ARTICLE
Auteur(s) : David A
Basketter1, John English2
1DABMEB Consultancy, Sharnbrook, Bedfordshire, UK
2Department of Dermatology, Nottingham University
Hospital, Nottingham, UK
accepté le 1 Janvier 2009
Consumer and occupational exposure to skin sensitising
ingredients contained in nearly all hair dyes has long been
associated with a history of allergic contact dermatitis (ACD)
[1-4]. The primary culprit in this respect has been recognised for
many years to be p-phenylenediamine (PPD), although precise details
of its chemical mechanism of sensitisation remain the subject of
investigation [2, 4, 5]. Through its routine use in almost all
standard patch test batteries, the frequency with which it gives
rise to a positive patch test in consecutive patients has been
described in many countries [6-9]. How this translates into a
frequency of allergy in the general adult population is a matter of
inexact extrapolation, but seems likely to be in the order of
1%-3%. Whilst a good proportion of these individuals, for a variety
of reasons, may not express ACD when exposed to PPD during hair
dyeing, it is evident that a significant number do suffer from hair
dye elicited eczema [10-12]. Furthermore, a modest proportion of
them experience adverse reactions to a degree that is beyond a mild
itchy rash, but rather is a more serious eczema and is sometimes
associated with a substantial degree of oedema, particularly of the
face and hand, often requiring a period of hospitalisation
[12-16].
The manufacturers of hair dyes have long recognised that their
products can cause allergy and whilst they might contest the
details of the frequency with which this occurs, for decades they
have recommended the use of a skin sensitivity test prior to each
use of hair dye. It is not the purpose of this paper to debate the
appropriateness of this recommendation. Rather it is to address
whether one particular approach has the potential to work in
practice. At present, there is no standardised system in place. One
major manufacturer has published details of how it considers
sensitivity testing should be undertaken and completed a study in
PPD allergic volunteers to demonstrate its utility [17, 18].
However, as far as the present authors are aware, the use of this
method in hair dyeing salons, at least in the UK, is very low
(probably < 10%). One reason for this is perhaps that the
technical aspects of using a poorly defined “blob” of an active
hair dye mix behind the ear (applied × 3 and dried), 2 days before
hair dyeing are relatively complex for the consumer and/or for
hairdressing salon staff. The Colourstart™ system is a simple rub
on transfer, applied with the use of a little water to wet it (figure 1), where ease
of use is likely to contribute substantially to compliance.
Recently, however, a small clinical study cast doubt on whether
Colourstart™ would in reality identify much more than half of those
at significant risk of a serious adverse reaction to hair dyes
[19]. Consequently, in this present work, we designed a more
structured study to investigate whether and to what extent the low
dose of PPD in the Colourstart™ system would be able to detect
sensitivity to PPD in a panel of volunteers with a previous full
clinical diagnosis of PPD allergy. Further, to gauge more
accurately the practical utility of Colourstart™, groups of 10
patients who had shown 3+, 2+ or 1+ diagnostic patch test
reactivity were assessed using Colourstart™ applied according to
the manufacturer’s instructions. This study cannot inform directly
on the performance of this product in hair dye salon customers, but
unless it can be shown to perform adequately in individuals already
known to be sensitised, then its practical utility would be open to
reasonable challenge. It should be noted that there is no intention
here to suggest that the system provides an alternate diagnostic
tool; the purpose is to try to gauge the extent to which
Colourstart™ has the capacity to provide an alert of a potential
problem prior to hair dyeing in a salon.
Materials and methods
The study was given independent ethical approval by Nottingham
Research Ethics Committee.
Subjects
30 PPD allergic subjects gave fully informed written consent to
participate. Gender (27F, 3M) and age details (range 19-81 years),
together with their patch test history are contained in table 1.
