 193-196.
5. Wilkinson S, Pollok B. Patch test sensitization after use of the Compositae mix. Contact
Dermatitis. 1999; 40, 277-291.
6.Sasseville D. Exacerbation of allergic contact dermatitis from amcinonide triggered by patch
testing. Contact Dermatitis. 2001. 45: 232-233.
7. Gawkrodger DJ, English. How safe is patch testing to PPD?. Br J Dermatol, 2006; 154: 10251027.
8. Hillen U, Jappe U, Frosch PJ, Becker D, Brasch J, Lilie M, Fuchs T, Kreft B, Pirker C, Geier J;
Late reactions to the patch-test preparations para-phenylenediamine and epoxy resin: a
prospective multicentre investigation of the German Contact Dermatitis Research Group. Br J
Dermatol. 2006 Apr;154(4):665-70.
9. Mose AP, Steenfeldt N, Adnerson K. Flare-up of dermatitis following patch testing is more
common inpolysensitized patients. Contact Dermatitis, 2010: 63: 289–290.
10. Uchida, Shusuke; Oiso, Naoki; Matsunaga, Kayoko; Kawada, Akira. Contact Dermatitis. Dec
2013, Vol. 69 Issue 6, p382-383.
11. Curto L, Carnero Ll, López-Aventin D, Traveria G, Roura G, Giménez-Arnau A. Fast itch relief
in an experimental model for methylprednisolone aceponate topical corticosteroid activity, base on
allergic contact eczema to nickel sulphate. Accepted 18 September 2013 JEADV 2003 Nov 4. doi:
10.1111/jdv.12292
12. Perfetti L1, Galdi E, Biale C, Garbelli N, Moscato G. Anaphylactoid reaction to patch testing
with ammonium persulfate Allergy. 2000 Jan;55(1):94-5.
13. Sperber BR1, Allee J, Elenitsas R, James WD. Papular dermatitis and a persistent patch test
reaction to gold sodium thiosulfate Contact Dermatitis. 2003 Apr;48(4):204-8.
IX. Final evaluation
Incl. IW corrections from 23.6. 2014; 3.7.2014 from JT
Authors: Jeanne Duus Johansen and Ian White
44
Literature was searched using PubMed with search terms: guideline, clinical relevance and patch test or contact
dermatitis or clinical relevance and patch test criteria or allergy criteria and xx publications were retrieved in June
2014. Textbooks were checked manually.
Diagnosis and clinical relevance
A morphological positive patch test reaction to a substance at a non-irritant patch test
concentration is a sign of contact sensitization (contact allergy) to the substance in question has
occurred. The next step is to determine how the patient may have been exposed to the allergen
and evaluate if the patient currently or in the past has had any clinical symptoms (allergic contact
dermatitis) caused by exposure to the substance (Bruze, 1990).
Therefore, establishing (diagnosing) allergic contact dermatitis involves a process with two major
steps:
- Demonstration of contact allergy
-
Assessment of clinical relevance
In the original guideline on the terminology of contact dermatitis from 1970 it is stated: ‘ a positive
patch test is considered ‘relevant’ if the allergen is traced (Wilkinson 1970).
This was later incorporated into the following criteria for clinical relevance by Bruze 1990:
1. an existing exposure to the sensitizer
2. presence of a dermatitis, which is understandable and explainable with regard to the exposure
on the one hand and type, localization, and course of the dermatitis on the other.
Recommendation
The dermatologist must always assess whether an established contact allergy is of present, past,
or unknown relevance or due to cross-reactivity
Elements of the relevance assessment
The following elements are part of the assessment of clinical relevance:
I. Clinical presentation of eczema:
- type
-
localisation
-
course
II. Exposure- main sources of information regarding exposure (Bruze 1990/Lacapelle):
Patient’s history
45
Own experience
Textbooks
Information from:
- packages/labels
-
data sheets
-
manufacturers/suppliers
Spot tests
Chemical analysis
III. Conclusion (diagnosis)
The patient’s history is crucial in the understanding of the causes of their eczema and in the
assessment of clinical relevance.
It is important to go through the patient’s history systematically and it can be helpful to ask about
rashes to specific product types e.g. perfumes, creams, gloves, shoes, tools, jewellery etc.
depending on the localisation of eczema and the allergy under investigation. Such standardized
questions have been used in various investigation of clinical relevance to new allergens or
screening markers of allergy e.g. to fragrance ingredients (Frosch 2005).
