European Society of Contact Dermatitis
Practical guideline for patch testing
Draft version 1: 19.June 2014
Background information for assessment
Agree guidline 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,
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
Occupational
Drug eruptions, medical implants
VII.
Testing of patients own materials
Alicia
Wolfgang,Carola,
Swen,
Margarida,
Andreas
2000 words
1000 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
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
Patients own materials ( COD-Textbook,
Occ.Handbook): present some general aspects
here
X.
Post-test Information to patients
(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
3
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
Dra. Alicia Cannavó, 25 de Mayo 1617, (B1638ABD) Vicente López. Provincia Buenos Aires. República
Argentina. E-mail: acannavo4@gmail.com
OBJECTIVES OF THE GUIDELINE
This guideline is intended for dermatologists involved in identifying the responsible contact allergen(s) in
patients (including children) suffering from allergic contact dermatitis. It represents an update of the paper
on ‘terminology of contact dermatitis’ (Acta Dermatovener 1970: 287-292), which makes it
consistent with current knowledge. The guideline includes information on 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.
JD insert: explain the process
PATCH TESTING
Definition
Patch testing is a well-established and simple method of diagnosing contact allergy, a delayed type
hypersensitivity (type IV) reaction (1). It aims to reproduce “in miniature’ an eczematous reaction
(2) by re-exposing patients with a possible allergic contact dermatitis to the suspected allergens
(products or materials) under controlled conditions.
Indication
Patch testing is performed in patients with a history or clinical picture of contact dermatitis or
eczema: acute eruptions are characterized by erythema, oedema, papules, vesicles (often
coalescent), or bullae, depending upon the intensity of the allergic response; chronic lesions
present as a thickened scaling, occasionally fissured dermatitis.
Patch testing is performed to identify or exclude contact sensitization as a possible cause of
eczema disease. In case of a positive patch test reaction to an allergen a current or previous
exposure to the allergen should be identified to make the diagnosis of allergic contact dermatitis
(see section IX).
Patch testing can be done in all patients in whom contact sensitization is suspected, regardless of
sex and age (see section VI Children) and anatomical site of eczema. Sometimes, patch testing
may be required for medico-legal reasons such as in case of suspected occupational causes of
eczema.
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.
Other presentations
Contact-allergic reactions may also present as non-eczematous eruptions (3), such as erythema
multiforme-like, lichen planus-like, or lymphomatoid reactions, 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
4
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), and
those due to endogenous exposure, such as via osteosynthesis or metal implants (6) - also stents(7).
Once the allergens have been identified, advice can be given regarding the allergens to avoid and
possible alternatives, e.g. topical drugs, skin care products, gloves, etc.
Recommendations to patch test in patients with:
- Contact Dermatitis,
- Other types of eczema and skin eruptions for which secondary contact allergy is suspected
- Delayed-type drug eruptions
- Chronic eczema that does not improve with treatment
- Dermatitis related to occupational exposures
When not to patch test
Patch testing should be avoided in patients with the following conditions:
-
Systemic active eczema
Dermatitis on the upper back or other body areas chosen to apply patch tests
Test sites have been treated with topical corticosteroids within the past xx days.
Patch testing during pregnancy is not recommended for medico-legal (not scientific)
reasons)
There are several factors, which may affect the out-come of patch testing (see section V).
Information to patients prior to patch testing
Patients should be told the purpose of patch testing, how it 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.
II. Materials (under revision)
5
III. Technique
Magnus Bruze, Magnus Lindberg, Vera Mahler, Mihály Matura,
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 sensitizer 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).
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 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 units are used the same dose/unit
area skin can be used. 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 micro-pipette. However, micro-pipettes 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 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/cm 2) and
15 µl of preparations in liquid vehicle
Liquids should be dosed with a micro pipette.
6
Anatomical site of patch test application
The traditional application site of patch tests is the skin of the upper back. Although in some cases
this area is not available or big enough for performing all tests planned. Nowadays more and more
patients show up with giant tattoos covering the back, others can display severe acne or scar
formation. 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.
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 a hapten applied. 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 at least 100 patch test substances.
It is less often affected by skin diseases, less often 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 available.
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 exposure of the outer surface of the horny layer to the haptens
applied in an occlusive patch test system.
In recent years a lot of effort has been made in order to standardize the process of patch testing.
The human immune system reacts in a dose-response relationship to contact allergens. It is not
the concentration but the applied dose (amount/skin surface unit) of the hapten that is crucial both
for sensitization and for elicitation. But the actual dose that, via penetration through the horny layer
reaches the immune system in the viable epidermis is further dependent on variables such as the
permeability of stratum corneum, the vehicle, and the solubility and the partition coefficient of the
hapten. The penetration is actually forced via occlusion and the quantitative aspects about this
process are not fully mapped. As 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)
varies hugely between different chemical substances. An ideal occlusion time established for
patch testing is just a practical compromise that makes it possible for us to apply patch tests of
several substances in the same time in the clinical practice.
7
Most handbooks and experts recommend an occlusion time of 48 hours.
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
response. 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 test
method.
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.
Neither the literature study of Manuskiatti and Maibach, nor the own data of Brasch et al revealed
proof for a general superiority of 24 or 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 2 days.
Recommendation
No proof for a general superiority of 24 or 48 hours occlusion exists
Most recommend an occlusion time of 48 hours.
For sake of standardization 48 hours occlusion are recommended.
Modifying the system
Definition of the system
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.
Key words here are the purity and stability of the test preparation and the concentration of
the substance (-s) or product tested. (2, 4)
b. The applied amount of the test preparation.
Key word here is the technique of application used to guarantee that the same amount is
applied every time. This can be achieved by weighing of non-liquid test preparations and
using a micro-pipette for liquid test preparations. (5,7)
c. The application technique used. There are several different techniques available for the
application of test substances to the skin. They vary in type of test chamber for the
application (material and form of the chamber) and type of application tape.