Table 1 Details of participants age, gender and patch
test history
|
PPD diagnostic patch test reaction
|
Age
|
Gender
|
Other patch test reactions
|
|
+++
|
19
|
Female
|
Caine mix III, DPPD
|
|
+++
|
18
|
Female
|
Caine mix III, fragrance mix I, compositae mix, PTD, NPPD, 3 &
4 aminophenol, hydroquinone
|
|
+++
|
19
|
Female
|
Caine mix III, fragrance mix II, IPPD, BHT
|
|
+++
|
18
|
Female
|
None
|
|
+++
|
52
|
Female
|
Ni
|
|
+++
|
47
|
Male
|
Fragrance mix II, PTD, NPPD, 3 & 4 aminophenol, tixocortol
pivalate
|
|
+++
|
35
|
Female
|
PTD
|
|
+++
|
41
|
Female
|
Ni, PTD, NPPD, 4-aminophenol
|
|
+++
|
64
|
Male
|
Ni, epoxy resin, direct orange 34
|
|
+++
|
46
|
Female
|
Caine mix III, Ni, disperse blue mix
|
|
++
|
48
|
Female
|
PTD, 4-aminophenol
|
|
++
|
35
|
Female
|
PTD, NPPD, resorcinol
|
|
++
|
65
|
Female
|
Ni
|
|
++
|
51
|
Female
|
Ni
|
|
++
|
59
|
Female
|
Neomycin, cobalt, quinoline mix, Balsam of Peru, fragrance mix I,
Ni, disperse blue mix, Fragrance mix II, Compositae mix,
benzalkonium chloride, framycetin, sodium metabisulphite, caine mix
IV
|
|
++
|
43
|
Female
|
None
|
|
++
|
42
|
Female
|
Epoxy resin, Ni
|
|
++
|
36
|
Female
|
None
|
|
++
|
40
|
Female
|
Ni, carba mix
|
|
++
|
42
|
Female
|
None
|
|
+
|
25
|
Female
|
None
|
|
+
|
43
|
Female
|
None
|
|
+
|
57
|
Male
|
Quaternium 15, MCI/MI
|
|
+
|
47
|
Female
|
Caine mix II, budesonide, NPPD, ammonium thioglycolate
|
|
+
|
53
|
Female
|
Methyldibromo glutaronitrile
|
|
+
|
36
|
Female
|
Ni
|
|
+
|
50
|
Female
|
Ni
|
|
+
|
61
|
Female
|
Balsam of Peru, EDTA
|
|
+
|
48
|
Female
|
Neomycin, Ni
|
|
+
|
81
|
Female
|
Balsam of Peru
|
Materials
Colourstart™ materials were provided as a gift by the manufacturer,
Trichocare Diagnostics Ltd, Ridgmont, UK. Colourstart™ has a shelf
life of 4 months; all material in this study was well within its
use-by date. The Colourstart™ product contains approximately
15 μg of PPD applied uniformly across an area of
0.5 cm2, leading to a dose of
30 μg/cm2.
Protocol
Patches were applied precisely according to the manufacturer’s
instructions (figure
2). The test sites were read at approximately 48h and
scored both as a simple yes/no, according to whether any sign of a
skin reaction was present, but also using the grading scheme for
diagnostic patch tests [20], so that there would be a standardised
point of comparison. All subjects were invited to report to the
hospital at any time, should adverse reactions occur.
Results
Table 1 shows the details of the
participants in the study. It is interesting to note that the 3
individuals with a history of a black henna tattoo all were
associated with a 3+ diagnostic patch test reaction. table 2 reports the outcome of the application of
Colourstart™. All the most allergic individuals reacted to
Colourstart™, many relatively strongly. Of the 10 individuals who
had a 2+ diagnostic patch test reaction to PPD, 8 reacted to
Colourstart™. Thus, 90% of those who were moderately to strongly
allergic to PPD according to the diagnostic tested were also
positive to Colourstart™. In contrast, only a single individual who
was a 1+ reactor to the diagnostic patch test to PPD also reacted
to Colourstart™; 9/10 were negative. Examples of the skin reactions
obtained to Colourstart™ are given in figure 3 which presents the
responses at test sites in six individuals, ranging from no
response (A) to both weaker (B-D) and much stronger levels of
reaction (E-F).
It is interesting to note that of the 3+ diagnostic patch test
reactors, 90% gave either a +++ or a ++ reaction to Colourstart™.