If a particular product is suspected based on the history, it is important to identify or qualify if the
sensitizer is in the product. This can, in case of cosmetic products, be done (in Europe) by
consulting the label of ingredients either on the product or the container (where there is full
ingredient labelling apart from partial labelling of fragrance substances). The nomenclature is
standardized into the INCI system, which makes it easier to identify allergens; however it should
be remembered that the names on the patch test preparations often are chemical names (eg INN)
and it can be necessary to look up synonyms to do an effective exposure assessment. Labelling on
medicinal products follows INN. Household detergents label preservatives and fragrances
according to the requirements of cosmetic products.
In case of other product types such as shoes, it will usually be impossible to get information about
its composition, but the a piece of the product can be tested (section xx) and textbooks can be
consulted to give an indication if the type of substance, which has caused a positive patch test can
be in that particular type of products.
In case of products intended for use in work places e.g. cutting oils, some information can be
found in the material safety sheet; however even though a particular substance is not mentioned,
it may be present, as allergens only have to be mentioned if they are present above a certain
concentration limit (Friis UF 2014) Therefore, it is advisable to contact the manufacturer or
supplier of the product(s) under suspicion to obtain a full list of ingredients. Clinically important
and frequent allergens may not be listed on material safety data sheets due to inadequate CLP
legislation.
46
For certain allergens: nickel, cobalt and formaldehyde spot tests exist, which are quick and easy
ways to assess exposures. The nickel spot test is the best validated and has a high specificity
(97.5%) and moderate sensitivity (59.3%) in detecting a level of nickel ion release, which may
cause dermatitis (Thyssen JP 2010). In case of suspected occupational exposures the nickel spot
test can be used directly on the hands (Julander A 2011) . The cobalt test is based on similar
principles, but is more difficult to read and there is less experience with the test (Thyssen JP 2010
). Still, important new sources of exposures to cobalt have been identified by using the cobalt spot
test (Thyssen JP 2013).The formaldehyde spot test requires laboratory facilities, but can detect
small levels of formaldehyde, which has been shown to be of clinical relevance in those sensitized
(Hauksson I et al. 2014)
Recommendation
In case of a positive patch test to nickel, cobalt or formaldehyde, it is recommended to use the
spot tests to identify sources of exposure at the workplace and at home. INCI nomenclarture must
be used for ingredients cosmetic and household detergents provides information on presence of
an allergen (but not amount).
Positive patch test reactions to mixtures
A special challenge occurs if the positive patch test is to a mixture, which is used for screening of
contact allergy to a group of substances such as fragrance mix, or mercapto mix or even as natural
mixtures such as Balsam of Peru (Myroxylon pereira). In such case it may not be possible to
pinpoint a particular sensitizer and the decision may have to be made based on the history of
rashes to particular product types in such patient categories or general knowledge from textbooks.
Cross-reactivity
Also the possibility of cross-reactivity should be kept in mind. This means that the sensitisation has
been caused by another not tested, but chemically similar substance. If the clinician looks for the
substance that has caused the positive patch test this may not be present in the environment; the
wrong conclusion may be drawn that the allergy is not relevant or if it is present the true culprit
exposure will not be identified.
Recommendation
In case of contact allergy to a chemically defined sensitizer, cross-reacting substances should also
be looked for in the environment.
Means of facilitating the assessment of clinical relevance (Bruze 1990):
Patch testing of products
Patch testing with extracts
Use tests
47
Principles of patch testing of products are given in section xx. A positive patch test reaction to a
product in which the sensitizer is an ingredient and to which the patient is exposed usually means
the contact allergy is relevant (Bruze 1990).
The dose required to elicit a positive patch test reaction is up to 28 times larger than the dose,
which is needed per open application to elicit a reaction in 14 days (Fischer). This means that a
negative patch test to a product does not exclude clinical relevance, and if a specific product is
suspected to have contributed to the dermatitis, but is negative at patch testing, a use test should
be performed (cf. section xx).
Extracts of solid products such as gloves may enhance the sensitivity of the patch test by
concentrating the allergen in question (Bruze, 1990), but requires special equipment.
A use test is often helpful in establishing clinical relevance, but is reserved to products, which are
intended for repeated skin contact such as creams and topical medicaments.
Even a negative use test does not exclude relevance. This means that in case relevance could not
be established: it is recorded as a patch test reaction of ‘unknown relevance’ (Wilkinson, 1970).
Past relevance
Past relevance reflects a past episode of contact dermatitis caused by exposure to the allergen,
e.g. previous rash to an earring in a person with a positive patch test to nickel.