Key point here is that the application method used should not irritate the skin and that the
tests will adhere well during the time for application. (6,13)
d. Time of application (time of occlusion). Standard time for exposure to the test substances is
48 hours. However, shorter exposure times have been tried. (13)
8
e. When to evaluate the test result (reading time (-s)). This question has been discussed to
some extent. Most clinics have adapted 2 readings following removal of the patch tests to
ensure that they do not miss positive reactions. However, the time for these readings
varies. (13)
f.
Evaluation of patch test morphology. The evaluation of patch test reactions is subjective
and based on the morphology. Clear cut, strong reactions do not cause many problems.
However, weak or doubtful reactions can be a problem when evaluating the result. It has
been suggested to use photo images to standardize the evaluations.
Key words are training and standardization of the readings at the clinic.(3, 10,11,12)
g. The status of the skin where the test are applied. If there is an inflammatory process (e.g.
eczema) this will influence the result. It has been discussed to use tape stripping (8) to
remove the outer parts of the horny layer or scarification (14,15) to increase the
penetration of the test substance. However, this is difficult to standardize. (8,14,15)
Definition of modifying
To modify is to change some parts of (something) while not changing other parts (www.merriamwebster.com/dictionary).
The patch test technique is constantly developing and all points mentioned above (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 baseline series and various national baseline series. By
changing one or several parts (a-g) of (modifying) 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)
Reading times
After 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].
There is no proof for a general superiority of one of these two exposure times [2]. 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 48h in agreement with the
latest recommendation from the ICDRG (9). A lower number of questionable and irritant patch test
reactions as well as a lower frequency of active sensitization was observed after a 24h-exposure
and first reading at day 1 [ 10,11].
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 sensitizer 7-30% of contact
allergies will be missed unless not reading after one week in addition to the reading on day3/4 (1214). In children, most authors pursue the same approach as in adults with an allergen exposure for
48 h, removal of the patches at day 2 and readings at day 2 and day 3 or day 4, whereas others
have suggested an allergen exposure for 24 h and readings at day 1, day 2 and day 3 [15-17]. Due
to geographic or organizational circumstances the reading times may vary.
Recommendation:
Reading of the patch test reactions are recommended at day 3/4 and day 7.
In addition a reading can be made at day 2.
Up to 30% of contact allergies may be missed if day 7 readings are not performed.
9
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
-
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 etiology 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].
Haptens 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 idenified
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.
For the interpretation it is necessary to keep in mind, that besides their properties as a patch test
allergen most patch test chemicals also do have to a certain degree an irritant potential [20], which
is more predominant in some allergens (e.g. Benzoylperoxid, Phenylquecksilberacetat,
Propylenglycol, Benzalkoniumchlorid, Octylgallat, Cocamidopropylbetain, 1,3-Diphenylguanidin)
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. A control patch test with an obligatory irritant
(SLS 0.25% aqu.) [24] may indicate a nonspecific skin irritability of the patch test location at the
back at the time of patch testing. It is no indicator for skin sensitivity in general. It does not give
evidence of the skin condition at another location or at another instant of time.
10
IV. other techniques
Semi-open, open, ROATs (under updating)
Alicia and Klaus
Photo patch testing
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. 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 to the general rules of patch tests readings but for
result interpretation it is necessary to compare reactions in the irradiated and non-irradiated site. 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,
eventually with photoaggravation if the irradiated test is at least 1+ more intense than the nonirradiated, or with photo-inhibition if the irradiation reaction is less intense. Morphology can help
distinguish a typically photo-allergic reaction (erythemato-papular or vesicular reaction extending
beyond the application area) from a phototoxic reaction (well limited erythematous reaction with
possible infiltration or bullae with a decrescendo pattern that usually progresses to
hyperpigmention), but this distinction is not always easy.
Non
irradiated
Irradiated
Final diagnosis
--
++
PhCA
++
++
CA
+
++/+++
Photoaugmenation
++
+
Photoinhibition
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
11
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 calculate 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.
V. Influence of individual factors
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 is available.
Medication
Little data is in the literature about of the effect of immunosuppressive agents and allergic patch
test reactions. Most suggest that suppression may result in false negative reactions. However,
positive reactions may occur despite immosuppressive 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. Table 1 provides
information on some of the more common medications and patch test response.
12
Table 1
Patch test during treatment with different immunosuppressive drugs
Doses at which positive
Half-live of the medicament
Reference
patch test was reported
to occur
2
Prednisolone*
10 mg
3-4 hours
3;4
azathioprine
100 mg
1 hour
alitretinoin
n.a.
2-10 hours
2;3
ciclosporin
300 mg
14-27 hours
2;3
infliximab
n.a.
9 days
3
adalimumab
n.a.
14 days
3
etanercept
n.a.
70 hours
5
ustekinumab
n.a.
21 days
3
methotrexate
n.a.
8-15 hours
2;3
mycophenolate mofetil
2g
14-16 hours
3
tacrolimus
n.a.
43 hours
*94 % of patients with contact allergy was reported to react positively when treated with 20 mg
prednisolone daily1.
Antihistamines and disodium cromoglycate are not reported to influence the allergic contact
dermatitis reaction1, and the same is the case for non-steroid anti-inflammatory drugs. Retinoinds
(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.
Skin type and racial differences
Black- and dark skinned people have been reported to be less prone to develop sensitization,
however, redness and inflammation may also be more difficult to detect on black skin. Differences
in sensitization pattern between different races probably reflect exposure rather than
predisposition to sensitisation15;16.
13
Recommandation: Evidence for influence of individual factors on result of patch testing is
remarkably low, and there is room for sound clinical judgement. If allergic contact dermatitis is
suspected in patients in immunosuppresive treatment it 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 test on a later stage.
Atopic dermatitis and concomitant active eczematous disease
The prevalence of contact sensitization in atopic dermatitis has been discussed regularly over the
years, and a definite understanding of the relationship has not been reached. Although studies
have shown conflicting results17;18, the traditional understanding is that contact sensitization is less
frequent in patients with atopic dermatitis, due to an impaired cellular immune response of the
skin leading to a decreased ability to combat skin infections and develop type IV allergies 19;20.