Among the 2+ patch test reactors, of the 8 who reacted to
Colourstart™, the reactions were generally weaker, with only a
single +++ response, whereas 5 gave a + response. The lone 1+
diagnostic patch test reactor who reacted to Colourstart™ also
reacted only at the 1+ level to Colourstart™.
None of the subjects reported back to the hospital with
strengthening delayed reactions to Colourstart™ after the 48 h
scoring point.
Table 2 Results of testing Colourstart™ in 30 PPD
allergic subjects
|
PPD diagnostic patch test reaction
|
Severity of hair dye reaction
|
Past henna tattoo reaction
|
Colourstart™ reaction
|
Grade of Colourstart™ reaction
|
|
+++
|
Very severe
|
Yes
|
Yes
|
+++
|
|
+++
|
Severe
|
Yes
|
Yes
|
++
|
|
+++
|
Severe
|
Yes
|
Yes
|
+++
|
|
+++
|
None
|
No
|
Yes
|
++
|
|
+++
|
Very severe
|
No
|
Yes
|
+
|
|
+++
|
Severe
|
No
|
Yes
|
+++
|
|
+++
|
Very severe
|
No
|
Yes
|
++
|
|
+++
|
Severe
|
No
|
Yes
|
++
|
|
+++
|
Severe
|
No
|
Yes
|
+++
|
|
+++
|
Very severe
|
No
|
Yes
|
+++
|
|
++
|
Severe
|
No
|
Yes
|
+
|
|
++
|
Severe
|
No
|
Yes
|
++
|
|
++
|
Moderate
|
No
|
Yes
|
+
|
|
++
|
Severe
|
No
|
No
|
Negative
|
|
++
|
Severe
|
No
|
Yes
|
+
|
|
++
|
Very severe
|
No
|
Yes
|
+
|
|
++
|
Very severe
|
No
|
Yes
|
++
|
|
++
|
None
|
No
|
Yes
|
+++
|
|
++
|
Severe
|
No
|
Yes
|
+
|
|
++
|
None
|
No
|
No
|
Negative
|
|
+
|
Severe
|
No
|
No
|
Negative
|
|
+
|
None
|
No
|
No
|
Negative
|
|
+
|
None
|
No
|
No
|
Negative
|
|
+
|
Moderate
|
No
|
No
|
Negative
|
|
+
|
None
|
No
|
No
|
Negative
|
|
+
|
None
|
No
|
Yes
|
+
|
|
+
|
None
|
No
|
No
|
Negative
|
|
+
|
None
|
No
|
No
|
Negative
|
|
+
|
None
|
No
|
No
|
Negative
|
|
+
|
Severe
|
No
|
No
|
Negative
|
Discussion
Allergy to hair dye is an unfortunately common problem and is one
which has usually been attributed to PPD and related chemicals
[1-13], although there are reports of cases where PPD or its
immediate derivatives are clearly not the skin sensitizer involved
[21, 22]. Associated with this is an ongoing effort to identify
whether there may be other chemicals in hair dyes which are
responsible for hair dye allergy [23]. Whatever the chemicals and
chemistry responsible may be however, what remains quite clear is
that hair dyes are associated with a distinct frequency of adverse
reactions and that the manufacturers continue to suggest that
consumers should undertake a sensitivity test prior to use of a
hair dye [17, 18]. This self testing is not without its own
problems, nor free from criticism [19, 24, 25]. These issues
include the basic question of whether such testing in reality
constitutes a medical diagnosis which should therefore only be
conducted by appropriately qualified personnel and whether the
increased exposure to hair dye that must be part of the test
process actually contributes to the risk of the induction of hair
dye allergy. However, the purpose of the present work has a
different intent, that of assessing how well one of the proposed
sensitivity testing systems (Colourstart™) performs, not least in
the light of a recent critique [19].