Unknown relevance
Fregert in his book from 1974 Manual of contact dermatitis () listed the following reasons for
patch test reactions of ‘unknown relevance’:
a. Lack of knowledge on the part of the examiner.
b. Some sources of the substance in question have not been traced.
c. The patient has not given sufficient information, partly perhaps because of the
inability of the examiner to ask the proper questions.
d. The substance occurs widely in everybody’s environment so that a significant
contact cannot be clarified by history.
e. The patient has never developed dermatitis from the substances as he has not been
exposed to sufficient amounts after sensitization.
f. Contact has occurred only with cross-reacting substance, which may have a quite
different usage.
The assessment of relevance is a complicated process with many pitfalls. The term ‘unknown’
relevance should be used with some caution and the points above addressed to check that all
potential sources of exposure have been identified.
Recommendation
48
In case of unknown relevance of a positive patch test it is recommended to repeat clinical
examination, check the history and exposure, to do use tests, spot tests, chemical analysis and
work-site visits, where indicated.
Final evaluation:
In some cases exposure to a sensitizer may explain the dermatitis entirely, but dermatitis with
multi-factorial background frequently occurs. Besides the exposure to the sensitizer, constitutional
factors may be of importance for the dermatitis and there may be exposure to irritants and other
allergens. It may be difficult to assess the relative significance of the various factors at a given time
(Bruze 1990).
In case of a current clinical relevance is found in a person with established contact allergy the
diagnosis: allergic contact dermatitis can be made. In case of unknown relevance, the person is
sensitized i.e. has a contact allergy, but the criteria for the diagnosis allergic contact dermatitis has
not been met currently. However the person is at risk of developing allergic contact dermatitis in
the future if sufficiently exposed to the allergen.
Relevance scoring systems
No commonly accepted system exists. In 1997 Lachapelle suggested a relevance scoring system
(Lachapelle, 1974), where scores from 0 to 3 were given with 0 as relevance not traced, 1 doubtful
2 possible and 3: likely relevance. The same scores were given for current and past relevance. A
similar system has been employed by other groups, some times with other terms such as possible,
probable and definite relevance (Fransway AF, Uter W), while others are displaying the supporting
evidence directly eg. current relevance based on allergen traced by chemical analysis (Heisterberg
M).
Interpretation of doubtful patch tests reactions
A patch test reaction scored as doubtful means that the morphology is not clear-cut ‘irritant’ or
‘allergic’. This means that further investigations may have to be done.
The patch test concentration may be too low and if increased a positive patch test reaction
develops, which may be of clinical relevance e.g. if formaldehyde is tested only at 1% instead of
2% positive reactions are missed, which were shown to be clinical relevant by use tests with
formaldehyde containing creams (Hauksson I). The weak patch test reaction may also be due to
cross-reactivity to another substance, which is the true cause of sensitization.
The patch test concentration may also be marginally irritant and the doubtful reaction is a sign of
skin irritation. Repeat patch testing or serial dilution patch testing may be helpful in clarifying the
nature of the reaction. Considerations should be given to the pattern of reactions. If doubtful
reactions to some chemicals from the same ‘family’ are doubtful and others (strong) positive, such
as reactions to formaldehyde releaser, rubber chemicals or fragrance substances, then it may be a
sign of the same contact allergy.
49
Interpretation of negative patch test reactions
As for doubtful patch test reactions, it should always be considered, particularly for nonstandardised substances, that false-negative reactions are possible e.g. due to inadequate patch
test concentration. If strongly suspected, testing should be repeated. Moreover, the culprit
substance may not have been included in the patch test programme at all. It is also advisable to
check for some of the factors which may influence a patch test response (see section xx),
especially if the test is unexpectedly negative.
X. Patient education
Including comments from Mark W. and Vera M (5th August 2014), JPT made corrections
Search terms in Pubmed: allergic contact dermatitis, adherence, compliance, contact allergy,
contact sensitization, education, information, memory, patch test, patient.
Results: 16 articles were identified as more or less relevant for this topic.
Author: Jacob P Thyssen
Allergic contact dermatitis can be completely cured following successful education of the patient on
allergen avoidance, also addressing workplace conditions (employer, accident insurance), as
required.