More recent studies, however, indicate that contact sensitization may vary with the severity of
atopic dermatitis, suggesting a more complex relationship 21;22, and a higher frequency of positive
patch tests in patients with severe atopic dermatitis has been reported23;24. In most studies the
frequency of positive patch tests in atopics is the same as in other dermatitis patients, and
therefore . patch testing of atopics is encouraged on the same indication as other patients, albeit
interpretation is diffucult due to their generally hyperreacting skin with risk of false positives
VI. Special groups
1. Children
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
INTRODUCTION
Allergic contact dermatitis (ACD) in children does occur, but has been unrecognized and only
recently more extensively studied, one of the reason’s being the physicians’ behavior. For
example, atopic dermatitis is sometimes the only diagnosis considered when babies or toddlers
suffer from eczema, while all children, including atopic ones, may become sensitized to
environmental chemicals. Moreover, there are the practical problems involved with patch testing
(1).
14
METHOD
The literature search was done using PubMed; key words were allergic contact dermatitis,
children, baseline series, active sensitization, patch testing. We have selected the more recent
articles about some epidemiologic data, or some adverse effects with an allergen, or some
discussion about concentration of an allergen or some abbreviated baseline series for testing
children.
PREVALENCE
Data on the prevalence of contact allergy in healthy children are scarce and studies in children
suspected to suffer from allergic contact dermatitis are difficult to compare because of differences
in age groups, environmental contacts, indications for patch testing, allergens tested, and atopic
condition.
For example, in a review of data obtained during the last decade (2) sensitization rates of 26.6 to
95.6% were observed in selected groups of children.
Regarding the potential sensitization sources, the youngest children may be prone to react to
topical pharmaceutical and skin-care products used, particularly if atopic, to products used by the
persons taking care of them, or to any other material contacted at that age. Adolescents, on the
contrary, are more likely to become sensitized to similar allergen sources as in adulthood, including
initial occupational contacts.
THE MOST FREQUENT ALLERGENS IN CHILDREN
In a Danish review (3) the most common allergens identified in children were nickel, cobalt,
thiomersal, and fragrance components, while another retrospective study (regarding older age
groups (4) included ammonium persulfate, gold, sodium thiosulfate, p-toluene diamine and the
methylchloroisothiazolonone/methylisothiazolinone mixture.
PATCH TESTING IN CHILDREN
Patch testing in children is considered to be safe and is indicated when allergic contact dermatitis
is suspected, but also when eczematous lesions are present at certain localizations, such as on
the hands and feet, eyes, peri-umbilical region, or sites of vaccination, and also in atopic children
when lesions persist notwithstanding therapy (5).
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 and hypermobility of younger children, which
sometimes makes the use of stronger adhesive tape necessary.
There is not a consensus though about the allergens to be tested nor about their concentrations,
the latter because of potential irritancy problems (6). Some authors advocate the use of the same
baseline series and concentrations as in adults, such as e.g. the North American Contact
Dermatitis Group (7), while others, particularly in Europe, have proposed a shortened patch-test
series for children (8). Moreover, some have recommended lower concentrations for specific
allergens such as nickel, chromium, and cobalt (being metals often producing follicular or irritant
reactions in atopic subjects, in particular), but also for formaldehyde, mercurials,
mercaptobenzothiazole, and thiuram mix (6).
Based on a study conducted by an expert panel, the German Contact Dermatitis Group (9)
recommended an abbreviated baseline series for children containing allergens having a rate of
positivity higher than 1%, and, since a risk of active sensitization can never be excluded, to add
15
some allergens only if present according to the personal history (e.g. PPD in tattoos). The RevidalGERDA (8) also takes the high relevance of positive patch tests into account, even if not frequently
positive.
The baseline series proposed by the German group (9) is useful, except for bufexamac and
methyldibromo glutaronitrile that have in the meantime been banned in Europe, with the addition of
nickel (a common allergen in children) and methylisothiazolinone, an allergen that also affects
children, not at least through the use of baby wipes. Compositae mix can be discussed regarding
the risk of active sensitization (10). Formaldehyde is in the French baseline series. It is useful
whatever the age because cosmetics and also products used in the house (houseware, do it
yourself) can contain and release it. Moreover epoxy resin is not relevant in children and can be
removed from the baseline series. PPD have to be tested if the clinical history is suggestive of
contact with it. In case of contact dermatitis after a 'henna tattoo', even much lower concentrations
or shorter exposure times or open testing may be advisable to avoid unneccessarily strong patch
test reactions (11)
Thus an European standard baseline can be proposed for testing children before 12 years of age
(table 1)
If doubtful results are obtained, such as with metal salts, open testing or patch testing at a lower
concentration can be performed. Last but not least, patch testing with the products the children
actually come in contact with, such as topical products, antiseptics, toys, etc., along with the
potential ingredients, is crucial. In the youngest, in particular, they may sometimes be the only
allergens to be tested! Furthermore, for children at the age of 12 years or above, the same
allergens as in adults should be tested.
Recommendation
Allergic contact dermatitis in children is not an uncommon finding. Patch testing is safe and,
therefore, should be carried out in all children suspected of allergic contact dermatitis, when
eczematous lesions are present at certain localizations, or when lesions persist notwithstanding
adequate treatment.
For the youngest an abbreviated baseline series is advisable, but certainly supplemented by the
products/materials and their ingredients they came in contact with.
Table 1
Abbreviated baseline patch test series for Young children.
European Society of Contact Dermatitis?
Allergens
Nickel sulfate
Potassium dichromate
Lanoline
Neomycine sulfate
Fragrance mix I
Colophonium
Myroxylon pereirae
Parabens mix
Thiuram mix
4 ter butyl phenol formaldehyde
Formaldehyde
Concentration
5% pet*
0,5% pet*
30% pet
20% pet
8% pet
20% pet
25% pet
16% pet
1% pet
1% pet
1% water
16
Pivalate de tixocortol
0.1%pet
Budésonide
0.1% pet
Cl Méthyl
0.01% pet
isothiazolinone/methylisothiazolinone
Lactone sesquiterpénique
0.1% pet
Mercapto mix or
mercaptobenzothiazol
Fragrance mix II
14% pet
methylisothiazolinone
2000ppm**
*open test before 3 years of age
PPD 1% pet is tested only if the clinical history is suggestive, first by open tests.