Colourstart™ is a skin transfer which contains a small amount of
PPD in a hexagonal shape at a dose of 30 μg/cm2. It
offers a standardised approach to the identification of individuals
with PPD sensitivity via its ease of use and relatively long shelf
life. What must be ensured however is that the system functions
properly, i.e. that it identifies those with a substantial,
potentially problematical degree of PPD allergy. It is already
known that PPD allergic individuals whose degree of reactivity is
relatively low can generally tolerate exposure and can continue to
dye their hair [26]. Of course, this may not be a wise strategy
since further exposure risks increasing their reactivity. Such
individuals contrast with those who have a greater degree of
sensitivity to PPD (giving a 2+ reaction to the diagnostic patch
test), of whom only about half say they could continue to dye their
hair, and even more so with the most sensitive individuals (those
giving a 3+ reaction to the diagnostic patch test), who universally
indicate that they can no longer tolerate hair dye exposure [26].
Consequently, a system such as Colourstart™, to be regarded as
appropriately functional, must identify all of those who were 3+
and ideally all of those who were2+; identification of 1+ reactors
might be regarded as more optional. The results presented here
indicate that this is very much how Colourstart™ performed, with
all 3+ reactors being picked up as well as 80% of the 2+ reactors.
The analysis carried out by Ho and colleagues shows that these are
the individuals most at risk of a significant adverse reaction
[26]. It is of note that a single 2+ individual who had experienced
a severe hair dye reaction was negative to Colourstart™. In the
light of the response of the remainder of the test group, one is
left to speculate whether in this individual, the hair dye chemical
responsible for the severity of her reaction was a material other
than PPD and which also does not cross react with it. Consistent
with this, the subject was negative on previous patch testing to
other hair dyes which normally cross react with PPD, her only other
contact allergy being to nickel. Inevitably, a weakness of any
system based only on PPD will be that it will not identify
sensitivity to hair dye chemicals which are neither PPD nor at
least substances that cross react with it well.
The above results with Colourstart™ are at first sight not fully
consistent with the recent data reported by Orton, who found that
only 3/7 PPD allergic patients responded to Colourstart™. Whilst
this overall rate of positivity (43%) is not dramatically different
to that of the present study (63%), it is important to examine the
patient group involved. In this earlier study, all of the 3+ PPD
positives in the diagnostic patch test were also positive to
Colourstart™ (although in one case the reaction was weak), a result
fully consistent with the present work. Furthermore, all of those
(3/3) who were 1+ reactors in the PPD diagnostic patch test were
negative to Colourstart, again a result very much consistent with
the present observations. This leaves only a single 2+ reactor, who
was negative to Colourstart™ in the Orton study; this represents in
reality the only real discrepancy. Since in our hands, Colourstart
was positive in 80% of 2+ reactors, then the individual in the
Orton study could by chance just be one of the “weaker” 2+
diagnostic patch test reactors, a view given credence by their
reaction to 1% PPD in petrolatum being 2+ only at 48h and just 1+
at the 96h scoring point.
To identify more of the 1+ reactors (Colourstart™ only
identified 10%) would require higher exposure to PPD, which may
well be inappropriate, as this must increase the risk of induction
of allergy. This might well be argued to be an inappropriate
strategy for self test systems such as Colourstart™. As noted in a
recent editorial: “A safe, sensitive and reproducible screening
self-test would be a welcome tool to prevent severe allergic
reactions to hair dye.” [24]. The present work provides a key part
of the evidence that this is what Colourstart™ might deliver. The
editorial also raises a number of other very pertinent questions,
not the least of which is the need for training/guidance of those
using self test systems. This might include not only the use and
interpretation of the test, but also suitable commentary on its
accuracy. Clearly, Colourstart™ is unlikely (by design?) to detect
those with only a weak contact allergy to PPD. Furthermore,
although it is likely also to detect those individuals with allergy
to hair dye chemicals closely related to, and which are known to
cross react with, PPD, it will not identify sensitivity to non-PPD
related hair dye allergens. For example, although there is
considerable cross reaction between PPD and PTD, occasional
isolated allergy to PTD is observed [27] and this probably is the
explanation for the failure of Colourstart™ to identify the lone
PTD allergic individual in the Orton study [19].
Acknowledgements
The authors are grateful to the University of Bedfordshire who
provided the necessary funding for this study via the M1 Knowledge
Exchange, a Higher Education Innovation Fund initiative.
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|