It is generally recommended to provide enough time to go over the allergies in detail with the
patient, explaining potential sources of exposure 2 and inform about how to avoid future skin
contact with the allergen. For example, nickel allergic patients should be guided away from skin
contact with risk products such as inexpensive jewellery, and be instructed on how to use the
nickel spot test on items that are likely to be in prolonged contact with the skin. Similar the cobalt
spot test can be used for metallic items that potentially could release cobalt. Ingredient label
reading of any personal product intended for use on their skin is recommended so that the patients
can identify whether the product is free of the allergen. However, this can be a challenge, even to
highly educated patients, because typical allergen names are long, difficult to spell, and often have
numerous complex synonyms.
The use of written regularly updated information containing the INCI names (in the realm of
cosmetics), as well as the different chemical terms of the compound together with the sources of
exposure is strongly recommended. This is of particular importance for patients with positive patch
test reactions to fragrances and preservatives 3. There is some evidence that written information
can be superior to oral information in regard to patients perception 4. The dermatologist needs to
consider that individuals from (educationally) disadvantaged backgrounds.and reduced personal
resources impair the ability to read and understand ingredient labels on cosmetic products 5. Also,
a social need to continue using a certain product can affect adherence, for example, some patients
with mild allergic reactions to p-phenylenediamine continue to dye their hair whereas those with
strong allergic reactions will tend to follow the recommendations 6. Notably, patients need to be
aware that ingredient labels sometimes can be misleading and not display all contact allergens in
the product 7. A reasonable advice for fragrance allergic patients can be to simply smell the
product prior to use, and only apply it if they do not sense any fragrances. Marketing terms such as
‘fragrance free’, ‘dermatology recommended’, ‘organic’, or ‘does not contain synthetic fragrances’
50
are often misleading and cannot be used for guidance. Many clinics provide a card with the
allergen names printed, which the patient can have in their wallet and easily access when
shopping.
To help the patient identify safe personal care products, databases have been developed. In the
United States, the Mayo Contact Allergen Replacement Database (CARD) has been in use since
1999 to assist patients in the avoidance of specific allergens by generating individual lists of skin
care products that are free of the given patient's allergens 8. CARD contains complete ingredient
lists of various widely available skin care products which are obtained by contacting individual
companies. Via the American Contact Dermatitis Society (ACDS) webpage, an alternative
database, the Contact Allergen Management Program (CAMP) can now be reached 9. CAMP also
generates a list of personal care products that can be safely used by the patient. It has information
on personal care products, household products, prescription topical agents, and gloves. The list
that is generated for the patient contains codes that allow the patient to access the database and
obtain an updated list as often as they like at no cost to the patient. In favour of a database
approach, a Swedish study showed that patients with lanolin allergy who used a list of lanolin
containing cosmetic and pharmaceutical products to avoid lanolin, had a better prognosis of their
dermatitis than those who did not use it 10. Moreover, a small randomized single-blind controlled
study showed that patient with allergen-free product lists generated from the CARD found them to
be either somewhat helpful or very helpful in managing contact dermatitis 11. There is a wealth of
internet sites with information on allergens in different products. Obviously, the quality varies, and
interested readers are referred to a recent review 9. Regarding occupational products, it is useful to
inform the patients that not all chemicals are labelled and that material safety data sheets are
required to get a better insight in potential allergens.
To underscore that patient education can be a challenge, a British study showed that among 135
patch tested patients, about 25% could not even recall having received any information about their
test results 2-3 months later 12. Also, an American survey, including 757 patch test patients who
were given a questionnaire on average 13 months after patch testing (the mean age of the patients
was 59 years), showed that only 50% of 238 patients with positive patch test reactions to 1 or 2
allergens remembered their allergies 13. Moreover, among 342 patients with 3 or more positive
patch test reactions, only 24% remembered their allergies. There was a tendency towards a better
recall of allergens among those aged 50-59 years of age as well as for women. While the
correlation was weak, recall decreased as expected together with the time since patch testing.
Importantly, all patients were given oral and written information about their allergies after patch
testing. Also, information about how to use a contact allergen avoidance database that provides a
list of safe skin care products was given. If possible, it might be useful to repeat the information at
a new appointment, for example months later.
occupational
QoL
Recommendations for patient education following patch testing
Advice and actions that the dermatologist can consider in a given patient:
Patients should be given written information which should be specific for their situation,
including the name(s) of allergens. In case of cosmetics allergens, INCI names must be
provided. CAS numbers are helpful in other fields. Information should be repeated upon followup visits.
51

Marketing terms such as ’free of synthetic fragrances’ or ’hypoallergenic’ can be
misleading.

Reading the ingredient labels routinely to avoid allergen exposure is recommended.

Remember that sometimes the label is only printed on the box that comes with the product,
and not on the cosmetic product itself. Discardingthe box can be a mistake.