**with a micropipette
2. Occupational contact dermatitis
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, 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
should be underscored that a visit to the patient’s workplace often will add crucial information
concerning the exposure.
Exposure analysis
After the collection of basic information from the patient’s history, it may 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 occupational
accident insurance. Exposure analysis has 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). Thin layer chromatography (TLC) can be used in selected
cases to identify certain organic chemicals, among them plastic resins and textile dyes. The
chromatograms can even be used for patch testing to identify culprit ingredients in products. The
TLC is useful in giving the possibility to identify an allergen, or possibly several, in a complex
solution or where a substance has oxidised or changed in an unknown manner (4). Spot tests,
such as those available for nickel (dimethylglyoxime (DMG) test) (5), cobalt (6, 7),
17
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 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).
Primary health care



Treatment
No patch testing
Early referal to general
dermatology or to occupational
dermatology/cutaneous allergy:
important to avoid delay
Occupational dermatology/
cutaneous allergy

General dermatology




Treatment
Diagnosis
Patch test
o Baseline series
o Some special series
o Some products and materials
”as is” (creams, protective
gloves, textiles)
Referal to occupational
dermatology/cutaneous allergy


Patch test
o Baseline series
o Special series
o Ingredients in products
o Products and materials ”as is”
o Dilutions
o Extracts
Other tests
o ROAT
o Prick test
o Photo patch test
o Chemical analysis of products
Other resources or service
o Workplace visit
o Occupational hygienist
o Counceller
o Occupational guidance
o Certificates, statements about
the disease
o Medicolegal opinion
Patch testing with commercial allergen preparations
Occupational health service
 No patch testing
General recommendations outlined in this text should be considered. In addition, guided by the
 Early
referal to
general
patient’s
occupation
and
individual exposures, special test series covering allergens to which the
dermatology
or
patient may be exposedoccupational
should be applied (Fig. x). Some textbooks or journal articles have offered
allergy: and test series, respectively (e.g. (1, 2)). Moreover,
guidancedermatology/cutaneous
on the selection of allergens
important
to
avoid
delay
allergens offered by the patch test manufacturers are arranged in ‘test series’ covering certain,
Descriptionexposure
of the workplace
e.g., occupational,
areas, and
in some cases following the recommendations of (inter-)
skin exposure
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
18
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 (Fig. x). Difficulties may be due to trade 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
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 atopy) or exogenous cofactors such as occlusion, friction etc. are involved.
Recommendation
Each diagnosis (there may be multiple) need to address affected site,
offending work material, causative allergen (or irritant), and endogenous
or exogenous co-factors, if relevant.
19
Figure: Check-list for work-up of patients with suspected occupation-related contact dermatitis
regarding factors related to occupational exposure; relevant non-occupational exposures should be
addressed in a similar fashion. If a “no” answer has no consequences (e.g., if no products are
eligible for patch testing) no arrow is drawn.
No
Yes
Stepwise work-up
[ ]
Verbal description/pictures/references/report from occupational hygienist
regarding work tasks and typical exposures obtained?
[ ]
[ ]
Products suspected by patient or physician to possibly cause dermatitis
identified?
[ ]
[ ]
[ ]
[ ]
[ ]
[ ]
[ ]
Products eligible for patch testing (at non-irritating/non-sensitising
concentration)?
[ ]
Special patch test series to be tested in addition to baseline series
identified/applied?
[ ]
Patch test to product(s) positive: break-down test feasible, including ways
to obtain fully declared single ingredients to prepare patch test allergens?
[ ]
Break-down test positive: patch testing of controls verified suitability of
allergen preparation?
[ ]
Given final reading of patch tests: (Further) exposure assessment
necessary e.g. by (i) spot tests, (ii) chemical analysis, (iii) (re-)consultation
of material safety data sheets or suitable inquiries?
[ ]
[ ]
[ ]
Contact with occupational hygienist or other suitable institution or
workplace visit possible for this purpose?
[ ]
Final evaluation established one (or more) diagnoses with sufficient
probability? (The concept of “diagnosis” is extended here to include the
combined information shown in the text box.)
[ ]
Referral to (more) specialised department necessary, or re-consultation of
the patient for follow-up on hitherto missing information/allergen
preparations?
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.
20
3.PATCH TESTING IN DRUG ERUPTIONS
Patch testing is also indicated in the study of non-immediate 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).
Patch testing should be performed at least 6 weeks after complete resolution of the CADR, using
all the possible culprit drugs. The 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 in the normal 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 non-reactive (Andrade, Brinca, & Gonçalo, 2011).
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 testing
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% (Barbaud,
Gonçalo, Bircher, & Bruynzeel, 2001), (Barbaud 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, loratadine. For
commercially available drug allergens no further controls are needed.
Patch test specificity is high but sensitivity is lower than in ACD (30-70%) and depends on the
culprit drug and the clinical pattern of CADR. Drugs like carbamazepine, tetrazepam, pristinamycin
induce positive reaction in more that 70% of cases, whereas for other drug like betalactam
antibiotics and clindamycin a low percentage of reactivity is expected (20-30%), reflecting probably
the need for concomitant factors for inducing the CADR. For allopurinol patch tests are usually
negative. Patch tests are frequently positive in maculo-papular exanthema, DRESS and AGEP,
whereas very seldom in SJS/TEN. Prick and intracutaneous (i.c.) tests, with immediate and late
readings can have an additional value in CADR, but they are out of the scope of these guidelines.
Patch testing is a safe technique, even in severe CADR, with exceptional cases of reactivation of
the CADR,
VII. Patch Testing of patients’ own materials
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).