Not every glove is suitable to prevent exposure from each allergen.

In the European Union, the coating of a metallic product shall only prevent nickel release
above 0.5 microgram/cm2/week for a 2-year period.

Recommend the regular use of a nickel spot test on purchased items to avoid products that
release nickel.

Regularly updated written information should be provided with INCI names as well as the
many synonyms of the chemical compound. A list of exposuresshould be added.

A print of safe and allergen free products can be given if updated and reliable.
X. References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Hald M, Agner T, Blands J, Ravn H, Johansen JD. Allergens associated with severe
symptoms of hand eczema and a poor prognosis. Contact Dermatitis 2009;61(2):101108.
Katta R. Common misconceptions in contact dermatitis counseling. Dermatol Online
J 2008;14(4):2.
Noiesen E, Munk MD, Larsen K, Johansen JD, Agner T. Difficulties in avoiding
exposure to allergens in cosmetics. Contact Dermatitis 2007;57(2):105-109.
Woo PN, Hay IC, Ormerod AD. An audit of the value of patch testing and its effect on
quality of life. Contact Dermatitis 2003;48(5):244-247.
Noiesen E, Larsen K, Agner T. Compliance in contact allergy with focus on cosmetic
labelling: a qualitative research project. Contact Dermatitis 2004;51(4):189-195.
Ho SG, Basketter DA, Jefferies D, Rycroft RJ, White IR, McFadden JP. Analysis of
para-phenylenediamine allergic patients in relation to strength of patch test reaction.
Br J Dermatol 2005;153(2):364-367.
Vanneste L, Persson L, Zimerson E, Bruze M, Luyckx R, Goossens A. Allergic
contact dermatitis caused by methylisothiazolinone from different sources, including
'mislabelled' household wet wipes. Contact Dermatitis 2013;69(5):311-312.
Yiannias JA, el-Azhary RA. Contact Allergen Avoidance Program: a topical skin care
product database. Am J Contact Dermat 2000;11(4):243-247.
Zirwas MJ. Contact alternatives and the internet. Dermatitis 2012;23(5):192-194.
Edman B. The usefulness of detailed information to patients with contact allergy.
Contact Dermatitis 1988;19(1):43-47.
Kist JM, el-Azhary RA, Hentz JG, Yiannias JA. The contact allergen replacement
database and treatment of allergic contact dermatitis. Arch Dermatol
2004;140(12):1448-1450.
Lewis FM, Cork MJ, McDonagh AJ, Gawkrodger DJ. An audit of the value of patch
testing: the patient's perspective. Contact Dermatitis 1994;30(4):214-216.
52
13.
Scalf LA, Genebriera J, Davis MD, Farmer SA, Yiannias JA. Patients' perceptions of
the usefulness and outcome of patch testing. J Am Acad Dermatol 2007;56(6):928932.
XI. Professional training in cutaneous allergy
Including comments from Wolfgang Uter 17th July 2014
Mark Wilkinson, Vera Mahler
Dermatology training
Investigation of cutaneous allergy is time intensive requiring a minimum of 3 visits over 5-7 days
and for effective use of resource it is important that the patient is seen at an appropriate centre
from the outset. Speciality training in dermatology provides core skills to develop the specific
competencies required to practise independently as a Dermatologisti. We consider this background
of training to be the minimum to enable an individual to fully consider the differential diagnosis and
management of a patient with a potential cutaneous allergic reaction.
● Skill: Investigation, diagnosis and management of patients with skin allergy, including
presentations of contact dermatitis (CD) and contact urticaria (CU)
Dermatologist with an interest in cutaneous allergy
Where a dermatologist spends a major part of their working career in the field of cutaneous allergy
a higher level of training should be expectedii. Specialist dermatology centres may provide
diagnostic services for complex cases e.g. those involving outbreaks of allergic dermatitis in the
workplace or wider community, multiple allergens and photo-allergy. Factory or work place visits as
well as specialist patch and photo testing and specialist pharmacy services are sometimes needed.
An individual would be expected to gain the knowledge and skills in cutaneous allergy set out
below (beyond the dermatological core skills) during an indicative duration of training of 12 months
with 250-300 patients seen during this period to achieve competence.
● Skill: Understanding of basic immunology and chemistry relevant to cutaneous allergy and
irritation; in detail:
-
explain detailed scientific findings and immunology mechanisms involved in allergic and
irritant CD
explain detailed chemistry of haptens and irritants
apply detailed immunology and chemical knowledge to the practical aspects of patch
testing and managing patients
identify and interpret relevant chemicals in material safety data sheets and other product
information formats
● Skill: Patch testing for diagnosis and management of cutaneous allergy and contact dermatitis,
i.e. ability to investigate, diagnose and manage patients with skin allergy including presentations of
CD. In detail:
- explain the detailed indications for patch testing
53
-
awareness of common allergens (metals, medicaments, rubber chemicals, fragrances,
preservatives, plants, hair dyes, resins) and their exposures
define clinical presentations requiring specific additional series such as hair dye allergy,
wound healing (leg ulcer) allergy, dental allergy and orthopaedic prosthesis allergy
select appropriate allergens for patch testing
discuss preparation of specific products for patch testing, including patient’s own products
describe detailed contraindications to patch testing
state limitations of patch test results
be aware of potential side effects
demonstrate application of patch tests and instructions to patients during the patch test
procedure
interpret patch test results
discuss relevance of patch test results & communicate results to patients
explain use of control patients
demonstrate use of repeated open application test
● Skill: Management of occupational skin diseases
To be able to investigate, diagnose and manage patients with common occupational dermatoses;
in detail:
-
distinguish clinical patterns of dermatitis likely to be associated with occupational dermatitis,
infection and neoplasms
explain the detailed indications for patch testing in occupational skin diseases
interpret material safety data sheets and other product information resources
discuss preparation of specific products for patch testing, including patient’s own
occupational products
contribute to multidisciplinary teams including specialist nurses, pharmacy and occupational
personnel
Standards of Care for management of occupational disease have been publishediii.
● Skill: Photopatch testing
Investigation, diagnosis and management of patients requiring photopatch testing, involving:
- explain detailed mechanisms involved in allergic photocontact dermatitis and distinction
from phototoxic reactions and have a knowledge of photosensitivity disorders
- distinguish clinical patterns of dermatitis likely to be associated with allergic and irritant
photocontact dermatitis
- selection and preparation of specific products for photopatch testing, including patient’s
own products
- determine UVA sensitivity threshold prior to photopatch testing in patients with a history of
persistent UV(A) sensitivity
- interpret and communicate photopatch test results
● Skill: Prick testing for diagnosis of cutaneous allergy and contact urticaria
Evaluation of patients for CU and type I-hypersensitivity including latex allergy, including:
- explain detailed pathomechanisms involved in immunological, non-immunological and
indeterminable CU
54
-
awareness of causes of CU and their environmental and occupational relevance
awareness of mucosal CU and its presentation (oral allergy/food pollen syndromes)
demonstrate knowledge of CU tests and instructions for patients during the test procedure
(specific IgE, skin prick tests, open tests, closed chamber test and challenge tests)
outline resuscitation techniques
discuss preparation of specific products for testing, including patient’s own
identify other potential cross reacting allergens
explain mandatory precautions, and indications for prescription of adrenaline autoinjector
device
awareness of medicolegal aspects of CU including latex allergy
● Skill: Drug allergy testing
Recognise use of appropriate testing in the assessment of drug allergy.
-
-
explain detailed mechanisms involved in drug reactions
demonstrate knowledge of investigations for drug allergy such as skin prick tests, patch
tests, intradermal and challenge testing e.g. to corticosteroids, antibiotics, antiepileptics,
local anaesthetics etc.
contribute to multidisciplinary teams including allergists to maximise patient benefit
● Skill: Knowledge of public health implications and epidemiology of cutaneous allergy
In detail:
- explain basic epidemiological principles in relation to CD
- awareness of occupational health reporting groups and use of surveillance database
resources within cutaneous allergy clinics
- demonstrate appropriate understanding of public health and epidemiological issues
relevant to cutaneous allergy and roles of cutaneous allergy societies and of the role and
function of regulatory authorities.
●
Maintenance of expertise
Minimum standards for provisioniv of a cutaneous allergy service have been defined in the UK. To
maintain competence it was recommended that clinicians should investigate at least 200 cases per
annum.
Investigation of cutaneous allergy is delivered by a multi-professional team. The team should have
regular meetings (at least 4 times per year). The broad aim of these regular clinical governance
meetings is to ensure that the service is focused on the need to provide timely, safe and effective
services to patients. Their agenda should include the following elements:
1. Review of activity since the previous meeting.
2. Review of waiting list data to assess demands on the service and issues for service delivery.
3. Review of adverse events.
4. Discussion of difficult or instructive cases.
5. Equipment issues.
It is recommended that results from investigations should be recorded in a database with a
minimum dataset. The results should be benchmarked annually against national pooled data as
part of departmental governance procedures. The outcome should be presented to the local
dermatology team annually to encourage best use of the service.