21
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,
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. 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
22
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) and in the end
the irritant properties of the possible new allergen are checked by testing the same substance on
unexposed control patients (or healthy individuals). For practical purposes, five negative controls
are sufficient, but in scientific work at least 20 are usually needed. However, under current legal
conditions it may be difficult to recruit control individuals for routine patch testing with novel
allergens. A general rule is that controls are tested with a concentration 10 times greater than the
concentration causing the weakest detectable reaction (7). 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 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,
23
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, plants, 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
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
 Form a general impression of the products’ composition by reading safety data sheets,
ingredient lists and other data
 Consult text books if you are not experienced
 Test individual components of patients’ own products separately if possible
 Check pH and adjust it with buffers if necessary
24






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.
The use of ultrasonic bath extracts is an alternative to testing solid materials
VIII. Potential side effects of Patch Testing
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 testing is the gold standard test to diagnose allergic contact sensitization. This test aims to
reproduce the biological reaction of contact eczema by applying allergens under occlusion onto the
skin. It is the in vivo visualization of the elicitation phase of a hypersensitivity reaction, mainly of a
type-IV delayed reaction 1. But can also result from type-I reactions such as contact-urticaria.
Patch Test Adverse Reactions:
1. Irritant Reaction:
Nowadays, few irritant reactions are seen with patch testing with standardized allergen
preparations as a result of international standardization of allergen concentrations, vehicles,
application materials and techniques, and increasing knowledge of the chemical and physical
properties of substances applied to the skin. Irritant reactions are usually due when nonstandard
allergens or products are tested, some time brought by the patient.
Different types of irritant reaction were described. Well demarcated erythematous reactions usually
are seen with fragrance mix, and thiuram mix. Purpuric reactions are commonly induced by metal
salts, e.g. cobalt chloride. Bullous reactions can be observed when certain substances are wrongly
patch tested e.g. gasoline, kerosene or turpentine peroxide. Pustular reactions are seen mainly
with non-noble metals like chromium, cobalt, and nickel. Finally, necrotic reaction which is the most
severe type occurs with substances as soda or kerosene among others, once again if are
incorrectly patch tested.
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.
2. Angry back syndrome:
25
A generalized erythema of the back, caused by one or more strong positive reactions, may result in
false-positivity to all or most of the tested allergens. A false positive reaction can be due by
different causes as impure contaminated test preparations, an irritant vehicle, excess of test
preparation applied, current or recent dermatitis, adhesive tape reactions or influence from
adjacent test reactions.
3. Patch test sensitization:
Although this could be rare, it is a serious complication of patch testing. It is defined as positive
patch test reaction 10 – 20 days after an initial negative response. In practice, it may be difficult to
differentiate between induction of sensitization due to patch test and a delayed patch-test elicitation
reaction4. To confirm the diagnosis of active sensitization, repeated patch testing can be
performed. Faster positive reactions, with ‘normal’ latency of elicitation (one to a few days) support
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, acrylates, and bleach accelerator
(PBA-1) 3 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.
It should be clear that despite the minor risk of active sensitization, the benefit of patch testing
outweighs the risk. Furthermore, the clinical relevance of iatrogenic sensitization by diagnostic
patch testing is neglectible . 8
4. Pigmentation changes:
A positive patch test reaction can result in either hyper- or hypopigmentation in the test area. Dark
colored patients are more susceptible. Sunlight exposure and severe irritant reaction are other
causes. The altered pigmentation usually clears over time.
5. Flare up of clinical dermatitis:
An interesting side-effect can be a flare of an existing, or sometimes a previous dermatitis
previously caused by the test allergen. Such flare was reported with nickel sulphate and topical
amcinonide6.
Flare-up of dermatitis was significantly more common in patients with multiple contact allergies
than in patients with one or two sensitizations only. The local skin memory response is a reliable
sign that the patient had been in re-exposed to the culprit chemical during patch testing9.
6. Persistent reaction:
A positive patch test reaction can sometimes persists 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 has also been reported to cause notorious
persistent reaction 1, 13.
7. Subjective complaints:
Various unrelated subjective complaints of patch tested patients were reported in the literature.
Among these: fatigue, fever, headache, vomiting, and dizziness are common 2. There is no
evidence of a cause-effect relationship.
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.
8. Scarring and necrosis:
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).
9. Infections:
26
Bacterial, viral, or even fungal skin infections can affect the site of patch testing when using fresh
plant parts.
10. Anaphylactoid reaction:
Very rare but most severe complication of patch testing that occurs within 30-60 minutes after
applying the patches. It was reported when testing antibiotics such as neomycin, bacitracin,
penicillin, or gentamycin, but also with ammonium persulphate.
27
IX. Final evaluation
Jeanne Duus Johansen, Ian White
Litterature 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 in June 2014. Further textbooks were checked manually. In total 19 relevant
publications were found.
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 to the substance in question has occurred.
The next step is to evaluate, if the patient currently or in the past have had any clinical
symptoms caused by the substance (Bruze, 1990).
This means that establishing allergic contact dermatitis involves a process with 2 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 (Wilkinsson 1970).
This has later been operationalized 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 assess whether an established contact allergy is of present, past,
or unknown relevance.
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
Own experience
28
Textbooks
Information from:
- packages
- data sheets
- manufacturers/suppliers
Spot tests
Chemical analysis
III. Conclusion (diagnosis)
The patients’ 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 patients’ 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. 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 and it can be necessary to look up synonyms to do an effective
exposure assessment.
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.
For certain allergens: nickel, cobalt and formaldehyde a spot test exists, 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 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
29
formaldehyde, which has been shown to be of clinical relevance in those sensitized
(Bruze?).
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.
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 periei). 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 positive
patch test reaction has been caused by another not tested, but chemically similar
substance. If you look for the substance which has caused the positive patch test this may
not be present in the environment and the wrong conclusion is drawn that the allergy is not
relevant or if it is present the true culprit exposure will not be identified. An example is
positive patch tests to the UV absorber octocrylene in patients sensitized to topical
ketoprofen (DeGroot 2014).
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
Principles of patch testing of products are given in section xx. A positive patch test 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 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.
30
A use test is often helpful in establishing clinical relevance, but is reserved 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’
(Wilkinsson, 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 is all potential sources of exposure have been identified.