55
There is a need for on-going training of team members. To ensure uniform inter individual reading
technique an online patch test reading course is provided by the German contact dermatitis
research groupv. New evidence-based practice, research, national standards, guidance and audit
results all need to be disseminated to staff to ensure the implementation of procedures which
achieve quality outcomes. Training and Clinical Professional Development (CPD) should be
discussed and planned to ensure that all team members fulfil professional requirements to be fully
up-to-date. It is recommended that the lead attend update meetings on contact allergy at least
once every year. The unit should have up-to-date reference books on contact allergy including
occupational skin disease and access to relevant journals.
XI. References
http://www.jrcptb.org.uk/trainingandcert/ST3-SpR/Pages/Dermatology.aspx
Draft: Cutaneous Allergy Post-CCT Curriculum 2014 Version 13 (MMU Chowdhury) Updated
4/12/2013. courtesy Dr MMU Chowdhoury Cardiff & Vale University Health Board, Wales.
Adisesh A, Robinson E, Nicholson PJ, Sen D, Wilkinson M; Standards of Care Working Group. U.K. standards
of care for occupational contact dermatitis and occupational contact urticaria. Br J Dermatol.
2013;168:1167-75
XII. Databases and Surveillance
Including comments from An Goossens and Alicia 21. August 2014 (the Revidal ref. has been
added)
Wolfgang Uter
In the practice of patch testing, the term “databases” refers to 2 aspects: (i) retrieval of information
for patient management or scientific publication, (ii) collection of departmental patch test results,
usually with a view on later analysis and publication. Sufficiently standardised patch test data
collected in the course of several years and/or by different centres can serve the important purpose
of contact allergy surveillance, i.e., the observation of time trends or geographical differences in
56
sensitisation prevalences. In this section, key issues of both aspects are briefly outlined; for further
details see (1).
Information sources
Nowadays, the Internet offers a wealth of information hardly ever fathomed. Regarding product
information, the full INCI labelling information of cosmetics can sometimes be found on the
manufacturer’s website if the patient is unable to produce the package. In other cases, it is helpful
to download material safety data sheets for review of the limited information provided by them.
However, the amount and accessibility of information offered by different companies varies vastly.
Chemical and toxicological information on allergens is available by services which either need
subscription (such as the CAS) or are freely available. The following list includes just some
selected examples in English language:
 the CosIng database [http://ec.europa.eu/consumers/cosmetics/cosing/],
 the expert opinions of the scientific committee on consumer safety and its predecessors
[http://ec.europa.eu/health/scientific_committees/consumer_safety/opinions/index_en.htm]
 toxicological monographs, including contact sensitization, by the German MAK Commission
[http://onlinelibrary.wiley.com/book/10.1002/3527600418/topics]
Patch test software
Every day, important information is collected in a patch test clinic: demographic and clinical data of
the patients tested, e.g., age, sex, the MOAHLFA factors, occupation, leisure activities, history of
dermatitis and clinical signs, and of course the results of patch testing with the baseline series, with
special batteries and with materials brought in by the patient. If this information is solely collected
on paper forms, it is lost to further use, namely, scientific analysis. This has been recognised by
several research networks as well as single departments for several decades, and presently
various ways of electronically collecting data are being employed. Solutions include simple
spreadsheets, in which one row represents one consultation of a patient and each column one
variable, e.g. age, occupation, and the patch test results. Evidently, spreadsheets are not flexible in
terms of adding special patch test results case-by-case or readings beyond the fixed grid chosen
and can get quite difficult to navigate in. As an advantage, they are easily analysed and imported
into other, e.g. statistical software. At the other end of the range of complexity relational database
systems have been developed and used which offer a user-friendly interface supporting daily
routines or at least lessening the burden of data entry to an unavoidable level, e.g.
WinAlldat/ESSCA (2). However, such programs do need some local IT support, especially when
used in a departmental network or having to be connected to a hospital information system.
Furthermore, analysis of collected data – beyond what is offered by the basic inbuilt reporting tools
– does need special resources (competent personnel, time).
Increasingly, suitably modular and sufficiently supported Hospital Information Systems may allow
the documentation of patch test results as an add-on to the electronic patient record. In such
settings, however, the export of the data in a format suitable for analysis in statistical software is
often an issue which needs to be clarified before embarking.