Recommendation
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 justified
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. have 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.
31
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.
Interpretation of negative patch test reactions
Like for doubtful patch test reactions, it should always be considered if the patch test
concentration is optimal or if it is the correct substance which is tested. 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.
32
X. Patient education
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
Once patch test reading and interpretation has been finalized, potentially the most crucial part of
the contact allergy work-up should now attract the physician’s full attention, namely ‘patient
education’. In fact, allergic contact dermatitis can be completely cured following successful
education of the patient on allergen avoidance. However, in some situations, it may be difficult, for
example at work places. Chromium allergy seems to cause more persistent dermatitis 1, but most
patients can be informed that with strict allergen avoidance and no other skin abnormalities or
conditions, their dermatitis should clear within 3-6 months.
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 measures on 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. Label ingredient
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 low social class 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 pphenylenediamine 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’ are often misleading and can
not be used for guidance. Many clinics cleverly provide a plastic card with the allergen names
printed, which the patient can have in their wallet and easily access when shopping.
To help patient identify safe personal care product, 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
33
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 favor 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.
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
Recommendations for patient education following patch testing
Advice and actions that the dermatologist can consider in a given patient:












Contact allergy is a persistent disorder but may gradually decrease over time
Both direct skin exposure as well as airborne exposure should be prevented.
Dermatitis will typically clear within 3-6 months, sometimes before, if the patient has no
other conditions and can strictly avoid allergen contact.
Marketing terms such as ’free of synthetic fragrances’ or ’hypoallergenic’ can be
misleading.
Sometimes the ingredient label is not correct.
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. Discarding the box can be a mistake.
Not every glove use 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 exposures should be added.
A print of safe and allergen free products can be given if updated and reliable.
34
XI. Training in cutaneous allergy
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.
●This includes investigation, diagnosis and management of patients with skin allergy, including
presentations of contact dermatitis (CD) and contact urticaria (CU)
Dematologist 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. It may involve factory or work
place visits as well as specialist patch and photo testing and specialist pharmacy services.
An individual would be expected to gain the knowledge and skills in cutaneaous 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.
● To understand basic immunology and chemistry relevant to cutaneous allergy and irritation
-
explain detailed science 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
interpret relevant chemicals in material safety data sheets
● Patch testing for diagnosis & management of Cutaneous Allergy & Contact Dermatitis
To be able to investigate, diagnose and manage patients with skin allergy including presentations
of CD
- explain the detailed indications for patch testing
- 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
35
● Occupational skin diseases
To be able to investigate, diagnose and manage patients with common occupational dermatoses
-
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
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.
● Photopatch testing
To be able to investigate, diagnose and manage patients requiring photopatch testing.
- 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
- interpret and communicate photopatch test results
● Prick Testing for diagnosis of Cutaneous Allergy & Contact Urticaria
To be able to evaluate patients for CU and type I-hypersensitivity including latex allergy
- explain detailed pathomechanisms involved in immunological, non-immunological and
indeterminable CU
- 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 (COSHH regulations)
● 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 eg to corticosteroids, antibiotics, antiepileptics,
local anaesthetics etc.
contribute to multidisciplinary teams including allergists to maximise patient outcomes
● Public Health and Epidemiology
To be aware of public health and epidemiology aspects of cutaneous allergy
- explain basic epidemiological principles in relation to CD
36
-
awareness of occupational health reporting groups and use of 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.
● Miscellaneous
To be aware of other specialty practices relevant to cutaneous allergy
- paediatric allergy including food and environmental allergy
- investigation and management of food allergy in adults
- bee/wasp sting investigation and desensitization techniques/pollen immunotherapy
- investigation and management of idiopathic anaphylaxis
- drug desensitisation regimes
- contribute to multidisciplinary teams including other medical (including allergy) teams,
nursing and paramedical staff in the management of the above
Maintenance of expertise
Minimum standards for provisioniv of a cutaneous allergy service in the UK have been defined. 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.
There is a need for ongoing 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 relevant journals.
i
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.
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;168:1167-75
iv
http://www.cutaneousallergy.org/BAD__BSCA_Working_Party_Report_on_Cutaneous_Allergy_Services_2012_Fina
lMW.pdf
v
http://dkg.ivdk.org/training.html
ii
37
XII. Databases and Surveillance
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
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 sensitisation, 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
38
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 standardisation and quality (3).
 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 sensitisation or susceptible subgroups, but also to optimise
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 #ref (Martine should say which is the most appropriate reference!).
and the IDOC in Germany (5).
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.
39
References
I. Introduction
1. Lindberg M and Matura M. Patch testing. In: Contact Dermatitis, 5th edition, Duus Johansen J,
Frosch P J, Lepoittevin J-P. Berlin Heidelberg, Springer-Verlag, 2011:439-464.
2. Lachapelle J-M, Maibach HI. Patch Testing and Prick Testing. A practical guide. Berlin Heidelberg,
Springer-Verlag, 2012: 35-77.
3. Goon A, Goh Chee-Leok. Non-eczematous contact reactions. In: Contact Dermatitis, 5th edition,
Duus Johansen J, Peter J. Frosch P J, Lepoittevin J-P. Berlin Heidelberg, Springer-Verlag,2012: 415-427.
4. Gonçalo M and Bruynzeel DP. Patch testing in Adverse Drug reactions. In: Contact Dermatitis, 5th edition,
Johansen J, Frosch P J, Lepoittevin J-P. Berlin Heidelberg, Springer-Verlag, 2011: 475-491.
5. Isaksson M. Dental materials. In: Contact Dermatitis, 5th edition, Duus Johansen J, Frosch PJ,
Lepoittevin J-P. Berlin Heidelberg, Springer-Verlag, 2011: 763-791.
6. Peter C. Schalock PC, Menné T, Johansen JD, Taylor JS, Maibach HI, Lidén C, Bruze M,
Thyssen JP. Hypersensitivity reactions to metallic implants – diagnostic algorithm and suggested
patch test series for clinical use. Contact Dermatitis 2012; 66: 4-19.