Contact allergy networks and surveillance
Collection of results of all patients patch tested, i.e. also including completely negative cases for
representativeness, by one department already offers interesting possibilities of data analysis.
However, a vast amount of added value can be derived from pooling and comparing data from
different departments within a national or even an international network:
 Benchmarking and quality control of one department’s results against the average of the
peer group, with the possibility of enhancing standardization and quality (3).
57

Pooling of those patch test results deemed of sufficient quality as basis for scientific
analyses (4), thus achieving a much larger and more representative body of data,
compared to single central data.
 Pooled analyses have a much greater power and precision, respectively, to detect time
trends, to identify risk factors for sensitization or susceptible subgroups, but also to optimize
patch test allergen preparations (vehicle, concentration) than data from single departments
(1).
The current scientific literature abounds with examples illustrating the value of networking and
comparative analyses in contact allergy research.
Cosmeto-/Pharmacovigilance
In this context, cosmetovigilance (or, similarly, pharmacovigilance) does not describe methods
used by companies to follow up on consumer’s complaints of unwanted effects, but different
concepts of a special type of contact allergy surveillance implemented by dermatologists. Basically,
a structured process needs to be developed, agreed on by all stakeholders, and subsequently
followed regarding the diagnosis of “new” allergens, the collection and analysis of patch test
results, and the interpretation and dissemination of results. Existing examples include the
REVIDAL/GERDA in France (5) and the IDOC in Germany (65.
These systems generally address patch test results with substances hitherto not commercially
available as allergen preparations, e.g. a cosmetic ingredient, or a (topical) drug. Usually, the
convincing history or the positive patch test results with a product is the starting point for further
investigation. This needs to involve a breakdown test of the products ingredients in adequate
vehicle and dilution. An efficient vigilance system offers structured support in obtaining the set of
single ingredients for patch testing. Not infrequently, the optimal patch test concentration and
vehicle is not known, so the shared experience and expert judgement of the group is needed. After
having tested a certain ingredient a couple of times, valuable evidence on (i) the appropriate patch
test preparation and (ii) the importance of the substance as contact allergen has been gathered
and can be used to include the new allergen into existing test series, if warranted.
References
1.
2.
3.
4.
Uter W, Schnuch A, Giménez-Arnau A, Orton D, Statham B. Databases and Networks. The
benefit for research and quality assurance in patch testing. In: Johansen J D, Frosch P J,
Lepoittevin J P, eds. Contact Dermatitis. Heidelberg: Springer, 2011: 1053-1063.
Uter W, Arnold R, Wilkinson J, Shaw S, Perrenoud D, Rili C, Vigan M, Ayala F, Krecisz B,
Hegewald J, Schnuch A. A multilingual European patch test software concept:
WinAlldat/ESSCA. Contact Dermatitis 2003: 49: 270-271.
Bourke J, Coulson I, English J. Guidelines for the management of contact dermatitis: an
update. Br J Dermatol 2009: 160: 946-954.
Uter W, Mackiewicz M, Schnuch A, Geier J. Interne Qualitätssicherung von EpikutantestDaten des multizentrischen Projektes "Informationsverbund Dermatologischer Kliniken"
(IVDK). Dermatol Beruf Umwelt 2005: 53: 107-114.
5.
Vigan M. [REVIDAL-GERDA: organization and collaboration with
pharmacovigilance].
[Article in French]. Therapie 2002;57: 263-264.6.
6.
Lessmann H, Uter W, Geier J, Schnuch A. Die Informations- und Dokumentationsstelle für
Kontaktallergien (IDOK) des Informationsverbundes Dermatologischer Kliniken (IVDK).
Dermatol Beruf Umwelt 2006: 54: 160-166.
58
Delete:
i http://www.jrcptb.org.uk/trainingandcert/ST3-SpR/Pages/Dermatology.aspx
ii
Draft: Cutaneous Allergy Post-CCT Curriculum 2014 Version 13 (MMU Chowdhury) Updated
4/12/2013. courtesy Dr MMU Chowdhoury Cardiff & Vale University Health Board, Wales.
iii
Adisesh A, Robinson E, Nicholson PJ, Sen D, Wilkinson M; Standards of Care Working Group. U.K.
standards of care for occupational contact dermatitis and occupational contact urticaria. Br J Dermatol. 2013;168:116775
iv
http://www.cutaneousallergy.org/BAD__BSCA_Working_Party_Report_on_Cutaneous_Allergy_Servi
ces_2012_FinalMW.pdf
v
http://dkg.ivdk.org/training.html
59