7.Cecilia Svedman C, Ekqvist S, Möller H, Björk J. Pripp C-M, Gruvberger B, Holmström E,
Gustavsson C-G, Bruze M. A correlation found between contact allergy to stent material and
restenosis of the coronary arteries. Contact Dermatitis 2009; 60: 158-164.(ref Svedman)
II. Materials
None yet
III. Technique
References dosing of chambers
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.
40
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.
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 2007:56:2815.
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.
41
References anatomical and occlusion
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.
references modifying the test system
1
2
3
4
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.
42
5
6
7
8
9
10
11
12
13
14.
15.
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.
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.
References: reading/time
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.
43
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.
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.
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.
44
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.
IV. Other techniques
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.
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. Individual factors
1. Feuerman E, Levy A. A study of the effect of prednisone and an antihistamine on patch test
reactions. Br J Dermatol 1972; 86: 68-71.
2. Rosmarin D, Gottlieb AB, Asarch A et al. Patch-testing while on systemic
immunosuppressants. Dermatitis 2009; 20: 265-70.
3. Wee JS, White JM, McFadden JP et al. Patch testing in patients treated with systemic
immunosuppression and cytokine inhibitors. Contact Dermatitis 2010; 62: 165-9.
4. Pigatto P, Cesarani A, Barozzi S et al. Positive response to nickel and azathioprine
treatment. J Eur Acad Dermatol Venereol 2008; 22: 891.
5. Nosbaum A, Rozieres A, Balme B et al. Blocking T helper 1/T helper 17 pathways has no
effect on patch testing. Contact Dermatitis 2013; 68: 58-9.
6. Clark RA, Rietschel RL. 0.1% triamcinolone acetonide ointment and patch test responses.
Arch Dermatol 1982; 118: 163-5.
7. Green C. The effect of topically applied corticosteroid on irritant and allergic patch test
reactions. Contact Dermatitis 1996; 35: 331-3.
45
8. Smeenk G. Influence of local triamcinolone acetonide on patch test reactions to nickel
sulfate. Dermatologica 1975; 150: 116-21.
9. Johnson MW, Maibach HI, Salmon SE. Brief communication: quantitative impairment of
primary inflammatory response in patients with cancer. J Natl Cancer Inst 1973; 51: 1075-6.
10. van der Harst-Oostveen CJ, van Vloten WA. Delayed-type hypersensitivity in patients with
mycosis fungoides. Dermatologica 1978; 157: 129-35.
11. Grossman J, Baum J, Gluckman J et al. The effect of aging and acute illness on delayed
hypersensitivity. J Allergy Clin Immunol 1975; 55: 268-75.
12. Cooper KD, Oberhelman L, Hamilton TA et al. UV exposure reduces immunization rates and
promotes tolerance to epicutaneous antigens in humans: relationship to dose, CD1a-DR+
epidermal macrophage induction, and Langerhans cell depletion. Proc Natl Acad Sci U S A
1992; 89: 8497-501.
13. Skov L, Hansen H, Barker JN et al. Contrasting effects of ultraviolet-A and ultraviolet-B
exposure on induction of contact sensitivity in human skin. Clin Exp Immunol 1997; 107:
585-8.
14. Thorvaldsen J, Volden G. PUVA-induced diminution of contact allergic and irritant skin
reactions. Clin Exp Dermatol 1980; 5: 43-6.
15. Collazo MH, Figueroa LD, Sanchez JL. Prevalence of contact allergens in a Hispanic
population. P R Health Sci J 2008; 27: 333-6.
16. Deleo VA, Taylor SC, Belsito DV et al. The effect of race and ethnicity on patch test results. J
Am Acad Dermatol 2002; 46: S107-S112.
17. Cronin E, McFadden JP. Patients with atopic eczema do become sensitized to contact
allergens. Contact Dermatitis 1993; 28: 225-8.
18. Lammintausta K, Kalimo K, Fagerlund VL. Patch test reactions in atopic patients. Contact
Dermatitis 1992; 26: 234-40.
19. Jones HE, Lewis CW, McMarlin SL. Allergic contact sensitivity in atopic dermatitis. Arch
Dermatol 1973; 107: 217-22.
20. Rystedt I. Atopic background in patients with occupational hand eczema. Contact
Dermatitis 1985; 12: 247-54.
21. Mailhol C, Lauwers-Cances V, Rance F et al. Prevalence and risk factors for allergic contact
dermatitis to topical treatment in atopic dermatitis: a study in 641 children. Allergy 2009;
64: 801-6.
22. Thyssen JP, Johansen JD, Linneberg A et al. The association between contact sensitization
and atopic disease by linkage of a clinical database and a nationwide patient registry.
Allergy 2012; 67: 1157-64.
23. Belhadjali H, Mohamed M, Youssef M et al. Contact sensitization in atopic dermatitis:
results of a prospective study of 89 cases in Tunisia. Contact Dermatitis 2008; 58: 188-9.
24. Clemmensen KB TSJGAT. Pattern of contact sensitization in patients with and without
atopic dermatitis in a hospital-based clinical database . Contact Dermatitis 2014.
46
VI: special groups: children
1. Morren M-A. Goossens A. Contact Allergy in Children. In Chapter 48: Contact Dermatitis, 5th 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.
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,
Szliska C. Patch testing in children – recommendations of the German Contact Dermatitis Research Group
(DKG). J Dtsch Dermatol Ges 2007; 5: 107-9
10 Isaksson M, Hansson C, Inerot A, Lidén C, Matura M, Stenberg B, Möller H, Bruze M, Swedish Contact
Dermatitis Research Group. Multicenter patch testing with compositae mix by the Swedisch Contact
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.
VI special groups : occupational
1.
2.
3.
4.
Rustemeyer T, Elsner P, John S M, Maibach H I. Kanerva's Occupational Dermatology.
Heidelberg etc.: Springer, 2012.
Johansen J D, Frosch P J, Lepoittevin J P. Contact Dermatitis. Heidelberg etc.: Springer,
2011.
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.
47
5.
6.
7.
8.
9.
10.
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.
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
Dermatitis 2011: 64: 32-36.
Lidén C, Skare L, Nise G, Vahter M. Deposition of nickel, chromium, and cobalt on the
skin in some occupations - assessment by acid wipe sampling. Contact Dermatitis 2008: 58:
347-354.
Julander A, Skare L, Vahter M, Lidén C. Nickel deposited on the skin-visualization by
DMG test. Contact Dermatitis 2011: 64: 151-157.
VI: special groups drug eruptions
Andrade, P., Brinca, A., & Gonçalo, M. (2011). Patch testing in fixed drug eruptions. A 20-year
review. Contact Dermatitis, 65(4), 195–201. doi:10.1111/j.1600-0536.2011.01946.x
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.
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.
3
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.
4
De Groot AC. Patch Testing 3rd Edition. Wapserveen, The Netherlands, 2008.
5
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
6
Zweites Gesetz zur Änderung arzneimittelrechtlicher und anderer Vorschriften vom
19.10.2012. Bundesgesetzblatt 2012; 50: 2192-227.
7
Fregert S. Publication of allergens. Contact Dermatitis 1985: 12: 123-4.
48
8
9
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: 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.
Dec2013, 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
Bruze M. What is a relevant contact allergy? 1990:23:224-225
Fregert S. Manual of Contact Dermatitis. Munksgaard, Copenhagen 1974.
Lachapelle J-M. A proposed relevance scoring system for positive allergic patch test reactions.
Practical implications and limitations. Contact Dermatitis 1997:36:39-43.
Lindberg M, Matura M. Patch Testing in Contact Dermatitis 5th ed, eds. Johansen JD, Frosch PJ,
Lepoittevin JP 2011: 24:439-464.
49
Wilkinsson DS, Fregert S, Magnusson B, Bandmann HJ, Calnan CD. Terminology of Contact
Dermatitis. Acta Dermatovener (Stockholm) 1970:50:287-292.
Hauksson I, Pontén A, Gruvberger B, Isaksson M, Bruze M. Clinically relevant contact allergy to
formaldehyde may be missed by testing with formaldehyde 1.0%. Br J Dermatol 2011:164(3): 56872.
Thyssen JP, Menné T, Johansen JD, Lidén C, Julander A, Møller P, Jellesen MS. A spot test for
detection of cobalt release – early experience and findings. Contact Dermatitis 2010:63:63-9.
Keegel T, Saunders H, LaMontagne AD, Nixon R.
Are material safety data sheets (MSDS) useful in the diagnosis and management of occupational
dermatitis?
Contact Dermatitis 2007:57:331-6.
Friis UF, Menné T,, Flyvholm M, Bonde JP, Johansen JD. Difficulties in using MSDS to analyse
occupational exposures to contact allergens. Contact dermatitis: 2014: sub.
Tillman C, Engfeldt M, Hindsén M, Bruze M. Usage test with palladium-coated earrings in patients
with contact allergy to palladium and nickel. Contact Dermatitis 2013:69:288-95
Heisterberg MV, Menné T, Johansen JD. Contact allergy to the 26 specific fragrance ingredients to
be declared on cosmetic products in accordance with the EU cosmetics directive. Contact
Dermatitis 2011:65:266-75
Thyssen JP, Skare L, Lundgren L, Menné T, Johansen JD, Maibach HI, Lidén C.
Sensitivity and specificity of the nickel spot (dimethylglyoxime) test.
Contact Dermatitis. 2010 May;62(5):279-88.
Julander A, Skare L, Vahter M, Lidén C.
Nickel deposited on the skin-visualization by DMG test.
Contact Dermatitis. 2011 Mar;64(3):151-7.
Frosch PJ, Pirker C, Rastogi SC, Andersen KE, Bruze M, Svedman C, Goossens A, White IR, Uter
W, Arnau EG, Lepoittevin JP, Menné T, Johansen JD.
Patch testing with a new fragrance mix detects additional patients sensitive to perfumes and
missed by the current fragrance mix.
Contact Dermatitis. 2005 Apr;52(4):207-15.
Thyssen JP, Johansen JD, Jellesen MS, Møller P, Sloth JJ, Zachariae C, Menné T.
Consumer leather exposure: an unrecognized cause of cobalt sensitization.
Contact Dermatitis. 2013 Nov;69(5):276-9
de Groot AC, Roberts DW.
Contact and photocontact allergy to octocrylene: a review.
Contact Dermatitis. 2014 Apr;70(4):193-204. doi: 10.1111/cod.12205.
Bruze ??formaldehyde I små niveauer
50
Fransway AF, Zug KA, Belsito DV, Deleo VA, Fowler JF Jr, Maibach HI, Marks JG, Mathias CG,
Pratt MD, Rietschel RL, Sasseville D, Storrs FJ, Taylor JS, Warshaw EM, Dekoven J, Zirwas M.
North American Contact Dermatitis Group patch test results for 2007-2008.
Dermatitis. 2013 Jan-Feb;24(1):10-21.
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.
X. Patient education
1. 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):101-108.
2. Katta R. Common misconceptions in contact dermatitis counseling. Dermatol Online J
2008;14(4):2.
3. 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.
4. 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.
5. 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.
6. Ho SG, Basketter DA, Jefferies D, Rycroft RJ, White IR, McFadden JP. Analysis of paraphenylenediamine allergic patients in relation to strength of patch test reaction. Br J Dermatol
2005;153(2):364-367.
7. 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.
8. Yiannias JA, el-Azhary RA. Contact Allergen Avoidance Program: a topical skin care product
database. Am J Contact Dermat 2000;11(4):243-247.
9. Zirwas MJ. Contact alternatives and the internet. Dermatitis 2012;23(5):192-194.
10. Edman B. The usefulness of detailed information to patients with contact allergy. Contact
Dermatitis 1988;19(1):43-47.
11. 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.
12. 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.
51
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):928-932.
XI. Training
see footnotes
XII: surveillance
1.
2.
3.
4.
5.
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.
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.
52